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http://www.europrise.org
The European HIV Prevention R&D Network
Europrise SCIENCE UPDATE
Issued on every Monday - The Companion to the EUROPRISE NEWS (issued on every Friday) - Sources: NCBI
(NLM/NIH) – MIS (Medical Intelligence Solutions) - Scope: S&T information of interest to any organisation
involved in HIV/AIDS PREVENTION RESEARCH AND INNOVATION – i.e. research re science, technology,
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This bulletin includes references of articles that are already printed as well as e-publications (ahead of print)
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EUROPRISE SCIENCE UPDATE N° 09-45
0022 N
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Maaiinn H
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Microbicides.............................................................................................................. 7
Diagnosis .................................................................................................................. 8
Epidemiology .......................................................................................................... 10
Health economics ................................................................................................... 20
Immunology ............................................................................................................ 22
Pathology ................................................................................................................ 36
Recommendations & Policies ............................................................................... 37
Therapy, others ....................................................................................................... 49
Vaccines, clinical .................................................................................................... 55
Vaccines, research ................................................................................................. 57
Virology ................................................................................................................... 62
--------------------------------------------------------
---------------------------------------------------------------------------------------------------------Free for Distribution to any interested reader - EUROPRISE contact: [email protected]
Searching within this issue use EDIT / SEARCH function of MS Word
Accuracy of information depends on reliability of sources
The Europrise members do not necessarily share the opinions expressed in the reported items
EUROPRISE SCIENCE UPDATE 09-45
CONTENTS
To go to item please click on page number in this table
To go to PubMed click on link below the abstract
When you have a subscription to the concerned source you can also access the
complete article from PubMed by clicking on source in the window
Please check with your library for copyright compliance in so doing
Microbicides.............................................................................................................. 7
Microbicides Development Programme: Design of a Phase III Trial to Measure the
Efficacy of the Vaginal Microbicide PRO 2000/5 for HIV Prevention ............................ 7
Macaca Fascicularis Are Highly Susceptible to an RT-SHIV Following Intravaginal
Inoculation: a New Model for Microbicide Evaluation ................................................... 7
Microbicide Data Show Promise ..................................................................................... 8
Diagnosis .................................................................................................................. 8
Comparison of the Performance of Rapid HIV Tests Using Samples Collected for
Surveillance in Mozambique ........................................................................................... 8
Use of Two HIV-POCT Tests to Identify False Reactives............................................... 9
Evaluation of the Cavidi ExaVir Load Assay (Version 3) for Plasma Human
Immunodeficiency Virus Type 1 Load Monitoring ......................................................... 9
Epidemiology .......................................................................................................... 10
HIV-1 Incidence Rates and Risk Factors in Agricultural Workers and Dependents in
Rural Kenya: 36-Month Follow-Up of the Kericho HIV Cohort Study ..........................10
HIV Prevalence and Related Risk Factors Among Male Sex Workers in Shenzhen,
China- Results From a Time-Location-Sampling Survey .............................................11
Concurrency Driving the African HIV Epidemics: Where Is the Evidence? - Author's
Reply ................................................................................................................................12
Concurrency Driving the African HIV Epidemics: Where Is the Evidence? ................12
Validation of AIDS-Related Mortality in Botswana ........................................................12
Behavioral Mechanisms in HIV Epidemiology and Prevention: Past, Present, and
Future Roles ....................................................................................................................13
Parental Protectiveness and Unprotected Sexual Activity Among Latino Adolescent
Mothers and Fathers .......................................................................................................14
Condom Attitudes, Perceived Vulnerability, and Sexual Risk Behaviors of Young
Latino Male Urban Street Gang Members: Implications for HIV Prevention ...............14
Familial and Cultural Influences on Sexual Risk Behaviors Among Mexican, Puerto
Rican, and Dominican Youth ..........................................................................................15
Increases in HIV Diagnoses at the U.S.-Mexico Border, 2003-2006 .............................15
Paediatric HIV in Central Sudan: High Sero-Prevalence and Poor Performance of
Clinical Case Definitions ................................................................................................16
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EUROPRISE SCIENCE UPDATE 09-45
The Changing Face of the HIV Epidemic in Taiwan: a New Challenge for Public
Health Policy Strategies .................................................................................................17
Young People in the United Kingdom and Ireland With Perinatally Acquired HIV: the
Pediatric Legacy for Adult Services ..............................................................................17
The Mathematics of Concurrent Partnerships and HIV: A Commentary on Lurie and
Rosenthal, 2009 ...............................................................................................................18
Occupational Blood Exposure Accidents in the Netherlands ......................................18
[Personnel at Risk for Occupational Blood Exposure in a University Hospital in West
Algeria].............................................................................................................................19
Health economics ................................................................................................... 20
Primary Care Consultations and Costs Among HIV Positive Individuals in UK
Primary Care 1995-2005: a Cohort Study ......................................................................20
HIV Drug Patents in the Spotlight ..................................................................................21
What Impact Might the Economic Crisis Have on HIV Epidemics in Southeast Asia?
..........................................................................................................................................21
Immunology ............................................................................................................ 22
Involvement of Tyrosine Phosphatase CD45 in Apoptosis ..........................................22
Integration of HIV-1 DNA Is Regulated by Interplay Between Viral Rev and Cellular
LEDGF/P75 Proteins .......................................................................................................22
HIV-1 MRNA 3' End Processing Is Distinctively Regulated by EIF3f, CDK11, and
Splice Factor 9G8 ............................................................................................................23
Mucosal Immunology of the Genital and Gastrointestinal Tracts and HIV-1 Infection
..........................................................................................................................................23
Clinical Outcomes of Elite Controllers, Viremic Controllers, and Long-Term
Nonprogressors in the US Department of Defense HIV Natural History Study ..........24
Natural Control of HIV-1 Replication and Long-Term Nonprogression: Overlapping
but Distinct Phenotypes .................................................................................................25
Spermatozoa Capture HIV-1 Through Heparan Sulfate and Efficiently Transmit the
Virus to Dendritic Cells ...................................................................................................25
HIV Sticks to Sperm ........................................................................................................26
Cell-Mediated Immunity to HIV in the Female Reproductive Tract ..............................26
[Influenza Vaccination of Immunocompromised Patients: Safe and Effective] ..........27
Treatment and CD4(+) T Cell Count Recovery Among Antiretroviral Therapy-Naive
Patients With HIV/AIDS ...................................................................................................27
T Cell Dynamics and the Response to HAART in a Cohort of HIV-1-Infected Elite
Suppressors ....................................................................................................................27
Imaging the Interaction of HIV-1 Genomes and Gag During Assembly of Individual
Viral Particles ..................................................................................................................28
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EUROPRISE SCIENCE UPDATE 09-45
[VIR576 Inhibits Antigen-Specific T Cell Activation by Binding to the Transmembrane
Domain of T Cell Receptor.] ...........................................................................................29
Bacille Calmette-Guerin Vaccine-Related Disease in HIV-Infected Children: a
Systematic Review ..........................................................................................................29
HIV1 Vpr Arrests the Cell Cycle by Recruiting DCAF1/VprBP, a Receptor of the Cul4DDB1 Ubiquitin Ligase....................................................................................................30
Simian Immunodeficiency Virus Envelope Glycoprotein Counteracts Tetherin/BST2/CD317 by Intracellular Sequestration .........................................................................30
Chronic CD70-Driven Costimulation Impairs IgG Responses by Instructing T Cells to
Inhibit Germinal Center B Cell Formation Through FasL-Fas Interactions .................31
LEDGF Interacts With the S-Phase Kinase Cdc7:ASK and Stimulates Its Enzymatic
Activity .............................................................................................................................32
Evaluation of CD4-CD4i Antibody Architectures Yields Potent, Broadly CrossReactive Anti-HIV Reagents ...........................................................................................32
Dual Mechanism for the Impairment of IL-7 Responses in HIV Infection: Decreased
IL-7 Binding and Abnormal Activation of the JAK/STAT5 Pathway.............................33
Bioorganic Synthesis of a Recombinant HIV-1 Fusion Inhibitor, SC35EK, With an NTerminal Pyroglutamate Capping Group .......................................................................34
The Influence of Variations in the DNA Repair (XRCC1) Gene on HIV-1/AIDS Among
Indian Population ............................................................................................................34
CD4 T Cell Subsets in the Mucosa Are CD28Ki-67HLA-DRCD69 but Show Differential
Infection Based on Alpha4beta7 Receptor Expression During Acute SIV Infection ..35
Pathology ................................................................................................................ 36
[Neoplasms and HIV in the Epidemic's Third Decade.] ................................................36
HIV and the Kidney..........................................................................................................36
HIV and the Brain: New Challenges in the Modern Era Edited by R. H. Paul , N. C.
Sacktor , V. Valcour , and K. T. Tashima New York: Humana Press, 2009. 350 Pp.
$139.00 (Hardcover) ........................................................................................................36
Tegumentary Leishmaniasis As the Cause of Immune Reconstitution Inflammatory
Syndrome in a Patient Co-Infected With Human Immunodeficiency Virus and
Leishmania Guyanensis .................................................................................................37
Recommendations & Policies ............................................................................... 37
[Communication of Health Risks : The Example of HIV/AIDS Prevention.].................37
Increasing HIV Testing in General Practice: Brief Advice Seems to Work .................38
Using Mathematical Modelling to Estimate the Impact of Periodic Presumptive
Treatment on the Transmission of STIs and HIV Amongst Female Sex Workers.......38
Model and Experiences of Initiating Collaboration With Traditional Healers in
Validation of Ethnomedicines for HIV/AIDS in Namibia ...............................................39
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EUROPRISE SCIENCE UPDATE 09-45
Integration of STI and HIV Prevention, Care, and Treatment into Family Planning
Services: a Review of the Literature ..............................................................................40
From Research to Community-Based Practice--Working With Latino Researchers to
Translate and Diffuse a Culturally Relevant Evidence-Based Intervention: the Modelo
De Intervencion Psicomedica (MIP) Experience ...........................................................41
The Implementation of a Culturally Based HIV Sexual Risk Reduction Program for
Latino Youth in a Denver Area High School ..................................................................41
Diffusion of Effective Behavioral Interventions and Hispanic/Latino Populations.....42
Hombres Sanos: Exposure and Response to a Social Marketing HIV Prevention
Campaign Targeting Heterosexually Identified Latino Men Who Have Sex With Men
and Women ......................................................................................................................42
A Quasi-Experimental Evaluation of a Community-Based HIV Prevention Intervention
for Mexican American Female Adolescents: the SHERO's Program ...........................43
Outcomes From a Community-Based, Participatory Lay Health Adviser HIV/STD
Prevention Intervention for Recently Arrived Immigrant Latino Men in Rural North
Carolina............................................................................................................................44
Drug Use and Hispanic Men Who Have Sex With Men in South Florida: Implications
for Intervention Development .........................................................................................44
Summary of Comments and Recommendations From the CDC Consultation on the
HIV/AIDS Epidemic and Prevention in the Hispanic/Latino Community .....................45
Foreword: HIV/AIDS Prevention in the Hispanic/Latino Community ...........................46
Use of Post-Natal Antiretroviral Prophylaxis for Prevention of Mother-to-Child
Transmission of HIV Is Increasing in Italy .....................................................................46
Knowledge of the Centers for Disease Control and Prevention's 2006 Routine HIV
Testing Recommendations Among New York City Internal Medicine Residents .......46
USA Looks Set to Repeal HIV Travel Ban ......................................................................47
Regarding Inconsistent Prevention of Mother-to-Child Transmission of HIV
Guidelines: Is WHO a Victim or Villain? ........................................................................47
Clinical Practice. Postexposure Prophylaxis for HIV Infection ....................................48
Contextual or Universal Ethics: a Non-Issue? Viewpoint.............................................48
Therapy, others ....................................................................................................... 49
Etravirine for HIV-1: Addressing the Limitations of the Nonnucleoside Reverse
Transcriptase Inhibitor Class .........................................................................................49
Early Nucleoside Reverse Transcriptase Inhibitors for the Treatment of HIV: A Brief
History of Stavudine (D4T) and Its Comparison With Other Dideoxynucleosides .....49
2.4 HIV Protease Inhibitors .............................................................................................50
Understanding and Managing the Adverse Effects of Antiretroviral Therapy ............50
Patient-Related Risks for Nonadherence to Antiretroviral Therapy Among HIVInfected Youth in the United States: a Study of Prevalence and Interactions ............51
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EUROPRISE SCIENCE UPDATE 09-45
Development and Efficacy of an Intervention to Enhance Readiness for Adherence
Among Adults Who Had Previously Failed HIV Treatment ..........................................52
Antiretroviral Treatment Initiation Among HIV-Infected Pregnant Women With Low
CD4+ Cell Counts in Gaborone, Botswana....................................................................53
Trends in Uptake of Recently Approved Antiretrovirals Within a National Healthcare
System .............................................................................................................................53
Clinical Pharmacology, Efficacy and Safety of Atazanavir: a Review .........................54
Vaccines, clinical .................................................................................................... 55
Full Data From Thai HIV Vaccine Study Show No Significant Protective Effect .........55
Jury Still Out on HIV Vaccine Results............................................................................55
Adenovirus Vector-Specific T Cells Demonstrate a Unique Memory Phenotype With
High Proliferative Potential and Coexpression of CCR5 and Integrin Alpha4beta7 ...55
Phylodynamics of HIV-1 From a Phase III AIDS Vaccine Trial in North America ........56
Vaccines, research ................................................................................................. 57
Variable Epitope Library-Based Vaccines: Shooting Moving Targets.........................57
Ovine Atadenovirus, a Novel and Highly Immunogenic Vector in Prime-Boost
Studies of a Candidate HIV-1 Vaccine ...........................................................................58
Polysaccharide-Based Vaccine Delivery Systems: Macromolecular Assembly,
Interactions With Antigen Presenting Cells, and in Vivo Immunomonitoring ............58
Monkeying Around With HIV Vaccines: Using Rhesus Macaques to Define
'Gatekeepers' for Clinical Trials .....................................................................................59
Improving the Expression of Recombinant Soluble HIV Envelope Glycoproteins
Using Pseudo-Stable Transient Transfection ...............................................................60
Prime-Boost Immunization of Codon Optimized HIV-1 CRF01_AE Gag in BCG With
Recombinant Vaccinia Virus Elicits MHC Class I and II Immune Responses in Mice 60
Vaccination With SIVmac239Deltanef Activates CD4 T Cells in the Absence of CD4 TCell Loss ..........................................................................................................................61
Enhancing Efficacy and Mucosa-Tropic Distribution of an Oral HIV-PsV DNA Vaccine
in Animal Models.............................................................................................................62
Virology ................................................................................................................... 62
Application of an Allele-Specific PCR to Clinical HIV Genotyping Samples Detects
Additional K103N Mutations in Both Therapy Naive and Experienced Patients .........62
Five-Year Follow Up of Genotypic Resistance Patterns in HIV-1 Subtype C Infected
Patients in Botswana After Failure of Thymidine Analogue-Based Regimens ...........63
The Capsid Protein of Human Immunodeficiency Virus: Molecular Recognition and
Design of Antiviral Agents..............................................................................................64
Diversity of HIV Strains Impacts Diagnostic Test Accuracy ........................................64
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EUROPRISE SCIENCE UPDATE 09-45
The Mechanism of Budding of Retroviruses From Cell Membranes ...........................64
Evolutionary Fingerprinting of Genes ...........................................................................65
Transient Virulence of Emerging Pathogens ................................................................66
Inferring Within-Patient HIV-1 Evolutionary Dynamics Under Anti-HIV Therapy Using
Serial Virus Samples With VSPA....................................................................................66
[A New Human Immunodeficiency Virus Derived From Gorillas] ................................67
--------------------------
Microbicides
Microbicides Development Programme: Design of a Phase III Trial
to Measure the Efficacy of the Vaginal Microbicide PRO 2000/5 for
HIV Prevention
NUNN A., McCormack, S., Crook, A. M., Pool, R., Rutterford, C., and Hayes, R.
Trials. 10 (1), 99 ,2009--ENG
ABSTRACT: BACKGROUND: With 2.5 million new HIV infections per year, effective
preventive methods against HIV are urgently needed, especially in sub-Saharan Africa.
MDP301 is an ongoing trial of the vaginal microbicide PRO 2000/5 being conducted by the
Microbicides Development Programme. The main objective of the trial is to determine the
efficacy and safety of 0.5% and 2% concentrations of PRO 2000/5 gel compared to placebo in
preventing vaginally acquired HIV infection. METHODS: MDP301 is a multicentre
randomised placebo-controlled Phase III trial. The design was informed by pre-trial
feasibility and pilot studies. The choice of trial population, assessments and endpoints are
discussed along with statistical and ethical considerations. Adaptations to the design were
made during the conduct of the trial; these included closing a study arm and changing the
timing of the primary endpoint. DISCUSSION: The development of effective microbicide
products remains one of the strongest hopes for new biomedical prevention tools. MDP301 is
the largest Phase III microbicide trial to date, with 9404 enrolments, and is scheduled for
completion in September 2009. Results are expected towards the end of 2009. Trial
registration: Current controlled trials ISRCTN64716212
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19860888
------------------------------------------------------
Macaca Fascicularis Are Highly Susceptible to an RT-SHIV
Following Intravaginal Inoculation: a New Model for Microbicide
Evaluation
JIANG Y., Tian, B., Agy, M. B., Saifuddin, M., and Tsai, C. C.
J.Med.Primatol. 38 (s126th Annual Symposium of Nonhuman Primate Models for AIDS), 3946 ,2009
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AD - Washington National Primate Research Center, University of Washington, Seattle, WA,
USA-ENG
Background Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a
major target for antiretroviral strategy to block or curtail HIV infection. A suitable RTSHIV/macaque model is urgently needed for the evaluation of HIV/AIDS therapies and
microbicides specifically targeting HIV-1 RT. Methods Fifteen cynomolgus macaques
(Macaca fascicularis) were divided into three groups (n = 5) and intravaginally inoculated
with 4800, 1200, or 300 TCID(50) of RT-SHIVtc. Systemic infections of RT-SHIVtc exposed
macaques were determined by both virological and immunologic parameters during 24
weeks post-challenge. Results Within 2 weeks post-inoculation, 13 of 15 macaques became
infected as confirmed by virus isolation, plasma viral RNA, proviral DNA, declined CD4(+)T
cell counts in peripheral blood and seroconversion. Conclusions Results serve to validate the
infectivity and pathogenicity of RT-SHIVtc following vaginal exposure in M. fascicularis.
This RT-SHIVtc/macaque model could be suitable for the pre-clinical evaluation of nonnucleoside RT inhibitor-based anti-HIV microbicides
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19863677
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Microbicide Data Show Promise
AIDS Patient.Care STDS. 23 (3), 223-224 ,2009
engLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19480060
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Diagnosis
Comparison of the Performance of Rapid HIV Tests Using Samples
Collected for Surveillance in Mozambique
MELO J., Nilsson, C., Mondlane, J., Osman, N., Biberfeld, G., Folgosa, E., and Andersson, S.
J.Med.Virol. 81 (12), 1991-1998 ,2009
AD - Department of Microbiology, Faculty of Medicine, University Eduardo Mondlane,
Maputo, Mozambique-ENG
Mozambique had low HIV prevalence until the mid-1990s, but recent data indicate
increasing rates. There is little information on HIV-2. Therefore, HIV seroprevalence was
assessed among pregnant women and field-ready HIV diagnostic strategies were evaluated.
A total of 6,930 samples collected by three health centers from 2002 to 2005 were tested on
site by nurses with two simple/rapid tests, Determine HIV-1/2 (Abbott Laboratories;
screening) and Uni-Gold HIV (Trinity Biotech; confirmation), which is the national HIV
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EUROPRISE SCIENCE UPDATE 09-45
testing strategy. The prevalence of HIV was 14.0% (2002), 17.8% (2003), 16.5% (2004), and
20.2% (2005). A subset of 888 samples collected 2003 was sent to the Central Microbiology
Laboratory, Maputo for evaluation of tests and testing strategies. The assays included for
comparison were Capillus HIV-1/HIV-2 (Trinity Biotech), DoubleCheckGold HIV-1&2
(Orgenics) and Enzygnost Anti-HIV-1/2 Plus (Behringwerke, reference ELISA).
Confirmation of reactive samples was done by Uni-Gold HIV and ImmunoComb II HIV-1&2
BiSpot (for HIV type differentiation). The Capillus HIV-1/ HIV-2 + ImmunoComb II HIV1&2 BiSpot combination was the gold standard. The sensitivity of the rapid/simple
screening assays (Determine HIV-1/2, DoubleCheckGold HIV-1&2) was 100% (N = 160) and
their (initial) specificities were 99.6% and 99.7%, respectively. Repeated testing and
combinations of assays increased the specificity. Four suspected cases of recent
seroconversion were found. Together with the increasing prevalence rates, this may indicate
that Mozambique is a high-incidence area, although further studies are needed to confirm
this. Testing strategies for on-site screening and confirmation based on the combination of
Determine HIV-1/2, Uni-Gold HIV and DoubleCheckGold HIV-1&2 are well suited for local
field use. J. Med. Virol. 81:1991-1998, 2009. (c) 2009 Wiley-Liss, Inc
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19856475
-----------------------------------------------------Diagnosis
Use of Two HIV-POCT Tests to Identify False Reactives
TEAGUE A., Rossi, M., Gilmour, C., Watson, L., Atkins, M., and McOwan, A.
Int.J.STD AIDS. 2009
AD - The Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK
ENGLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19854884
-----------------------------------------------------Diagnosis
Evaluation of the Cavidi ExaVir Load Assay (Version 3) for Plasma
Human Immunodeficiency Virus Type 1 Load Monitoring
GREENGRASS V. L., Plate, M. M., Steele, P. M., Denholm, J. T., Cherry, C. L., Morris, L. M.,
Hearps, A., and Crowe, S. M.
J.Clin.Microbiol. 47 (9), 3011-3013 ,2009
AD - Clinical Research Laboratory, Centre for Virology, Macfarlane Burnet Institute for
Medical Research and Public Health, 85 Commercial Road, Melbourne, Australia--eng
We evaluated the new low-cost ExaVir Load (version 3) reverse transcriptase viral load assay
against the Roche Cobas Amplicor assay. Results for samples tested using the reverse
transcriptase assay correlated well with those obtained with the Roche assay (r = 0.85; n =
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EUROPRISE SCIENCE UPDATE 09-45
202). The version 3 reverse transcriptase assay shows improved sensitivity compared to the
previous version
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19605583
------------------------------------------------------
Epidemiology
HIV-1 Incidence Rates and Risk Factors in Agricultural Workers and
Dependents in Rural Kenya: 36-Month Follow-Up of the Kericho HIV
Cohort Study
SHAFFER D. N., Ngetich, I. K., Bautista, C. T., Sawe, F. K., Renzullo, P. O., Scott, P. T.,
Kibaya, R. M., Imbuki, K. O., Michael, N. L., Birx, D. L., Wasunna, M. K., and Robb, M. L.
J.Acquir.Immune.Defic.Syndr. 2009
AD - From the *US Military HIV Research Program, Rockville, MD, USA; daggerUnited
States Army Medical Research Unit, Kericho, Kenya; double daggerWalter Reed Army
Institute of Research, Rockville, MD, USA; section signKenya Medical Research Institute,
Kericho and Nairobi, Kenya; ||Henry M Jackson Foundation for the Advancement of
Military Medicine, Inc, Rockville, MD, USA; paragraph signDivision of AIDS, National
Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD,
USA; and #D L Birx is currently affiliated with the Global AIDS Program, US Centers for
Disease Control and Prevention, Atlanta, GA--ENG
BACKGROUND:: Incidence data from prospective cohort studies using rigorous laboratory
methods are important in designing and evaluating HIV vaccine and therapeutic clinical
trials and health care programs. We report 36-month HIV-1 incidence rates and demographic
and psychosocial risks from the Kericho cohort in rural Kenya's southern Rift Valley
Province. METHODS:: Thirty-six month, prospective, closed, observational cohort study of
adult plantation workers and dependents followed biannually. HIV-1 incidence rates per 100
person-years (py) were calculated, and Cox regression analyses were used to estimate
hazards ratios (HR) associated with seroconversion. RESULTS:: Two thousand four hundred
volunteers (mean age +/- SD = 30.1 +/- 8.5 years; 36.5% women) participated. Twenty-nine
new HIV cases were identified in year 1 of follow-up, which increased to cumulative totals of
49 and 63 cases in years 2 and 3, respectively. The corresponding 1-, 2-, and 3-year incidence
rates were 1.41 [95% confidence interval (CI) = 0.95-2.02], 1.16 (95% CI = 0.86-1.54), and 1.00
(95% CI = 0.77-1.28) per 100 py. Risk factors associated with HIV seroconversion included
the following: of the Luo tribe (HR = 3.31; 95% CI = 1.65-6.63), marriage more than once (HR
= 2.83; 95% CI = 1.20-6.69), self-reported male circumcision (HR = 0.32; 95% CI = 0.17-0.60),
history of sexually transmitted infection (HR = 2.40; 95% CI = 1.09-5.26), history of substance
abuse during sex (HR = 2.44; 95% CI = 1.16-5.13), and history of transactional sex (HR = 3.30;
95% CI = 1.79-6.09). CONCLUSIONS:: HIV-1 incidence rates were relatively low in adult
plantation workers and dependents in rural Kenya. Cohorts including higher risk
populations (eg, commercial sex workers) warrant consideration for regional HIV preventive
vaccine trials. Even low incidence, well-described cohorts generate valuable epidemiological
clinical trial data
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Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19855286
-----------------------------------------------------Epidemiology
HIV Prevalence and Related Risk Factors Among Male Sex Workers
in Shenzhen, China- Results From a Time-Location-Sampling
Survey
CAI W. D., Zhao, J., Zhao, J. K., Raymond, H. F., Feng, Y. J., Liu, J., McFarland, W., Gan, Y.
X., Yang, Z. R., Zhang, Y., Tan, J. G., He, M. L., Wang, X. R., Chen, L., and Cheng, J. Q.
Sex Transm.Infect. 2009
AD - Shenzhen Center for Disease Control and Prevention, China;-ENG
BACKGROUND: HIV transmission among men who have sex with men has become a major
concern recently in China. However, little is known about HIV transmission among male sex
workers (MSWs). This study aimed to investigate HIV infection prevalence and risk factors
among MSWs in Shenzhen, China. Materials and METHODS: Following formative research,
a cross-sectional study was conducted using time-location sampling (TLS) among MSWs in
Shenzhen, from April to July, 2008. Behavioral and serologic data on HIV and syphilis were
collected. The risk factors for HIV infection were analyzed using a logistic regression model.
RESULTS: In total, 394 male sex workers were recruited for the survey. The prevalence of
HIV and syphilis among these workers was 5.3% and 14.3%, respectively. Only a quarter of
the MSWs self-identified as homosexual. More than 70% had sex with both men and women.
HIV-related knowledge levels were high regardless of HIV sero-status. Consistent condom
use was low (37.1%) and varied by type of sexual partner. Factors including more noncommercial male partners, working in small home-based family clubs, being drunk prior to
sexual intercourse, having a history of HIV tests, syphilis infection and short period of
residence in Shenzhen were associated with an increased risk of HIV infection.
CONCLUSIONS: High-risk sexual practices were common among male sex workers
regardless of their high level of HIV awareness. The working venues were associated with
HIV infection and a recent test for HIV was a potential predictor for HIV infection. The TLS
method was found to be an appropriate way of recruiting male sex workers for this study,
especially those without fixed working places
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19854703
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Epidemiology
Concurrency Driving the African HIV Epidemics: Where Is the
Evidence? - Author's Reply
SHELTON J. D.
Lancet. 374 (9699), 1420-1421 ,2009
AD - US Agency for International Development, Washington, DC 20523, USA
engLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19854370
-----------------------------------------------------Epidemiology
Concurrency Driving the African HIV Epidemics: Where Is the
Evidence?
LURIE M., Rosenthal, S., and Williams, B.
Lancet. 374 (9699), 1420 ,2009
AD - International Health Institute, Warren Alpert Medical School, Brown University,
Providence,
RI
02912,
USA
engLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19854369
-----------------------------------------------------Epidemiology
Validation of AIDS-Related Mortality in Botswana
TAFFA N., Will, J. C., Bodika, S., Packel, L., Motlapete, D., Stein, E., Roels, T. H., Kennedy,
G., and Shenaaz, E. H.
J.Int.AIDS Soc. 12 (1), 24 ,2009--ENG
ABSTRACT: BACKGROUND: Mortality data are used to conduct disease surveillance,
describe health status and inform planning processes for health service provision and
resource allocation. In many countries, HIV- and AIDS-related deaths are believed to be
under-reported in government statistics. METHODS: To estimate the extent of underreporting of HIV- and AIDS-related deaths in Botswana, we conducted a retrospective study
of a sample of deaths reported in the government vital registration database from eight
hospitals, where more than 40% of deaths in the country in 2005 occurred. We used the
consensus of three physicians conducting independent reviews of medical records as the
gold standard comparison. We examined the sensitivity, specificity and other validity
statistics. RESULTS: Of the 5276 deaths registered in the eight hospitals, 29% were HIV- and
AIDS-related. The percentage of HIV- and AIDS-related deaths confirmed by physician
consensus (positive predictive value) was 95.4%; however, the percentage of non-HIV- and
non-AIDS-related deaths confirmed (negative predictive value) was only 69.1%. The
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sensitivity and specificity of the vital registration system was 55.7% and 97.3%, respectively.
After correcting for misclassification, the percentage of HIV- and AIDS--related deaths was
estimated to be in the range of 48.8% to 54.4%, depending on the definition. CONCLUSION:
Improvements in hospitals and within government offices are necessary to strengthen the
vital registration system. These should include such strategies as training physicians and
coders in accurate reporting and recording of death statistics, implementing continuous
quality assurance methods, and working with the government to underscore the importance
of using mortality statistics in future evidence-based planning
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19852854
-----------------------------------------------------Epidemiology
Behavioral Mechanisms in HIV Epidemiology and Prevention: Past,
Present, and Future Roles
BINGENHEIMER J. B. and Geronimus, A. T.
Stud.Fam.Plann. 40 (3), 187-204 ,2009
AD - Population Research Institute, Pennsylvania State University, 601 Oswald Tower,
University Park, PA 16802, USA [email protected]
In the 1980s, behavioral variations across geographically and socially defined populations
were the central focus of AIDS research, and behavior change was seen as the primary means
of controlling HIV epidemics. Today, biological mechanisms--especially other sexually
transmitted infections, antiretroviral therapy, and male circumcision--predominate in HIV
epidemiology and prevention. We describe several reasons for this shift in emphasis.
Although the shift is understandable, we argue for a sustained focus on behavioral
mechanisms in HIV research in order to realize the theoretical promise of interventions
targeting the biological aspects of HIV risk. We also provide evidence to suggest that large
reductions in HIV prevalence may be accomplished by small changes in behavior. Moreover,
we contend that behavioral mechanisms will find their proper place in HIV epidemiology
and prevention only when investigators adopt a conceptual model that treats prevalence as a
determinant as well as an outcome of behavior and that explicitly recognizes the dynamic
interdependence between behavior and other epidemiological and demographic parameters
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19852409
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Epidemiology
Parental Protectiveness and Unprotected Sexual Activity Among
Latino Adolescent Mothers and Fathers
LESSER J., Koniak-Griffin, D., Huang, R., Takayanagi, S., and Cumberland, W. G.
AIDS Educ.Prev. 21 (5 Suppl), 88-102 ,2009
AD - University of Texas Health Science Center, School of Nursing, San Antonio, TX 782293900, USA [email protected]
Latino pregnant and parenting adolescents living in inner cities are one of the populations at
risk for acquiring HIV. Although teen parenthood has been predominantly looked at with a
focus on potential adverse physical, emotional, and socioeconomic outcomes for the mother
and child; a growing body of literature has documented the strengths and resiliency of
young parents. Respeto/Proteger: Respecting and Protecting Our Relationships is a
culturally rooted couple-focused and asset-based HIV prevention program developed for
young Latino parents. In this program, parental protectiveness (defined as the parent-child
emotional attachment that positively influences parental behavior) is viewed as an intrinsic
and developing critical factor that supports resiliency and motivates behavioral change. The
primary purpose of this article is to describe the longitudinal randomized study evaluating
the effect of this intervention on unprotected vaginal sex 6 months post intervention and to
determine whether parental protectiveness had a moderating effect on the intervention. The
unique features of our database allow for examination of both individual and couple
outcomes
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19824837
-----------------------------------------------------Epidemiology
Condom Attitudes, Perceived Vulnerability, and Sexual Risk
Behaviors of Young Latino Male Urban Street Gang Members:
Implications for HIV Prevention
BROOKS R. A., Lee, S. J., Stover, G. N., and Barkley, T. W., Jr.
AIDS Educ.Prev. 21 (5 Suppl), 80-87 ,2009
AD - Center for HIV Identification, Prevention, and Treatment Services, Semel Institute,
University of California, Los Angeles, CA, USA [email protected]
We examined condom attitudes, perceived vulnerability to HIV, HIV testing experiences,
and sexual and substance use risk behaviors of 161 active Latino male gang members, aged
18-26 years old, living in Los Angeles, California. Gang members reported negative condom
attitudes and a perceived vulnerability to HIV. The majority (53%) of gang members
reported unprotected vaginal intercourse (UVI) in the previous 12 months. Multivariate
analyses indicated that participants who engaged in the following behaviors were more
likely to report UVI: had sex with someone they just met (adjusted odds ratio [AOR] = 3.66),
received money or drugs for sex (AOR = 5.05), or had sex with someone who had a sexually
transmitted disease (AOR = 4.99). Participants with a higher perceived vulnerability to HIV
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were less likely to report UVI (AOR = 0.82). Our findings offer implications for development
of an HIV prevention intervention for Latino male gang members
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19824836
-----------------------------------------------------Epidemiology
Familial and Cultural Influences on Sexual Risk Behaviors Among
Mexican, Puerto Rican, and Dominican Youth
GUILAMO-RAMOS V., Bouris, A., Jaccard, J., Lesesne, C., and Ballan, M.
AIDS Educ.Prev. 21 (5 Suppl), 61-79 ,2009
AD - School of Social Work, Columbia University, New York, NY 10027, USA
[email protected]
The present study examined the relationship among acculturation, familismo, and HIVrelated adolescent sexual risk behavior. Data were collected from Latino mother-adolescent
dyads to permit parent and adolescent analyses of familismo for predicting oral, vaginal, and
anal sexual behaviors. A random sample of 702 Latino eighth-grade students and their
mothers was recruited from New York City. The sample included Mexicans (n = 203), Puerto
Ricans (n = 239), and Dominicans (n = 260). Acculturation was unrelated to sexual behavior,
but adolescent familismo was related to girls' but not boys' sexual behavior. The most
important facet of familismo was subjugation to the family, which was negatively associated
with girls' sexual behavior. The implications for HIV prevention programs for Latino youth
are discussed
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19824835
-----------------------------------------------------Epidemiology
Increases in HIV Diagnoses at the U.S.-Mexico Border, 2003-2006
ESPINOZA L., Hall, H. I., and Hu, X.
AIDS Educ.Prev. 21 (5 Suppl), 19-33 ,2009
AD - Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis,
STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333,
USA [email protected]
The population at the U.S.-Mexico border has experienced growth, more than double the
U.S. national average. Movements of populations in this region have contributed to
increased incidence of certain infectious diseases. We used information on persons
diagnosed with HIV during 2003 to 2006 and aged 13 years or older (n = 4,279) reported to
the Centers for Disease Control and Prevention for 45 U.S. border counties. We estimated the
annual percent change and rates with Poisson regression. Overall, 47% of persons diagnosed
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with HIV in the border region were Hispanic; 39% nonHispanic white; and 10% nonHispanic
black. During 2003 to 2006, HIV diagnoses increased 7.8% per year. Increases were observed
among males, particularly among men who have sex with men. Among females, HIV
diagnoses remained stable but decreased among females in nonborder regions. The number
of HIV diagnoses at the border has increased. To decrease incidence of HIV disease it is
necessary to develop prevention and education programs specific to this region
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19824832
-----------------------------------------------------Epidemiology
Paediatric HIV in Central Sudan: High Sero-Prevalence and Poor
Performance of Clinical Case Definitions
ABBAS A. A., Gabo, N. E., Babiker, Z. O., and Herieka, E. A.
J.Clin.Virol. 2009
AD - Faculty of Medicine, University of Medical Sciences and Technology, P O Box 12810,
Khartoum, Sudan--ENG
BACKGROUND: Paediatric clinical case definitions (CCDs) for the human
immunodeficiency virus (HIV) have been proposed as screening tools in resource-limited
countries. OBJECTIVES: We assessed the performance of the World Health Organisation
CCD (WHO-CCD), the Bloemfontein CCD (B-CCD) and a locally modified version of the
Bloemfontein CCD (MB-CCD) in comparison with HIV serology in acutely hospitalised
children aged 1.5-14 years. We also determined the HIV sero-prevalence among this group of
children. STUDY DESIGN: A cohort of 106 consecutive acute paediatric admissions to a
major teaching hospital in central Sudan was recruited over a 3-month period. RESULTS:
The WHO-CCD, B-CCD, and MB-CCD were relatively specific with estimates of 96.0% (95%
confidence interval [CI] 90.1-98.9), 88.0% (95% CI 80.0-93.6), and 74.0% (95% CI 64.3-82.3),
respectively. However, corresponding sensitivities were poor with estimates of 16.7% (95%
CI 0.4-64.1), 33.3% (95% CI 4.3-77.7), and 66.7% (95% CI 22.3-95.7), respectively. The HIV
sero-prevalence was high at 5.7% (95% CI 2.1-11.9). CONCLUSIONS: CCDs performed
poorly against HIV serology in acutely hospitalised children aged 1.5-14 years in central
Sudan and, therefore, we advocate improving access to serological diagnostic tools. The high
HIV sero-prevalence rate among this group of children poses serious challenges to policy
makers and warrants further research
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19857992
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Epidemiology
The Changing Face of the HIV Epidemic in Taiwan: a New Challenge
for Public Health Policy Strategies
CHEN K. T., Chang, H. L., Chen, C. T., and Chen, Y. A.
AIDS Patient.Care STDS. 23 (3), 195-201 ,2009
AD - Department of Public Health, College of Medicine, National Cheng Kung University,
No 1, University Road, Tainan 70101, Taiwan [email protected]
The goals of this study were to examine trends, risk factors, and survival rates of people
diagnosed with HIV/AIDS. We used national surveillance data reported to the Taiwan
Center for Disease Control (Taiwan CDC). The subjects of this study were all confirmed HIV
and AIDS cases in Taiwan. From 1990 through 2005, the number of people that have been
reported to have HIV/AIDS is 9961. Among individuals with HIV/AIDS, the male-to-female
ratio was 11:1, the median age was 32 years. The number of HIV and AIDS diagnoses
increased significantly for both men and women during the study period. The number of
HIV cases among men who have sex with men (MSM) increased from 24 in 1990 to 527 in
2005, while diagnoses among injection drug users (IDUs) rose rapidly from 3 in 1990 to 2450
in 2005. The incidence-to-prevalence ratio (IPR) has risen sharply in recent years and has
exceeded the epidemic threshold (IPR(t) = 0.1) for IDUs, indicating a growing epidemic. The
corresponding hazard ratios for the highly active antiretroviral therapy (HAART) era versus
pre-HAART era in the earlier and late HIV diagnosis groups were 0.45 (95% confidence
interval [CI] 0.36-0.54) and 0.39 (95% CI 0.31-0.49), respectively. There was no significant
difference in the survival rate of HIV testers. The increasing number of HIV infection places
Taiwan among the worst IDU-concentrated epidemic areas in Asia. HIV intervention and
prevention strategies, especially targeting IDUs, are urgently needed to reduce the ongoing
spread of HIV infections in Taiwan
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19866537
-----------------------------------------------------Epidemiology
Young People in the United Kingdom and Ireland With Perinatally
Acquired HIV: the Pediatric Legacy for Adult Services
FOSTER C., Judd, A., Tookey, P., Tudor-Williams, G., Dunn, D., Shingadia, D., Butler, K.,
Sharland, M., Gibb, D., and Lyall, H.
AIDS Patient.Care STDS. 23 (3), 159-166 ,2009
AD - Family Clinic Imperial College Healthcare NHS Trust, 6th floor QEQM, St Mary's
Hospital, London W2 1NY, United Kingdom [email protected]
Children with perinatally acquired HIV-1 infection are surviving into adolescence and
increasingly transitioning toward adult services. Planning appropriate services in adult life
requires an understanding of their progress through pediatric care. We describe the
demographic features, disease progression, antiretroviral therapy (ART), and resistance in
young people aged 10 years or more living in the United Kingdom and Ireland reported to
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the National Study of HIV in Pregnancy and Childhood (NSHPC) with prospective annual
follow-up in the Collaborative HIV Paediatric Study (CHIPS) between 1996 and September
2007. Six hundred fifty-four perinatally infected young people were identified; 76% black
African, 57% born abroad. Median age at presentation and duration of follow-up was 1 and
11 years, respectively, if born in the United Kingdom/Ireland, and 8 and 5 years if born
elsewhere. One hundred sixty-nine (26%) ever had an AIDS-defining illness. Ten died during
adolescence. At last follow-up, 64% were on ART, 18% off treatment having previously
received ART and 18% were ART naive. Of 518 who had received highly active antiretroviral
therapy (HAART), 47% were triple class experienced. At last follow-up 77 (12%) had CD4
counts less than 200 per microliter; of those on HAART, 78% had HIV-1 RNA </=400 copies
per milliliter, median CD4 count 554 (interquartile range [IQR] 324-802). Among 166 with
resistance assays on HAART, 52% and 12% had dual- and triple-class HIV-1-associated
resistance mutations, respectively. One hundred three (16%) young people had transferred to
adult services. Young adults with perinatally acquired HIV-1 infection require coordinated
multidisciplinary transitional care services and careful long-term follow-up in adult life
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19866533
-----------------------------------------------------Epidemiology
The Mathematics of Concurrent Partnerships and HIV: A
Commentary on Lurie and Rosenthal, 2009
EPSTEIN H.
AIDS Behav. 2009
AD - , 424 West 144th street, New York, NY, 10031, USA, [email protected]
ENGLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19866354
-----------------------------------------------------Epidemiology
Occupational Blood Exposure Accidents in the Netherlands
VAN WIJK P. T., Schneeberger, P. M., Heimeriks, K., Boland, G. J., Karagiannis, I., Geraedts,
J., and Ruijs, W. L.
Eur.J.Public Health. 2009
AD - 1 Department of Medical Microbiology and Infection Control, Jeroen Bosch Hospital, 'sHertogenbosch, The Netherlands--ENG
BACKGROUND: To make proper evaluation of prevention policies possible, data on the
incidence and associated medical costs of occupational blood exposure accidents in the
Netherlands are needed. METHODS: Descriptive analysis of blood exposure accidents and
risk estimates for occupational groups. Costs of handling accidents were calculated.
RESULTS: Each year, an estimated 13 000-15 000 blood exposure accidents are reported in
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the Netherlands, 95% in occupational settings. Hepatitis B (HBV) vaccination is offered free
of charge only to people in risk groups, the seroprevalence of HBV, hepatitis C (HCV) and
human immunodeficiency virus (HIV) is low and few infections are related to blood
exposure accidents. High-risk accidents occur mainly in hospitals. In nursing homes and
home care settings, the majority of the accidents are low-risk. Limited data are available
about occurrence of accidents in other occupational groups. Associated medical costs from
occupational blood exposure accidents are mainly determined by the initial risk
management. CONCLUSIONS: Accidents must be managed effectively to prevent infection
and reduce anxiety in injured employees. While strategies to reduce HCV and HIV infection
should be primarily aimed at reducing the occurrence of high-risk accidents, vaccination can
prevent HBV infection and cut the costs of handling low-risk accidents. The implementation
of vaccination strategies, safe working policies and the proper use of safe equipment should
be monitored better
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19864365
-----------------------------------------------------Epidemiology
[Personnel at Risk for Occupational Blood Exposure in a University
Hospital in West Algeria]
BEGHDADLI B., Ghomari, O., Taleb, M., Belhaj, Z., Belabed, A., Kandouci del, A. K., and
Fanello, S.
Sante Publique. 21 (3), 253-261 ,2009
AD - Universite de Sidi Bel-Abbes, Laboratoire de Recherche en Environnement et Sante,
Algerie-fre
The accidental occupational exposure of health care workers to blood or other body fluids
after skin injury or mucous contact, constitutes a risk for the transmission of the hepatitis B
virus (HBV), hepatitis C virus (HCV) or human immunodeficiency viruses (HIV). This paper
presents the results of a survey carried out over two years (January 2005 - December 2006) on
reported occupational blood exposures (OBE). The study aimed to determine incidence,
workers and professional categories at risk, and circumstances of OBE occurrence in order to
identify avoidable cases and to orient prevention measures. Personal and professional data,
immunization status, circumstances of OBE incidents, preventive measures, workers'
behaviour post-exposure, and serology surveillance were collected. 108 exposures were
reported by 70 women and 38 men. In total, 44 accidents were reported in 2005, and 64 in
2006. Needle stick injuries represented 81% of cases. Source patient serology was unknown
in most of the cases, negative in 9% of cases and positive in 10% of cases. 62% of exposed
health workers received immediate serology, follow up and screening as of the first day of
exposure, 12% after 3 months and 36% after 6 months. No seroconversion case was noted.
Cleaning staff and hygiene workers are at high risk of blood contamination as well as nurses,
and more than one-third of injuries occurred because of mismanagement of healthcare waste
produced in the hospital environment, where needles were not disposed of appropriately in
a hard container. Thus, 41.66% of injuries could be avoided if objects were thrown away
correctly in specific containers. It is urgent to raise awareness of health care personnel and
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EUROPRISE SCIENCE UPDATE 09-45
strengthen adherence to standard precautions as well as to provide suitable containers for
the collection and disposal of needles and sharp objects
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19863016
------------------------------------------------------
Health economics
Primary Care Consultations and Costs Among HIV Positive
Individuals in UK Primary Care 1995-2005: a Cohort Study
EVANS H. E., Tsourapas, A., Mercer, C. H., Rait, G., Bryan, S., Hamill, M., Delpech, V.,
Hughes, G., Brook, G., Williams, T., Johnson, A. M., Singh, S., Petersen, I., Chadborn, T., and
Cassell, J. A.
Sex Transm.Infect. 2009
AD - University College London, United Kingdom;--ENG
OBJECTIVES: To investigate the role of primary care in the management of HIV and estimate
primary care associated costs at a time of rising prevalence. METHODS: Retrospective cohort
study between 1995-2005, using data from general practices contributing data to the United
Kingdom General Practice Research Database (GPRD). We analysed patterns of consultation
and morbidity, and associated consultation costs, among all practice-registered patients for
whom HIV positive status was recorded in the general practice record. RESULTS: 348
practices yielded 5,504 person years (py) of follow up for known HIV positive patients, who
consult in GP general practice frequently (4.3 consultations/py, 5.2 consultations/py females
in 2005) for a range of conditions. Consultation rates declined in the late 1990s from 5.2 and
7.4 consultations/py in 1995 in males and females, respectively, converging to rates similar
to the wider population. Costs of consultation (GP & nurse, combined) reflecting these
changes, at pound100.27 for male patients and pound117.08 for female patients in 2005.
Approximately 1 in 6 medications prescribed in primary care for HIV positive individuals
has the potential for major interaction with antiretroviral medications. CONCLUSION: HIV
positive individuals known to the GP now consult on a similar scale to the wider population.
Further research should be undertaken to explore how primary care can best contribute to
improving the health outcomes of this group with chronic illness. Their substantial use of
primary care suggests there may be potential to develop effective integrated care pathways
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19854699
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Health economics
HIV Drug Patents in the Spotlight
MORRIS K.
Lancet Infect.Dis. 9 (11), 660-661 ,2009
engLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19860026
-----------------------------------------------------Health economics
What Impact Might the Economic Crisis Have on HIV Epidemics in
Southeast Asia?
GRAY R. T., Heymer, K. J., Hoare, A., Kwon, J. A., Thein, H. H., Lote, N., Siba, P., Saramony,
S., Saphonn, V., Worth, H., Kaldor, J. M., and Wilson, D. P.
Curr.HIV.Res. 2009
AD - Level 2, 376 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia
[email protected]
Objective: To evaluate the potential impact of the current global economic crisis (GEC) on the
spread of HIV. Design: To evaluate the impact of the economic downturn we studied two
distinct HIV epidemics in Southeast Asia: the generalized epidemic in Cambodia where
incidence is declining and the epidemic in Papua New Guinea (PNG) which is in an
expansion phase. Methods: Major HIV-related risk factors that may change due to the GEC
were identified and a dynamic mathematical transmission model was developed and used to
forecast HIV prevalence, diagnoses, and incidence in Cambodia and PNG over the next 3
years. Results: In Cambodia, the total numbers of HIV diagnoses are not expected to be
largely affected. However, an estimated increase of up to 10% in incident cases of HIV, due
to potential changes in behavior, may not be observed by the surveillance system. In PNG,
HIV incidence and diagnoses could be more affected by the GEC, resulting in respective
increases of up to 17% and 11% over the next 3 years. Decreases in VCT and education
programs are the factors that may be of greatest concern in both settings. A reduction in the
rollout of antiretroviral therapy could increase the number of AIDS-related deaths (by up to
7.5% after 3 years). Conclusions: The GEC is likely to have a modest impact on HIV
epidemics. However, there are plausible conditions under which the economic downturns
can noticeably influence epidemic trends. This study highlights the high importance of
maintaining funding for HIV programs
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19863480
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Immunology
Involvement of Tyrosine Phosphatase CD45 in Apoptosis
DUPERE-MINIER G., Desharnais, P., and Bernier, J.
Apoptosis. 2009
AD - INRS-Institut Armand-Frappier, 531 boul des Prairies, Laval, QC, H7V 1B7, Canada-ENG
CD45 is a transmembrane molecule with phosphatase activity expressed in all nucleated
haematopoietic cells and plays a major role in immune cells. It is a protein tyrosine
phosphatase that is essential for antigen-receptor-mediated signal transduction by regulating
Src family members that initiate TCR signaling. CD45 is being attributed a new emerging
role as an apoptosis regulator. Cross-linking of the extracellular portion of the CD45 by
monoclonal antibodies and by galectin-1, can induce apoptosis in T and B cells. Interestingly,
this phosphatase has also been involved in nuclear apoptosis induced by mitochondrial
perturbing agents. Furthermore, it is involved in apoptosis induced by HIV-1. CD45 defect is
implicated in various diseases such as severe-combined immunodeficiency disease (SCID),
acquired immunodeficiency syndrome (AIDS), lymphoma and multiple myelomas. The
understanding of the mechanisms by which CD45 regulates apoptosis would be very useful
in disease treatment
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19856105
-----------------------------------------------------Immunology
Integration of HIV-1 DNA Is Regulated by Interplay Between Viral
Rev and Cellular LEDGF/P75 Proteins
LEVIN A., Rosenbluh, J., Hayouka, Z., Friedler, A., and Loyter, A.
Mol.Med. 2009
AD - Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences
and--ENG
The present work describes a new-not yet described-interaction between the Human
immunodeficiency virus type 1 (HIV-1) Rev protein and the cellular lens epithelium-derived
growth factor p75 (LEDGF/p75) protein in-vitro and in virus-infected cells. Here we show,
for the first time, that formation of a Rev-LEDGF/p75 complex is a crucial step in regulating
the viral cDNA integration. Co-immunoprecipitation experiments at various times after
virus infection revealed that first an integrase(IN)-LEDGF/p75 complex is formed, which is
then replaced by a Rev-LEDGF/p75 and Rev-IN complexes. This was supported by in-vitro
experiments showing that Rev promotes dissociation of the IN-LEDGF/p75 complex.
Combination of the viral IN and the cellular LEDGF/p75 is required for proper integration
of the viral cDNA into the host chromosomal DNA. Our findings suggest a new mechanism
demonstrating that integration of HIV-1 cDNA is regulated by an interplay between viral
Rev and the host-cell LEDGF/p75 proteins
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Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19855849
-----------------------------------------------------Immunology
HIV-1 MRNA 3' End Processing Is Distinctively Regulated by EIF3f,
CDK11, and Splice Factor 9G8
VALENTE S. T., Gilmartin, G. M., Venkatarama, K., Arriagada, G., and Goff, S. P.
Mol.Cell. 36 (2), 279-289 ,2009
AD - Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia
University, HHSC 1310c, 701 West 168th Street, New York, NY 10032, USA; Department of
Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia
University, HHSC 1310c, 701 West 168th Street, New York, NY 10032, USA-eng
A genetic screen previously identified the N-terminal 91 amino acids of the eukaryotic
initiation factor 3 subunit f (N91-eIF3f) as a potent inhibitor of HIV-1 replication.
Overexpression of N91-eIF3f or full-length eIF3f reduced the level of HIV-1 mRNAs in the
infected cell. Here we show that N91-eIF3f and eIF3f act by specifically blocking the 3' end
processing of the HIV-1 pre-mRNA both in vivo and in vitro. Furthermore, the results
suggest that eIF3f mediates this restriction of HIV-1 expression through the previously
unsuspected involvement of a set of factors that includes eIF3f, the SR protein 9G8, and the
cyclin-dependent kinase 11 (CDK11). eIF3f affects HIV-1 3' end processing by modulating the
sequence-specific recognition of the HIV-1 pre-mRNA by 9G8
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19854136
-----------------------------------------------------Immunology
Mucosal Immunology of the Genital and Gastrointestinal Tracts and
HIV-1 Infection
MESTECKY J., Moldoveanu, Z., Smith, P. D., Hel, Z., and Alexander, R. C.
J.Reprod.Immunol. 2009
AD - Department of Microbiology, University of Alabama at Birmingham, USA; Department
of Medicine, University of Alabama at Birmingham, USA; Department of Microbiology and
Immunology, Charles University, Prague, Czech Republic--ENG
The male and female genital tracts are protected by a local immune system that displays
features distinguishing them from other mucosal sites. In contrast to the intestinal tract,
where locally produced IgA is the dominant Ig, secretions of the male and female genital
tract contain predominantly IgG of both local and systemic origin. Genital tract tissues also
lack mucosal lymphoepithelial inductive sites analogous to intestinal Peyer's patches;
consequently, local immunization or infections with sexually transmitted pathogens induce
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low immune responses. Human immunodeficiency virus 1 (HIV-1) infection must be
primarily considered as a mucosal disease with extensive involvement of the systemic
immune compartment. Although the majority of infections is acquired through the genital
mucosa, a high rate of virus replication and profound CD4(+) T cell depletion occurs in the
intestinal mucosa and other mucosal tissues shortly after infection. Evaluation of HIVspecific antibodies in sera and external secretions, including vaginal washes and semen,
unexpectedly revealed a selective lack of IgA responses. Moreover, specific antibodysecreting cells in peripheral blood were of the IgG isotype, even in mucosally infected
individuals. Whether humoral responses to previously or newly encountered antigens are
compromised in HIV-1-infected persons is under current investigation
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19853927
-----------------------------------------------------Immunology
Clinical Outcomes of Elite Controllers, Viremic Controllers, and
Long-Term Nonprogressors in the US Department of Defense HIV
Natural History Study
OKULICZ J. F., Marconi, V. C., Landrum, M. L., Wegner, S., Weintrob, A., Ganesan, A., Hale,
B., Crum-Cianflone, N., Delmar, J., Barthel, V., Quinnan, G., Agan, B. K., and Dolan, M. J.
J.Infect.Dis. 2009
AD - Infectious Disease Clinical Research Program, Uniformed Services University of the
Health Sciences, and 2Infectious Disease Clinic, National Naval Medical Center, Bethesda,
Maryland; 3Infectious Disease Service, San Antonio Military Medical Center, Brooke Army
Medical Center, Fort Sam Houston, and 4Henry M Jackson Foundation, Wilford Hall United
States Air Force Medical Center, Lackland Air Force Base, Texas; 5Infectious Disease Clinic,
Walter Reed Army Medical Center, Washington, DC; 6Infectious Disease Clinic, Naval
Medical Center San Diego, San Diego, California; 7Infectious Disease Clinic, Naval Medical
Center Portsmouth, Portsmouth, Virginia--ENG
Durable control of human immunodeficiency virus (HIV) replication and lack of disease
progression in the absence of antiretroviral therapy were studied in a military cohort of 4586
subjects. We examined groups of elite controllers (ie, subjects with plasma HIV RNA levels
of <50 copies/mL; prevalence, 0.55% [95% confidence interval {CI}, 0.35%-0.80%]), viremic
controllers (ie, subjects with plasma HIV RNA levels of 50-2000 copies/mL; prevalence,
3.34% [95% CI, 2.83%-3.91%]), and subjects with a lack of disease progression (ie, long-term
nonprogressors [LTNPs]) through 7 years of follow-up (LTNP7s; prevalence, 3.32% [95% CI,
2.70%-4.01%]) or 10 years of follow-up (LTNP10s; prevalence, 2.04% [95% CI, 1.52%-2.68%]).
For elite and viremic controllers, spontaneous virologic control was established early and
was typically observed when the initial viral load measurement was obtained within 1 year
of estimated seroconversion. Elite controllers had favorable time to development of AIDS
([Formula: see text]), a CD4 cell count of 350 cells/muL ([Formula: see text]), and more-stable
CD4 cell trends, compared with viremic controllers. LTNPs defined by 10-year versus 7-year
criteria had a longer survival time ([Formula: see text]), even after adjustment for differing
periods of invulnerability ([Formula: see text]). Definitions of controllers and LTNPs describe
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distinct populations whose differing clinical outcomes improve with the stringency of
criteria, underscoring the need for comparability between study populations
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19852669
-----------------------------------------------------Immunology
Natural Control of HIV-1 Replication and Long-Term
Nonprogression: Overlapping but Distinct Phenotypes
HUNT P. W.
J.Infect.Dis. 2009
AD - Positive Health Program, San Francisco General Hospital, University of California, San
Francisco
ENGLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19852668
-----------------------------------------------------Immunology
Spermatozoa Capture HIV-1 Through Heparan Sulfate and
Efficiently Transmit the Virus to Dendritic Cells
CEBALLOS A., Remes, Lenicov F., Sabatte, J., Rodriguez, Rodrigues C., Cabrini, M., Jancic,
C., Raiden, S., Donaldson, M., Agustin, Pasqualini R., Jr., Marin-Briggiler, C., Vazquez-Levin,
M., Capani, F., Amigorena, S., and Geffner, J.
J.Exp.Med. 2009
AD - Centro Nacional de Referencia para el SIDA, Facultad de Medicina, Universidad de
Buenos Aires, Buenos Aires C1121ABG, Argentina--ENG
Semen is the main vector for HIV-1 dissemination worldwide. It contains three major sources
of infectious virus: free virions, infected leukocytes, and spermatozoa-associated virions. We
focused on the interaction of HIV-1 with human spermatozoa and dendritic cells (DCs). We
report that heparan sulfate is expressed in spermatozoa and plays an important role in the
capture of HIV-1. Spermatozoa-attached virus is efficiently transmitted to DCs,
macrophages, and T cells. Interaction of spermatozoa with DCs not only leads to the
transmission of HIV-1 and the internalization of the spermatozoa but also results in the
phenotypic maturation of DCs and the production of IL-10 but not IL-12p70. At low values
of extracellular pH ( approximately 6.5 pH units), similar to those found in the vaginal
mucosa after sexual intercourse, the binding of HIV-1 to the spermatozoa and the
consequent transmission of HIV-1 to DCs were strongly enhanced. Our observations support
the notion that far from being a passive carrier, spermatozoa acting in concert with DCs
might affect the early course of sexual transmission of HIV-1 infection
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Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19858326
-----------------------------------------------------Immunology
HIV Sticks to Sperm
MAXMEN A.
J.Exp.Med. 2009
ENGLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19858323
-----------------------------------------------------Immunology
Cell-Mediated Immunity to HIV in the Female Reproductive Tract
SHACKLETT B. L.
J.Reprod.Immunol. 2009
AD - Department of Medical Microbiology and Immunology, School of Medicine, University
of California, Davis, CA 95616, USA; Department of Internal Medicine, Division of Infectious
Diseases, School of Medicine, University of California, Davis, CA 95616, USA-ENG
The majority of HIV infections occur via sexual transmission across a mucosal barrier. In the
case of male-to-female transmission, HIV-susceptible target cells are abundant in the
ectocervix and vagina but are also present in the upper reproductive tract (endocervix and
uterus). While the mechanisms of HIV transmission in the female reproductive tract are an
active area of investigation, cell-mediated immune responses in reproductive tissues have
not been thoroughly characterized. HIV-specific CD8+ T cells are present in reproductive
tissues, to some extent mirroring populations present in the blood and gastrointestinal
mucosa. Innate natural killer (NK) cells and regulatory T cells are also present in the genital
tract. Furthermore, there is mounting evidence that the female reproductive tract may be
uniquely susceptible to infection at specific times during the menstrual cycle, due to
hormonal regulation of both innate and adaptive immune responses. This review provides
an overview of recent findings on cell-mediated immunity to HIV in the female reproductive
tract
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19857902
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Immunology
[Influenza Vaccination of Immunocompromised Patients: Safe and
Effective]
OPSTELTEN W., Rimmelzwaan, G. F., van Essen, G. A., and Bijlsma, J. W.
Ned.Tijdschr.Geneeskd. 153. pii: A902., A902 ,2009
AD - Nederlands Huisartsen Genootschap, afd Richtlijnontwikkeling en Wetenschap,
Utrecht, The Netherlands [email protected]
Influenza vaccination is important in order to limit flu-related morbidity and mortality. This
especially applies to immunocompromised patients, such as HIV-infected individuals and
patients on immunosuppressive treatment, who have an increased risk for developing
complications from influenza. Influenza vaccine can be safely administered to all
immunocompromised patients, but the effectiveness of the vaccine may be reduced.
Uncertainty still exists concerning the value of an increased vaccine dose or booster
vaccination: if positive effects exist, they are probably only of marginal clinical importance.
Despite clearly reduced effectiveness, vaccination of immunocompromised patients is still
valuable in view of the high absolute risk of infection and complications
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19857314
-----------------------------------------------------Immunology
Treatment and CD4(+) T Cell Count Recovery Among Antiretroviral
Therapy-Naive Patients With HIV/AIDS
NAGGIE S., Hseih, T., Reckleff, J., Castellano, J., and Hicks, C. B.
Clin.Infect.Dis. 49 (10), 1619-1620 ,2009
AD - Division of Infectious Diseases, Duke University Medical Center, Durham, North
Carolina; 2Institute of Medical Science, Tzu Chi University, Hualien, Taiwan
engLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19857170
-----------------------------------------------------Immunology
T Cell Dynamics and the Response to HAART in a Cohort of HIV-1Infected Elite Suppressors
SEDAGHAT A. R., Rastegar, D. A., O'Connell, K. A., Dinoso, J. B., Wilke, C. O., and
Blankson, J. N.
Clin.Infect.Dis. 2009
AD - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore
Maryland; and 2Section of Integrative Biology, Center for Computational Biology and
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Bioinformatics, and 3Institute for Cell and Molecular Biology, University of Texas at Austin,
Austin-ENG
Elite controllers or suppressors are untreated human immunodeficiency virus type 1 (HIV1)-infected patients who maintain undetectable viral loads. In this study, we show that most
elite suppressors do not experience significant changes in T cell counts over a 10-year period.
Interestingly, treatment of an elite suppressor with highly active antiretroviral therapy
(HAART) led to a marked decrease in immune activation
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19857162
-----------------------------------------------------Immunology
Imaging the Interaction of HIV-1 Genomes and Gag During
Assembly of Individual Viral Particles
JOUVENET N., Simon, S. M., and Bieniasz, P. D.
Proc.Natl.Acad.Sci.U.S.A. 2009
AD - Aaron Diamond AIDS Research Center and Laboratory of Cellular Biophysics, The
Rockefeller University, New York, NY 10065-ENG
The incorporation of viral genomes into particles has never previously been imaged in live
infected cells. Thus, for many viruses it is unknown how the recruitment and packaging of
genomes into virions is temporally and spatially related to particle assembly. Here, we
devised approaches to simultaneously image HIV-1 genomes, as well as the major HIV-1
structural protein, Gag, to reveal their dynamics and functional interactions during the
assembly of individual viral particles. In the absence of Gag, HIV-1 RNA was highly
dynamic, moving in and out of the proximity of the plasma membrane. Conversely, in the
presence of Gag, RNA molecules docked at the membrane where their lateral movement
slowed and then ceased as Gag assembled around them and they became irreversibly
anchored. Viral genomes were not retained at the membrane when their packaging signals
were mutated, nor when expressed with a Gag mutant that was not myristoylated. In the
presence of a Gag mutant that retained membrane- and RNA-binding activities but could not
assemble into particles, the viral RNA docked at the membrane but continued to drift
laterally and then often dissociated from the membrane. These results, which provide
visualization of the recruitment and packaging of genomes into individual virus particles,
demonstrate that a small number of Gag molecules recruit viral genomes to the plasma
membrane where they nucleate the assembly of complete virions
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19861549
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Immunology
[VIR576 Inhibits Antigen-Specific T Cell Activation by Binding to the
Transmembrane Domain of T Cell Receptor.]
ZHANG R. T., Li, X. J., Li, R. M., Hu, Y. P., Jiang, S. B., and Liu, S. W.
Nan.Fang Yi.Ke.Da.Xue.Xue.Bao. 29 (10), 1960-1964 ,2009
AD - School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515,
China E-mail: [email protected]
OBJECTIVE: To study the mechanism underlying the inhibitory effect of the anti-HIV
peptide VIR576 on antigen-specific T cell activation. METHODS: CCK-8 assay was used to
investigate the effect of VIR576 on the proliferation of splenocytes of OVA-specific DO11.10
Tg mice in response to chicken OVA. Hemolysis test, hemolysis inhibition assay and
fluorescence binding assay were used to investigate the interaction of VIR576 with the
transmembrane domain (TMD) of the T cell receptor (TCR). RESULTS: VIR576 inhibited HIV
glycoprotein gp41 fusion peptide-mediated antigen specific T cell activation, and VIR576
itself also inhibited splenocyte proliferation in responses to OVA (P<0.05). Hemolysis test,
hemolysis inhibition assay and fluorescence binding assay demonstrated that VIR576
suppressed TCR-TMD-mediated hemolysis and competitively inhibited Rho-VIR576 binding
to TCR-TMD peptide. CONCLUSION: VIR576 is effective in suppressing the antigen-specific
T cell activation via TCR and can interact with TCR-TMD. VIR576 may serve as a potent
microbicide candidate to block sexual transmission of HIV due to of its inhibitory effect on
both HIV entry and antigen-specific T cell activation
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19861241
-----------------------------------------------------Immunology
Bacille Calmette-Guerin Vaccine-Related Disease in HIV-Infected
Children: a Systematic Review
AZZOPARDI P., Bennett, C. M., Graham, S. M., and Duke, T.
Int.J.Tuberc.Lung Dis. 13 (11), 1331-1344 ,2009
AD - Melbourne School of Population Health, The University of Melbourne, Melbourne,
Victoria, Australia; Centre for International Child Health, The University of Melbourne
Department of Paediatrics and Murdoch Children's Research Institute, Royal Children's
Hospital, Melbourne, Victoria, Australia--eng
OBJECTIVE: To describe the characteristics and risk of bacille Calmette-Guerin (BCG)
vaccine related disease in human immunodeficiency virus (HIV) infected infants.
METHODS: Systematic literature review of articles published from 1950 to April 2009 in the
English language. We identified all microbiologically confirmed cases of disseminated BCG
disease in vertically HIV-infected children reported in the literature. RESULTS: Sixteen
observational studies and 11 case reports/series were included. Observational studies
suffered from high rates of loss to follow-up and death. Loco-regional BCG disease was
reported in both HIV-infected and non-infected children. Disseminated BCG disease was
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EUROPRISE SCIENCE UPDATE 09-45
reported only in children with immunodeficiency and only in studies employing
sophisticated laboratory techniques. Sixty-nine cases of disseminated BCG were identified in
the literature: 47 cases were reported in six observational studies, the majority (41/47) from
the Western Cape of South Africa. A Brazilian cohort study reported no cases of
disseminated BCG amongst 66 HIV-infected children observed over a 7-year period. A recent
South African surveillance study reported 32 cases of disseminated BCG over a 3-year
period, estimating the risk of disseminated BCG to be 992 per 100 000 vaccinations in HIVinfected children. Few cases of severe disseminated TB were reported in the cohort studies
among HIV-infected children vaccinated with BCG. CONCLUSION: Data on the risk of BCG
vaccination in HIV-infected children are limited. Targeted surveillance for BCG
complications employing sophisticated diagnostic techniques is required to inform
vaccination policy
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19861003
-----------------------------------------------------Immunology
HIV1 Vpr Arrests the Cell Cycle by Recruiting DCAF1/VprBP, a
Receptor of the Cul4-DDB1 Ubiquitin Ligase
TRANSY C. and Margottin-Goguet, F.
Cell Cycle. 8 (16), 2489-2490 ,2009
engLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19667756
-----------------------------------------------------Immunology
Simian Immunodeficiency Virus Envelope Glycoprotein
Counteracts Tetherin/BST-2/CD317 by Intracellular Sequestration
GUPTA R. K., Mlcochova, P., Pelchen-Matthews, A., Petit, S. J., Mattiuzzo, G., Pillay, D.,
Takeuchi, Y., Marsh, M., and Towers, G. J.
Proc.Natl.Acad.Sci.U.S.A. 2009
AD - Medical Research Council Centre for Medical Molecular Virology, Division of Infection
and Immunity, University College London, 46 Cleveland Street, London W1T 4JF, United
Kingdom-ENG
Tetherin is an IFN-inducible restriction factor that inhibits HIV-1 particle release in the
absence of the HIV-1 countermeasure, viral protein U (Vpu). Although ubiquitous in HIV-1
and simian immunodeficiency viruses from chimpanzees, greater spot nosed monkeys,
mustached monkeys, and Mona monkeys, other primate lentiviruses do not encode a Vpu
protein. Here we demonstrate that SIV from Tantalus monkeys (SIVtan) encodes an envelope
glycoprotein (SIVtan Env) able to counteract tetherin from Tantalus monkeys, rhesus
monkeys, sooty mangabeys, and humans, but not from pigs. We show that sensitivity to Vpu
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EUROPRISE SCIENCE UPDATE 09-45
but not SIVtan Env can be transferred with the human tetherin transmembrane region. We
also identify a mutation in the tetherin extracellular domain, which almost completely
abolishes sensitivity of human tetherin to SIVtan Env without compromising antiviral
activity or sensitivity to Vpu. SIVtan Env expression results in a reduction of surface tetherin,
as well as reduction in tetherin co-localization with mature surface-associated virus.
Immuno-electron microscopy reveals co-localization of SIVtan Env with tetherin in
intracellular tubulo-vesicular structures, suggesting that tetherin is sequestered away from
budding virions at the cell surface. Along with HIV-1 Vpu and SIV Nef, envelope
glycoprotein is the third and most broadly active lentiviral-encoded tetherin countermeasure
to be described. Our observations emphasize the importance of tetherin in protecting
mammals against viral infection and suggest that HIV-1 Vpu inhibitors may select active
envelope mutants
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19864625
-----------------------------------------------------Immunology
Chronic CD70-Driven Costimulation Impairs IgG Responses by
Instructing T Cells to Inhibit Germinal Center B Cell Formation
Through FasL-Fas Interactions
BEISHUIZEN C. R., Kragten, N. A., Boon, L., Nolte, M. A., van Lier, R. A., and van
Gisbergen, K. P.
J.Immunol. 2009
AD - Department of Experimental Immunology, Academic Medical Center, Amsterdam, The
Netherlands--ENG
CD70 provides costimulation that enhances effector T cell differentiation upon binding of its
receptor, CD27. During chronic immune activation, CD70 is constitutively expressed on
activated immune cells, and this induces T cell-driven disruption of neutralizing Ab
responses via an unknown mechanism. We used CD70-transgenic mice to investigate the
effect of constitutive expression of CD70 on T cell-dependent B cell responses. CD70 induced
up-regulation of the B cell follicle homing chemokine receptor CXCR5 on T cells, enabling
not only CD4 but also CD8 T cells to infiltrate the B cell follicles. CD70-transgenic mice failed
to develop productive germinal center formation and displayed impaired IgG Ab responses.
Defective germinal center B cell differentiation was critically dependent on CD70-mediated
CD27 signaling in T cells, and involved Fas-dependent impairment of germinal center B cell
differentiation. Thus, CD70-driven costimulation enables T cells to terminate B cell
responses, thereby compromising durable Ab production. Our findings imply that the CD70and CD27-driven costimulatory axis may be involved in shutdown of B cell responses before
clearance of Ag. Because CD70 is expressed constitutively in chronic viral infections such as
HIV-1 infection, this mechanism may also contribute to defects in humoral immunity
associated with this disease
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19864607
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-----------------------------------------------------Immunology
LEDGF Interacts With the S-Phase Kinase Cdc7:ASK and
Stimulates Its Enzymatic Activity
HUGHES S., Jenkins, V., Dar, M. J., Engelman, A., and Cherepanov, P.
J.Biol.Chem. 2009
AD - Imperial College London, United Kingdom;-ENG
LEDGF is an important co-factor of HIV DNA integration, however its cellular functions are
poorly characterized. We now report identification of the heterodimeric S-phase kinase
Cdc7:ASK as a novel interactor of LEDGF. Both kinase subunits co-immuno-precipitated
with endogenous LEDGF from human cell extracts. Truncation analyses identified the
integrase-binding domain (IBD) of LEDGF as essential and minimally sufficient for the
interaction with Cdc7:ASK. Reciprocally, the interaction required autophosphorylation of the
kinase and the presence of 50 C-terminal residues of ASK. The kinase phosphorylated
LEDGF in vitro, with Ser206 being the major target, and LEDGF phosphorylated at this
residue could be detected during S phase of the cell cycle. LEDGF potently stimulated the
enzymatic activity of Cdc7:ASK, increasing phosphorylation of MCM2 in vitro by more than
10-fold. This enzymatic stimulation as well as phosphorylation of LEDGF depended on the
protein-protein interaction. Intriguingly, removing the C-terminal region of ASK, involved in
the interaction with LEDGF, resulted in a hyper-active kinase. Our results indicate that the
interaction with LEDGF relieves auto-inhibition of Cdc7:ASK kinase, imposed by the Cterminus of ASK
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19864417
-----------------------------------------------------Immunology
Evaluation of CD4-CD4i Antibody Architectures Yields Potent,
Broadly Cross-Reactive Anti-HIV Reagents
WEST A. P., JR., Galimidi, R. P., Foglesong, C. P., Gnanapragasam, P. N., Klein, J. S., and
Bjorkman, P. J.
J.Virol. 2009
AD - Division of Biology, Howard Hughes Medical Institute, and the Caltech Protein
Expression Center, California Institute of Technology, 1200 E California Blvd, Pasadena, CA
91125-ENG
The envelope glycoprotein of Human Immunodeficiency Virus-1 (HIV-1) has several
adaptations that allow the virus to evade antibody neutralization. Nevertheless, a few
broadly cross reactive neutralizing antibodies as well as reagents containing portions of CD4,
the HIV receptor, have demonstrated partial efficacy in suppressing viral replication. One
type of reagent designed for improved HIV neutralization fuses the CD4 D1-D2 domains to
the variable regions of an antibody recognizing the CD4-induced (CD4i) coreceptor binding
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EUROPRISE SCIENCE UPDATE 09-45
site on the gp120 portion of the HIV envelope spike. We designed, expressed, purified, and
tested the neutralization potencies of CD4-CD4i antibody reagents with different
architectures, antibody combining sites, and linkers. We found that fusing CD4 to the heavy
chain of the CD4i antibody E51 yields a bivalent reagent including an antibody Fc region that
expresses well, is expected to have a long serum half-life, and has comparable to or greater
neutralization activity than well-known broadly neutralizing anti-HIV antibodies. A CD4
fusion with the anti-HIV carbohydrate antibody 2G12 also results in a potent neutralizing
reagent with more broadly neutralizing activity than 2G12 alone
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19864392
-----------------------------------------------------Immunology
Dual Mechanism for the Impairment of IL-7 Responses in HIV
Infection: Decreased IL-7 Binding and Abnormal Activation of the
JAK/STAT5 Pathway
JUFFROY O., Bugault, F., Lambotte, O., Landires, I., Viard, J. P., Niel, L., Fontanet, A.,
Delfraissy, J. F., Theze, J., and Chakrabarti, L. A.
J.Virol. 2009
AD - Unite d'Immunogenetique Cellulaire, Institut Pasteur, Paris, France; AP-HP,
Department of Internal Medicine and Infectious Diseases, Bicetre Hospital, France; INSERM
U802; Universite Paris-Sud, Le Kremlin-Bicetre, France; Service des Maladies Infectieuses et
Tropicales, Hopital Necker, Paris, France; CTSA, Percy Hospital, Clamart, France; Unite
d'Epidemiologie des Maladies Emergentes, Institut Pasteur, Paris, France-ENG
Interleukin-7 (IL-7) plays a central role in controlling the homeostasis of both naive and longterm memory CD4+ T cells. To better understand how HIV perturbs CD4+ T cell
homeostasis, we performed a detailed analysis of IL-7R expression, IL-7 binding, and IL-7dependent early and late signaling events in CD4+ T cell subsets from viremic and efficiently
treated patients. HIV infection differentially affected the expression of IL-7R chains, with a
decrease in IL-7Ralpha/CD127 expression in the memory subset and an increase in
gammac/CD132 expression in all CD4+ T cells. This resulted in preserved IL-7 binding in
the naive compartment, and decreased IL-7 binding in the memory compartment of viremic
patients. Accordingly, the percentage of cells signaling in response to IL-7, as measured by
pSTAT5 induction, was decreased in memory subsets, including conventional CD4+ T cells
and Tregs. However, the level of pSTAT5 induction per responding cell, as measured by
pSTAT5 fluorescence intensity, was increased within all naive and memory CD4+ T cell
subsets of viremic patients. The basal level of pSTAT5 was also increased, indicating a
constitutive activation of the JAK/STAT5 pathway. IL-7 functional responses, as measured
by Bcl-2, CD25 and Foxp3 induction, were impaired in viremic patient CD4+ T cells,
suggesting that chronic activation led to downstream defects in the STAT5 signaling
pathway. Thus, HIV infection perturbs IL-7 responses at both receptor binding and signaling
steps, which likely compromises the regenerative capacity of the CD4+ T cell pool, and may
contribute to CD4+ T cell depletion
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Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19864382
-----------------------------------------------------Immunology
Bioorganic Synthesis of a Recombinant HIV-1 Fusion Inhibitor,
SC35EK, With an N-Terminal Pyroglutamate Capping Group
KAJIWARA K., Watanabe, K., Tokiwa, R., Kurose, T., Ohno, H., Tsutsumi, H., Hata, Y.,
Izumi, K., Kodama, E., Matsuoka, M., Oishi, S., and Fujii, N.
Bioorg.Med.Chem. 2009
AD - Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 6068501, Japan; JST Innovation Plaza Kyoto, Japan Science and Technology Agency, Nishigyoku, Kyoto 615-8245, Japan-ENG
The bioorganic synthesis of an end-capped anti-HIV peptide from a recombinant protein was
investigated. Cyanogen bromide-mediated cleavage of two Met-Gln sites across the target
anti-HIV sequence generated an HIV-1 fusion inhibitor (SC35EK) analog bearing an Nterminal pyroglutamate (pGlu) residue and a C-terminal homoserine lactone (Hsl) residue.
The end-capped peptide, pGlu-SC35EK-Hsl, had similar bioactivity and biophysical
properties to the parent peptide, and an improved resistance to peptidase-mediated
degradation was observed compared with the non-end-capped peptide obtained using
standard recombinant technology
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19864148
-----------------------------------------------------Immunology
The Influence of Variations in the DNA Repair (XRCC1) Gene on
HIV-1/AIDS Among Indian Population
SOBTI R. C., Mahdi, S. A., Berhane, N., Hosseini, S. A., Kler, R., Kuttiat, V., and Wanchu, A.
Folia Biol.(Praha). 55 (5), 183-186 ,2009
AD - Department of Biotechnology, Panjab University, Chandigarh, India-eng
Genetic polymorphisms in DNA repair genes may influence individual variations in the
DNA repair capacity. Polymorphisms in the XRCC1 gene that cause amino acid substitutions
may impair the interaction of its proteins (XRCC1) with the other enzymatic proteins and
consequently alter DNA repair function, which may be associated with the risk of HIV1/AIDS disease. In this study, we aimed to determine the frequency of polymorphisms in
XRCC1 codon 399 in a sample of Indian population with HIV-1/AIDS to evaluate its
association with the disease. Polymerase chain reaction and restriction fragment length
polymorphism were used to analyse XRCC1 Arg399Gln polymorphisms in 300 positively
diagnosed cases with HIV-1/AIDS and an equal number of negatively diagnosed controls of
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the matched age. The XRCC1 homozygous variant genotype Gln399Gln was associated with
an increased risk of HIV-1/AIDS disease (OR = 1.8, 95% CI 1.10-2.94), while no association
was found with the Arg399Gln genotype. Polymorphisms in the XRCC1 homozygous
variant genotype for the 399Gln allele were associated with the risk of HIV-1/AIDS disease
in a sample of North Indian population
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19863846
-----------------------------------------------------Immunology
CD4 T Cell Subsets in the Mucosa Are CD28Ki-67HLA-DRCD69 but
Show Differential Infection Based on Alpha4beta7 Receptor
Expression During Acute SIV Infection
KADER M., Bixler, S., Roederer, M., Veazey, R., and Mattapallil, J. J.
J.Med.Primatol. 38 (s126th Annual Symposium of Nonhuman Primate Models for AIDS), 2431 ,2009
AD - Uniformed Services University of the Health Sciences, Bethesda, MD, USA-ENG
Background CD4 T cell depletion in the mucosa has been well documented during acute HIV
and SIV infections. The demonstration the HIV/SIVcan use the alpha4beta7 receptor for viral
entry suggests that these viruses selectively target CD4 T cells in the mucosa that express
high levels of alpha4beta7 receptor. Methods Mucosal samples obtained from SIV infected
rhesus macaques during the early phase of infection were used for immunophenotypic
analysis. CD4 T cell subsets were sorted based on the expression of beta7 and CD95 to
quantify the level of SIV infection in different subsets of CD4 T cells. Changes in IL-17, IL-21,
IL-23 and TGFbeta mRNA expression was determined using Taqman PCR. Results CD4 T
cells in the mucosa were found to harbor two major population of cells; -25% of CD4 T cells
expressed the alpha4(+)beta7(hi) phenotype, whereas the rest of the 75% expressed an
alpha4(+)beta7(int) phenotype. Both the subsets were predominantly CD28(+)Ki-67(-)HLADR(-) but CD69(+), and expressed detectable levels of CCR5 on their surface. Interestingly,
however, alpha4(+)beta7(hi)CD4 T cells were found to harbor more SIV than the
alpha4(+)beta7(int) subsets at day 10 pi. Early infection was associated with a dramatic
increase in the expression of IL-17, and IL-17 promoting cytokines IL-21, IL-23, and TGFbeta
that stayed high even after the loss of mucosal CD4 T cells. Conclusions Our results suggest
that the differential expression of the alpha4beta7 receptor contributes to the differences in
the extent of infection in CD4 T cell subsets in the mucosa. Early infection is associated
dysregulation of the IL-17 network in mucosal tissues involves other non-Th-17 cells that
likely contributes to the pro-inflammatory environment in the mucosa during acute stages of
SIV infection
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19863675
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Pathology
[Neoplasms and HIV in the Epidemic's Third Decade.]
SANTOS J.
Med.Clin.(Barc.). 2009
AD - Unidad de Gestion Clinica de Enfermedades Infecciosas, Hospital Clinico Virgen de la
Victoria,
Malaga,
Espana
SPALink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19853875
-----------------------------------------------------Pathology
HIV and the Kidney
BRUGGEMAN L. A., Bark, C., and Kalayjian, R. C.
Curr.Infect.Dis.Rep. 11 (6), 479-485 ,2009
AD - Division of Infectious Diseases, MetroHealth Medical Center and Case Western Reserve
University School of Medicine, 2500 MetroHealth Drive, Cleveland, OH 44102, USA
[email protected]
Direct effects of HIV-1 infection on the kidney combine with immune and genetic factors,
comorbidities, coinfections, and medication toxicities to induce a spectrum of kidney
disorders in HIV disease. The most dramatic of these, HIV-associated nephropathy
(HIVAN), emerges almost exclusively in persons of African descent and is associated with
rapid progression to end-stage renal disease in the absence of antiretroviral therapy (ART).
ART modifies the natural history of HIVAN, but the renal benefits of ART may not be
limited to HIVAN. ART is often under prescribed or incorrectly dosed in persons with
kidney disease. Vigilant attention to renal function and an understanding of the complex
associations involving the kidneys are necessary for optimal care of these patients
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19857388
-----------------------------------------------------Pathology
HIV and the Brain: New Challenges in the Modern Era Edited by R.
H. Paul , N. C. Sacktor , V. Valcour , and K. T. Tashima New York:
Humana Press, 2009. 350 Pp. $139.00 (Hardcover)
PAUL R. H., Sacktor, N. C., Valcour, V., Tashima, K. T., and Temesgen, Z.
Clin.Infect.Dis. 49 (10), 1625-1626 ,2009
AD - Division of Infectious Diseases, Mayo Clinic, Rochester,
engLink
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Minnesota
:
EUROPRISE SCIENCE UPDATE 09-45
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19857175
-----------------------------------------------------Pathology
Tegumentary Leishmaniasis As the Cause of Immune
Reconstitution Inflammatory Syndrome in a Patient Co-Infected
With Human Immunodeficiency Virus and Leishmania Guyanensis
CHRUSCIAK-TALHARI A., Ribeiro-Rodrigues, R., Talhari, C., Silva, R. M., Jr., Ferreira, L.
C., Botileiro, S. F., Santos, L. O., Dietze, R., and Talhari, S.
Am.J.Trop.Med.Hyg. 81 (4), 559-564 ,2009
AD - Fundacao de Medicina Tropical do Amazonas, Manaus, Amazonas, Brazil--eng
We report a case of immune reconstitution inflammatory syndrome (IRIS) in a 32-year-old
man infected with human immunodeficiency virus and Leishmania guyanensis. Three
months after initiation of highly active anti-retroviral therapy (HAART), the patient had
disseminated cutaneous leishmaniasis and started anti-leishmanial therapy. The patient's
leishmaniasis manifestations during HAART ranged form an anergic response (46 CD4+ T
cells/microL) to a disseminated cutaneous leishmaniasis (112 CD4+ T cells/microL). Eight
weeks later (168 CD4+ T cells/microL, skin biopsy specimens showed inflammatory
infiltrates with no detectable amastigotes. The patient then became comatose. Prednisone
therapy (60 mg/day) was initiated with a significant improvement within 48 hours. Three
months later (CD4+ T cell count = 184 cell/microL), localized, classic, cutaneous
leishmaniasis developed in the patient and anti-leishmanial treatment was re-introduced. On
that occasion, frequency of T regulatory cells was 1.82% of all CD4+ cells. Our data suggest a
pivotal role for CD4+ T cells in the onset of IRIS and lesion ulceration and their association
with a low frequency of T regulatory cells
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19815866
------------------------------------------------------
Recommendations & Policies
[Communication of Health Risks : The Example of HIV/AIDS
Prevention.]
LEHMANN H. and Toppich, J.
Bundesgesundheitsblatt.Gesundheitsforschung.Gesundheitsschutz. 2009
AD - Bundeszentrale fur gesundheitliche Aufklarung, Koln, Ostmerheimer Str 220, 51109,
Koln, Deutschland, [email protected]
Those seeking to educate the public about health need to communicate health risks
effectively. This involves providing evidence-based information about factors and behaviors
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that are dangerous to people's health and making recommendations regarding how risks can
be avoided or minimized. This communication usually aims to motivate people to act in a
way that promotes health or prevents disease. Organized 'health education' that seeks to
communicate risks is always embedded in a contextual framework that in turn influences the
issues and content to be communicated and the form of communication that is chosen. The
scope of available scientific knowledge is an important part of this framework as is the extent
to which risks are presented in the media as being dangerous. The media's message has a
strong influence on how the public and specific subgroups within it react. The article
describes conditions that contribute to successful risk communication based on the example
of HIV/AIDS prevention. We chose this particular case because it can serve as an example of
how to deal with future epidemics that may potentially generate substantial media coverage.
This field report shows how risk communication about HIV/AIDS in the mass media in
Germany in the mid-1980s elicited a risk consciousness among the general public that in
itself was in danger of becoming a health risk, especially for people affected by the disease,
and how 'health education' responded to this challenge. It concludes by describing how these
experiences with risk communication can be applied to similar types of risk communication
today
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19855941
-----------------------------------------------------Recommendations & Policies
Increasing HIV Testing in General Practice: Brief Advice Seems to
Work
PHILLIPS M., Lazaro, N., Sweeney, J., Hesketh, L., and Lamden, K.
Int.J.STD AIDS. 2009
AD - (Med Student) University of Manchester, Royal Preston Hospital Campus
ENGLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19854880
-----------------------------------------------------Recommendations & Policies
Using Mathematical Modelling to Estimate the Impact of Periodic
Presumptive Treatment on the Transmission of STIs and HIV
Amongst Female Sex Workers
VICKERMAN P. T., Ndowa, F., O'Farrell, N., Steen, R., Alary, M., and any-Moretlwe, S.
Sex Transm.Infect. 2009
AD - London School of Hygiene and Tropical Medicine, United Kingdom;ENG
BACKGROUND: In settings with poor STI control in high-risk groups, periodic presumptive
treatment (PPT) can quickly reduce the prevalence of genital ulcers, Neisseria gonorrhoeae
(Ng) and Chlamydia trachomatis (Ct). However, few studies have assessed the impact on
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HIV. Mathematical modeling is used to quantify the likely HIV-impact of different PPT
interventions. METHODS: A mathematical model was developed to project the impact of
PPT on STI/HIV transmission amongst a homogeneous population of FSWs and clients.
Using data from Johannesburg, the impact of PPT interventions with different coverages and
PPT frequencies was estimated. A sensitivity analysis explored how the projections were
affected by different model parameters, or if the intervention was undertaken elsewhere.
RESULTS: Substantial decreases in Ng/Ct prevalence are achieved amongst FSWs receiving
PPT. Although less impact is achieved amongst all FSWs, large decreases in Ng/Ct
prevalence (>50%) are possible with >30% coverage and supplying PPT every month. Higher
PPT frequencies achieve little additional impact, whereas improving coverage increases
impact until Ng/Ct becomes negligible. The impact on HIV incidence is smaller, longer to
achieve, and depends heavily on the assumed Ng/Ct cofactors, whether they are additive,
the assumed STI/HIV transmission probabilities and STI durations. Greater HIV-impact can
be achieved in settings with lower sexual activity (except at high coverage), less STI
treatment, or high prevalences of Haemophilus ducreyi. CONCLUSIONS: Despite the
model's assumption of homogeneous risk behaviour probably resulting in optimistic
projections, and uncertainty in STI cofactors and transmission probabilities, projections
suggest PPT interventions with sufficient coverage (>/=40%) and follow-up (>/=2 years)
could noticeably decrease the HIV incidence (>20%) amongst FSW populations with
inadequate STI treatment
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19854700
-----------------------------------------------------Recommendations & Policies
Model and Experiences of Initiating Collaboration With Traditional
Healers in Validation of Ethnomedicines for HIV/AIDS in Namibia
CHINSEMBU K. C.
J.Ethnobiol.Ethnomed. 5 (1), 30 ,2009--ENG
ABSTRACT:
Many people
with
Human
Immunodeficiency
Virus/Acquired
Immunodeficiency Syndrome (HIV/AIDS) in Namibia have access to antiretroviral drugs
but some still use traditional medicines to treat opportunistic infections and offset sideeffects from antiretroviral medication. Namibia has a rich biodiversity of indigenous plants
that could contain novel anti-HIV agents. However, such medicinal plants have not been
identified and properly documented. Various ethnomedicines used to treat HIV/AIDS
opportunistic infections have not been scientifically validated for safety and efficacy. These
limitations are mostly attributable to the lack of collaboration between biomedical scientists
and traditional healers. This paper presents a five-step contextual model for initiating
collaboration with Namibian traditional healers in order that candidate plants that may
contain novel anti-HIV agents are identified, and traditional medicines used to treat
HIV/AIDS opportunistic infections are subjected to scientific validation. The model includes
key structures and processes used to initiate collaboration with traditional healers in
Namibia; namely, the National Biosciences Forum, a steering committee with the University
of Namibia (UNAM) as the focal point, a study tour to Zambia and South Africa where other
collaborative frameworks were examined, commemorations of the African Traditional
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Medicine Day (ATMD), and consultations with stakeholders in north-eastern Namibia.
Experiences from these structures and processes are discussed. All traditional healers in
north-eastern Namibia were willing to collaborate with UNAM in order that their traditional
medicines could be subjected to scientific validation. The current study provides a
framework for future collaboration with traditional healers and the selection of candidate
anti-HIV medicinal plants and ethnomedicines for scientific testing in Namibia
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19852791
-----------------------------------------------------Recommendations & Policies
Integration of STI and HIV Prevention, Care, and Treatment into
Family Planning Services: a Review of the Literature
CHURCH K. and Mayhew, S. H.
Stud.Fam.Plann. 40 (3), 171-186 ,2009
AD - Centre for Population Studies, London School of Hygiene & Tropical Medicine, 50
Bedford Square, London, WC1B 3DP [email protected]
The last comprehensive literature review to examine the effectiveness of family planning
(FP) services in delivering STI and HIV prevention and care was published in 2000. This
review updates that report by examining evidence of the impact of integrating any
component of STI or HIV prevention, care, and treatment into a family planning setting in
developing countries. Forty-four reports were identified from a comprehensive search of
published databases and "grey literature". The weight of evidence demonstrates that
integrated services can have a positive impact on client satisfaction, improve access to
component services, and reduce clinic-based HIV-related stigma, and that they are costeffective. Evidence of FP services reaching men and adolescents and of their impact on
health outcomes is inconclusive. Several studies found that providers frequently miss
opportunities to integrate care and that the capacity to maintain the quality of care is also
influenced by many programmatic challenges. The range of experiences indicates that
managers need to determine appropriate health-care service-delivery models based on a
consideration of epidemiological, structural, and health-systems factors
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19852408
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EUROPRISE SCIENCE UPDATE 09-45
Recommendations & Policies
From Research to Community-Based Practice--Working With Latino
Researchers to Translate and Diffuse a Culturally Relevant
Evidence-Based Intervention: the Modelo De Intervencion
Psicomedica (MIP) Experience
PEMBERTON G., Andia, J., Robles, R., Collins, C., Colon-Cartagena, N., Perez Del, Pilar O.,
and Vega, T. S.
AIDS Educ.Prev. 21 (5 Suppl), 171-185 ,2009
AD - PROCEED, Inc, Elizabeth, NJ, USA-eng
Efforts to translate, package, and diffuse HIV/AIDS research into practice have gained
momentum with the Centers for Disease Control and Prevention's (CDC's) launch of three
projects: the Prevention Research Synthesis Project, which identifies evidence-based
interventions studies; the Replicating Effective Programs Project, which supports the
translation of evidence-based interventions into materials suitable for use in local prevention
programs; and the Diffusion of Effective Behavioral Interventions Project, which moves
behavioral interventions into full-scale practice across the United States. This article
describes the CDC's fast-track process of translation, packaging, and diffusion of an HIV
intervention for Hispanic/Latino injection drug users, the Modelo de Intervencion
Psicomedica conducted by the Diffusion of Effective Behavioral Interventions Project in
collaboration with a CBA organization and the original researchers
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19824844
-----------------------------------------------------Recommendations & Policies
The Implementation of a Culturally Based HIV Sexual Risk
Reduction Program for Latino Youth in a Denver Area High School
MUELLER T. E., Castaneda, C. A., Sainer, S., Martinez, D., Herbst, J. H., Wilkes, A. L., and
Villarruel, A. M.
AIDS Educ.Prev. 21 (5 Suppl), 164-170 ,2009
AD - Division of Reproductive Health, Centers for Disease Control and Prevention (CDC),
Atlanta, GA 30341, USA [email protected]
In the United States, Latino youth experience disproportionately higher rates of teen
pregnancy and sexually transmitted infections (STIs) than non-Latino Whites. As a result,
organizations serving Latino youth seek culturally appropriate evidence-based prevention
programs that promote sexual abstinence and condom use. Cuidate! is an efficacious HIV
sexual risk reduction program for Latino youth aged 13-18. The program incorporates
cultural beliefs that are common among Latino youth and associated with sexual risk
behavior, and uses these beliefs to frame abstinence and condom use as culturally accepted
and effective ways to prevent unintended pregnancy and STIs, including HIV/AIDS.
Cuidate! has been successfully delivered in community agencies and after-school programs
but has not been integrated into an existing school curriculum. This brief case study
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EUROPRISE SCIENCE UPDATE 09-45
describes efforts to implement Cuidate! in a predominantly Latino urban high school in
Denver. Ninety-three youth participated in the program from October 2007 to May 2008.
Cuidate! was adapted to accommodate the typical class period by delivering program
content over a larger number of sessions and extending the total amount of time of the
program to allow for additional activities. Major challenges of program implementation
included student recruitment and the "opt in" policy for participation. Despite these
challenges, Cuidate! was implemented with minor adaptations in a school setting
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19824843
-----------------------------------------------------Recommendations & Policies
Diffusion of Effective Behavioral Interventions and Hispanic/Latino
Populations
STALLWORTH J. M., Andia, J. F., Burgess, R., Alvarez, M. E., and Collins, C.
AIDS Educ.Prev. 21 (5 Suppl), 152-163 ,2009
AD - Capacity Building Branch, Division of HIV/AIDS Prevention (CDC), Centers for
Disease Control and Prevention, Atlanta, GA 30333, USA [email protected]
The national HIV/AIDS prevention program, the Diffusion of Effective Behavioral
Interventions (DEBI), is described in the context of addressing Hispanics/Latinos at risk for
HIV/AIDS in the United States and Puerto Rico. The eight-step DEBI model is referenced in
terms of the interventions and Division of HIV/AIDS Prevention/Capacity Building Branch
(DHAP/CBB) Latino Diffusion Team activities. A summary of activities and examples
addressing diffusion needs for the diverse Hispanic/Latino populations is discussed.
Challenges and successes in diffusion and partner collaborations are also presented, with
comment on future directions such as translations and trainings to serve the needs of the
Hispanic/Latino-serving community-based organizations and their communities
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19824842
-----------------------------------------------------Recommendations & Policies
Hombres Sanos: Exposure and Response to a Social Marketing HIV
Prevention Campaign Targeting Heterosexually Identified Latino
Men Who Have Sex With Men and Women
MARTINEZ-DONATE A. P., Zellner, J. A., Fernandez-Cerdeno, A., Sanudo, F., Hovell, M. F.,
Sipan, C. L., Engelberg, M., and Ji, M.
AIDS Educ.Prev. 21 (5 Suppl), 124-136 ,2009
AD - Department of Population Health Sciences, School of Medicine and Public Health,
University of Wisconsin-Madison, Madison, WI 53726-2397, USA [email protected]
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This study examined the reach and impact of a social marketing intervention to reduce HIV
risk among heterosexually identified (HI) Latino men who have sex with men and women
(MSMW). Repeated cross-sectional intercept surveys were conducted in selected community
venues during and after the campaign with 1,137 HI Latino men. Of them, 6% were classified
as HI Latino MSMW. On average, 85.9% of the heterosexual respondents and 86.8% of the HI
MSMW subsample reported exposure to the campaign. Responses to the campaign included
having made an appointment for a male health exam that included HIV testing and using
condoms. Campaign exposure was significantly associated with HIV testing behavior and
intentions and with knowledge of where to get tested. The campaign reached its
underserved target audience and stimulated preventive behaviors. Social marketing
represents a promising approach for HIV prevention among HI Latinos, in general, and HI
Latino MSMW, in particular
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19824840
-----------------------------------------------------Recommendations & Policies
A Quasi-Experimental Evaluation of a Community-Based HIV
Prevention Intervention for Mexican American Female Adolescents:
the SHERO's Program
HARPER G. W., Bangi, A. K., Sanchez, B., Doll, M., and Pedraza, A.
AIDS Educ.Prev. 21 (5 Suppl), 109-123 ,2009
AD - Department of Psychology, DePaul University, Chicago, IL 60614, USA
[email protected]
This article describes a quasi-experimental evaluation of a community-based, culturally and
ecologically tailored HIV prevention intervention for Mexican American female adolescents
grounded in the AIDS risk reduction model. A total of 378 Mexican American female
adolescents (mean age = 15.2) participated in either the nine-session SHERO's (a femalegendered version of the word hero) intervention or a single session information-only HIV
prevention intervention. Assessment data were collected at pretest, posttest, and 2-month
follow up. Significant improvements across all time points were revealed on measures of
self-esteem, condom attitudes, beliefs regarding a woman's control of her sexuality, beliefs
regarding sexual assault, perceived peer norms, and HIV/AIDS and STI knowledge. At
posttest SHERO's participants were more likely to carry condoms and to report abstaining
from vaginal sex in the previous 2 months; and at 2-month follow up they reported using
condoms more often in the preceding 2 months and planned on using them more frequently
in the coming 2 months. Findings support the development of community-based adolescent
HIV prevention interventions that address culturally specific ecological factors
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19824839
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EUROPRISE SCIENCE UPDATE 09-45
Recommendations & Policies
Outcomes From a Community-Based, Participatory Lay Health
Adviser HIV/STD Prevention Intervention for Recently Arrived
Immigrant Latino Men in Rural North Carolina
RHODES S. D., Hergenrather, K. C., Bloom, F. R., Leichliter, J. S., and Montano, J.
AIDS Educ.Prev. 21 (5 Suppl), 103-108 ,2009
AD - Department of Social Sciences and Health Policy, Department of Internal Medicine, and
the Maya Angelou Center for Health Equity, Wake Forest University Health Sciences,
Winston-Salem, NC 27157-1063, USA [email protected]
Latinos in the United States are at increased risk for HIV and sexually transmitted disease
(STD) infection. We evaluated the efficacy of a pilot lay health adviser (LHA) intervention
designed to increase condom use and HIV testing among Latino men. Fifteen LHAs (mean
age = 35.6; range 23-60 years) from 15 Latino soccer teams were trained and worked with
their teammates for 18 months. Another 15 teams served as the control group. Data were
collected at baseline and at 18 months post-LHA training from a random sample of
teammates from intervention and control teams. Data were collected from 222 men (mean
age = 29 years) who participated in one of the 30 teams. Relative to the control condition,
participants in the intervention reported more consistent condom use in the 30 days
preceding follow-up (unadjusted analysis, intervention, 65.6% vs. control, 41.3%; p < .001).
Participants in the intervention were more likely to report condom use (adjusted odds ratio
[AOR] = 2.3; confidence interval [CI = 1.2-4.3) and HIV testing (AOR = 2.5; CI = 1.5-4.3). LHA
interventions for Latino men that are developed in partnership with community members,
rely on male-centered intrapersonal networks, and are culturally congruent can enhance
preventive behaviors and may reduce HIV infection
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19824838
-----------------------------------------------------Recommendations & Policies
Drug Use and Hispanic Men Who Have Sex With Men in South
Florida: Implications for Intervention Development
FERNANDEZ M. I., Jacobs, R. J., Warren, J. C., Sanchez, J., and Bowen, G. S.
AIDS Educ.Prev. 21 (5 Suppl), 45-60 ,2009
AD - Public Health and Preventive Medicine, Nova Southeastern University, College of
Osteopathic Medicine, Fort Lauderdale, FL 33314, USA [email protected]
Despite continued high HIV risk among Hispanic men who have sex with men (HMSM),
culturally tailored, theoretically based interventions have yet to be developed and tested. As
a first step toward intervention development, we collected quantitative and qualitative data
on sociocultural and psychological factors associated with drug use and risky sex among 566
HMSM recruited from community and Internet venues. Participants reported high rates of
drug use (43%), unprotected anal sex (45%), and multiple sex partners (median 4) in the past
6 months. In multivariate analyses, use of drugs was associated with HIV seropositivity, less
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EUROPRISE SCIENCE UPDATE 09-45
orientation to the Hispanic community, stronger attachment to the gay community, lower
levels of homophobia, higher numbers of sex partners and more unprotected anal sex. The
need for acceptance and desire to please partners emerged as core drivers of HIV risk in the
qualitative data. Findings were used to guide development of Proyecto SOL, a theoretically
grounded intervention that targets core determinants of HIV risk, builds on protective
cultural influences, and strengthens positive social connections
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19824834
-----------------------------------------------------Recommendations & Policies
Summary of Comments and Recommendations From the CDC
Consultation on the HIV/AIDS Epidemic and Prevention in the
Hispanic/Latino Community
ALVAREZ M. E., Jakhmola, P., Painter, T. M., Taillepierre, J. D., Romaguera, R. A., Herbst, J.
H., and Wolitski, R. J.
AIDS Educ.Prev. 21 (5 Suppl), 7-18 ,2009
AD - Office of the Director and Capacity Building Branch, Division of HIV/AIDS Prevention,
NCHHSTP, CDC, Atlanta, GA 30333, USA [email protected]
In April 2008, the U.S. Centers for Disease Control and Prevention (CDC) hosted a national
consultation meeting of academic researchers, public health officials, service providers, and
community leaders to examine the HIV/AIDS epidemic and prevention needs of
Hispanics/Latinos in the United States and its territories. The consultation engaged key
stakeholders to review available information on HIV-related behavioral research and
prevention efforts, describe gaps in current HIV prevention programs and research on
Hispanics/Latinos, and identify community and societal-level factors that can increase
vulnerability of Hispanics/Latinos for acquiring or transmitting HIV infection.
Recommendations were also made to CDC for future collaboration with the Hispanic/Latino
community in areas of HIV prevention research and prevention programs. This article
summarizes participants' recommendations for HIV prevention research, program and
capacity building, policy and planning, and partnerships and communication. These
recommendations will be used by CDC to inform the development of a National Plan of
Action for HIV/AIDS prevention among Hispanics/Latinos, and can provide a framework
for use by other federal and non-federal agencies, academic researchers, community-based
organizations, and policymakers as they seek to curtail the HIV epidemic among
Hispanics/Latinos
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19824831
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Recommendations & Policies
Foreword: HIV/AIDS Prevention in the Hispanic/Latino Community
DEAN H. D.
AIDS Educ.Prev. 21 (5 Suppl), 1-2 ,2009
AD - Office of the Director, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB
Prevention, Coordinating Center for Infectious Diseases, Centers for Disease Control and
Prevention,
Atlanta,
Georgia
30333,
USA
[email protected]
engLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19824829
-----------------------------------------------------Recommendations & Policies
Use of Post-Natal Antiretroviral Prophylaxis for Prevention of
Mother-to-Child Transmission of HIV Is Increasing in Italy
CHIAPPINI E., Galli, L., Tovo, P. A., Gabiano, C., Buffolano, W., Cellini, M., Portelli, V.,
Esposito, S., Gotta, C., and de, Martino M.
Clin.Infect.Dis. 49 (10), 1618-1619 ,2009
AD - Departments of Pediatrics, University of Florence, Florence, 2Department of Pediatrics,
University of Turin, Turin, 3Department of Pediatrics, Federico II University, Naples,
4Department of Mother and Child, University of Modena, Modena, 5Ospedale dei Bambini
G Di Cristina, Infectious Diseases Unit, Palermo, 6Department of Maternal and Pediatric
Sciences, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico,
Mangiagalli e Regina Elena, Milan, and 7University of Genoa, San Martino Hospital, Genoa,
Italy
ENGLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19857169
-----------------------------------------------------Recommendations & Policies
Knowledge of the Centers for Disease Control and Prevention's
2006 Routine HIV Testing Recommendations Among New York City
Internal Medicine Residents
JAIN C. L., Wyatt, C. M., Burke, R., Sepkowitz, K., and Begier, E. M.
AIDS Patient.Care STDS. 23 (3), 167-176 ,2009
AD - Bureau of HIV/AIDS Prevention and Control, New York City Department of Health
and Mental Hygiene, 346 Broadway, Room 701, New York, NY 10013, USA
[email protected]
In 2006, the Centers for Disease Control and Prevention (CDC) endorsed routine voluntary
HIV testing in health care settings to identify the many HIV-infected but undiagnosed
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persons. Realizing this goal will require primary care providers including internal medicine
physicians to order HIV tests routinely. In particular, urban internal medicine trainees who
work in high HIV prevalence settings need to adopt this approach. We therefore examined
the practice of routine HIV testing and to identify factors that correlate with offering HIV
testing to this group. We conducted a self-administered electronic cross-sectional survey of
New York City's (NYC) internal medicine residents on HIV testing-related knowledge,
attitudes, and behaviors with 29 close-ended questions. Fifteen of 42 NYC internal medicine
residency programs participated in early 2007. Of 1175 residents, 450 (38.3%) responded.
Most (63.9%) ordered approximately 10 HIV tests in the past 6 months; 32.6% were aware of
the 2006 guidelines; 35.8% utilized a routine testing approach. Respondents aware of current
guidelines were more likely to practice routine testing (odds ratio [OR] 3.7, 95% confidence
interval [CI]: 2.4-5.6). Two common barriers to testing were procedural: time-consuming
consent process (27.1%); difficulty locating consent forms (19.3%). Most (68.4%) respondents
indicated that oral consent would facilitate more testing. Most NYC internal medicine
residents are not routinely offering HIV tests as advised by the 2006 CDC HIV testing
guidelines and continue to test patients according to perceived patient HIV risk. This is likely
contributing to their low testing rates. Most identified institutional and policy barriers to
routine testing. Efforts should be made to improve dissemination of guidelines and address
institutional and policy barriers to allow more people to learn their HIV status
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19866534
-----------------------------------------------------Recommendations & Policies
USA Looks Set to Repeal HIV Travel Ban
BRISTOL N.
Lancet. 374 (9699), 1409 ,2009
engLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19866518
-----------------------------------------------------Recommendations & Policies
Regarding Inconsistent Prevention of Mother-to-Child Transmission
of HIV Guidelines: Is WHO a Victim or Villain?
ATEKA G. K.
AIDS. 23 (17), 2373-2374 ,2009
engLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19865032
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EUROPRISE SCIENCE UPDATE 09-45
Recommendations & Policies
Clinical Practice. Postexposure Prophylaxis for HIV Infection
LANDOVITZ R. J. and Currier, J. S.
N.Engl.J.Med. 361 (18), 1768-1775 ,2009
AD - University of California at Los Angeles Center for Clinical AIDS Research and
Education and the David Geffen School of Medicine at UCLA, Los Angeles, CA 90035, USA
[email protected]
engLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19864675
-----------------------------------------------------Recommendations & Policies
Contextual or Universal Ethics: a Non-Issue? Viewpoint
ANGLARET X. and Msellati, P.
J.Int.Bioethique. 20 (1-2), 65 ,2009
AD - INSERM Centre 897, Universite Victor Segalen Bordeaux 2, Bordeaux, France-eng
A universal ethical principle is the respect of the individual, and this implies universal rules:
informed consent, confidentiality, scientific rigor and the limiting of risks. Applying them
involves difficulties which are not limited just to the developing countries and which
sometimes pose real problems. To assess the quality of means implemented for making sure
that these rules are respected, indicators exist which are either direct (evaluation of good
practice, recourse to ethical committees) or indirect (quality of patient management, choice of
subjects to be studied). Doubts concerning the application of these rules and the value of
these indicators in some developing countries have led to an over-simplification of the issue
on the part of those countries which consider themselves as paragons of ethical virtue. This
has resulted in the concept of "contextual ethics". This concept is dangerous because: (1) it
creates the impression that any doubts expressed or questions unresolved can only be
encountered in poor countries, whereas they underpin all thinking about ethics; (2) it
precludes the need for rich countries to call into question the research they perform intra
muros without making any reference to the universal right to health care
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19803066
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Therapy, others
Etravirine for HIV-1: Addressing the Limitations of the
Nonnucleoside Reverse Transcriptase Inhibitor Class
GRENNAN J. T. and Walmsley, S.
J.Int.Assoc.Physicians AIDS Care (Chic.Ill.). 2009--ENG
Etravirine (ETR) is a second-generation nonnucleoside reverse transcriptase inhibitor
(NNRTI) specifically designed for treatment-experienced patients infected with HIV-1. Its
unique strength over other, older agents in the NNRTI class is its higher genetic barrier to
resistance, allowing it to be used effectively in patients with limited treatment options. The
arrival of ETR in the market has made sequential NNRTI therapy possible for the first time
in the history of HIV treatment, as it can maintain virologic activity in the presence of certain
(and sometimes multiple) NNRTI mutations. Although ETR has demonstrated efficacy in
treatment-experienced and NNRTI-resistant patients in large trials, further analyses on its
resistance profile are ongoing. As new data emerge on the weighting of ETR's resistanceassociated mutations (RAMs), investigators and clinicians will no doubt be able to further
characterize its specific place in the HIV treatment armamentarium
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19855100
-----------------------------------------------------Therapy, others
Early Nucleoside Reverse Transcriptase Inhibitors for the
Treatment of HIV: A Brief History of Stavudine (D4T) and Its
Comparison With Other Dideoxynucleosides
MARTIN J. C., Hitchcock, M. J., De, Clercq E., and Prusoff, W. H.
Antiviral Res. 2009
AD - Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404--ENG
The occasion of this twenty-fifth anniversary issue encouraged us to reminisce about the
important history of the discovery of the dideoxynucleoside analogues for the treatment of
HIV/AIDS and to chronicle our thoughts about a particular exciting and rewarding period
of our scientific careers. Following the identification of the anti-HIV activity of zidovudine
(AZT), we participated in the urgent quest to discover optimal treatments of HIV infection
and AIDS. A number of previously synthesized nucleoside analogues were comparatively
evaluated, and stavudine (D4T) emerged as a promising candidate for development.
Following clinical evaluation, D4T became a mainstay of the initial antiretroviral
combination therapy, prolonging and saving numerous lives. It has only recently been
supplanted by better-tolerated treatments. This article forms part of a special issue of
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EUROPRISE SCIENCE UPDATE 09-45
Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and
development, Vol 85, issue 1, 2010
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19854224
-----------------------------------------------------Therapy, others
2.4 HIV Protease Inhibitors
WENSING A. M., van Maarseveen, N. M., and Nijhuis, M.
Antiviral Res. 2009
AD - Dept of Virology, University Medical Center Utrecht, Utrecht, The Netherlands--ENG
HIV protease plays a crucial role in the viral life cycle and is essential for the generation of
mature infectious virus particles. Detailed knowledge of the structure of HIV protease and
its substrate has led to the design of specific HIV protease inhibitors. Unfortunately,
resistance to all protease inhibitors (PI) has been observed and the genetic basis of resistance
has been well documented over the past 15 years. The arrival of the early PIs was a pivotal
moment in the development of antiretroviral therapy. They made possible the dual class
triple combination therapy that became known as HAART. However, the clinical utility of
the first generation of PIs was limited by low bioavailability and high pill burdens, which
ultimately reduced adherence and limited long-term viral inhibition. When therapy failure
occurred multiple protease resistance mutations were observed, often resulting in broad
class resistance. To combat PI resistance development, second generation approaches have
been developed. The first advance was to increase the level of existing PIs in the plasma by
boosting with ritonavir. The second was to develop novel PIs with high potency against the
known PI-resistant HIV protease variants. Both approaches increased the number of protease
mutations required for clinical resistance, thereby raising the genetic barrier. This review
provides an overview of the history of protease inhibitor therapy, its current status and
future perspectives. It forms part of a special issue of Antiviral Research marking the 25th
anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19853627
-----------------------------------------------------Therapy, others
Understanding and Managing the Adverse Effects of Antiretroviral
Therapy
HAWKINS T.
Antiviral Res. 2009
AD - Department of Family Practice, University of New Mexico and, Southwest CARE
Center, Santa Fe, New Mexico-ENG
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EUROPRISE SCIENCE UPDATE 09-45
Highly active antiretroviral therapy (HAART) has changed the landscape of HIV disease in a
way that seemed unthinkable a decade ago; from an almost uniformly fatal disease to a
chronic manageable one. The first HAART regimens worked in suppressing virus, but were
encumbered by a variety of short term and long term side effects. More recent regimens
became simpler, easier to take, and with fewer adverse events. As we look to people living
perhaps a normal life span with HIV, the increasing number of antiretroviral agents
available means that individualizing treatment has become more feasible and the longer
downstream adverse events related to HAART, such as its effect on cardiovascular disease
and diabetes, renal and hepatic disease, have begun to dominate our choice of drugs. A
knowledge of both the short and long term adverse events associated with HAART is
essential for providers and for patients. For new drugs to be acceptable in the current field,
they will have to pass a litmus test of tolerability. Since adverse events are often remarkably
idiosyncratic, pharmacogenomics may offer a way of predicting side effects and their
severity from a particular drug or drug class in individual patients. This article forms part of
a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug
discovery and development, Vol 85, issue 1, 2010
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19857521
-----------------------------------------------------Therapy, others
Patient-Related Risks for Nonadherence to Antiretroviral Therapy
Among HIV-Infected Youth in the United States: a Study of
Prevalence and Interactions
RUDY B. J., Murphy, D. A., Harris, D. R., Muenz, L., and Ellen, J.
AIDS Patient.Care STDS. 23 (3), 185-194 ,2009
AD - Children's Hospital of Philadelphia, 3535 Market Street, Suite 1517, Philadelphia, PA
19104, USA [email protected]
Adherence continues to be a major barrier to successful treatment with highly active
antiretroviral therapy (HAART) for HIV-infected individuals. HIV-infected adolescents and
young adults face a lifetime of treatment with HAART. Often, individuals who struggle with
adherence to HAART face multiple barriers that would therefore impact on the success of
any single modality intervention. Thus, we conducted a cross-sectional, observational study
to determine the prevalence of personal barriers to adherence and to identify associations
between these barriers in HIV-infected subjects, 12 to 24. We studied the following personal
barriers to adherence: mental health barriers, high/low self-efficacy and outcome
expectancy, and the presence of specific structural barriers. There were 396 subjects infected
after age 9 recruited from sites from the Adolescent Trials Network for HIV/AIDS
Interventions or the Pediatric AIDS Clinical Trials Group. Of the 396 subjects, 148 (37.4%)
self-identified as nonadherent. No significant differences were found between adherent and
nonadherent subjects for the presence of mental health disorders. Adherence was
significantly associated with all but one structural barrier. Both self-efficacy and outcome
expectancy were higher among adherent versus nonadherent subjects (p < 0.0001). Grouping
subjects according to low self-efficacy and outcome expectancy for adherence, adherence
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EUROPRISE SCIENCE UPDATE 09-45
differed according to the presence or absence of mental health disorders and structural
barriers (p < 0.0001). Our data suggest that adolescents have significant rates of nonadherence and face multiple personal barriers. Adherence interventions must address
multiple barriers to have the maximum chance for positive effects
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19866536
-----------------------------------------------------Therapy, others
Development and Efficacy of an Intervention to Enhance Readiness
for Adherence Among Adults Who Had Previously Failed HIV
Treatment
ENRIQUEZ M., Cheng, A. L., McKinsey, D. S., and Stanford, J.
AIDS Patient.Care STDS. 23 (3), 177-184 ,2009
AD - Department of Nursing, University of Missouri-Kansas City, 2464 Charlotte, Kansas
City, MO 64108, USA [email protected]
This paper outlines the development and initial testing of the READY intervention that was
designed to enhance readiness for adherence among adults with a history of nonadherence
to HIV treatment. Participants in this study were adults (n = 28) who ranged in age from 24
to 57: most were male (75%) and African American (64%). Participants had failed an average
of four prior HIV treatment regimens due to nonadherence and were beginning a new
regimen of protease inhibitor (PI)-based antiretroviral medications. The study was
conducted from 2003 to 2006, prior to the standard use of boosted PI regimens. Results
indicated that 50% of participants became adherent and had suppressed viral loads to less
than 50 copies per milliliter at the 3-month postintervention follow-up time point. Of those
who became adherent, 79% remained adherent at the 12-month postintervention follow-up
time point. Implementation of the intervention was found to be feasible in a real-world
setting and participants reported that they liked the intervention. A 6-session length of the
intervention was found to have the same impact on adherence outcomes as a 12-session
length. No differences were found in outcomes with regard to the intervention's start time:
before or at the same time the new antiretroviral regimen was initiated. These results suggest
that the READY intervention may have merit and that the 6-session length may be more
acceptable. However, a larger controlled study is indicated to examine intervention efficacy
further
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19866535
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EUROPRISE SCIENCE UPDATE 09-45
Therapy, others
Antiretroviral Treatment Initiation Among HIV-Infected Pregnant
Women With Low CD4+ Cell Counts in Gaborone, Botswana
CHEN J. Y., Ogwu, A. C., Svab, P., Lockman, S., Moffat, H. J., Gaolathe, T., Moilwa, S.,
Stordal, K., Dryden-Peterson, S., Moffat, C., Makhema, J., Essex, M., and Shapiro, R. L.
J.Acquir.Immune.Defic.Syndr. 2009
AD - From the *Harvard Medical School, Boston, MA; daggerBotswana Harvard AIDS
Institute, Bontleng, Gaborone, Botswana; double daggerPrincess Marina Hospital, Gaborone,
Botswana; section signBrigham and Women's Hospital, Infectious Disease Unit, Boston, MA;
parallelDepartment of Immunology and Infectious Diseases, Harvard School of Public
Health, Boston, MA; paragraph signBotswana Ministry of Health, Health Inspectorate,
Gaborone, Botswana; #Botswana Harvard PEPFAR Master Trainer Program, Gaborone,
Botswana; **Infectious Disease Unit, Massachusetts General Hospital, Boston, MA; and
daggerdaggerDivision of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston,
MA--ENG
BACKGROUND:: Botswana has the most comprehensive public program in Africa for
providing antiretroviral therapy to treat HIV and prevent mother-to-child transmission
(PMTCT). Botswana guidelines prioritize CD4 cell count testing during pregnancy and
initiation of highly active antiretroviral treatment (HAART) for women who qualify for
treatment. We analyzed rates of HIV testing, CD4 cell count testing, and HAART initiation
during pregnancy. METHODS:: From October 2007 through June 2008, we reviewed
obstetric and laboratory records of women at Princess Marina Hospital in Gaborone,
Botswana. RESULTS:: We recorded information from 3056 women. Of 2675 women eligible
for the PMTCT program, 2623 (98%) had a documented HIV status, of whom 793 (30%) were
HIV infected. Among women who were treatment naive at pregnancy conception, 397 (59%)
had recorded CD4 cell counts, of whom 62 (16%) had a CD4 cell count <200 cells per cubic
millimeter. Among this subset, 23 (37%) initiated HAART during pregnancy, 26 (42%)
received zidovudine prophylaxis, and 13 (21%) received no therapy. CONCLUSIONS:: We
observed low rates of CD4 cell count testing and HAART initiation during pregnancy.
Antenatal clinics should prioritize CD4 cell count testing and referral of women who qualify
for HAART to maximize benefits of maternal treatment and PMTCT
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19864957
-----------------------------------------------------Therapy, others
Trends in Uptake of Recently Approved Antiretrovirals Within a
National Healthcare System
BELPERIO P., Mole, L., Boothroyd, D., and Backus, L.
HIV.Med. 2009
AD - Department of Veterans Affairs, Center for Quality Management in Public Health, Palo
Alto, CA, USA--ENG
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EUROPRISE SCIENCE UPDATE 09-45
Objective The aim of the study was to describe Veterans Healthcare Administration (VHA)
system-wide uptake of three HIV protease inhibitors: atazanavir, darunavir and tipranavir.
Methods This retrospective cohort study evaluated VHA uptake of three target
antiretrovirals and lopinavir/ritonavir in each complete 90-day quarter since approval to
December 2007 using VHA HIV Clinical Case Registry data. We assessed uptake using
number of new prescriptions, number of providers and facilities prescribing target agents,
provider type, clinic type, facility size and location within four US regions. Results Overall,
6551 HIV-infected veterans received target antiretrovirals. Uptake was generally greatest
within the first year after Food and Drug Administration (FDA) approval, and then slightly
declined and plateaued. Geographically, early adoption of new antiretroviral drugs tended
to occur in the Western USA, as evidenced by comparison of uptake patterns of new
antiretrovirals to use of all antiretroviral agents. A small percentage of prescribers of all
antiretrovirals were responsible for new prescriptions for target medications, particularly for
darunavir and tipranavir. Providers at almost 50% of VHA facilities were prescribing these
agents within the first year. Conclusions Uptake of new antiretrovirals in the VHA generally
reflected overall prescribing of all antiretrovirals, suggesting a lack of VHA impediments to
new antiretrovirals in the healthcare system. Some regional variation in uptake among the
targeted antiretrovirals occurred over time but tended to resolve after the first several
months. Providers responsible for early prescribing of the target medications were limited to
a fraction of providers who tended to be physicians who practised in infectious disease (ID)
clinics at medium-sized facilities
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19863620
-----------------------------------------------------Therapy, others
Clinical Pharmacology, Efficacy and Safety of Atazanavir: a Review
TUE-FERRER D., Arvieux, C., Tribut, O., Ruffault, A., and Bellissant, E.
Expert.Opin.Drug Metab Toxicol. 5 (11), 1455-1468 ,2009
AD - Centre Hospitalier Universitaire de Rennes, Hopital de Pontchaillou, France-eng
BACKGROUND: Atazanavir (ATV) is a potent and safe protease inhibitor (PI) initially
approved in adult HIV-1 infected patients in combination with other antiretroviral drugs
with once daily administration. In combination with nucleoside reverse transcriptase
inhibitors (NRTIs) and boosted with ritonavir, it has been established as the preferred initial
regimen in published guidelines. OBJECTIVE: This article reviews relevant
pharmacodynamic, pharmacokinetic, efficacy and safety data of ATV, administered boosted
with ritonavir or unboosted, in comparison with other PIs and/or non-NRTIs, with special
focus on recent studies. METHODS: Review articles, recent primary literature and scientific
meeting reports were analyzed. RESULTS: Compared to most PIs with similar efficacy, the
advantages of ATV are a once daily administration with only 100 mg ritonavir when
boosted, a good gastrointestinal tolerance with limited diarrhea, a neutral effect on
cholesterol and triglycerides, and a favorable resistance profile. However, highly frequent
hyperbilirubinemia is observed resulting in some cases in clinical jaundice. Unboosted ATV
must be cautiously used because increased resistances have been described. CONCLUSION:
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EUROPRISE SCIENCE UPDATE 09-45
The combination of a similar efficacy, a better tolerance and a low pill burden, as compared
to other PIs, makes boosted ATV one of the best options, in combination with NRTIs, in PInaive HIV-1 infected patients
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19863454
------------------------------------------------------
Vaccines, clinical
Full Data From Thai HIV Vaccine Study Show No Significant
Protective Effect
ROEHR B.
BMJ. 339:b4370. doi: 10.1136/bmj.b4370., b4370 ,2009
engLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19854826
-----------------------------------------------------Vaccines, clinical
Jury Still Out on HIV Vaccine Results
BUTLER D.
Nature. 461 (7268), 1187 ,2009
engLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19865138
-----------------------------------------------------Vaccines, clinical
Adenovirus Vector-Specific T Cells Demonstrate a Unique Memory
Phenotype With High Proliferative Potential and Coexpression of
CCR5 and Integrin Alpha4beta7
CHAKUPURAKAL G., Onion, D., Cobbold, M., Mautner, V., and Moss, P. A.
AIDS. 2009
AD - aCR UK Centre, School of Cancer Sciences, UK bSchool of Immunity and Infection,
University of Birmingham, Birmingham, UK 1 Authors contributed equally to the work-ENG
BACKGROUND:: The Step Study was a randomized trial to reduce HIV infection through
vaccination with an adenovirus type 5 (Ad5)-based gag/pol/nef construct; analysis
following early cessation of the trial revealed an excess of HIV seroconversion in Ad5
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EUROPRISE SCIENCE UPDATE 09-45
seropositive men. This led to the suggestion that the Ad based vector may boost the number
of CD4 chemokine receptor 5 (CCR5) T cells, target cells for HIV infection. OBJECTIVES:: We
sought to determine the immunophenotype and proliferative capacity of Ad5-specific T cells
in the peripheral blood of adult donors to determine whether stimulation with replication
defective Ad5 vectors could result in the significant expansion of a CD4 CCR5 T-cell subset.
METHODS:: Ad5-specific T cells were identified in the peripheral blood of healthy donors by
interferon-gamma secretion assay and proliferative response was measured by
carboxyfluorescein succinimidyl ester labelling. Cells were analyzed by flow cytometry to
determine T-cell differentiation marker, CCR5 and alpha4beta7 expression on memory and
proliferated cells. RESULTS:: Ad5-specific CD4 T cells within healthy adult donors exhibit a
unique minimally differentiated memory phenotype with coexpression of CD45RA, CD45RO
and CCR7. Stimulation with Ad vector leads to rapid expansion in vitro and a switch to an
effector memory phenotype. Both short-term reactivated and proliferating Ad5-specific CD4
T cells express the HIV coreceptor CCR5 and the HIV gp120-binding integrin alpha4beta7.
CONCLUSION:: Ad5-specific T cells demonstrate a phenotype and proliferative potential
that would support HIV infection; these results are pertinent to the findings of the Step
Study and future use of Ad5 as a vaccine vector
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19864932
-----------------------------------------------------Vaccines, clinical
Phylodynamics of HIV-1 From a Phase III AIDS Vaccine Trial in
North America
PEREZ-LOSADA M., Jobes, D. V., Sinangil, F., Crandall, K. A., Posada, D., and Berman, P.
W.
Mol.Biol.Evol. 2009
AD - CIBIO, Centro de Investigacao em Biodiversidade e Recursos Geneticos, Universidade
do Porto, Campus Agrario de Vairao, 4485-661 Vairao, Portugal-ENG
In 2003, a phase III placebo-controlled trial (VAX004) of a candidate HIV-1 vaccine
(AIDSVAX B/B) was completed in 5,403 volunteers at high risk for HIV-1 infection from
North America and the Netherlands. A total of 368 individuals became infected with HIV-1
during the trial. The envelope glycoprotein gene (gp120) from the HIV-1 subtype B viruses
infecting 349 patients was sequenced from clinical samples taken as close as possible to the
time of diagnosis, rendering a final data set of 1,047 sequences (1,032 from North America
and 15 from the Netherlands). Here, we used these data in combination with other sequences
available in public databases to assess HIV-1 variation as a function of vaccination treatment,
geographic region, race, risk behavior, and viral load. Viral samples did not show any
phylogenetic structure for any of these factors, but individuals with different viral loads
showed significant differences (P = 0.009) in genetic diversity. The estimated time of
emergence of HIV-1 subtype B in USA was around 1966-1970. Despite the fact that the
number of AIDS cases has decreased in North America since the early nineties, HIV-1 genetic
diversity seems to have remained almost constant over time. This study represents one of the
largest molecular epidemiologic surveys of viruses responsible for new HIV-1 infections in
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EUROPRISE SCIENCE UPDATE 09-45
North America and could help the selection of epidemiologically representative vaccine
antigens to include in the next generation of candidate HIV-1 vaccines
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19864468
------------------------------------------------------
Vaccines, research
Variable Epitope Library-Based Vaccines: Shooting Moving Targets
PEDROZA-ROLDAN C., Charles-Nino, C., Saavedra, R., Govezensky, T., Vaca, L., vanissAghajani, E., Gevorkian, G., and Manoutcharian, K.
Mol.Immunol. 2009
AD - Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico
(UNAM), AP 70228, Cuidad Universitaria, Mexico DF 04510, Mexico-ENG
While the antigenic variability is the major obstacle for developing vaccines against
antigenically variable pathogens (AVPs) and cancer, this issue is not addressed adequately in
current vaccine efforts. We developed a novel variable epitope library (VEL)-based vaccine
strategy using immunogens carrying a mixture of thousands of variants of a single epitope.
In this proof-of-concept study, we used an immunodominant HIV-1-derived CD8+ cytotoxic
T-lymphocyte (CTL) epitope as a model antigen to construct immunogens in the form of
plasmid DNA and recombinant M13 bacteriophages. We generated combinatorial libraries
expressing epitope variants with random amino acid substitutions at 2-5 amino acid
positions within the epitope. Mice immunized with these immunogens developed epitopespecific CD8+ IFN-gamma+ T-cell responses that recognized more than 50% of heavily
mutated variants of wild-type epitope, as demonstrated in T-cell proliferation assays and
FACS analysis. Strikingly, these potent and broad epitope-specific immune responses were
long lasting: after 12 months of priming, epitope variants were recognized by CD8+ cells and
effector memory T cells were induced. In addition, we showed, for the first time, the
inhibition of T-cell responses at the molecular level by immune interference: the mice primed
with wild-type epitope and 8 or 12 months later immunized with VELs, were not able to
recognize variant epitopes efficiently. These data may give a mechanistic explanation for the
failure of recent HIV vaccine trials as well as highlight specific hurdles in current molecular
vaccine efforts targeting other important antigenically variable pathogens and diseases.
These findings suggest that the VEL-based strategy for immunogen construction can be used
as a reliable technological platform for the generation of vaccines against AVPs and cancer,
and contribute to better understanding complex host-pathogen interactions
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19853920
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Vaccines, research
Ovine Atadenovirus, a Novel and Highly Immunogenic Vector in
Prime-Boost Studies of a Candidate HIV-1 Vaccine
BRIDGEMAN A., Roshorm, Y., Lockett, L. J., Xu, Z. Z., Hopkins, R., Shaw, J., Both, G. W.,
and Hanke, T.
Vaccine. 2009
AD - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine,
University of Oxford, The John Radcliffe, Oxford OX3 9DS, United Kingdom-ENG
Ovine adenovirus type 7 (OAdV) is the prototype member of the genus Atadenovirus. No
immunity to the virus has so far been detected in human sera. We describe the construction
and evaluation of a candidate HIV-1 vaccine based on OAdV and its utilisation alone and in
combination with plasmid-, human adenovirus type 5 (HAdV5; a Mastadenovirus)-, and
modified vaccinia Ankara (MVA)-vectored vaccines. All vectors expressed HIVA, an
immunogen consisting of HIV-1 clade A consensus Gag-derived protein coupled to a T cell
polyepitope. OAdV.HIVA was genetically stable, grew well and expressed high levels of
protein from the Rous sarcoma virus promoter. OAdV.HIVA was highly immunogenic in
mice and efficiently primed and boosted HIV-1-specific T cell responses alone and in
combination with heterologous HIVA-expressing vectors. There were significant differences
between OAdV and HAdV5 vectors in priming of naive CD8(+) T cell responses to HIVA
and in the persistence of MHC class I-restricted epitope presentation in the local draining
lymph nodes. OAdV.HIVA primed T cells more rapidly but was less persistent than
AdV5.HIVA and thus induced a qualitatively distinct T cell response. Nevertheless, both
vectors primed a response in mice that reduced viral titres in a surrogate challenge model by
three to four orders of magnitude. Thus, OAdV is a novel, underexplored vaccine vector
with potential for further development for HIV-1 and other vaccines. The data are discussed
in the context of the latest HIV-1 vaccine developments
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19853074
-----------------------------------------------------Vaccines, research
Polysaccharide-Based Vaccine Delivery Systems: Macromolecular
Assembly, Interactions With Antigen Presenting Cells, and in Vivo
Immunomonitoring
WEBER C., Drogoz, A., David, L., Domard, A., Charles, M. H., Verrier, B., and Delair, T.
J.Biomed.Mater.Res.A. 2009
AD - Institut de Biologie et Chimie des Proteines, 69367 Lyon Cedex 07, France-ENG
Using a strategy of macromolecular assembly, a colloidal vaccine delivery system was
obtained from chitosan and dextran sulfate and loaded with an antigenic protein (p24, the
capsid protein of HIV-1). The colloidal polyelectrolyte complexes (PECs) were obtained by
charge neutralization of the polyanion and polycation at a charge ratio (n(+)/n(-)) of 2
(CHDS). The conditions of assembly were tuned to maintain the colloidal properties of the
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EUROPRISE SCIENCE UPDATE 09-45
carrier in high salt environment. The relative molar masses of the two polyions and the
degree of acetylation (DA) of chitosan were essential parameters to achieve this goal, and
this could be related to the nanometric scale organization of the colloids observed by Small
Angle X-rays Scattering experiments. The binding of p24 to the colloidal carrier was
achieved and the release of the antigen was investigated. Antigen presenting cells [dendritic
cells (DCs)], obtained from monocytes, could internalize the colloids. Immature DCs (iDCs)
were not matured by the colloidal PECs either loaded or not loaded with p24, as proved by
Fluorescent Activated Cell Sorting (FACS) analysis. Despite this lack of in vitro interaction, a
specific immune response was observed in mice with a high production of antibodies, after
subcutaneous injection. The analysis of the interleukin production shows that both the
cellular and the humoral responses were stimulated. This work brings a physico-chemical
insight on polysaccharide-based antigen delivery systems and opens up new perspectives for
their use as vaccine carriers. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19859973
-----------------------------------------------------Vaccines, research
Monkeying Around With HIV Vaccines: Using Rhesus Macaques to
Define 'Gatekeepers' for Clinical Trials
SHEDLOCK D. J., Silvestri, G., and Weiner, D. B.
Nat.Rev.Immunol. 9 (10), 717-728 ,2009
AD - Department of Pathology and Laboratory Medicine, University of Pennsylvania School
of Medicine, Philadelphia, PA 19104, USA-eng
Rhesus macaques are an important animal model for the study of human disease and the
development of vaccines against HIV and AIDS. HIV vaccines have been benchmarked in
rhesus macaque preclinical challenge studies using chimeric viruses made up of parts of HIV
and simian immunodeficiency viruses. However, the lack of efficacy in a recent clinical trial
calls for a re-evaluation of the scientific assumptions regarding the predictive value of using
data generated from rhesus macaques as a 'gatekeeper' for the advancement of candidate
vaccines into the clinic. In this context, there is significant consensus among HIV
vaccinologists that next-generation HIV vaccines must generate 'better' immunity in rhesus
macaques than clinically unsuccessful vaccines generated using validated assays. Defining
better immunity is the core challenge of HIV vaccine development in this system and is the
focus of this Review
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19859066
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Vaccines, research
Improving the Expression of Recombinant Soluble HIV Envelope
Glycoproteins Using Pseudo-Stable Transient Transfection
SELLHORN G., Caldwell, Z., Mineart, C., and Stamatatos, L.
Vaccine. 2009
AD - Seattle Biomedical Research Institute, Seattle, WA 98109, United States--ENG
The Envelope glycoprotein (Env) of the human immunodeficiency virus (HIV) is the target of
neutralizing antibodies (NAbs). So far, HIV Env-derived immunogens have not been able to
elicit broad neutralizing antibody responses against primary isolates. Identifying conditions
that will permit the efficient production of different soluble HIV Env proteins will facilitate a
high throughput comparative analysis of the immunogenicity of diverse Env constructs,
potentially identifying Env forms that are more conducive to the elicitation of anti-HIV
NAbs. Here we compared different cell types, transfection reagents, transfection conditions
and different DNA expression vectors on soluble HIV Envelope expression levels. We
identified optimal expression conditions and developed a protocol to streamline and
maximize production of diverse HIV Env constructs. Using this optimized platform,
milligram quantities of purified soluble HIV Env trimer can be routinely achieved in a rapid
and cost-effective manner
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19857451
-----------------------------------------------------Vaccines, research
Prime-Boost Immunization of Codon Optimized HIV-1 CRF01_AE
Gag in BCG With Recombinant Vaccinia Virus Elicits MHC Class I
and II Immune Responses in Mice
PROMKHATKAEW D., Pinyosukhee, N., Thongdeejaroen, W., Teeka, J., Wutthinantiwong,
P., Leangaramgul, P., Sawanpanyalert, P., and Warachit, P.
Immunol.Invest. 38 (8), 762-779 ,2009
AD - Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi,
Thailand--eng
The HIV-1 CRF01_AE gag gene was modified by codon restriction for Mycobacterium spp.
and transformed into BCG; and it was designated as rBCG/codon optimized gagE. This
produced 11 fold higher HIV-1 gag protein expression than the recombinant native gene
rBCG/HIV-1gagE. In mice, CTL activity could be induced either by a single immunization of
the codon optimized construct or by using it as a priming antigen in the prime-boost
modality with recombinant Vaccinia virus expressing native HIV-1 gag. Specific secreted
cytokine responses were also investigated. Only when rBCG gag was codon optimized did
the prime-boost immunization produce significantly enhanced IFN-gamma and IL-2
secretion indicating recognition via CD4+ and CD8+ T cells, and these responses seemed to
be codon optimized immunogen dose-responsive. On contrary, the prime-boost vaccination
using an equal amount of native rBCG/HIV-1gagE instead, or a single rBCG/codon
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EUROPRISE SCIENCE UPDATE 09-45
optimized gagE immunization, had no similar effect on the cytokine secretion. These
findings suggest that the use of recombinant codon BCG construct with recombinant
Vaccinia virus encoding CRF01_AE gag as the prime-boost HIV vaccine candidate, will
induce CD4+ Th1 and CD8+ T cell cytokine secretions in addition to enhancing CD8+ CTL
response
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19860587
-----------------------------------------------------Vaccines, research
Vaccination With SIVmac239Deltanef Activates CD4 T Cells in the
Absence of CD4 T-Cell Loss
REEVES R. K., Gillis, J., Wong, F. E., and Johnson, R. P.
J.Med.Primatol. 38 (s126th Annual Symposium of Nonhuman Primate Models for AIDS), 816 ,2009
AD - Division of Immunology, New England Primate Research Center, Harvard Medical
School, Southborough, MA, USA-ENG
Background Pathogenic HIV and SIV infections characteristically deplete central memory
CD4(+) T cells and induce chronic immune activation, but it is controversial whether this
also occurs after vaccination with attenuated SIVs and whether depletion or activation of
CD4(+) T-cell play roles in protection against wild-type virus challenge. Methods Rhesus
macaques were vaccinated with SIVmac239Deltanef and quantitative and phenotypic
polychromatic flow cytometry analyses were performed on mononuclear cells from blood,
lymph nodes and rectal biopsies. Results Animals vaccinated with SIVmac239Deltanef
demonstrated no loss of CD4(+) T cells in any tissue, and in fact CCR5(+) and
CD28(+)CD95(+) central memory CD4(+) T cells were significantly increased. In contrast,
CD4(+) T-cell numbers and CCR5 expression significantly declined in unvaccinated controls
challenged with SIVmac239. Also, intracellular Ki67 increased acutely as much as 3-fold over
baseline in all tissues after SIVmac239Deltanef vaccination then declined following primary
infection. Conclusion We demonstrated in this study that SIVmac239Deltanef vaccination
did not deplete CD4(+) T cells but transiently activated and expanded the memory cell
population. However, increases in numbers and activation of memory CD4(+) T cells did not
appear to influence protective immunity
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19863673
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EUROPRISE SCIENCE UPDATE 09-45
Vaccines, research
Enhancing Efficacy and Mucosa-Tropic Distribution of an Oral HIVPsV DNA Vaccine in Animal Models
FU J., Bian, G., Zhao, B., Dong, Z., Sun, X., Chen, F., Ou, L., and Song, H.
J.Drug Target. 17 (10), 763-772 ,2009
AD - Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine,
Beijing, People's Republic of China--eng
A strategy combined the oral delivery route and bovine papillomavirus (BPV) pseudovirus
(PsV)-based human immunodeficiency virus (HIV) DNA vaccine, which has been proven to
enhance the mucosal immunization compared with the systemic immunization and in
general does not induce effective mucosal immune responses. In this study, the immune
responses against the BPV expressing HIV gp41 epitopes (ELDKWA, NWFDIT) after oral
administration in Cynomolgus monkeys (Macaca fascicularis) were assessed, and the
biodistribution of plasmid DNA encapsulated in the papillomavirus-like particles (VLPs)
were evaluated in murine models. Results showed that oral immunization with the HIV-PsV
DNA vaccine in monkey generated p24 and gp41 epitopes-specific serum IgG. Importantly,
these induced antibodies had been shown to neutralize HIV-1 primary strain. In addition,
the advantage of VLPs as vehicles delivering genes had been first revealed in biodistribution
results. Therefore, orally administered HIV-PsV DNA vaccine was well-tolerated, enhanced
the mucosa targeting property of the plasmid DNA, and reduced the nontargeting
distribution, which indicate that it would reduce stress associated with systemic vaccination
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19863197
------------------------------------------------------
Virology
Application of an Allele-Specific PCR to Clinical HIV Genotyping
Samples Detects Additional K103N Mutations in Both Therapy
Naive and Experienced Patients
CARR J. M., Green, T., Shaw, D., Daly, L., Hart, W., Ratcliff, R., Higgins, G., Burrell, C. J., Li,
P., and Qiao, M.
J.Med.Virol. 81 (12), 1983-1990 ,2009
AD - Infectious Diseases Laboratories, SA Pathology, Adelaide, South Australia, AustraliaENG
Low-level drug resistance is not detected by routine consensus sequence genotype analysis
(CSA) but low levels of specific mutations, such as the non-nucleoside reverse transcriptase
inhibitor (NNRTI)-resistant mutation K103N, can be quantitated by allele-specific PCR
(ASP). This study has applied an ASP to quantitate low-level K103N in patients presenting
for clinical HIV genotyping and assess the correlation with antiretroviral treatment history
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EUROPRISE SCIENCE UPDATE 09-45
and outcomes. HIV RNA was extracted from patient plasma and subjected to PCR
amplification of the reverse transcriptase (RT) region followed by genotyping by CSA and
real-time ASP for K103N. When applied to samples from patients presenting for genotyping,
the ASP detects K103N, not K103 nor K103R, but cross-reacts with K103S. ASP identified all
samples that were K103N by CSA (10.5%) and an additional 14% by ASP only, representing
patients who were therapy naive and with NNRTI treatment history. ASP detected therapyacquired K103N at low levels up to 6 years after cessation of NNRTI therapy. In three
patients with new HIV diagnosis and K103N detected by ASP only, K103N virus declined
rapidly from the circulation but persisted in PBMC DNA at >12 months post-diagnosis.
Efavirenz (EFV) combination therapy in three patients with low-level K103N suppressed
successfully viral load, although one patient developed failure and CSA-detectable K103N
after 15 months of therapy. Thus, analysis of K103N by ASP in conjunction with CSA
genotyping provides additional information that reflects K103N transmission and
persistence but detection of low-level K103N does not preclude successful EFV-containing
combination therapy. J. Med. Virol. 81:1983-1990, 2009. (c) 2009 Wiley-Liss, Inc
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19856473
-----------------------------------------------------Virology
Five-Year Follow Up of Genotypic Resistance Patterns in HIV-1
Subtype C Infected Patients in Botswana After Failure of Thymidine
Analogue-Based Regimens
DOUALLA-BELL F., Gaolathe, T., Avalos, A., Cloutier, S., Ndwapi, N., Holcroft, C., Moffat,
H., Dickinson, D., Essex, M., Wainberg, M. A., and Mine, M.
J.Int.AIDS Soc. 12 (1), 25 ,2009-ENG
ABSTRACT: OBJECTIVE: Our objective was to establish genotypic resistance profiles among
the 4% of Batswana patients who experienced virologic failure while being followed within
Botswana's National Antiretroviral Treatment Program between 2002 and 2007. METHODS:
At the beginning of the national program in 2002, almost all patients received stavudine
(d4T), together with didanosine (ddI), as part of their first nucleoside reverse transcriptase
inhibitor (NRTI)-based regimen (Group 1). In contrast, the standard of care for all patients
subsequently enrolled (2002-2007) included zidovudine/lamivudine (ZDV/3TC) (Group 2).
Genotypes were analyzed in 26 patients from Group 1 and 37 patients from Group 2.
Associations between mutations were determined using Pearson's correlation coefficient and
Jaccard's coefficient of similarity. RESULTS: Seventy-eight percent of genotyped patients
possessed mutations associated with protease inhibitor (PI) resistance while 87% and 90%,
respectively, exhibited mutations associated with NRTIs and non-nucleoside reverse
transcriptase inhibitors (NNRTIs). The most frequent PI mutations involving resistance to
NFV were L90M (25.2%) and D30N (16.2%), but mutations at positions K45Q and D30N
were often observed in tandem (P=60.5, J=50; p=0.002; Group 2) alongside Q61E in 42.8% of
patients who received ZDV/3TC. Both major patterns of thymidine analogue mutations,
TAM 1 (48%) and TAM 2 (59%), were represented in patients from Group 1 and 2, although
M184V was higher among individuals who had initially received ddI (61% versus 40.5%). In
contrast, L74V was more frequent among individuals from Group 2 (16.2% versus 7.7%).
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EUROPRISE SCIENCE UPDATE 09-45
Differences in regard to NNRTI mutations were also observed between Group 1 and Group 2
patients. CONCLUSIONS: Despite a low rate of therapeutic failure (4%) among these
patients, those who failed possessed high numbers of resistance mutations as well as novel
resistance mutations and/or polymorphisms at sites within reverse transcriptase and
protease
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19852859
-----------------------------------------------------Virology
The Capsid Protein of Human Immunodeficiency Virus: Molecular
Recognition and Design of Antiviral Agents
NEIRA J. L.
FEBS J. 276 (21), 6097 ,2009
AD - Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, Alicante,
Spain
engLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19825043
-----------------------------------------------------Virology
Diversity of HIV Strains Impacts Diagnostic Test Accuracy
AIDS Patient.Care STDS. 23 (3), 220 ,2009
engLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19866540
-----------------------------------------------------Virology
The Mechanism of Budding of Retroviruses From Cell Membranes
PINCETIC A. and Leis, J.
Adv.Virol. 2009:6239691-6239699., 6239691-6239699 ,2009
AD - Department of Microbiology and Immunology, Northwestern University Feinberg
School of Medicine, Chicago, IL 60611-ENG
Retroviruses have evolved a mechanism for the release of particles from the cell membrane
that appropriates cellular protein complexes, referred to as ESCRT-I, -II, -III, normally
involved in the biogenesis of multivesicular bodies. Three different classes of late assembly
(L) domains encoded in Gag, with core sequences of PPXY, PTAP, and YPXL, recruit
different components of the ESCRT machinery to form a budding complex for virus release.
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EUROPRISE SCIENCE UPDATE 09-45
Here, we highlight recent progress in identifying the role of different ESCRT complexes in
facilitating budding, ubiquitination, and membrane targeting of avian sarcoma and leukosis
virus (ASLV) and human immunodeficiency virus, type 1 (HIV-1). These findings show that
retroviruses adopt parallel budding pathways by recruiting different host factors from
common cellular machinery for particle release
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19865606
-----------------------------------------------------Virology
Evolutionary Fingerprinting of Genes
KOSAKOVSKY POND S. L., Scheffler, K., Gravenor, M. B., Poon, A. F., and Frost, S. D.
Mol.Biol.Evol. 2009
AD - Department of Medicine, University of California, San Diego, CA, USA-ENG
Over time, natural selection molds every gene into a unique mosaic of sites evolving rapidly
or resisting change - an 'evolutionary fingerprint' of the gene. Aspects of this evolutionary
fingerprint, such as the site-specific ratio of nonsynonymous to synonymous substitution
rates (dN/dS), are commonly used to identify genetic features of potential biological interest;
however, no framework exists for comparing evolutionary fingerprints between genes. We
hypothesize that protein coding genes with similar protein structure and/or function tend to
have similar evolutionary fingerprints, and that comparing evolutionary fingerprints can be
useful for discovering similarities between genes in a way that is analogous to, but
independent of, discovery of similarity via sequence-based comparison tools such as BLAST.
To test this hypothesis, we develop a novel model of coding sequence evolution that uses a
general bivariate discrete parameterization of the evolutionary rates. We show that this
approach provides a better fit to the data using a smaller number of parameters than existing
models. Next, we use the model to represent evolutionary fingerprints as probability
distributions and present a methodology for comparing these distributions in a way that is
robust against variations in data set size and divergence. Finally, using sequences of three
rapidly evolving RNA viruses (HIV-1, Hepatitis C virus and Influenza A virus) we
demonstrate that genes within the same functional group tend to have similar evolutionary
fingerprints. Our framework provides a sound statistical foundation for efficient inference
and comparison of evolutionary rate patterns in arbitrary collections of gene alignments,
clustering homologous and non-homologous genes and investigation of biological and
functional correlates of evolutionary rates
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19864470
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Virology
Transient Virulence of Emerging Pathogens
BOLKER B. M., Nanda, A., and Shah, D.
J.R.Soc.Interface. 2009
AD - Department of Biology, PO Box 118525, University of Florida, , Gainesville, FL 32611,
USA--ENG
Should emerging pathogens be unusually virulent? If so, why? Existing theories of virulence
evolution based on a tradeoff between high transmission rates and long infectious periods
imply that epidemic growth conditions will select for higher virulence, possibly leading to a
transient peak in virulence near the beginning of an epidemic. This transient selection could
lead to high virulence in emerging pathogens. Using a simple model of the epidemiological
and evolutionary dynamics of emerging pathogens, along with rough estimates of
parameters for pathogens such as severe acute respiratory syndrome, West Nile virus and
myxomatosis, we estimated the potential magnitude and timing of such transient virulence
peaks. Pathogens that are moderately evolvable, highly transmissible, and highly virulent at
equilibrium could briefly double their virulence during an epidemic; thus, epidemic-phase
selection could contribute significantly to the virulence of emerging pathogens. In order to
further assess the potential significance of this mechanism, we bring together data from the
literature for the shapes of tradeoff curves for several pathogens (myxomatosis, HIV, and a
parasite of Daphnia) and the level of genetic variation for virulence for one (myxomatosis).
We discuss the need for better data on tradeoff curves and genetic variance in order to
evaluate the plausibility of various scenarios of virulence evolution
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19864267
-----------------------------------------------------Virology
Inferring Within-Patient HIV-1 Evolutionary Dynamics Under AntiHIV Therapy Using Serial Virus Samples With VSPA
HASEGAWA N., Sugiura, W., Shibata, J., Matsuda, M., Ren, F., and Tanaka, H.
BMC.Bioinformatics. 10 (1), 360 ,2009--ENG
ABSTRACT: BACKGROUND: Analysis of within-patient HIV evolution under anti-HIV
therapy is crucial to better understand the possible mechanisms of HIV drug-resistance
acquisition. The high evolutionary rate of HIV allows us to trace its evolutionary process in
real time by analyzing virus samples serially collected from the same patient. However, such
studies are still uncommon due to the lack of powerful computational methods designed for
serial virus samples. In this study, we develop a computational method, vSPA (viral
Sequential Pathway Analysis), which groups viral sequences from the same sampling time
into clusters and traces the evolution between clusters over sampling times. The method
makes use of information of different sampling times and traces the evolution of important
amino acid mutations. Second, a permutation test at the codon level is conducted to
determine the threshold of the correlation coefficient for clustering viral quasispecies. We
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EUROPRISE SCIENCE UPDATE 09-45
applied vSPA to four large data sets of HIV-1 protease and reverse transcriptase genes
serially collected from two AIDS patients undergoing anti-HIV therapy over several years.
RESULTS: The results show that vSPA can trace within-patient HIV evolution by detecting
many amino acid changes, including important drug-resistant mutations, and by classifying
different viral quasispecies coexisting during different periods of the therapy.
CONCLUSIONS: Given that many new anti-HIV drugs will be available in the near future,
vSPA may be useful for quickly providing information on the acquisition of HIV drugresistant mutations by monitoring the within-patient HIV evolution under anti-HIV therapy
as a computational approach
Link
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19863822
-----------------------------------------------------Virology
[A New Human Immunodeficiency Virus Derived From Gorillas]
NAU J. Y.
Rev.Med.Suisse. 5 (215), 1741 ,2009
AD
[email protected]
freLink
:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&li
st_uids=PM:19803230
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