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Find video protocols related to scientific articles indexed in Pubmed.
Medication Adherence Among Men Who Have Sex with Men at Risk for HIV Infection in the United States: Implications for Pre-Exposure Prophylaxis Implementation.
AIDS Patient Care STDS
PUBLISHED: 11-15-2014
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Abstract Pre-exposure prophylaxis (PrEP) is a promising HIV prevention approach for men who have sex with men (MSM), however non-adherence could limit its effectiveness. Understanding the experiences of HIV-uninfected MSM taking routine medications can provide valuable insights into open label PrEP adherence in real world settings and guide development of PrEP adherence interventions. In this study, we examined self-reported medication-taking experiences and facilitators and barriers of medication adherence among a geographically-diverse online sample of HIV-uninfected US MSM. Among 1480 participants, 806 (54%) reported taking medications regularly, of whom 80% reported taking medications for treatment and 55% for prevention purposes. Facilitators of medication adherence included establishing a routine, keeping medication visible, and using a pill-box; barriers included forgetting, changes in routine, and being busy or away from home. Only 45% rated their medication-taking ability as excellent, and 36% reported not missing any doses in the past 30 days. In multivariable analyses, older men and those not reporting any adherence barriers were more likely to report excellent adherence, and men willing to use PrEP were more likely to report perfect 30-day adherence. Counseling strategies to build pill-taking routines and support younger MSM are suggested to maximize the public health impact of PrEP.
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Sources of racial/ethnic differences in awareness of HIV vaccine trials.
Am J Public Health
PUBLISHED: 06-12-2014
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We explored the relative effects of 2 awareness components-exposure and attention-on racial/ethnic differences in HIV vaccine trial awareness among men who have sex with men (MSM).
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CROI 2014: new tools to track the epidemic and prevent HIV infections.
Top Antivir Med
PUBLISHED: 06-06-2014
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As discussed at the 2014 Conference on Retroviruses and Opportunistic Infections (CROI), substantial advances have been achieved in using laboratory tools to track the leading edge of HIV transmissions globally. Phylogenetic and phylodynamic studies have identified clusters of new infections occurring along geographic routes and in different groups, including young men who have sex with men. New assays for detecting acute HIV infection are promising; however, additional strategies are needed to increase uptake of HIV testing in a number of populations. Globally, people who inject drugs face numerous barriers to accessing HIV prevention and treatment services and are in need of integrated approaches to deliver services, address stigma and discrimination, and reform drug policies. Young women and individuals in serodiscordant relationships continue to be at high risk for HIV acquisition. Injectable hormonal contraception with progestins may increase the risk of HIV infection. Bacterial vaginosis may also increase HIV acquisition and transmission. Additional evidence suggests antiretroviral therapy lowers HIV transmission in serodiscordant couples, but high levels of diagnosis, linkage, retention, and viral suppression are needed to reduce population-level HIV incidence. Several programs evaluating the implementation of preexposure prophylaxis (PrEP) have shown high uptake in the United States and resource-limited settings. As adherence is a crucial determinant of PrEP efficacy, long-acting PrEP agents are promising approaches being tested.
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Acceptability of self-conducted home-based HIV testing among men who have sex with men in Brazil: data from an on-line survey.
Cad Saude Publica
PUBLISHED: 06-05-2014
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The Brazilian HIV/AIDS epidemic is concentrated among men who have sex with men (MSM), however HIV testing rates among MSM are not commensurate with their risk. Strategies to expand early diagnosis may include use of self-conducted home-based testing kits, which are now available for purchase in the US. In April 2011 we conducted a survey with Brazilian MSM using Facebook to assess HIV testing preferences and acceptability of home-based testing. Among 356 previously tested, HIV-negative MSM, 47% reported a preference for home-based testing, 27% preferred clinic-based testing, and 26% had no preference. Less frequent testers and those who had considered testing but failed to test were more likely to prefer home-based testing. Close to 90% reported that they would use self-test kits; 62% and 54% said they would use home-based testing to make choices about unprotected sex with regular and new partners, respectively. Concerns included difficulty to understand the tests (32%) and receiving results alone (23%). Overall, home-based testing may appeal to MSM and result in increased testing frequency. Research on feasibility and utilization of self-tests in practice is needed.
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Regulatory Variation in HIV-1 Dependency Factor ZNRD1 Associates with Host Resistance to HIV-1 Acquisition.
J. Infect. Dis.
PUBLISHED: 05-19-2014
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ZNRD1 was identified as a host protein required for the completion of the human immunodeficiency virus (HIV) lifecycle in a genome-wide screen using small interfering RNA gene silencing. Subsequently, a genome-wide association study (GWAS) of host determinants for HIV-1 disease identified an association of single nucleotide polymorphisms (SNPs) in the ZNRD1 region with CD4(+) T-cell depletion.
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HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial.
J. Infect. Dis.
PUBLISHED: 04-16-2014
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The iPrEx study demonstrated that combination oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) as preexposure prophylaxis (PrEP) protects against HIV acquisition in men who have sex with men and transgender women. Selection for drug resistance could offset PrEP benefits.
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Genotypic and functional impact of HIV-1 adaptation to its host population during the North American epidemic.
PLoS Genet.
PUBLISHED: 04-01-2014
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HLA-restricted immune escape mutations that persist following HIV transmission could gradually spread through the viral population, thereby compromising host antiviral immunity as the epidemic progresses. To assess the extent and phenotypic impact of this phenomenon in an immunogenetically diverse population, we genotypically and functionally compared linked HLA and HIV (Gag/Nef) sequences from 358 historic (1979-1989) and 382 modern (2000-2011) specimens from four key cities in the North American epidemic (New York, Boston, San Francisco, Vancouver). Inferred HIV phylogenies were star-like, with approximately two-fold greater mean pairwise distances in modern versus historic sequences. The reconstructed epidemic ancestral (founder) HIV sequence was essentially identical to the North American subtype B consensus. Consistent with gradual diversification of a "consensus-like" founder virus, the median "background" frequencies of individual HLA-associated polymorphisms in HIV (in individuals lacking the restricting HLA[s]) were ? 2-fold higher in modern versus historic HIV sequences, though these remained notably low overall (e.g. in Gag, medians were 3.7% in the 2000s versus 2.0% in the 1980s). HIV polymorphisms exhibiting the greatest relative spread were those restricted by protective HLAs. Despite these increases, when HIV sequences were analyzed as a whole, their total average burden of polymorphisms that were "pre-adapted" to the average host HLA profile was only ? 2% greater in modern versus historic eras. Furthermore, HLA-associated polymorphisms identified in historic HIV sequences were consistent with those detectable today, with none identified that could explain the few HIV codons where the inferred epidemic ancestor differed from the modern consensus. Results are therefore consistent with slow HIV adaptation to HLA, but at a rate unlikely to yield imminent negative implications for cellular immunity, at least in North America. Intriguingly, temporal changes in protein activity of patient-derived Nef (though not Gag) sequences were observed, suggesting functional implications of population-level HIV evolution on certain viral proteins.
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HIV pre-exposure prophylaxis in men who have sex with men and transgender women: a secondary analysis of a phase 3 randomised controlled efficacy trial.
Lancet Infect Dis
PUBLISHED: 03-07-2014
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For maximum effect pre-exposure prophylaxis should be targeted to the subpopulations that account for the largest proportion of infections (population-attributable fraction [PAF]) and for whom the number needed to treat (NNT) to prevent infection is lowest. We aimed to estimate the PAF and NNT of participants in the iPrEx (Pre-Exposure Prophylaxis Initiative) trial.
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LILRB2 interaction with HLA class I correlates with control of HIV-1 infection.
PLoS Genet.
PUBLISHED: 03-01-2014
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Natural progression of HIV-1 infection depends on genetic variation in the human major histocompatibility complex (MHC) class I locus, and the CD8+ T cell response is thought to be a primary mechanism of this effect. However, polymorphism within the MHC may also alter innate immune activity against human immunodeficiency virus type 1 (HIV-1) by changing interactions of human leukocyte antigen (HLA) class I molecules with leukocyte immunoglobulin-like receptors (LILR), a group of immunoregulatory receptors mainly expressed on myelomonocytic cells including dendritic cells (DCs). We used previously characterized HLA allotype-specific binding capacities of LILRB1 and LILRB2 as well as data from a large cohort of HIV-1-infected individuals (N = 5126) to test whether LILR-HLA class I interactions influence viral load in HIV-1 infection. Our analyses in persons of European descent, the largest ethnic group examined, show that the effect of HLA-B alleles on HIV-1 control correlates with the binding strength between corresponding HLA-B allotypes and LILRB2 (p = 10(-2)). Moreover, overall binding strength of LILRB2 to classical HLA class I allotypes, defined by the HLA-A/B/C genotypes in each patient, positively associates with viral replication in the absence of therapy in patients of both European (p = 10(-11)-10(-9)) and African (p = 10(-5)-10(-3)) descent. This effect appears to be driven by variations in LILRB2 binding affinities to HLA-B and is independent of individual class I allelic effects that are not related to the LILRB2 function. Correspondingly, in vitro experiments suggest that strong LILRB2-HLA binding negatively affects antigen-presenting properties of DCs. Thus, we propose an impact of LILRB2 on HIV-1 disease outcomes through altered regulation of DCs by LILRB2-HLA engagement.
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Over-the-counter human immunodeficiency virus self-test kits: time to explore their use for men who have sex with men in Brazil.
Braz J Infect Dis
PUBLISHED: 02-20-2014
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Increasing access and frequency of human immunodeficiency virus testing are critical to stemming the epidemic. In Brazil's concentrated epidemic, human immunodeficiency virus prevalence in the men who have sex with men/transgender population far exceeds that in the general population, but testing rates fall below what is needed to ensure early detection and treatment. Over-the-counter human immunodeficiency virus self-testing kits, now available in stores in the U.S., have enormous potential to increase testing access and frequency and to facilitate early detection and treatment. With the advent of human immunodeficiency virus self-testing upon us, it is timely to engage the scientific community, government, and civil society in a dialog around how to best utilize this technology in Brazil. We summarize recent research on over-the-counter testing among men who have sex with men, raise potential questions and challenges to using self-tests, suggest implementation strategies, and outline a research agenda moving forward.
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Age, race/ethnicity, and behavioral risk factors associated with per contact risk of HIV infection among men who have sex with men in the United States.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 01-15-2014
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Young men who have sex with men (MSM) and MSM of color have the highest HIV incidence in the United States. To explore possible explanations for these disparities and known individual risk factors, we analyzed the per contact risk (PCR) of HIV seroconversion in the early highly active antiretroviral therapy era.
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Specificity and 6-month durability of immune responses induced by DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles.
J. Infect. Dis.
PUBLISHED: 01-07-2014
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Clade B DNA and recombinant modified vaccinia Ankara (MVA) vaccines producing virus-like particles displaying trimeric membrane-bound envelope glycoprotein (Env) were tested in a phase 2a trial in human immunodeficiency virus (HIV)-uninfected adults for safety, immunogenicity, and 6-month durability of immune responses.
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Can male circumcision have an impact on the HIV epidemic in men who have sex with men?
PLoS ONE
PUBLISHED: 01-01-2014
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Three trials have demonstrated the prophylactic effect of male circumcision (MC) for HIV acquisition among heterosexuals, and MC interventions are underway throughout sub-Saharan Africa. Similar efforts for men who have sex with men (MSM) are stymied by the potential for circumcised MSM to acquire HIV easily through receptive sex and transmit easily through insertive sex. Existing work suggests that MC for MSM should reach its maximum potential in settings where sexual role segregation is historically high and relatively stable across the lifecourse; HIV incidence among MSM is high; reported willingness for prophylactic circumcision is high; and pre-existing circumcision rates are low. We aim to identify the likely public health impact that MC interventions among MSM would have in one setting that fulfills these conditions-Peru-as a theoretical upper bound for their effectiveness among MSM generally.
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A comparison of two measures of HIV diversity in multi-assay algorithms for HIV incidence estimation.
PLoS ONE
PUBLISHED: 01-01-2014
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Multi-assay algorithms (MAAs) can be used to estimate HIV incidence in cross-sectional surveys. We compared the performance of two MAAs that use HIV diversity as one of four biomarkers for analysis of HIV incidence.
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Strong relationship between oral dose and tenofovir hair levels in a randomized trial: hair as a potential adherence measure for pre-exposure prophylaxis (PrEP).
PLoS ONE
PUBLISHED: 01-01-2014
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Pre-exposure prophylaxis (PrEP) trials using tenofovir-based regimens have demonstrated that high levels of adherence are required to evaluate efficacy; the incorporation of objective biomarkers of adherence in trial design has been essential to interpretation, given the inaccuracy of self-report. Antiretroviral measurements in scalp hair have been useful as a marker of long-term exposure in the HIV treatment setting, and hair samples are relatively easy and inexpensive to collect, transport, and store for analysis. To evaluate the relationship between dose and tenofovir concentrations in hair, we examined the dose proportionality of tenofovir in hair in healthy, HIV-uninfected adults.
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HIV Diversity as a Biomarker for HIV Incidence Estimation: Including a High-Resolution Melting Diversity Assay in a Multiassay Algorithm.
J. Clin. Microbiol.
PUBLISHED: 10-23-2013
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Multiassay algorithms (MAAs) can be used to estimate cross-sectional HIV incidence. We previously identified a robust MAA that includes the BED capture enzyme immunoassay (BED-CEIA), the Bio-Rad Avidity assay, viral load, and CD4 cell count. In this report, we evaluated MAAs that include a high-resolution melting (HRM) diversity assay that does not require sequencing. HRM scores were determined for eight regions of the HIV genome (2 in gag, 1 in pol, and 5 in env). The MAAs that were evaluated included the BED-CEIA, the Bio-Rad Avidity assay, viral load, and the HRM diversity assay, using HRM scores from different regions and a range of region-specific HRM diversity assay cutoffs. The performance characteristics based on the proportion of samples that were classified as MAA positive by duration of infection were determined for each MAA, including the mean window period. The cross-sectional incidence estimates obtained using optimized MAAs were compared to longitudinal incidence estimates for three cohorts in the United States. The performance of the HRM-based MAA was nearly identical to that of the MAA that included CD4 cell count. The HRM-based MAA had a mean window period of 154 days and provided cross-sectional incidence estimates that were similar to those based on cohort follow-up. HIV diversity is a useful biomarker for estimating HIV incidence. MAAs that include the HRM diversity assay can provide accurate HIV incidence estimates using stored blood plasma or serum samples without a requirement for CD4 cell count data.
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The HVTN503/Phambili HIV vaccine trial: A comparison of younger and older participants.
Int J STD AIDS
PUBLISHED: 10-08-2013
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By comparing younger to older participants enrolled in a HIV vaccine efficacy trial, we aimed to gain insights into the inclusion of adolescents in future trials. This was a sub-analysis of a multisite HIV vaccine randomized clinical trial in South Africa, conducted January-September 2007. Motivations for trial enrolment, social harms, adverse events and loss to follow-up were compared between younger (18-20 years old) and older participants (21-35 years old). Both younger (n?=?238) and older participants (n?=?563) were equally likely to report enrolling for altruistic reasons. Younger females were less likely than older participants to join for trial reimbursement (p?=?0.005), while younger males were more likely to enrol because the vaccine may provide protection from HIV-acquisition (p?
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Participant experiences and facilitators and barriers to pill use among men who have sex with men in the iPrEx pre-exposure prophylaxis trial in San Francisco.
AIDS Patient Care STDS
PUBLISHED: 10-08-2013
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In 2010, the iPrEx study demonstrated efficacy of daily emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) pre-exposure prophylaxis (PrEP) in reducing HIV acquisition among men who have sex with men. Adherence to study product was critical for PrEP efficacy, and varied considerably, with FTC/TDF detection rates highest in the United States. We conducted a qualitative study to gain insights into the experiences of iPrEx participants in San Francisco (SF) where there was high confirmed adherence, to understand individual and contextual factors influencing study product use in this community. In 2009 and 2011, we conducted focus groups and in-depth interviews in 36 and 16 SF iPrEx participants, respectively. Qualitative analyses indicate that participants joined the study out of altruism. They had a clear understanding of study product use, and pill taking was facilitated by establishing or building on an existing routine. Participants valued healthcare provided by the study and relationships with staff, whom they perceived as nonjudgmental, and found client-centered counseling to be an important part of the PrEP package. This facilitated pill taking and accurate reporting of missed doses. Adherence barriers included changes in routine, side effects/intercurrent illnesses, and stress. Future PrEP adherence interventions should leverage existing routines and establish client-centered relationships/ environments to support pill taking and promote accurate reporting.
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Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine.
N. Engl. J. Med.
PUBLISHED: 10-07-2013
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A safe and effective vaccine for the prevention of human immunodeficiency virus type 1 (HIV-1) infection is a global priority. We tested the efficacy of a DNA prime-recombinant adenovirus type 5 boost (DNA/rAd5) vaccine regimen in persons at increased risk for HIV-1 infection in the United States.
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Nondisclosure of HIV Status in a Clinical Trial Setting: Antiretroviral Drug Screening Can Help Distinguish Between Newly Diagnosed and Previously Diagnosed HIV Infection.
Clin. Infect. Dis.
PUBLISHED: 10-02-2013
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In The HIV Prevention Trials Network 061 study, 155 human immunodeficiency virus (HIV)-infected men reported no prior HIV diagnosis; 83 of those men had HIV RNA levels of <1000 copies/mL at enrollment. Antiretroviral drug testing revealed that 65 of the 83 (78.3%) men were on antiretroviral treatment. Antiretroviral drug testing can help distinguish between newly diagnosed and previously diagnosed HIV infection.
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Anal sex role segregation and versatility among men who have sex with men: EXPLORE Study.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 08-16-2013
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Anal sex role patterns and correlates during unprotected anal sex were examined longitudinally among HIV-negative men who have sex with men. Nearly 9.6% were exclusively receptive, 16.7% exclusively insertive, and 63.0% versatile. Versatility was more likely with primary and HIV-negative/unknown status partners and among younger men and substance users but less likely among Blacks and with higher number of partners. Exclusively receptive role was more likely with HIV-negative/unknown status partners and among younger men and substance users but less likely with higher number of partners. Examining anal sex role patterns helps understand the factors that drive the epidemic among men who have sex with men.
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Association study of common genetic variants and HIV-1 acquisition in 6,300 infected cases and 7,200 controls.
PLoS Pathog.
PUBLISHED: 07-01-2013
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Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP) data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1). After imputation using the 1,000 Genomes Project reference panel, we tested approximately 8 million common DNA variants (SNPs and indels) for association with HIV-1 acquisition in 6,334 infected patients and 7,247 population samples of European ancestry. Initial association testing identified the SNP rs4418214, the C allele of which is known to tag the HLA-B*57:01 and B*27:05 alleles, as genome-wide significant (p = 3.6 × 10(-11)). However, restricting analysis to individuals with a known date of seroconversion suggested that this association was due to the frailty bias in studies of lethal diseases. Further analyses including testing recessive genetic models, testing for bulk effects of non-genome-wide significant variants, stratifying by sexual or parenteral transmission risk and testing previously reported associations showed no evidence for genetic influence on HIV-1 acquisition (with the exception of CCR5?32 homozygosity). Thus, these data suggest that genetic influences on HIV acquisition are either rare or have smaller effects than can be detected by this sample size.
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Risk behavior among women enrolled in a randomized controlled efficacy trial of an adenoviral vector vaccine to prevent HIV acquisition.
AIDS
PUBLISHED: 06-29-2013
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Report of risk behavior, HIV incidence, and pregnancy rates among women participating in the STEP study, which is a phase IIB trial of MRKAd5 HIV-1 gag/pol/nef vaccine in HIV-negative individuals who were at high risk of HIV-1.
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In pursuit of an HIV vaccine: designing efficacy trials in the context of partially effective nonvaccine prevention modalities.
AIDS Res. Hum. Retroviruses
PUBLISHED: 06-25-2013
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The HIV prevention landscape is evolving rapidly, and future efficacy trials of candidate vaccines, which remain the best long-term option for stemming the HIV epidemic, will be conducted in the context of partially effective nonvaccine prevention modalities. It is essential that these trials provide for valid and efficient evaluation of vaccine efficacy and immune correlates. The availability of partially effective prevention modalities presents opportunities to study their interactions with vaccines to maximally reduce HIV incidence. This article proposes an approach for conducting future vaccine efficacy trials in the context of background use of partially effective nonvaccine prevention modalities, and for conducting future vaccine efficacy trials that provide nonvaccine prevention modalities in one or more of the randomized study groups. Strategies are discussed for responding to emerging evidence on nonvaccine prevention modalities during ongoing vaccine trials. Next-generation HIV vaccine efficacy trials will almost certainly be more complex in their design and implementation but may become more relevant to at-risk populations and better suited to the ultimate goal of reducing HIV incidence at the population level.
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Integrated strategies for combination HIV prevention: principles and examples for men who have sex with men in the Americas and heterosexual African populations.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 06-15-2013
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Combination HIV prevention is of high priority for increasing the impact of partially efficacious HIV prevention interventions for specific populations and settings. Developing the package requires critical review of local epidemiology of HIV infection regarding most-impacted populations and those at high risk of HIV transmission and acquisition, drivers of HIV infection, and available interventions to address these risk factors. Interventions should be considered in terms of the evidence basis for efficacy, potential synergies, and feasibility of delivery at scale, which is important to achieve high coverage and impact, coupled with high acceptability to populations, which will impact uptake, adherence, and retention. Evaluation requires process measures of uptake, adherence, retention, and outcome measures of reduction in HIV infectiousness and acquisition. Three examples of combination prevention concepts are summarized for men who have sex with men in the Americas, young women in sub-Saharan Africa, and HIV serodiscordant couples.
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HIV-1 vaccine-induced T-cell responses cluster in epitope hotspots that differ from those induced in natural infection with HIV-1.
PLoS Pathog.
PUBLISHED: 06-01-2013
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Several recent large clinical trials evaluated HIV vaccine candidates that were based on recombinant adenovirus serotype 5 (rAd-5) vectors expressing HIV-derived antigens. These vaccines primarily elicited T-cell responses, which are known to be critical for controlling HIV infection. In the current study, we present a meta-analysis of epitope mapping data from 177 participants in three clinical trials that tested two different HIV vaccines: MRKAd-5 HIV and VRC-HIVAD014-00VP. We characterized the population-level epitope responses in these trials by generating population-based epitope maps, and also designed such maps using a large cohort of 372 naturally infected individuals. We used these maps to address several questions: (1) Are vaccine-induced responses randomly distributed across vaccine inserts, or do they cluster into immunodominant epitope hotspots? (2) Are the immunodominance patterns observed for these two vaccines in three vaccine trials different from one another? (3) Do vaccine-induced hotspots overlap with epitope hotspots induced by chronic natural infection with HIV-1? (4) Do immunodominant hotspots target evolutionarily conserved regions of the HIV genome? (5) Can epitope prediction methods be used to identify these hotspots? We found that vaccine responses clustered into epitope hotspots in all three vaccine trials and some of these hotspots were not observed in chronic natural infection. We also found significant differences between the immunodominance patterns generated in each trial, even comparing two trials that tested the same vaccine in different populations. Some of the vaccine-induced immunodominant hotspots were located in highly variable regions of the HIV genome, and this was more evident for the MRKAd-5 HIV vaccine. Finally, we found that epitope prediction methods can partially predict the location of vaccine-induced epitope hotspots. Our findings have implications for vaccine design and suggest a framework by which different vaccine candidates can be compared in early phases of evaluation.
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CROI 2013: New tools to understand transmission dynamics and prevent HIV infections.
Top Antivir Med
PUBLISHED: 05-18-2013
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New tools to track HIV incidence and identify transmission networks are providing insights about the leading edge of new HIV infections globally. Phylogenetic analyses point to the continued global nature of HIV transmission patterns and the challenges to reducing HIV infections through targeted antiretroviral programs alone. New methods for measuring acute infection and HIV incidence using cross-sectional surveys are proving useful in tracking the impact of prevention programs at the population level. Globally, men who have sex with men, and young men and women continue to be at highest risk of HIV acquisition; the US South also bears a disparate burden of new HIV infections and poor HIV-related outcomes. The use of injectable hormonal contraception may increase HIV acquisition risk; new, effective contraceptive methods and contraceptive counseling are needed, as simply removing this strategy could lead to a net increase in deaths due to unintended pregnancies. Another preexposure prophylaxis efficacy trial failed to show protection, likely because of poor adherence by women in the trial. Fortunately, new strategies are being developed that could substantially reduce new infections globally, such as methods to increase adherence and the use of long-acting antiretroviral agents.
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Influence of HLA-C expression level on HIV control.
Science
PUBLISHED: 04-06-2013
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A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA allelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohns disease, suggesting a broader influence of HLA expression levels in human disease.
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Sexual risk behavior among HIV-uninfected men who have sex with men participating in a tenofovir preexposure prophylaxis randomized trial in the United States.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 03-14-2013
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To evaluate for changes in sexual behaviors associated with daily pill use among men who have sex with men (MSM) participating in a preexposure prophylaxis trial.
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Performance of a Limiting-Antigen Avidity Enzyme Immunoassay for Cross-Sectional Estimation of HIV Incidence in the United States.
PLoS ONE
PUBLISHED: 01-01-2013
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A limiting antigen avidity enzyme immunoassay (HIV-1 LAg-Avidity assay) was recently developed for cross-sectional HIV incidence estimation. We evaluated the performance of the LAg-Avidity assay alone and in multi-assay algorithms (MAAs) that included other biomarkers.
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No Evidence of Sexual Risk Compensation in the iPrEx Trial of Daily Oral HIV Preexposure Prophylaxis.
PLoS ONE
PUBLISHED: 01-01-2013
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Preexposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) reduced HIV acquisition in the iPrEx trial among men who have sex with men and transgender women. Self-reported sexual risk behavior decreased overall, but may be affected by reporting bias. We evaluated potential risk compensation using biomarkers of sexual risk behavior.
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Correlates of HIV acquisition in a cohort of Black men who have sex with men in the United States: HIV prevention trials network (HPTN) 061.
PLoS ONE
PUBLISHED: 01-01-2013
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Black men who have sex with men (MSM) in the United States (US) are affected by HIV at disproportionate rates compared to MSM of other race/ethnicities. Current HIV incidence estimates in this group are needed to appropriately target prevention efforts.
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A Sequential Phase 2b Trial Design for Evaluating Vaccine Efficacy and Immune Correlates for Multiple HIV Vaccine Regimens.
Stat Commun Infect Dis
PUBLISHED: 09-16-2011
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Five preventative HIV vaccine efficacy trials have been conducted over the last 12 years, all of which evaluated vaccine efficacy (VE) to prevent HIV infection for a single vaccine regimen versus placebo. Now that one of these trials has supported partial VE of a prime-boost vaccine regimen, there is interest in conducting efficacy trials that simultaneously evaluate multiple prime-boost vaccine regimens against a shared placebo group in the same geographic region, for accelerating the pace of vaccine development. This article proposes such a design, which has main objectives (1) to evaluate VE of each regimen versus placebo against HIV exposures occurring near the time of the immunizations; (2) to evaluate durability of VE for each vaccine regimen showing reliable evidence for positive VE; (3) to expeditiously evaluate the immune correlates of protection if any vaccine regimen shows reliable evidence for positive VE; and (4) to compare VE among the vaccine regimens. The design uses sequential monitoring for the events of vaccine harm, non-efficacy, and high efficacy, selected to weed out poor vaccines as rapidly as possible while guarding against prematurely weeding out a vaccine that does not confer efficacy until most of the immunizations are received. The evaluation of the design shows that testing multiple vaccine regimens is important for providing a well-powered assessment of the correlation of vaccine-induced immune responses with HIV infection, and is critically important for providing a reasonably powered assessment of the value of identified correlates as surrogate endpoints for HIV infection.
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HIV epidemiology and breakthroughs in prevention 30 years into the AIDS epidemic.
Top Antivir Med
PUBLISHED: 08-27-2011
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Thirty years after the first AIDS cases were reported in the United States, the HIV epidemic continues to be heavily concentrated among men who have sex with men (MSM) in the United States. MSM are heavily impacted throughout most of the world and are the predominant risk group throughout the Americas and Western Europe; heterosexuals are the predominant risk group in sub-Saharan Africa; and injection drug users predominate throughout Eastern Europe and Southeast Asia. In the United States, blacks and Latinos continue to be disproportionately affected, despite overall advances in HIV testing and care. The 2011 Conference on Retroviruses and Opportunistic Infections focused on populations heavily impacted throughout the world: adolescents, women, MSM, and serodiscordant couples. Several presentations focused on the unique relationship between herpes simplex virus type 2 (HSV-2) and HIV-1; although many opportunistic infections increase HIV acquisition risk, HSV-2 is likely the only one whose effective prevention or treatment could substantially influence HIV infection rates, because of the high prevalence and persistence of HSV-2. The 2011 conference also celebrated the substantial advances made in the use of antiretroviral drugs for prevention of HIV acquisition (eg, oral preexposure prophylaxis, topical microbicides) and transmission (eg, antiretroviral therapy). Further progress is also being made in evaluating other prevention strategies and their rollout, including male condoms, male circumcision, and HIV testing and linkage to care.
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Impact of herpes simplex virus type 2 on HIV-1 acquisition and progression in an HIV vaccine trial (the Step study).
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 08-24-2011
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Extensive observational data suggest that herpes simplex virus type 2 (HSV-2) infection may facilitate HIV acquisition, increase HIV viral load, and accelerate HIV progression and onward transmission. To explore these relationships, we examined the impact of preexisting HSV-2 infection in an international HIV vaccine trial.
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Human adenovirus-specific T cells modulate HIV-specific T cell responses to an Ad5-vectored HIV-1 vaccine.
J. Clin. Invest.
PUBLISHED: 07-27-2011
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Recombinant viruses hold promise as vectors for vaccines to prevent infectious diseases with significant global health impacts. One of their major limitations is that preexisting anti-vector neutralizing antibodies can reduce T cell responses to the insert antigens; however, the impact of vector-specific cellular immunity on subsequent insert-specific T cell responses has not been assessed in humans. Here, we have identified and compared adenovirus-specific and HIV-specific T cell responses in subjects participating in two HIV-1 vaccine trials using a vaccine vectored by adenovirus serotype 5 (Ad5). Higher frequencies of pre-immunization adenovirus-specific CD4? T cells were associated with substantially decreased magnitude of HIV-specific CD4? T cell responses and decreased breadth of HIV-specific CD8? T cell responses in vaccine recipients, independent of type-specific preexisting Ad5-specific neutralizing antibody titers. Further, epitopes recognized by adenovirus-specific T cells were commonly conserved across many adenovirus serotypes, suggesting that cross-reactivity of preexisting adenovirus-specific T cells can extend to adenovirus vectors derived from rare serotypes. These findings provide what we believe to be a new understanding of how preexisting viral immunity may impact the efficacy of vaccines under current evaluation for prevention of HIV, tuberculosis, and malaria.
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Use of a high resolution melting (HRM) assay to compare gag, pol, and env diversity in adults with different stages of HIV infection.
PLoS ONE
PUBLISHED: 07-20-2011
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Cross-sectional assessment of HIV incidence relies on laboratory methods to discriminate between recent and non-recent HIV infection. Because HIV diversifies over time in infected individuals, HIV diversity may serve as a biomarker for assessing HIV incidence. We used a high resolution melting (HRM) diversity assay to compare HIV diversity in adults with different stages of HIV infection. This assay provides a single numeric HRM score that reflects the level of genetic diversity of HIV in a sample from an infected individual.
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Male circumcision and risk of HIV acquisition among MSM.
AIDS
PUBLISHED: 06-07-2011
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To assess the association between male circumcision, insertive anal sex practices, and HIV acquisition in a cohort of MSM.
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Bone mineral density in HIV-negative men participating in a tenofovir pre-exposure prophylaxis randomized clinical trial in San Francisco.
PLoS ONE
PUBLISHED: 04-24-2011
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Pre-exposure prophylaxis (PrEP) trials are evaluating regimens containing tenofovir-disoproxil fumarate (TDF) for HIV prevention. We determined the baseline prevalence of low bone mineral density (BMD) and the effect of TDF on BMD in men who have sex with men (MSM) in a PrEP trial in San Francisco.
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Genome-wide association study implicates PARD3B-based AIDS restriction.
J. Infect. Dis.
PUBLISHED: 04-20-2011
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Host genetic variation influences human immunodeficiency virus (HIV) infection and progression to AIDS. Here we used clinically well-characterized subjects from 5 pretreatment HIV/AIDS cohorts for a genome-wide association study to identify gene associations with rate of AIDS progression.
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Role of exonic variation in chemokine receptor genes on AIDS: CCRL2 F167Y association with pneumocystis pneumonia.
PLoS Genet.
PUBLISHED: 02-28-2011
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Chromosome 3p21-22 harbors two clusters of chemokine receptor genes, several of which serve as major or minor coreceptors of HIV-1. Although the genetic association of CCR5 and CCR2 variants with HIV-1 pathogenesis is well known, the role of variation in other nearby chemokine receptor genes remain unresolved. We genotyped exonic single nucleotide polymorphisms (SNPs) in chemokine receptor genes: CCR3, CCRL2, and CXCR6 (at 3p21) and CCR8 and CX3CR1 (at 3p22), the majority of which were non-synonymous. The individual SNPs were tested for their effects on disease progression and outcomes in five treatment-naïve HIV-1/AIDS natural history cohorts. In addition to the known CCR5 and CCR2 associations, significant associations were identified for CCR3, CCR8, and CCRL2 on progression to AIDS. A multivariate survival analysis pointed to a previously undetected association of a non-conservative amino acid change F167Y in CCRL2 with AIDS progression: 167F is associated with accelerated progression to AIDS (RH = 1.90, P = 0.002, corrected). Further analysis indicated that CCRL2-167F was specifically associated with more rapid development of pneumocystis pneumonia (PCP) (RH = 2.84, 95% CI 1.28-6.31) among four major AIDS-defining conditions. Considering the newly defined role of CCRL2 in lung dendritic cell trafficking, this atypical chemokine receptor may affect PCP through immune regulation and inducing inflammation.
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What is the potential impact of adult circumcision on the HIV epidemic among men who have sex with men in San Francisco?
Sex Transm Dis
PUBLISHED: 02-24-2011
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With the help of a community-based survey, we assess the potential effect of circumcision on the HIV epidemic among men who have sex with men (MSM) in San Francisco. Only a small minority of MSM would both derive benefit from circumcision (i.e., were uncircumcised, HIV-negative, predominantly insertive, and reported unprotected insertive anal sex) and be willing to participate in circumcision trials (0.7%) or be circumcised if proven effective as a prevention strategy (0.9%). Circumcision would have limited public health significance for MSM in San Francisco.
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Pre-exposure prophylaxis and the promise of combination prevention approaches.
AIDS Behav
PUBLISHED: 02-19-2011
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Pre-exposure prophylaxis (PrEP) for HIV prevention is a promising experimental approach currently being tested globally. A number of PrEP trials are evaluating the safety and effectiveness of PrEP in men who have sex with men (MSM) and other populations at risk for HIV, and results will be available from this first generation of efficacy trials over the next few years. Here we review the rationale for orally-administered antiretrovirals for prevention, and outline issues the first generation trials will address as well as questions that may be addressed in future studies. We also describe the rationale for combination prevention approaches that may combine PrEP with other prevention modalities as part of a larger prevention package.
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Absence of reproducibly detectable low-level HIV viremia in highly exposed seronegative men and women.
AIDS
PUBLISHED: 02-08-2011
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Transient HIV infections have been invoked to account for the cellular immune responses detected in highly virus-exposed individuals who have remained HIV-seronegative. We tested for very low levels of HIV RNA in 524 seronegative plasma samples from 311 highly exposed women and men from three longitudinal HIV cohorts.
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Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial.
Nat. Med.
PUBLISHED: 01-31-2011
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We analyzed HIV-1 genome sequences from 68 newly infected volunteers in the STEP HIV-1 vaccine trial. To determine whether the vaccine exerted selective T cell pressure on breakthrough viruses, we identified potential T cell epitopes in the founder sequences and compared them to epitopes in the vaccine. We found greater distances to the vaccine sequence for sequences from vaccine recipients than from placebo recipients. The most significant signature site distinguishing vaccine from placebo recipients was Gag amino acid 84, a site encompassed by several epitopes contained in the vaccine and restricted by human leukocyte antigen (HLA) alleles common in the study cohort. Moreover, the extended divergence was confined to the vaccine components of the virus (HIV-1 Gag, Pol and Nef) and not found in other HIV-1 proteins. These results represent what is to our knowledge the first evidence of selective pressure from vaccine-induced T cell responses on HIV-1 infection in humans.
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International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations.
Vaccine
PUBLISHED: 01-09-2011
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Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for HIV-1 and other pathogens have been shown to be limited by high titers of Ad5 neutralizing antibodies (NAbs) in the developing world. Alternative serotype rAd vectors have therefore been constructed. Here we report Ad5, Ad26, Ad35, and Ad48 NAb titers in 4381 individuals from North America, South America, sub-Saharan Africa, and Southeast Asia. As expected, Ad5 NAb titers were both frequent and high magnitude in sub-Saharan Africa and Southeast Asia. In contrast, Ad35 NAb titers proved infrequent and low in all regions studied, and Ad48 NAbs were rare in all regions except East Africa. Ad26 NAbs were moderately common in adults in sub-Saharan Africa and Southeast Asia, but Ad26 NAb titers proved markedly lower than Ad5 NAb titers in all regions, and these relatively low Ad26 NAb titers did not detectably suppress the immunogenicity of 4×10(10)vp of a rAd26-Gag/Pol/Env/Nef vaccine in rhesus monkeys. These data inform the clinical development of alternative serotype rAd vaccine vectors in the developing world.
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Genetic associations of variants in genes encoding HIV-dependency factors required for HIV-1 infection.
J. Infect. Dis.
PUBLISHED: 11-19-2010
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High-throughput genome-wide techniques have facilitated the identification of previously unknown host proteins involved in cellular human immunodeficiency virus (HIV) infection. Recently, 3 independent studies have used small interfering RNA technology to silence each gene in the human genome to determine the importance of each in HIV infection. Genes conferring a significant effect were termed HIV-dependency factors (HDFs).
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Overview of STEP and Phambili trial results: two phase IIb test-of-concept studies investigating the efficacy of MRK adenovirus type 5 gag/pol/nef subtype B HIV vaccine.
Curr Opin HIV AIDS
PUBLISHED: 10-28-2010
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Two phase IIb test-of-concept studies evaluated the replication-defective adenovirus type 5 (Ad5) vaccine MRK gag/pol/nef HIV vaccine to prevent infection or decrease early plasma viral load in disparate populations. The STEP study enrolled men and women in the Americas, Caribbean and Australia; the Phambili trial enrolled men and women in South Africa, where the modes of sexual transmission and HIV-1 risk, subtypes of HIV-1, and background Ad5 seroprevalence differed.
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IL28B polymorphism does not determine outcomes of hepatitis B virus or HIV infection.
J. Infect. Dis.
PUBLISHED: 10-26-2010
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An IL28B haplotype strongly determines the outcome of natural and interferon-? treated hepatitis C virus (HCV) infection. To assess whether the polymorphism marking the haplotype (rs12979860) also affects other interferon-? responsive chronic viral illnesses, namely hepatitis B virus (HBV) and human immunodeficiency virus (HIV) type 1 infections, we genotyped 226 individuals with HBV persistence, 384 with HBV recovery, and 2548 with or at high risk for HIV infection. The C/C genotype of rs12979860 was not associated with HBV recovery (odds ratio, 0.99), resistance to HIV infection (odds ratio, 0.97), or HIV disease progression (P > .05). This IL28B single-nucleotide polymorphism affects the immune response to HCV but not to HBV or HIV.
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Lessons drawn from recent HIV vaccine efficacy trials.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 09-06-2010
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A safe and effective HIV vaccine is needed to curtail the US and global epidemics. However, the search for one has been elusive despite more than 25 years of focused research. Results from the RV144 Thai efficacy trial have renewed hope that a vaccine may protect against HIV acquisition. We can draw several scientific and operational lessons from RV144 and other recent tests-of-concept efficacy trials. Here we describe how trial results, some unexpected, highlight the fundamental role these clinical studies play in HIV vaccine discovery. These trials also teach us that transparency in data analysis and results dissemination can yield substantial rewards and that efforts to engage communities, particularly those most heavily affected by the epidemic, are needed to augment research literacy and trial recruitment. Future efficacy trial designs may incorporate novel, partially effective prevention strategies. Although greater in size and complexity, these trials may offer unique opportunities to explore synergies with vaccines under study.
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Serosorting is associated with a decreased risk of HIV seroconversion in the EXPLORE Study Cohort.
PLoS ONE
PUBLISHED: 07-19-2010
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Seroadaptation strategies such as serosorting and seropositioning originated within communities of men who have sex with men (MSM), but there are limited data about their effectiveness in preventing HIV transmission when utilized by HIV-negative men.
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Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
PLoS ONE
PUBLISHED: 06-11-2010
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The human mitochondrial genome includes only 13 coding genes while nuclear-encoded genes account for 99% of proteins responsible for mitochondrial morphology, redox regulation, and energetics. Mitochondrial pathogenesis occurs in HIV patients and genetically, mitochondrial DNA haplogroups with presumed functional differences have been associated with differential AIDS progression.
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HIV epidemiology, testing strategies, and prevention interventions.
Top HIV Med
PUBLISHED: 06-03-2010
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As the HIV epidemic has matured, a substantial proportion of new infections worldwide may be occurring within stable partnerships. Within the United States, blacks are disproportionately affected by HIV disease, and the drivers of this epidemic involve behavioral and structural factors. The 17th Conference on Retroviruses and Opportunistic Infections highlighted new insights into drivers of HIV infection in both of these populations. The conference also focused on new strategies to track the epidemic and to prevent HIV infection, including scale-up of HIV testing and of treatment of HIV-seropositive persons, and the use of oral and topical antiretroviral drugs to prevent HIV acquisition among HIV-uninfected persons.
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Multistage genomewide association study identifies a locus at 1q41 associated with rate of HIV-1 disease progression to clinical AIDS.
J. Infect. Dis.
PUBLISHED: 01-13-2010
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A mean of 9-10 years of human immunodeficiency virus type 1 (HIV-1) infection elapse before clinical AIDS develops in untreated persons, but this rate of disease progression varies substantially among individuals. To investigate host genetic determinants of the rate of progression to clinical AIDS, we performed a multistage genomewide association study.
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APOBEC3B deletion and risk of HIV-1 acquisition.
J. Infect. Dis.
PUBLISHED: 08-25-2009
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The human APOBEC3 family of cytidine deaminases provides intrinsic immunity to retroviral infection. A naturally occurring 29.5-kb deletion removes the entire APOBEC3B gene. We examined the impact of the APOBEC3B gene deletion in >4000 individuals from 5 human immunodeficiency virus type 1 (HIV-1) natural history cohorts. The hemizygous genotype had no effect on either acquisition of HIV-1 infection or progression to AIDS. However, the homozygous deletion was significantly associated with unfavorable outcomes for HIV-1 acquisition (odds ratio, 7.37; P= .024), progression to AIDS (relative hazard, 4.01; P=. 03), and viral set point (P= .04). These findings suggest that the loss of APOBEC3B may increase host susceptibility to HIV-1 acquisition and progression to AIDS and warrant further study.
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HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C.
Nat. Genet.
PUBLISHED: 07-21-2009
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A variant 35 kb upstream of the HLA-C gene (-35C/T) was previously shown to associate with HLA-C mRNA expression level and steady-state plasma HIV RNA levels. We genotyped this variant in 1,698 patients of European ancestry with HIV. Individuals with known seroconversion dates were used for disease progression analysis and those with longitudinal viral load data were used for viral load analysis. We further tested cell surface expression of HLA-C in normal donors using an HLA-C-specific antibody. We show that the -35C allele is a proxy for high HLA-C cell surface expression, and that individuals with high-expressing HLA-C alleles progress more slowly to AIDS and control viremia significantly better than individuals with low HLA-C expressing alleles. These data strongly implicate high HLA-C expression levels in more effective control of HIV-1, potentially through better antigen presentation to cytotoxic T lymphocytes or recognition and killing of infected cells by natural killer cells.
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Estimating the proportion of HIV transmissions from main sex partners among men who have sex with men in five US cities.
AIDS
PUBLISHED: 05-07-2009
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HIV incidence in the United States among men who have sex with men (MSM) has been increasing since 2000, and MSM remain the most heavily impacted risk group in the US HIV epidemic.
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The epidemiology of new HIV infections and interventions to limit HIV transmission.
Top HIV Med
PUBLISHED: 04-30-2009
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After the disappointing news reported at the 2008 (15th) Conference on Retroviruses and Opportunistic Infections regarding HIV vaccines, microbicides, and herpes virus suppression trials, the 16th conference this year brought welcome advances in the HIV prevention field. In particular, substantial progress is being made in approaches to preexposure prophylaxis in preclinical and clinical trials, and an efficacy trial of a vaginal microbicide appeared to provide women in Africa and the United States with modest protection against HIV acquisition. This review covers presentations on the epidemiology of HIV infection in specific global populations, strategies to improve the uptake of HIV testing, lessons from previous negative prevention trials, and progress in the development of new biomedical interventions.
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Anal human papillomavirus infection is associated with HIV acquisition in men who have sex with men.
AIDS
PUBLISHED: 04-25-2009
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Human papillomavirus (HPV) is a common sexually transmitted agent that causes anogenital cancer and precancer lesions that have an inflammatory infiltrate, may be friable and bleed. Our aim was to determine the association between anal HPV infection and HIV acquisition.
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What drives the US and Peruvian HIV epidemics in men who have sex with men (MSM)?
PLoS ONE
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In this work, we estimate the proportions of transmissions occurring in main vs. casual partnerships, and by the sexual role, infection stage, and testing and treatment history of the infected partner, for men who have sex with men (MSM) in the US and Peru. We use dynamic, stochastic models based in exponential random graph models (ERGMs), obtaining inputs from multiple large-scale MSM surveys. Parallel main partnership and casual sexual networks are simulated. Each man is characterized by age, race, circumcision status, sexual role behavior, and propensity for unprotected anal intercourse (UAI); his history is modeled from entry into the adult population, with potential transitions including HIV infection, detection, treatment, AIDS diagnosis, and death. We implemented two model variants differing in assumptions about acute infectiousness, and assessed sensitivity to other key inputs. Our two models suggested that only 4-5% (Model 1) or 22-29% (Model 2) of HIV transmission results from contacts with acute-stage partners; the plurality (80-81% and 49%, respectively) stem from chronic-stage partners and the remainder (14-16% and 27-35%, respectively) from AIDS-stage partners. Similar proportions of infections stem from partners whose infection is undiagnosed (24-31%), diagnosed but untreated (36-46%), and currently being treated (30-36%). Roughly one-third of infections (32-39%) occur within main partnerships. Results by country were qualitatively similar, despite key behavioral differences; one exception was that transmission from the receptive to insertive partner appears more important in Peru (34%) than the US (21%). The broad balance in transmission contexts suggests that education about risk, careful assessment, pre-exposure prophylaxis, more frequent testing, earlier treatment, and risk-reduction, disclosure, and adherence counseling may all contribute substantially to reducing the HIV incidence among MSM in the US and Peru.
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Seroadaptive practices: association with HIV acquisition among HIV-negative men who have sex with men.
PLoS ONE
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Although efficacy is unknown, many men who have sex with men (MSM) attempt to reduce HIV risk by adapting condom use, partner selection, or sexual position to the partners HIV serostatus. We assessed the association of seroadaptive practices with HIV acquisition.
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Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men.
Sci Transl Med
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Drug concentrations associated with protection from HIV-1 acquisition have not been determined. We evaluated drug concentrations among men who have sex with men in a substudy of the iPrEx trial (1). In this randomized placebo-controlled trial, daily oral doses of emtricitabine/tenofovir disoproxil fumarate were used as pre-exposure prophylaxis (PrEP) in men who have sex with men. Drug was detected less frequently in blood plasma and in viable cryopreserved peripheral blood mononuclear cells (PBMCs) in HIV-infected cases at the visit when HIV was first discovered compared with controls at the matched time point of the study (8% versus 44%; P < 0.001) and in the 90 days before that visit (11% versus 51%; P < 0.001). An intracellular concentration of the active form of tenofovir, tenofovir-diphosphate (TFV-DP), of 16 fmol per million PBMCs was associated with a 90% reduction in HIV acquisition relative to the placebo arm. Directly observed dosing in a separate study, the STRAND trial, yielded TFV-DP concentrations that, when analyzed according to the iPrEx model, corresponded to an HIV-1 risk reduction of 76% for two doses per week, 96% for four doses per week, and 99% for seven doses per week. Prophylactic benefits were observed over a range of doses and drug concentrations, suggesting ways to optimize PrEP regimens for this population.
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Antiretroviral use for prevention and other factors affecting the course of the HIV-1 epidemic.
Top Antivir Med
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Antiretroviral therapy has tremendous potential to alter the HIV-1 epidemic trajectory. However, gaps in the continuum from HIV diagnosis, through linkage to care and uptake and adherence to antiretroviral therapy, are substantially limiting to the actual impact. In the United States, gaps in HIV diagnosis and care are greatest among African Americans, substance users, and persons living below the poverty line. Globally, HIV diagnosis rates are highest in women, but HIV incidence may be declining more rapidly in men, due to lower transmission rates from female partners and greater uptake of medical male circumcision. The 2012 Conference on Retroviruses and Opportunistic Infections explored gaps in the continuum of care and potential strategies to address them, and also addressed the disparate results from preexposure prophylaxis efficacy trials. The role of injectable contraceptives in increasing the risk of HIV acquisition in women was debated, as was the potential harm that could arise from limiting this contraceptive method due to increased maternal mortality. Similarly, the potential benefits and harms of serosorting were explored. Investigators explored scale-up of prevention strategies to have the biggest and most cost-effective impact on the global epidemic.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.