High-risk Sexual Behavior is Associated with Post-Exposure Prophylaxis Non-adherence among Men who have Sex with Men Enrolled in a Combination Prevention Intervention.

Methamphetamine use among men who have sex with men (MSM) is associated with increased HIV prevalence, due to increased engagement in high-risk sexual behavior. Fifty-three HIV-negative, methamphetamine-using MSM were enrolled in a biobehavioral combination prevention intervention in Los Angeles, CA, to assess the feasibility of administering postexposure prophylaxis (PEP) in combination with contingency management (CM) to prevent HIV seroconversion. The study combined a CM behavioral intervention targeting reductions in methamphetamine use with a PEP biomedical intervention for HIV prevention. Those who reported recent exposure to HIV were initiated on tenofovir/emtricitabine- (Truvada)-based PEP (n=35). This secondary analysis sought to determine whether recent and/or lifetime sexual risk taking was associated with PEP adherence. Regression analyses controlling for participant sociodemographics demonstrated that, at baseline, increased number of lifetime sexually transmitted diseases (STDs; Coef.=-0.07; 95% CI=(-0.12) - (-0.01)) and recent episodes of unprotected anal intercourse (UAI; Coef.=-0.01; 95% CI= (-.01) - (-0.002)) were each associated with reductions in medication adherence. Given these associations between baseline sexual risk and PEP adherence, providers working with high-risk MSM may look to target reductions in sexual risk taking; this will reduce direct risk of HIV infection and may work to optimize medication adherence in the case of PEP initiation. Clinicaltrials.gov identifier: NCT00856323

Recommendations for the follow-up of study participants with breakthrough HIV infections during HIV/AIDS biomedical prevention studies.

CAPRISA_2013.Objective: To facilitate collection of cumulative data on longitudinal HIV disease outcomes during HIV prevention studies by developing recommendations for follow-up of the relatively few study participants with breakthrough infections. Design: We formed a working group to compare and contrast the various approaches taken in recent HIV prevention trials, to summarize the advantages and disadvantages associated with each, and to explore the feasibility of developing protocols for the long-term follow-up of seroconverters. Methods: We reviewed study designs, objectives, and assessments in 15 interventional studies that followed HIV seroconverters. Protocol team members joined discussions of the various approaches and developed recommendations. Results: Most HIV prevention clinical trials share a core set of objectives, including the description/comparison of virological, immunological, and clinical course of HIV, and sometimes a comparison of preseroconversion and postseroconversion behavior. Long-term follow-up of seroconverters can be conducted in separate studies if the transition from parent protocol is effectively managed. Conclusion: We recommend the development of harmonized seroconverter protocols. Although specific research questions in the postseroconversion period may differ depending on prevention modality, harmonizing key evaluations would create an opportunity to ask overarching questions that inform the prevention field with respect to design and implementation of future combination prevention studies. Follow-up immediately postseroconversion should be conducted in the parent protocol before roll over into a follow-up protocol. Development of specimen repositories with ample volumes for future assays, standardized definitions of infection, diagnosis and seroconversion dates, and harmonization of study objectives and sample collections at key time points are important

Screening for UGT1A1 Genotype in Study A5257 Would Have Markedly Reduced Premature Discontinuation of Atazanavir for Hyperbilirubinemia

Background. Some patients are not prescribed atazanavir because of concern about possible jaundice. Atazanavir-associated hyperbilirubinemia correlates with UGT1A1 rs887829 genotype. We examined bilirubin-related discontinuation of atazanavir in participants from AIDS Clinical Trials Group Study A5257. Methods. Discriminatory properties of UGT1A1 T/T genotype for predicting bilirubin-related atazanavir discontinuation through 96 weeks after antiretroviral initiation were estimated. Results. Genetic analyses involved 1450 participants, including 481 who initiated randomized atazanavir/ritonavir. Positive predictive values of rs887829 T/T for bilirubin-related discontinuation of atazanavir (with 95% confidence intervals [CIs]) were 20% (CI, 9%–36%) in Black, 60% (CI, 32%–84%) in White, and 29% (CI, 8%–58%) in Hispanic participants; negative predictive values were 97% (CI, 93%–99%), 95% (CI, 90%–98%), and 97% (CI, 90%–100%), respectively. Conclusions. Bilirubin-related discontinuation of atazanavir was rare in participants not homozygous for rs887829 T/T, regardless of race or ethnicity. We hypothesize that the higher rate of discontinuation among White participants homozygous for rs887829 T/T may reflect differences in physical manifestations of jaundice by race and ethnicity. Selective avoidance of atazanavir initiation among individuals with T/T genotypes would markedly reduce the likelihood of bilirubin-related discontinuation of atazanavir while allowing atazanavir to be prescribed to the majority of individuals. This genetic association will also affect atazanavir/cobicistat

Perspectives of US women participating in a candidate PrEP study: adherence, acceptability and future use intentions

Introduction Limited data exist on acceptability of candidate pre‐exposure prophylaxis (PrEP) regimens among US women. We evaluated PrEP experiences, attitudes and future use intentions among sexually active women who completed the US‐based HIV Prevention Trials Network 069/AIDS Clinical Trials Group 5305 study. Methods Women participated in the study between March 2013 and November 2015. We analysed computer‐assisted self‐interview (CASI) surveys among 130 women and conducted in‐depth interviews among a subset of 26 women from three sites. Interviews were conducted in mid/late‐2015. Results Most women (57%) reported very good/excellent PrEP adherence on CASI, although 21% acknowledged over‐reporting adherence at least some of the time. Commitment to preventing HIV infection, a sense of ownership of the study, and keeping pills stored in a visible location facilitated adherence. Adherence barriers included “simply forgetting” and being away from home. Most women interviewed did not intend to use PrEP in the future because of lack of perceived need due to their own (as opposed to their partners’) low‐risk behaviour and concerns about affordability – but not because of side effects or other characteristics of the regimens. Conclusions Improving HIV prevention options for US women will require access to affordable PrEP as well as expanding women\u27s understanding of relationship‐ and community‐level factors that increase their risk of acquiring HIV

Perspectives of US women participating in a candidate PrEP study: adherence, acceptability and future use intentions

IntroductionLimited data exist on acceptability of candidate preâ exposure prophylaxis (PrEP) regimens among US women. We evaluated PrEP experiences, attitudes and future use intentions among sexually active women who completed the USâ based HIV Prevention Trials Network 069/AIDS Clinical Trials Group 5305 study.MethodsWomen participated in the study between March 2013 and November 2015. We analysed computerâ assisted selfâ interview (CASI) surveys among 130 women and conducted inâ depth interviews among a subset of 26 women from three sites. Interviews were conducted in mid/lateâ 2015.ResultsMost women (57%) reported very good/excellent PrEP adherence on CASI, although 21% acknowledged overâ reporting adherence at least some of the time. Commitment to preventing HIV infection, a sense of ownership of the study, and keeping pills stored in a visible location facilitated adherence. Adherence barriers included â simply forgettingâ and being away from home. Most women interviewed did not intend to use PrEP in the future because of lack of perceived need due to their own (as opposed to their partnersâ ) lowâ risk behaviour and concerns about affordability â but not because of side effects or other characteristics of the regimens.DiscussionImproving HIV prevention options for US women will require access to affordable PrEP as well as expanding women’s understanding of relationshipâ and communityâ level factors that increase their risk of acquiring HIV.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148389/1/jia225247_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148389/2/jia225247.pd

Comparison of the Metabolic Effects of Ritonavir-Boosted Darunavir or Atazanavir Versus Raltegravir, and the Impact of Ritonavir Plasma Exposure: ACTG 5257

Background. Metabolic effects following combination antiretroviral therapy (cART) vary by regimen type. Changes in metabolic effects were assessed following cART in the AIDS Clinical Trials Group (ACTG) A5257 study, and correlated with plasma ritonavir trough concentrations (C24)

Comparison of the Metabolic Effects of Ritonavir-Boosted Darunavir or Atazanavir Versus Raltegravir, and the Impact of Ritonavir Plasma Exposure: ACTG 5257

Background. Metabolic effects following combination antiretroviral therapy (cART) vary by regimen type. Changes in metabolic effects were assessed following cART in the AIDS Clinical Trials Group (ACTG) A5257 study, and correlated with plasma ritonavir trough concentrations (C24)

Predicted effects of the introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study.

BACKGROUND: Long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) is recommended by WHO as an additional option for HIV prevention in sub-Saharan Africa, but there is concern that its introduction could lead to an increase in integrase-inhibitor resistance undermining treatment programmes that rely on dolutegravir. We aimed to project the health benefits and risks of cabotegravir-PrEP introduction in settings in sub-Saharan Africa. METHODS: With HIV Synthesis, an individual-based HIV model, we simulated 1000 setting-scenarios reflecting both variability and uncertainty about HIV epidemics in sub-Saharan Africa and compared outcomes for each with and without cabotegravir-PrEP introduction. PrEP use is assumed to be risk-informed and to be used only in 3-month periods (the time step for the model) when having condomless sex. We consider three groups at risk of integrase-inhibitor resistance emergence: people who start cabotegravir-PrEP after (unknowingly) being infected with HIV, those who seroconvert while on PrEP, and those with HIV who have residual cabotegravir drugs concentrations during the early tail period after recently stopping PrEP. We projected the outcomes of policies of cabotegravir-PrEP introduction and of no introduction in 2022 across 50 years. In 50% of setting-scenarios we considered that more sensitive nucleic-acid-based HIV diagnostic testing (NAT), rather than regular antibody-based HIV rapid testing, might be used to reduce resistance risk. For cost-effectiveness analysis we assumed in our base case a cost of cabotegravir-PrEP drug to be similar to oral PrEP, resulting in a total annual cost of USD$144 per year ($114 per year and $264 per year considered in sensitivity analyses), a cost-effectiveness threshold of$500 per disability-adjusted life years averted, and a discount rate of 3% per year. FINDINGS: Reflecting our assumptions on the appeal of cabotegravir-PrEP, its introduction is predicted to lead to a substantial increase in PrEP use with approximately 2·6% of the adult population (and 46% of those with a current indication for PrEP) receiving PrEP compared with 1·5% (28%) without cabotegravir-PrEP introduction across 20 years. As a result, HIV incidence is expected to be lower by 29% (90% range across setting-scenarios 6-52%) across the same period compared with no introduction of cabotegravir-PrEP. In people initiating antiretroviral therapy, the proportion with integrase-inhibitor resistance after 20 years is projected to be 1·7% (0-6·4%) without cabotegravir-PrEP introduction but 13·1% (4·1-30·9%) with. Cabotegravir-PrEP introduction is predicted to lower the proportion of all people on antiretroviral therapy with viral loads less than 1000 copies per mL by 0·9% (-2·5% to 0·3%) at 20 years. For an adult population of 10 million an overall decrease in number of AIDS deaths of about 4540 per year (-13 000 to -300) across 50 years is predicted, with little discernible benefit with NAT when compared with standard antibody-based rapid testing. AIDS deaths are predicted to be averted with cabotegravir-PrEP introduction in 99% of setting-scenarios. Across the 50-year time horizon, overall HIV programme costs are predicted to be similar regardless of whether cabotegravir-PrEP is introduced (total mean discounted annual HIV programme costs per year across 50 years is $151·3 million vs$150·7 million), assuming the use of standard antibody testing. With antibody-based rapid HIV testing, the introduction of cabotegravir-PrEP is predicted to be cost-effective under an assumed threshold of $500 per disability-adjusted life year averted in 82$144 per year, in 52% at $264, and in 87$114. INTERPRETATION: Despite leading to increases in integrase-inhibitor drug resistance, cabotegravir-PrEP introduction is likely to reduce AIDS deaths in addition to HIV incidence. Long-acting cabotegravir-PrEP is predicted to be cost-effective if delivered at similar cost to oral PrEP with antibody-based rapid HIV testing. FUNDING: Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases of the National Institutes of Health