Predicted Effectiveness of Daily and Nondaily Preexposure Prophylaxis for Men Who Have Sex With Men Based on Sex and Pill-taking Patterns From the Human Immuno Virus Prevention Trials Network 067/ADAPT Study.

BACKGROUND: The HIV Prevention Trials Network (HPTN) 067/Alternative Dosing to Augment PrEP Pill Taking (ADAPT) Study evaluated the feasibility of daily and nondaily human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) regimens among high-risk populations, including men who have sex with men (MSM) and transgender women, in Bangkok, Thailand and Harlem, New York. We used a mathematical model to predict the efficacy and effectiveness of different dosing regimens. METHODS: An individual-based mathematical model was used to simulate annual HIV incidence among MSM cohorts. PrEP efficacy for covered sex acts, as defined in the HPTN 067/ADAPT protocol, was estimated using subgroup efficacy estimates from the preexposure prophylaxis initiative (iPrEx) trial. Effectiveness was estimated by comparison of the HIV incidence with and without PrEP use. RESULTS: We estimated that PrEP was highly protective (85%-96% efficacy across regimens and sites) for fully covered acts. PrEP was more protective for partially covered acts in Bangkok (71%-88% efficacy) than in Harlem (62%-81% efficacy). Our model projects 80%, 62%, and 68% effectiveness of daily, time-driven, and event-driven PrEP for MSM in Harlem compared with 90%, 85%, and 79% for MSM in Bangkok. Halving the efficacy for partially covered acts decreases effectiveness by 8-9 percentage points in Harlem and by 5-9 percentage points in Bangkok across regimens. CONCLUSIONS: Our analysis suggests that PrEP was more effective among MSM in Thailand than in the United States as a result of more fully covered sex acts and more pills taken around partially covered acts. Overall, nondaily PrEP was less effective than daily PrEP, especially in the United States where the sex act coverage associated with daily use was substantially higher.

Development and Validation of the Personalized Sexual Health Promotion (SexPro) HIV Risk Prediction Model for Men Who Have Sex with Men in the United States.

Accurate HIV risk assessment among men who have sex with men (MSM) is important to help providers assess risk, and target HIV prevention interventions. We sought to develop an evidence-based HIV risk assessment tool for US MSM that is inclusive of Black MSM. Data from four large longitudinal cohorts of MSM were used to develop (EXPLORE), and validate (VAX004, HPTN061, and HVTN505). These data included visits in which participants self-reported HIV risk behavior and underwent HIV testing. We developed a pooled logistic model for incident HIV infection based on self-reported risk behaviors during the 6 months before each study visit. A total of 4069 MSM were used for the development cohort, and 8047 MSM in the three validation cohorts through 2013. The final model includes age (< 35, ≥ 35); Black race and Latino ethnicity; numbers of HIV-negative anal sex partners; number of insertive or receptive anal intercourse episodes; having 1 HIV-negative partner only; self-reported substance use; and bacterial sexually transmitted infection diagnosis. The model showed good discrimination in internal validation (C-statistic = 79.5). The external validation cohorts also showed good discrimination, with C-statistics of 73.1, 71.0, 71.9 in VAX004, HPTN061, and HVTN505 respectively, and acceptable calibration. We developed and validated an HIV risk assessment tool for MSM, which showed good predictive ability, including among the largest cohort of HIV-uninfected Black MSM in the US. This tool is available online (mysexpro.org) and can be used by providers to support targeting of HIV prevention interventions such as pre-exposure prophylaxis for MSM.

Daily and Nondaily Oral Preexposure Prophylaxis in Men and Transgender Women Who Have Sex With Men: The Human Immunodeficiency Virus Prevention Trials Network 067/ADAPT Study.

Background: Nondaily dosing of oral preexposure prophylaxis (PrEP) may provide equivalent coverage of sex events compared with daily dosing. Methods: At-risk men and transgender women who have sex with men were randomly assigned to 1 of 3 dosing regimens: 1 tablet daily, 1 tablet twice weekly with a postsex dose (time-driven), or 1 tablet before and after sex (event-driven), and were followed for coverage of sex events with pre- and postsex dosing measured by weekly self-report, drug concentrations, and electronic drug monitoring. Results: From July 2012 to May 2014, 357 participants were randomized. In Bangkok, the coverage of sex events was 85% for the daily arm compared with 84% for the time-driven arm (P = .79) and 74% for the event-driven arm (P = .02). In Harlem, coverage was 66%, 47% (P = .01), and 52% (P = .01) for these groups. In Bangkok, PrEP medication concentrations in blood were consistent with use of ≥2 tablets per week in >95% of visits when sex was reported in the prior week, while in Harlem, such medication concentrations occurred in 48.5% in the daily arm, 30.9% in the time-driven arm, and 16.7% in the event-driven arm (P < .0001). Creatinine elevations were more common in the daily arm (P = .050), although they were not dose limiting. Conclusions: Daily dosing recommendations increased coverage and protective drug concentrations in the Harlem cohort, while daily and nondaily regimens led to comparably favorable outcomes in Bangkok, where participants had higher levels of education and employment. Clinical Trials Registration: NCT01327651.

Sex, PrEP, and Stigma: Experiences with HIV Pre-exposure Prophylaxis Among New York City MSM Participating in the HPTN 067/ADAPT Study.

The HPTN 067/Alternative Dosing to Augment Pre-Exposure Prophylaxis Pill Taking (ADAPT) study evaluated daily and non-daily dosing schedules for oral pre-exposure prophylaxis (PrEP) to prevent HIV. A qualitative sub-study including focus groups and in-depth interviews was conducted among men who have sex with men participating in New York City to understand their experience with PrEP and study dosing schedules. The 37 sub-study participants were 68% black, 11% white, and 8% Asian; 27% were of Hispanic/Latino ethnicity. Mean age was 34 years. Themes resulting from qualitative analysis include: PrEP is a significant advance for HIV prevention; non-daily dosing of PrEP is congruent with HIV risk; and pervasive stigma connected to HIV and risk behavior is a barrier to PrEP adherence, especially for non-daily dosing schedules. The findings underscore how PrEP intersects with other HIV prevention practices and highlight the need to understand and address multidimensional stigma related to PrEP use.

Limited awareness of pre-exposure prophylaxis among black men who have sex with men and transgender women in New York city.

Awareness of Pre-exposure prophylaxis (PrEP) was assessed among a cohort of substance-using black men who have sex with men and transgender women (MSM/TGW) participating in the STAR Study, which recruited black MSM/TGW in New York City for HIV testing and linked HIV-infected individuals into care from July 2012 to April 2015. Sociodemographic, psychosocial, known HIV risk factors, and PrEP awareness were assessed among participants. Multivariable logistic regression was conducted to assess factors associated with PrEP awareness. Of 1673 participants, median age was 43 years and 25% were under age 30. Most participants (85.8%) reported having insufficient income for basic necessities at least occasionally, 54.8% were homeless, and 71.3% were unemployed. Awareness of PrEP was reported among 18.2% of participants. PrEP awareness was associated with younger age (adjusted odds ratio [aOR] 0.87, per 5 years), gay identity (aOR 2.46), higher education (aOR 1.70), more frequent past HIV testing (aOR 3.18), less HIV stigma (aOR 0.61), less hazardous/harmful alcohol use (aOR 0.61), and more sexual partners (aOR 1.04, per additional partner in past 30 days). In this substance-using black MSM/TGW cohort with high rates of poverty and homelessness, PrEP awareness was low. This study demonstrates the need for targeted dissemination of PrEP information to key populations to increase awareness and ultimately improve uptake and utilization of PrEP.

A Longitudinal Analysis of Treatment Optimism and HIV Acquisition and Transmission Risk Behaviors Among Black Men Who Have Sex with Men in HPTN 061.

Little is known about HIV treatment optimism and risk behaviors among Black men who have sex with men (BMSM). Using longitudinal data from BMSM in the HPTN 061 study, we examined participants' self-reported comfort with having condomless sex due to optimistic beliefs regarding HIV treatment. We assessed correlates of treatment optimism and its association with subsequent risk behaviors for HIV acquisition or transmission using multivariable logistic regression with generalized estimating equations. Independent correlates of treatment optimism included age ≥35 years, annual household income <$20,000, depressive symptoms, high HIV conspiracy beliefs, problematic alcohol use, and previous HIV diagnosis. Treatment optimism was independently associated with subsequent condomless anal sex with a male partner of serodiscordant/unknown HIV status among HIV-infected men, but this association was not statistically significant among HIV-uninfected men. HIV providers should engage men in counseling conversations to assess and minimize willingness to have condomless sex that is rooted in optimistic treatment beliefs without knowledge of viral suppression.

Lessons Learned From the Implementation of Seek, Test, Treat, Retain Interventions Using Mobile Phones and Text Messaging to Improve Engagement in HIV Care for Vulnerable Populations in the United States.

In the United States, little is known about interventions that rely on mobile phones and/or text messaging to improve engagement in HIV care for vulnerable populations. Domestic studies using these technologies as part of the National Institute on Drug Abuse "Seek, Test, Treat, Retain" research initiative were queried regarding intervention components, implementation issues, participant characteristics, and descriptive statistics of mobile phone service delivery. Across five studies with 1,135 predominantly male, minority participants, implementation challenges occurred in three categories: (1) service interruptions; (2) billing/overage issues, and; (3) the participant user experience. Response rules for automated text messages frequently frustrated participants. The inability to reload minutes/texting capacity remotely was a significant barrier to intervention delivery. No study encountered confidentiality breaches. Service interruption was common, even if studies provided mobile phones and plans. Future studies should attend to the type of mobile phone and service, the participant user experience, and human subjects concerns.

Violence Against Women in Selected Areas of the United States.

OBJECTIVES: We determined the prevalence of recent emotional, physical, and sexual violence against women and their associations with HIV-related risk factors in women living in the United States. METHODS: We performed an assessment of women ages 18 to 44 years with a history of unprotected sex and 1 or more personal or partner HIV risk factors in the past 6 months from 2009 to 2010. We used multivariable logistic regression to examine the association of experiencing violence. RESULTS: Among 2099 women, the prevalence of emotional abuse, physical violence, and sexual violence in the previous 6 months was 31%, 19%, and 7%, respectively. Nonmarried status, food insecurity, childhood abuse, depression symptomology, and posttraumatic stress disorder were significantly associated with multiple types of violence. All types of violence were associated with at least 3 different partner or personal HIV risk behaviors, including unprotected anal sex, previous sexually transmitted infection diagnosis, sex work, or partner substance abuse. CONCLUSIONS: Our data suggested that personal and partner HIV risk behaviors, mental illness, and specific forms of violence frequently co-occurred in the lives of impoverished women. We shed light on factors purported to contribute to a syndemic in this population. HIV prevention programs in similar populations should address these co-occurring issues in a comprehensive manner.

Nondisclosure of HIV status in a clinical trial setting: antiretroviral drug screening can help distinguish between newly diagnosed and previously diagnosed HIV infection.

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.

Failure to identify HIV-infected individuals in a clinical trial using a single HIV rapid test for screening.

BACKGROUND: In the HIV Prevention Trials Network (HPTN) 061 study, 8 (2.3%) of 348 HIV-infected participants identified as HIV uninfected at study enrollment using a single HIV rapid test for screening were found to be HIV infected after additional testing. OBJECTIVES: To evaluate the performance of different HIV assays for detection of HIV infection in HPTN 061 participants with missed infection and individuals with viral suppression. METHODS: Plasma samples from 8 HPTN 061 participants, 17 elite controllers, and 101 individuals on antiretroviral treatment (ART) were tested for HIV with 3 rapid tests, 2 laboratory-based immunoassays, and a Western blot assay. The HPTN 061 samples were also tested with 2 HIV RNA assays and an antiretroviral drug assay. RESULTS: Of the 8 HPTN 061 participants with missed infection, 1 was an elite controller, 1 was taking ART, 2 were missed because of testing or clerical errors, 1 had recent HIV infection (identified using a multi-assay algorithm), and 3 had acute HIV infection. Two (1.7%) of 118 individuals with viral suppression (both taking ART) had at least 1 false-negative test. CONCLUSIONS: In clinical trials, HIV infections can be missed for a variety of reasons. Using more than one assay to screen for HIV infection may reduce the number of missed infections.

HIV acquisition among women from selected areas of the United States: a cohort study.

BACKGROUND: Women account for 23% of newly diagnosed HIV infections in the United States, but there are few recent, well-characterized cohorts of U.S. women in whom behavior characteristics and HIV acquisition have been well-described. OBJECTIVE: To evaluate HIV incidence and describe behaviors among U.S. women residing in areas of high HIV prevalence. DESIGN: Multisite, longitudinal cohort of women who had HIV rapid testing and audio computer-assisted self-interviews at baseline and every 6 months for up to 12 months. (ClinicalTrials.gov: NCT00995176) SETTING: 10 urban and periurban communities with high HIV prevalence and poverty rates, located in the northeastern and southeastern United States. PATIENTS: Venue-based sampling was used to recruit women aged 18 to 44 years who recently had unprotected sex and had 1 or more additional personal or partner risk factors and no self-reported previous HIV diagnosis. MEASUREMENTS: HIV prevalence and incidence, frequency of HIV risk behaviors, and health status perceptions. RESULTS: Among 2099 high-risk women (85.9% black and 11.7% of Hispanic ethnicity), 32 (1.5%) were diagnosed with HIV infection at enrollment. Annual HIV incidence was 0.32% (95% CI, 0.14% to 0.74%). Older age, substance use, and knowing a partner had HIV were associated with HIV prevalence. Ten women died during the study (0.61% per year). LIMITATIONS: Longitudinal assessment of risk behaviors was limited to a maximum of 12 months. There were few incident HIV infections, precluding identification of characteristics predictive of HIV acquisition. CONCLUSION: This study enrolled a cohort of women with HIV incidence substantially higher than the Centers for Disease Control and Prevention national estimate in the general population of U.S. black women. Concerted efforts to improve preventive health care strategies for HIV and overall health status are needed for similar populations. PRIMARY FUNDING SOURCE: National Institutes of Health.

Factors associated with adherence amongst 5295 people receiving antiretroviral therapy as part of an international trial.

BACKGROUND: We assessed factors associated with antiretroviral therapy (ART) adherence, including specific ART medications. METHODS: The Strategies for Management of Antiretroviral Therapy study was an international antiretroviral therapy (ART) strategy trial that compared intermittent ART, using CD4(+) T-cell count as a guide, to continuous ART. Adherence during the 7 days before each visit was measured using self-report. We defined high adherence as self-report of taking "all" pills for each prescribed ART medication; all other reports were defined as suboptimal adherence. Factors associated with adherence were assessed using logistic regression with generalized estimating equations. RESULTS: Participants reported suboptimal adherence at 6016 of 35 695 study visits (17%). Factors independently associated with suboptimal adherence were black race, protease inhibitor-containing regimens, greater pill burden, higher maximum number of doses per day, and smoking. Factors independently associated with higher adherence were older age, higher education, region of residence, episodic treatment, higher latest (at the time of adherence) CD4(+) T-cell count, and being prescribed concomitant drugs (ie, medications for comorbidities). Of specific drugs investigated, atazanavir, atazanavir/ritonavir, fosamprenavir, indinavir, indinavir/ritonavir, and lopinavir/ritonavir were associated with suboptimal adherence, and tenofovir disoproxil fumarate/emtricitabine was associated with higher adherence. CONCLUSIONS: In this, the largest analysis of ART adherence to date, some protease inhibitor-containing regimens and regimens with >1 dose per day were associated with suboptimal adherence.

Safety, tolerability, pharmacokinetics, and immunological activity of dual-combinations and triple-combinations of anti-HIV monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered intravenously to HIV-uninfected adults: a phase 1 randomised trial.

BACKGROUND: Preclinical and clinical studies suggest that combinations of broadly neutralising antibodies (bnAbs) targeting different HIV envelope epitopes might be required for sufficient prevention of infection. We aimed to evaluate the dual and triple anti-HIV bnAb combinations of PGDM1400 (V2 Apex), PGT121 (V3 glycan), 10-1074 (V3 glycan), and VRC07-523LS (CD4 binding site). METHODS: In this phase 1 trial (HVTN 130/HPTN 089), adults without HIV were randomly assigned (1:1:1) to three dual-bnAb treatment groups simultaneously, or the triple-bnAb group, receiving 20 mg/kg of each antibody administered intravenously at four centres in the USA. Participants received a single dose of PGT121 + VRC07-523LS (treatment one; n=6), PGDM1400 + VRC07-523LS (treatment two; n=6), or 10-1074 + VRC07-523LS (treatment three; n=6), and two doses of PGDM1400 + PGT121 + VRC07-523LS (treatment four; n=9). Primary outcomes were safety, pharmacokinetics, and neutralising activity. Safety was determined by monitoring for 60 min after infusions and throughout the study by collecting laboratory assessments (ie, blood count, chemistry, urinalysis, and HIV), and solicited and unsolicited adverse events (via case report forms and participant diaries). Serum concentrations of each bnAb were measured by binding antibody assays on days 0, 3, 6, 14, 28, 56, 112, 168, 224, 280, and 336, and by serum neutralisation titres against Env-pseudotyped viruses on days 0, 3, 28, 56, and 112. Pharmacokinetic parameters were estimated by use of two-compartment population pharmacokinetic models; combination bnAb neutralisation titres were directly measured and assessed with different interaction models. This trial is registered with ClinicalTrials.gov, NCT03928821, and has been completed. FINDINGS: 27 participants were enrolled from July 31, to Dec 20, 2019. The median age was 26 years (range 19-50), 16 (58%) of 27 participants were assigned female sex at birth, and 24 (89%) participants were non-Hispanic White. Infusions were safe and well tolerated. There were no statistically significant differences in pharmacokinetic patterns between the dual and triple combinations of PGT121, PGDM1400, and VRC07-523LS. The median estimated elimination half-lives of PGT121, PGDM1400, 10-1074, and VRC07-523LS were 32·2, 25·4, 27·5, and 52·9 days, respectively. Neutralisation coverage against a panel of 12 viruses was greater in the triple-bnAb versus dual-bnAb groups: area under the magnitude-breadth curve at day 28 was 3·1, 2·9, 3·0, and 3·4 for treatments one to four, respectively. The Bliss-Hill multiplicative interaction model, which assumes complementary neutralisation with no antagonism or synergism among the bnAbs, best described combination bnAb titres in the dual-bnAb and triple-bnAb groups. INTERPRETATION: No pharmacokinetic interactions among the bnAbs and no loss of complementary neutralisation were observed in the dual and triple combinations. This study lays the foundation for designing future combination bnAb HIV prevention efficacy trials. FUNDING: US National Institute of Allergy and Infectious Diseases, US National Institute on Drug Abuse, US National Institute of Mental Health, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

COVID-19 Vaccine Uptake and Factors Associated With Being Unvaccinated Among Lesbian, Gay, Bisexual, Transgender, Queer, and Other Sexual Identities (LGBTQ+) New Yorkers.

Routine data on vaccine uptake are not disaggregated by lesbian, gay, bisexual, transgender, queer, and other sexual identities (LGBTQ+) populations, despite higher risk of infection and severe disease. We found comparable vaccination uptake patterns among 1032 LGBTQ+ New Yorkers and the general population. We identified critical socioeconomic factors that were associated with vaccine hesitancy in this economically vulnerable population.

The Magnetic Couples Study: protocol for a mixed methods prospective cohort study of HIV-serodifferent heterosexual couples' perspectives and use of pre-exposure prophylaxis (PrEP).

INTRODUCTION: HIV transmission within serodifferent heterosexual couples plays a key role in sustaining the global HIV pandemic. In the USA, transmission within established mixed-status couples accounts for up to half of all new HIV infections among heterosexuals. Oral HIV pre-exposure prophylaxis (PrEP) is a highly effective prevention method, although underutilised among serodifferent couples. Moreover, there is a dearth of research on US HIV-serodifferent couples' perspectives and use of PrEP, alone or in combination with other prevention methods. In this paper, we describe the study protocol for the Magnetic Couples Study, designed to fill critical knowledge gaps regarding HIV-serodifferent heterosexual couples' perspectives, experiences and utilisation of PrEP. METHODS AND ANALYSIS: The Magnetic Couples Study is a mixed methods prospective cohort study designed to describe temporal patterns and identify determinants at multiple levels (individual, couple, HCF) of PrEP outcomes along the care continuum (PrEP awareness, linkage, uptake, retention and medication adherence) among HIV-serodifferent heterosexual couples residing in New York City. The study will also examine clinical management of PrEP, side effects and changes in sexual-related and substance use-related behaviour. A prospective cohort of 230 mixed-status couples already on oral PrEP was recruited, with quarterly assessments over 18 months; in addition, a cross-sectional sample of 150 mixed-status couples not currently on PrEP was recruited. In-depth semistructured qualitative interviews were conducted with a subsample of 25 couples. Actor-partner interdependence modelling using multilevel analysis will be employed for the analysis of longitudinal dyadic data. Framework analysis will be used to analyse qualitative data. A parallel convergent design will be used for mixed methods integration. ETHICS AND DISSEMINATION: The study was approved by the University of Rochester Institutional Review Board (RSRB00052766). Study findings will be disseminated to community members and providers and to researchers and policy makers.

Factors Associated With Sex-Related Pre-exposure Prophylaxis Adherence Among Men Who Have Sex With Men in New York City in HPTN 067.

BACKGROUND: HPTN 067 assessed the feasibility of daily and non-daily dosing of open-label emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)-based pre-exposure prophylaxis (PrEP). METHODS: Factors associated with sex-related PrEP adherence were assessed among men who have sex with men (MSM) randomized to one of 3 PrEP dosing arms in HPTN 067 in New York City. Sex-related PrEP adherence was defined per protocol as at least 1 PrEP tablet taken within 4 days pre-sex and at least 1 additional PrEP tablet taken within 24 hours post-sex, assessed via electronic drug monitoring and weekly interviews. Demographic data and behavioral measures were evaluated for association with sex-related PrEP adherence. Logistic regression for clustered data was used to estimate the unadjusted and adjusted odds ratios. RESULTS: Of 176 randomized MSM participants, 59% were Black, 10% White, 25% Hispanic, and 6% other; median age was 31 years. In the multivariable analyses, higher sex-related PrEP adherence was significantly associated with daily dosing arm, older age, employment, and higher PrEP adherence behavioral skills. Lower sex-related PrEP adherence was significantly associated with identifying as Black or Hispanic (compared with White), opiate use, and reporting "I forgot" as an adherence barrier. CONCLUSIONS: This analysis identified populations of MSM who might benefit from additional support to optimize PrEP adherence, including those who are younger, unemployed, or opiate users. MSM with lower PrEP behavioral skills may benefit from targeted interventions. Further study is needed to assess racial and ethnic disparities in PrEP adherence, which may reflect broader social and economic inequalities not captured in this study.

Incomplete ART adherence is associated with higher inflammation in individuals who achieved virologic suppression in the START study.

INTRODUCTION: Suboptimal ART adherence, despite HIV viral suppression, has been associated with chronic residual inflammation. Whether this association extends to individuals who initiate ART during early HIV infection remains unknown, which was the objective of this study. METHODS: Plasma levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein, serum amyloid A protein (SAA), IL-27, soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, D-dimer and the CD4+/CD8+ T-cell ratio, were analysed at baseline and eight months after ART initiation in treatment-naïve participants with HIV and CD4+ T-cells >500 cells/mm3 enrolled in the immediate arm of START. Adherence was assessed by seven-day self-report. Multivariable linear regression was utilized to analyse the association between ART adherence and each biomarker at the eight-month visit in participants who achieved virologic suppression (<50 copies/mL). RESULTS: We evaluated 1627 participants (422 female) who achieved virologic suppression at the eight-month visit in the period between 2009 and 2013. Median (IQR) CD4+ T-cell count before ART was 651 (585, 769) cells/mm3 . Incomplete adherence was reported in 109 (7%) participants at the eight month visit. After adjusting for covariates, plasma IL-6 was 1.12 (95% CI, 1.00 to 1.26; p = 0.047) fold higher in participants reporting incomplete versus 100% adherence. A similar association for SAA was observed in an exploratory analysis (1.29 (95% CI 1.04 to 1.60); p = 0.02). No significant differences in other biomarkers were observed. CONCLUSIONS: Incomplete ART adherence was associated with higher IL-6 levels in individuals who achieved virologic suppression early after ART initiation in START. A potential similar association for SAA requires confirmation. These findings suggest a role for identifying strategies to maximize ART adherence even during virologic suppression. ClinicalTrials.gov number: NCT00867048.

Low Disclosure of PrEP Nonadherence and HIV-Risk Behaviors Associated With Poor HIV PrEP Adherence in the HPTN 067/ADAPT Study.

OBJECTIVE: We evaluated the relationship between 2 types of social relationships, ie, (1) external support for use of HIV pre-exposure prophylaxis (PrEP) and related study supplies and (2) participants' disclosure of PrEP use and condom use and HIV PrEP adherence among daily-dosing regimen participants in HIV Prevention Trials Network (HPTN) 067, an open-label trial of oral tenofovir (TFV) disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg. METHODS: Using HPTN 067 survey data, we developed scales examining (1) Low Perceived External Support for PrEP: low perceived support by others for PrEP use or perceived negative reactions to the pill case (scoring ranges from 0 to 2) and (2) Participant-Staff Disclosure Challenges Scale, which identifies challenges to sharing nonuse of PrEP or condoms to study staff (scoring ranges from 0 to 4); these scales are the primary independent variables. Adherence, the dependent variable, was determined using log-transformed plasma TFV concentrations. generalized estimating equation (GEE) linear regression was used to assess the association between both scales and adherence. RESULTS: Participants (n = 161) included HIV-uninfected women in South Africa, and men who have sex with men and transgender women, in Thailand and the United States. In multivariable analyses, higher scores in the Participant-Staff Disclosure Challenges Scale were significantly associated with lower PrEP adherence [exp(ß) = 0.62, 95% CI: (0.46 to 0.84); P = 0.002] as were increased days since the last PrEP dose [exp(ß) = 0.73, 95% CI: (0.65 to 0.83); P ≤ 0.001]. CONCLUSIONS: Given the association with adherence, study staff-participant interactions and participants' disclosure of PrEP challenges may be worthwhile intervention targets for improving PrEP adherence in confirmatory studies.

Short- and Long-Term Pharmacologic Measures of HIV Pre-exposure Prophylaxis Use Among High-Risk Men Who Have Sex With Men in HPTN 067/ADAPT.

BACKGROUND: The effectiveness of oral emtricitabine (FTC)/tenofovir (TFV) disoproxil fumarate-based HIV pre-exposure prophylaxis (PrEP) depends on adherence. Pharmacologic measures help interpret patterns and predictors of PrEP adherence. SETTING: We analyzed data from the subsample of men who have sex with men enrolled in HPTN 067/ADAPT in Bangkok, Thailand, and Harlem, NY, U.S. METHODS: After a 5-week directly observed therapy period, participants were randomized to daily, time-driven, or event-driven PrEP. Follow-up occurred at weeks 4, 12, and 24 after randomization. Plasma and hair FTC/TFV levels indicated short- and long-term PrEP use, respectively. Electronic pill bottle data (Wisepill) were collected weekly. Pearson correlation coefficients between PrEP use measures were calculated; linear mixed models assessed predictors of plasma and hair drug concentrations. RESULTS: Among 350 participants (median age: 31 years, interquartile range: 25-38), 49.7% were from Harlem, half had less than college education, and 21% reported heavy alcohol use. In multivariable models, being enrolled in Harlem, being in non-daily arms, and having less than college education were associated with lower hair FTC/TFV concentrations; heavy alcohol use was associated with higher concentrations. Similar results were found for plasma concentrations by site and arm, but older age and greater number of sex partners were associated with higher concentrations. Hair and plasma FTC/TFV concentrations were moderately correlated with Wisepill data (r ≥ 0.29) across visits. CONCLUSIONS: In HPTN067, plasma, hair, and Wisepill data correlated with one another and served as complementary adherence measures. Site, arm, education, age, alcohol, and sexual behavior influenced patterns of adherence.

Mild-to-moderate symptoms during the first year of antiretroviral therapy worsen quality of life in HIV-infected individuals.

Symptoms and quality of life were assessed among human immunodeficiency virus (HIV)-infected individuals initiating their first course of antiretroviral therapy. Symptoms, which were mostly mild or moderate, were common in the first year and significantly affected the patients' quality of life. Quality of life was inversely related to the number of symptoms and in the change in the number of symptoms from baseline.