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Characterization of HIV Seroconverters in a TDF/FTC PrEP Study: HPTN 067/ADAPT.

ABSTRACT: BACKGROUND:HIV Prevention Trials Network (HPTN) 067/ADAPT evaluated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis (PrEP) in women (South Africa) and men who have sex with men (Thailand, US). Participants received once-weekly directly observed therapy (DOT) of TDF/FTC, and were then randomized to daily, time-driven, or event-driven PrEP. This report describes characterization of 12 HIV seroconversion events in this trial. METHODS:HIV rapid testing was performed at study sites. Retrospective testing included fourth generation assays, HIV RNA testing, Western blot, an HIV-1/2 discriminatory assay, resistance testing, and antiretroviral drug testing. RESULTS:Six of the 12 seroconverters received TDF/FTC in the DOT phase, but were not randomized (3 were acutely infected at enrollment; 2 were infected during the DOT phase; 1 was not randomized because of pregnancy). One of the 6 randomized participants had acute infection at randomization but was not diagnosed for 3-4 months because HIV rapid tests were nonreactive; continued daily PrEP use was associated with false-negative antibody tests and low HIV RNA levels. The 5 participants infected after randomization included 4 with low adherence to the PrEP regimen, and one who reported a 7-day period without dosing before infection. Three participants had TDF/FTC resistance (M184I, K65R), including 2 who received only 4 once-weekly TDF/FTC doses; most TDF/FTC mutations were detected by next generation sequencing only. CONCLUSIONS:In HPTN 067/ADAPT, participants who acquired HIV infection had infrequent PrEP dosing or low/suboptimal adherence. Sensitive assays improved detection of HIV infection and drug resistance. Drug resistance was observed with limited PrEP exposure.

SUBMITTER: Sivay MV

PROVIDER: S-EPMC5472493 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Characterization of HIV Seroconverters in a TDF/FTC PrEP Study: HPTN 067/ADAPT.

Sivay Mariya V MV Li Maoji M Piwowar-Manning Estelle E Zhang Yinfeng Y Hudelson Sarah E SE Marzinke Mark A MA Amico Rivet K RK Redd Andrew A Hendrix Craig W CW Anderson Peter L PL Bokoch Kevin K Bekker Linda-Gail LG van Griensven Frits F Mannheimer Sharon S Hughes James P JP Grant Robert R Eshleman Susan H SH

Journal of acquired immune deficiency syndromes (1999) 20170701 3

<h4>Background</h4>HIV Prevention Trials Network (HPTN) 067/ADAPT evaluated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis (PrEP) in women (South Africa) and men who have sex with men (Thailand, US). Participants received once-weekly directly observed therapy (DOT) of TDF/FTC, and were then randomized to daily, time-driven, or event-driven PrEP. This report describes characterization of 12 HIV seroconversion events in this trial.<h4>Methods</h4>HIV rapid testing w ...[more]

PMID: 28328548

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Project description:Oral pre-exposure prophylaxis (PrEP) is highly efficacious but low adherence undermines effectiveness. Depression, common in African women, may be a barrier to consistent PrEP use. We aimed to assess the relationship between depression, psychosocial mediators, and PrEP adherence among South African women. We analyzed data from 174 South African women in HPTN 067, an open-label oral PrEP trial conducted from 2011 to 2013. Participants were followed for 24 weeks. PrEP adherence was measured via Wisepill™ and weekly self-report interview data. We considered participants "adherent" at week 24 if Wisepill™ and interviews indicated that ≥ 80% of expected doses were taken in the prior month. Elevated depressive symptoms were assessed using the 20-item Center for Epidemiological Studies-Depression (CES-D) scale. We used marginal structural models to estimate the effect of elevated symptoms at baseline on PrEP adherence at week 24 and to assess whether the direct effect changed meaningfully after accounting for mediating effects of stigma, social support, and PrEP optimism. High PrEP adherence occurred less often among women with elevated depressive symptoms (N = 35; 44.3%) compared with those without (N = 52; 54.7%; adjusted relative risk [aRR]: 0.79; 95% confidence interval [CI] 0.63-0.99). The effect of elevated depressive symptoms on PrEP adherence persisted in models accounting for the mediating influence of stigma (aRR: 0.74; 95% CI 0.51-0.97) and PrEP optimism (aRR: 0.75; 95% CI 0.55-0.99). We also found a direct effect of similar magnitude and direction when accounting for social support as the mediating variable, although this adjusted relative risk estimate was not statistically significant (aRR: 0.77; 95% CI 0.57-1.03). Depressive symptoms were common and associated with lower PrEP adherence among South African women. Future work is needed to determine whether depression services integrated with PrEP delivery could improve PrEP effectiveness among African women.

Project description:The relative feasibility and acceptability of daily versus non-daily dosing of oral HIV pre-exposure prophylaxis (PrEP) among women are unknown. We aimed to investigate the feasibility of non-daily PrEP regimens in adult women.We did a randomised, open-label, phase 2 clinical trial (HPTN 067/ADAPT) of oral PrEP with emtricitabine plus tenofovir disoproxil fumarate at a research centre in Cape Town, South Africa. Participants were adult women (age ?18 years) who received directly observed dosing once a week for 5 weeks followed by random assignment (1:1:1) at week 6 to one of three unblinded PrEP regimens for self-administered dosing over 24 weeks: daily; time-driven (twice a week plus a post-sex dose); or event-driven (one tablet both before and after sex). Primary outcomes were PrEP coverage (at least one dose within the 4 days before sex and one dose within 24 h after sex), pills needed or used to achieve regimen-specific adherence and coverage, and symptoms and side-effects. All analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01327651; the trial is completed and this report presents the final analysis.Between Sept 12, 2011, and Oct 3, 2012, 191 women were enrolled to the trial. 178 (93%) completed directly observed dosing and were randomly assigned one of the three PrEP regimens for the self-administered phase: 59 were allocated the daily regimen, 59 the time-driven regimen, and 60 the event-driven regimen. Median age of women was 26 years (IQR 21-37; range 18-52). In women allocated the daily regimen, 1459 (75%) of 1952 sex events were covered by PrEP, compared with 599 (56%) of 1074 sex events among those assigned the time-driven regimen (odds ratio [OR] 2·35, 95% CI 1·43-3·83; p=0·0007) and 798 (52%) of 1542 sex events among those allotted the event-driven regimen (2·76, 1·68-4·53; p<0·0001). Fewer pills were needed for complete adherence in women allocated non-daily regimens (vs daily regimen, relative mean 2·53 [95% CI 2·39-2·69] for the time-driven regimen and 4·16 [3·59-4·82] for the event-driven regimen; p<0·0001). Side-effects were uncommon. Eight HIV seroconversions occurred overall, with four documented during the self-administered phase (two with the time-driven regimen and two with the event-driven regimen). Adherence to the assigned regimen was 75% (7283 of 9652 doses taken) for women allocated the daily regimen compared with 65% for those assigned the time-driven regimen (2367 of 3616 doses taken; p=0·0028) and 53% for those allotted the event-driven regimen (1161 of 2203 doses taken; p<0·0001). When sex was reported in the previous week, PrEP drugs were detected (above the lower limits of quantification) more frequently in women assigned the daily regimen (73 [68%] of 107 samples) than in those allocated the time-driven regimen (42 [58%] of 72 samples) and the event-driven regimen (41 [41%] of 99 samples).Daily PrEP dosing resulted in higher coverage of sex events, increased adherence to the regimen, and augmented drug concentrations than did either time-driven or event-driven dosing. These findings support recommendations for daily use of PrEP with oral emtricitabine plus tenofovir disoproxil fumarate in women.HIV Prevention Trials Network.

Dataset Information

Characterization of HIV Seroconverters in a TDF/FTC PrEP Study: HPTN 067/ADAPT.

Publications

Characterization of HIV Seroconverters in a TDF/FTC PrEP Study: HPTN 067/ADAPT.

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