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Lancet HIV. 2018 Feb;5(2):e68-e78. doi: 10.1016/S2352-3018(17)30156-X. Epub 2017 Oct 3.

Daily and non-daily pre-exposure prophylaxis in African women (HPTN 067/ADAPT Cape Town Trial): a randomised, open-label, phase 2 trial.

Author information

1
The Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa. Electronic address: Linda-Gail.Bekker@hiv-research.org.za.
2
Synexus Clinical Research SA, Somerset West, Cape Town, South Africa.
3
The Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.
4
School of Public Health, University of Michigan, Ann Arbor, MI, USA.
5
Department of Biostatistics, University of Washington, Seattle, WA, USA; Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
6
Department of Medicine, Johns Hopkins University, Baltimore, MD, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
7
Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
8
Department of Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA.
9
Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD USA.
10
Division of AIDS Research, National Institute of Mental Health, National Institutes of Health, Bethesda, MD USA.
11
Gilead Sciences, Foster City, CA, USA.
12
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
13
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
14
FHI 360, Durham, NC, USA.
15
Gladstone Institutes, University of California, and San Francisco AIDS Foundation, San Francisco, CA, USA.

Abstract

BACKGROUND:

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.

METHODS:

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.

FINDINGS:

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).

INTERPRETATION:

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.

FUNDING:

HIV Prevention Trials Network.

PMID:
28986029
PMCID:
PMC6107917
DOI:
10.1016/S2352-3018(17)30156-X
[Indexed for MEDLINE]
Free PMC Article

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