Safety, adherence and acceptability of intermittent tenofovir/emtricitabine as HIV pre-exposure prophylaxis (PrEP) among HIV-uninfected Ugandan volunteers living in HIV-serodiscordant relationships: a randomized, clinical trial

Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of i...

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Published inPloS one Vol. 8; no. 9; p. e74314
Main Authors Kibengo, Freddie M, Ruzagira, Eugene, Katende, David, Bwanika, Agnes N, Bahemuka, Ubaldo, Haberer, Jessica E, Bangsberg, David R, Barin, Burc, Rooney, James F, Mark, David, Chetty, Paramesh, Fast, Patricia, Kamali, Anatoli, Priddy, Frances H
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 26.09.2013
Public Library of Science (PLoS)
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Summary:Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens. Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada) or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment. Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS) and self-report. Sexual activity data were collected via daily short text message (SMS) and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT. Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100) for daily PrEP regimen, 91% (IQR: 73-97) for fixed intermittent dosing and 45% (IQR: 20-63) for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen. Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be feasible especially if a minimum effective drug concentration correlating with HIV prevention can be achieved with this dosing. Clinicaltrials.gov number NCT00931346.
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Competing Interests: Gilead Sciences provided the study drug and placebo tablets at no cost. Co-author James Rooney is employed by Gilead Sciences. Gilead Sciences developed and is marketing the study drug, Truvada, for treatment of HIV infection. Co-author Burc Barin is employed by the EMMES Corporation, and does not have any relevant declarations relating to consultancy, patents, products in development or marketed products. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
Conceived and designed the experiments: AK JEH DRB BB PF FHP DM. Performed the experiments: FMK ER DK UB ANB PC. Analyzed the data: BB. Contributed reagents/materials/analysis tools: DM JFR. Wrote the manuscript: FMK ER DK ANB UB AK JEH DRB BB JFR PF FHP. N/A.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0074314