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J Acquir Immune Defic Syndr. 2014 Jul 1;66(3):340-8. doi: 10.1097/QAI.0000000000000172.

HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention.

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  • 1*Department of Global Health University of Washington and Vaccine and Infectious Disease Institute Fred Hutchinson Cancer Research Center, Seattle, WA; Departments of †Global Health; ‡Medicine; §Epidemiology, University of Washington, Seattle, WA; Departments of ‖Pharmacology and Molecular Sciences; ¶Medicine, Johns Hopkins University, Baltimore, MD; #Center for Global Health, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA; **Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda; ††Department of Obstetrics and Gynecology, University of Nairobi and Kenyatta National Hospital, Nairobi; and ‡‡Department of Epidemiology, Johns Hopkins University, Baltimore, MD.

Abstract

BACKGROUND:

Antiretroviral pre-exposure prophylaxis (PrEP) is a novel HIV prevention strategy for which adherence is a known determinant of efficacy. Blood concentrations of PrEP medications are one objective marker of adherence.

METHODS:

In a placebo-controlled PrEP efficacy trial of tenofovir disoproxil fumarate (TDF) and TDF with emtricitabine (FTC/TDF) among 4747 African women and men with an HIV-infected partner, we measured plasma tenofovir concentrations from participants in the active PrEP arms: 29 HIV seroconverters (cases) and 196 randomly selected controls who remained uninfected.

RESULTS:

Among controls, 71% of visits had tenofovir concentrations >40 ng/mL, consistent with steady-state daily dosing, compared with 21% of cases at the visit HIV was first detected. Pill count data indicated that 96% of controls and 66% of cases had >80% adherence for these same visits. The estimated protective effect of PrEP against HIV, based on concentrations >40 ng/mL, was 88% (95% confidence interval: 60 to 96, P < 0.001) for individuals receiving TDF and 91% (95% confidence interval: 47 to 98, P = 0.008) for individuals receiving FTC/TDF. Controls had consistent patterns of PrEP concentrations during follow-up; among the 81% with concentrations >40 ng/mL at month 1, 75% maintained this concentration at month 12. Only 5 of 29 seroconverters seemed to be consistently adherent to PrEP. Tenofovir concentrations >40 ng/mL were associated with older age and shorter time on study; concentrations ≤40 ng/mL occurred more commonly when participants reported no sex with their HIV-infected partner.

CONCLUSIONS:

Plasma concentrations of tenofovir consistent with daily dosing were highly predictive of protection from HIV acquisition. Most of those who took PrEP seemed to have high and consistent adherence.

PMID:
24784763
[PubMed - indexed for MEDLINE]
PMCID:
PMC4059553
Free PMC Article
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