Research ArticleHIV

Emtricitabine-Tenofovir Concentrations and Pre-Exposure Prophylaxis Efficacy in Men Who Have Sex with Men

Science Translational Medicine  12 Sep 2012:
Vol. 4, Issue 151, pp. 151ra125
DOI: 10.1126/scitranslmed.3004006

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PrEParing to Stop HIV Acquisition

Pre-exposure prophylaxis (PrEP) using the antiretroviral drugs emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) is a recently proven strategy for preventing HIV acquisition. These drugs require phosphorylation in mononuclear cells to the pharmacologically active triphosphate moieties, called emtricitabine-triphosphate (FTC-TP) and tenofovir-diphosphate (TFV-DP). The iPrEx study was a randomized placebo-controlled trial of daily oral doses of FTC-TDF as PrEP in HIV-negative men who have sex with men. Participants all received a comprehensive package of HIV prevention services. HIV infections were reduced by 44% overall in the FTC-TDF arm relative to placebo. HIV risk was reduced by more than 90% among those having detectable drug in blood, indicating that adherence was a powerful determinant of drug efficacy at preventing HIV acquisition. A new study by Anderson et al. estimates specific drug concentrations and adherence levels associated with protection from HIV-1 acquisition in the iPrEx trial. A regression analysis predicted that a TFV-DP concentration of 16 fmol/106 peripheral blood mononuclear cells (PBMCs) (95% confidence interval, 3 to 28) was associated with a 90% reduction in HIV acquisition relative to placebo in the iPrEx study. To determine the number of tablets required to achieve this drug concentration, TFV-DP concentrations from another study called STRAND were used to establish expected TFV-DP concentrations. TFV-DP was detected in the blood at all dosing levels in all participants with a median (interquartile range) TFV-DP concentration of 11 fmol/106 PBMCs (6 to 13) after two doses per week, 32 fmol/106 PBMCs (25 to 39) after four doses per week, and 42 fmol/106 PBMCs (31 to 47) after seven doses per week. When the iPrEx study’s regression model was used to analyze the STRAND TFV-DP concentrations, the predicted HIV risk reductions were 76, 96, and 99% for two, four, and seven doses per week, respectively. These findings suggest that PrEP using oral FTC-TDF tablets is a robust intervention for preventing HIV acquisition among men who have sex with men.