Single oral dose for HIV pre or post-exposure prophylaxis: user desirability and biological efficacy in macaques

Abstract

Background Daily oral pre- or post-exposure prophylaxis (PrEP or PEP) is highly effective in preventing HIV infection. However, many people find it challenging to adhere to a daily oral regimen. Chemoprophylaxis with single oral doses of antiretroviral drugs taken before or after sex may better adapt to changing or unanticipated sexual practices and be a desirable alternative to daily PrEP or PEP. We investigated willingness to use a single oral pill before or after sex among men who have sex with men (MSM) and assessed the biological efficacy of a potent antiretroviral combination containing elvitegravir (EVG), emtricitabine (FTC), and tenofovir alafenamide (TAF). Methods Data on willingness to use single-dose PrEP or PEP were obtained from the 2017 cycle of the American Men's Internet Survey (AMIS), an annual online behavioral surveillance survey of MSM in the United States. Antiretroviral drug levels were measured in humans and macaques to define drug distribution in rectal tissue and identify clinically relevant doses for macaque modeling studies. The biological efficacy of a single dose of FTC/TAF/EVG as PrEP or PEP was investigated using a repeat-challenge macaque model of rectal HIV infection. Findings Through pharmacokinetic assessment in humans and macaques we found that EVG penetrates and concentrates in rectal tissues supporting its addition to FTC/TAF to boost and extend chemoprophylactic activity. Efficacy estimates for a single oral dose given to macaques 4h before or 2h after SHIV exposure was 91•7%[35•7%-98•9%] and 100%, respectively, compared to 80•1%[13•9%-95•4%] and 64•6%[-19•4%-89•5%] when single doses were given 6 and 24h post challenge, respectively. A two-dose regimen at 24h and 48h after exposure was also protective [77•1%[1•7%-94•7%]. Interpretation Informed by user willingness, human and macaque pharmacokinetic data, and preclinical efficacy we show that single-dose prophylaxis before or after sex is a promising HIV prevention strategy. Carefully designed clinical trials are needed to determine if any of these strategies will be effective in humans. Funding Funded by CDC intramural funds, CDC contract HCVJCG2-2016-03948 (to CFK), and a grant from the MAC AIDS Fund and by the National Institutes of Health [P30AI050409] – the Emory Center for AIDS Research (to MZ and TS).

HIV prevention for the next decade: Appropriate, person-centred, prioritised, effective, combination prevention

“…This could also cut the costs of ARV-based HIV prevention for some populations. New single dose post-exposure prophylaxis could therefore be a significant advance for many people [ 44 ].…”

Awareness and Use of Post-exposure Prophylaxis for HIV Prevention Among Men Who Have Sex With Men: A Systematic Review and Meta-Analysis

“…In many countries, tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) is the preferred backbone drug ( 57 , 58 ). However, in the MSM population, the vast majority of MSM prefer to use a single dose of PEP as opposed to a multitablet regimen formulation, and single-dose regimens show better adherence ( 59 , 60 ). An optimized regimen with good tolerability and simplified use improves PEP adherence.…”

Two-dose emtricitabine/tenofovir alafenamide plus bictegravir prophylaxis protects macaques against SHIV infection

“…Notably, a recent report examining one- and two-dose schedules of FTC/TAF in combination with a cobicistat-boosted integrase inhibitor, elvitegravir, similarly demonstrated that an NRTI plus an INSTI regimen provides protective benefit as both PrEP and PEP, where the time to treatment initiation postexposure correlates with the level of protection. 34 …”