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Title: Estimating efficacy in a randomized trial with product nonadherence: application of multiple methods to a trial of preexposure prophylaxis for HIV prevention
Authors: Murnane, Pamela M.
Brown, Elizabeth R.
Mugo, Nelly
Mujugira, Andrew
Celum, Connie
Baeten, Jared M.
Were, Edwin
Bukusi, Elizabeth
Wangisi, Jonathan
Kiarie, James
Keywords: Pre exposure prophylaxis
HIV-1 prevention
Randomized controlled trials
Medication adherence
Issue Date: 2015
Publisher: Oxford University Press
Abstract: Antiretroviral pre exposure prophylaxis (PrEP) for persons at high risk of human immunodeficiency virus infection is a promising new prevention strategy. Six randomized trials of oral PrEP were recently conducted and demonstrated efficacy estimates ranging from 75% to no effect, with non adherence likely resulting in attenuated estimates of the protective effect of PrEP. In 1 of these trials, the Partners PrEP Study (Kenya and Uganda, 2008–2011), participants (4,747 serodiscordant heterosexual couples) were randomized to receipt of tenofovir (TDF), coformulated TDF/emtricitabine (FTC), or placebo. Intention-to-treat analyses found efficacy estimates of 67% for TDF and 75% for TDF/FTC. We applied multiple methods to data from that trial to estimate the efficacy of PrEP with high adherence, including principal stratification and inverse-probability-of-censoring (IPC) weights. Results were further from the null when correcting for nonadherence: 1) among the strata with an estimated 100% probability of high adherence (TDF hazard ratio (HR) = 0.19, 95% confidence interval (CI): 0.07, 0.56; TDF/FTC HR = 0.12, 95% CI: 0.03, 0.52); 2) with IPC weights used to approximate a continuously adherent population (TDF HR = 0.18, 95% CI: 0.06, 0.53; TDF/FTC HR = 0.15, 95% CI: 0.04, 0.52); and 3) in per-protocol analysis (TDF HR = 0.18, 95% CI: 0.06, 0.53; TDF/FTC HR = 0.16, 95% CI: 0.05, 0.53). Our results suggest that the efficacy of PrEP with high adherence is over 80%.
Appears in Collections:School of Medicine

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