Efficacy estimates of oral pre-exposure prophylaxis for HIV prevention in cisgender women with partial adherence

Abstract

Pre-exposure prophylaxis (PrEP) with tenofovir (TFV) disoproxil fumarate and emtricitabine administered orally daily is effective in preventing human immunodeficiency virus (HIV) acquisition in both men and women with sufficient adherence; however, the adherence–efficacy relationship in cisgender women has not been well established. We calculated the adherence–efficacy curve for cisgender women by using HIV incidence and plasma TFV concentration data from three trials (FEM-PrEP, VOICE and Partners PrEP). We imputed TFV diphosphate (TFV-DP) concentrations, a measure of long-term adherence, from TFV quantification by using data from the HIV Prevention Trials Network 082 study, which measured both TFV-DP and TFV concentrations. Two, four and seven pills per week reduced HIV incidence by 59.3% (95% credible interval (CrI) 29.9–95.8%), 83.8% (95% CI 51.7–99.8%) and 95.9% (95% CI 72.6–100%), respectively. Our adherence–efficacy curve can be validated and updated by HIV prevention studies that directly measure TFV-DP concentrations. The curve suggests that high adherence confers high protection in cisgender women. However, the lower efficacy with partial adherence highlights the need for new PrEP products and interventions to increase adherence. Pre-exposure prophylaxis (PrEP) with daily antiretrovirals to prevent human immunodeficiency virus type 1 acquisition has not been shown to be consistently effective in cisgender women. Modeling adherence to daily PrEP clarifies how robust protection can be achieved.