Abstract
Background: Controlled pharmacokinetic (PK) studies in United States populations have defined categories of tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) for various pre-exposure prophylaxis (PrEP) adherence targets. It is unknown how these categories perform in other populations. Therefore, we evaluated the sensitivity and specificity of these PK-derived categories compared to daily medication electronic adherence monitoring (MEMS) data among East African men and women using daily PrEP.Methods: Participants were enrolled as members of HIV serodiscordant couples as part of an open-label PrEP study in Kenya and Uganda. Blood samples were taken at quarterly visits and stored as DBS, which were analyzed for TFV-DP concentrations.Results: Among 150 samples from 103 participants, MEMs data indicated that 87 (58%) took ≥4 doses and 62 (41%) took ≥6 per week consistently over the 4 weeks prior to sample collection. Sensitivities of DBS TFV-DP levels were 62% for the ≥4 doses/week category (≥700 fmol/punch TFV-DP) and 44% for the ≥6 doses/week category (≥1050 fmol/punch TFV-DP); specificities were 86 and 94%, respectively. There were no statistically significant differences in these sensitivities and specificities by gender.Conclusion: In this sample of East African PrEP users, categories of TFV-DP concentrations developed from directly observed PrEP use among United States populations had high specificity but lower than expected sensitivity. Sensitivity was lowest when MEMS data indicated high adherence (i.e., ≥6 doses/week). PrEP studies and implementation programs should carefully consider the sensitivity and specificity of the TFV-DP levels used for adherence feedback.
Highlights
Clinical trials have shown that pre-exposure prophylaxis (PrEP) is highly effective for preventing HIV (Grant et al, 2010; Baeten et al, 2012; Thigpen et al, 2012)
Intensive, controlled pharmacokinetic studies in United States populations were conducted with directly observed treatment (DOT) to estimate the expected levels of TFV-DP for specific adherence targets (i.e., ≥2 or ≥4 doses/week) (Anderson et al, 2017); these levels have been associated with HIV protection among men who have sex with men in the iPrEx placebo-controlled trial conducted in the United States, South America, Thailand and South Africa (Grant et al, 2014; Liu et al, 2016)
We considered three adherence targets as recorded by MEMS consistently for the 4 weeks prior to sample collection, and corresponding TFV-DP categories based on previous DOT analyses (Castillo-Mancilla et al, 2012; Anderson et al, 2017): ≥700 fmol/punch for ≥4 doses, ≥1050 fmol/punch for ≥6 doses, and ≥1250 fmol/punch for 7 doses/week
Summary
Clinical trials have shown that pre-exposure prophylaxis (PrEP) is highly effective for preventing HIV (Grant et al, 2010; Baeten et al, 2012; Thigpen et al, 2012). Our goal was to evaluate the sensitivity and specificity of these categories in African men and women, using electronic adherence monitoring data for comparison. Controlled pharmacokinetic (PK) studies in United States populations have defined categories of tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) for various pre-exposure prophylaxis (PrEP) adherence targets. It is unknown how these categories perform in other populations. We evaluated the sensitivity and specificity of these PK-derived categories compared to daily medication electronic adherence monitoring (MEMS) data among East African men and women using daily PrEP
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