Tenofovir and tenofovir-diphosphate concentrations during pregnancy among HIV-uninfected women using oral pre-exposure prophylaxis

OBJECTIVES: Pregnancy is a time of increased HIV acquisition risk and pregnancy reduces concentrations of antiretrovirals used for treatment. We assessed whether pregnancy lowers concentrations of tenofovir (TFV) and tenofovir-diphosphate (TFV-DP) among HIV-uninfected women using oral pre-exposure prophylaxis (PrEP). METHODS: We analyzed data from an open-label PrEP study, comparing concentrations of TFV in plasma and TFV-DP in dried blood spots (DBS) among 37 pregnant women and 97 non-pregnant women. Analyses controlled for adherence from daily electronic monitoring. RESULTS: The average plasma concentration of TFV among pregnant women was 34.7 ng/mL with 22.2 average recorded doses over the prior month versus 86.5 ng/mL with 23.1 doses among non-pregnant women. After controlling for adherence, TFV concentrations were 58% lower among pregnant women, a statistically significant difference of −50.4 ng/mL (95%CI −68.3 to −32.5). The average TFV-DP concentration was 450.3 fmol/punch among pregnant women and 636.7 fmol/punch among non-pregnant women. This difference was not statistically significant after adjusting for adherence; however, among those with quantifiable TFV-DP, concentrations were 27% lower during pregnancy (−202 fmol/punch [95%CI −384 to −19]). Among participants with samples before and during pregnancy, there were significant decreases during pregnancy, controlling for adherence: −28.1 ng/mL TFV (95%CI −52.3 to −4.0) and −289.2 fmol/punch TFV-DP (95%CI −439.0 to −139.3). CONCLUSIONS: Consistent with studies among HIV-infected women on ART, we found TFV and TFV-DP concentrations were lower during pregnancy. There is no established TFV concentration threshold to achieve HIV prevention. Additional pharmacokinetic studies and studies of PrEP efficacy in pregnancy are needed.