Tenofovir and tenofovir-diphosphate concentrations during pregnancy among HIV-uninfected women using oral preexposure prophylaxis.

ABSTRACT: 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 preexposure 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 nonpregnant 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 nonpregnant 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 nonpregnant 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). CONCLUSION: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.

SUBMITTER: Pyra M 

PROVIDER: S-EPMC6061961 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature