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.