The perinatal period is a time of high HIV risk for some women. PrEP may offer HIV protection, but pregnancy could alter PrEP pharmacokinetics. We examined differences in tenofovir-diphosphate (TFV-DP) concentrations during pregnancy among HIV-uninfected women on daily oral PrEP.
Concentrations of TFV-DP were analyzed from dried blood spot samples collected from 31 pregnant and 32 non-pregnant women using PrEP in an open-label study in East Africa. The lower limit of quantification (LLQ) was 31.3 fmol/punch, using an LC-MS/MS assay. PrEP adherence was assessed by electronic monitoring (MEMS caps) as the number of days opened in the prior month. The primary analysis was a comparison of TFV-DP concentrations between pregnant and non-pregnant women; a GEE model compared each trimester, adjusted for adherence, baseline age, and BMI. Additional analyses compared concentrations in a subset of 12 women with samples before and during pregnancy; generalized linear mixed effects models were used, adjusted for adherence.
TFV-DP concentrations were lower during pregnancy than during non-pregnant periods, after controlling for adherence: overall, average TFV-DP concentration 637 fmol/punch in non-pregnant women versus 450 fmol/punch in pregnant women (n=102 samples). Adjusting for adherence and baseline characteristics, differences were largest in the 2nd and 3rd trimesters: -52 fmol/punch in 1st trimester (p=0.59), -187 fmol/punch in 2nd trimester (p=0.04), and -179 fmol/punch in 3rd trimester (p=0.07). Results were larger in magnitude and significant when restricted to 83 samples with detectable TFV-DP: -104 fmol/punch in 1st trimester (p=0.27), -278 fmol/punch in 2nd trimester (p=0.004), and -260 fmol/punch in 3rd trimester (p=0.01). Among 12 women with samples before and during pregnancy, TFV-DP concentrations were 289 fmol/punch (95% CI -439 to -139, p=0.005) lower on average during compared to before pregnancy, adjusted for adherence.
Similar to studies of plasma tenofovir concentrations among HIV-infected women on ART, we found evidence that TFV-DP levels during pregnancy are ~70% of non-pregnant levels, even after adjusting for adherence. The difference could be due to changes in clearance, volume of distribution, or adherence effects not fully accounted for by MEMS measurement. Additional studies are needed to understand these mechanisms and whether lower TFV-DP concentrations during pregnancy affect PrEP efficacy.