Background: Combination antiretroviral therapy (ART) is recommended for all HIV-infected pregnant women worldwide. Adequate antiretroviral (ARV) exposure is critical to maintain maternal health and reduce transmission to infants and partners. Hair concentrations are a non-invasive measure of cumulative ARV exposure that integrate adherence and pharmacokinetics and are the strongest predictor of viral suppression in large prospective cohorts. However, hair concentrations of ARVs have not yet been examined in the peripartum period.
Methods: The PROMOTE trial (NCT00993031) enrolled HIV-infected, ART-naïve pregnant Ugandan women at 12-28 weeks gestation who were randomized to initiate lopinavir (LPV) or efavirenz (EFV)-based ART. Small hair samples were collected at 30-34 weeks gestation and 12 weeks postpartum. EFV and LPV hair concentrations were measured via liquid chromatography/tandem mass spectrometry. Multivariate logistic regression models examined predictors of viral suppression (HIV-1 RNA <400 c/ml) at delivery and 24 weeks postpartum in women on ART for ≥6 weeks. Potential predictors included log-transformed ARV hair concentration (interpolated for delivery), age, pretreatment HIV-1 RNA, self-reported adherence, and time on ART.
Results: Among 325 women, mean age was 30 years (SD 5.4) and median CD4 cell count was 366 cells/mm3 (IQR 270-488) at ART initiation. Median time on ART at delivery was 17 weeks (IQR 14-21). Mean self-reported adherence was >97% in each arm. Viral suppression was achieved by 98% (EFV) and 87% (LPV) at delivery and 93% (EFV) and 91% (LPV) at 24 weeks postpartum. In multivariate models including self-reported adherence and pretreatment HIV-1 RNA (Table), ARV hair concentrations were the strongest predictor of viral suppression at delivery (EFV: aOR 1.86 per doubling in concentration [95% CI: 1.14-3.1], p=0.01; LPV: aOR 1.90 [95% CI: 1.33-2.7], p=0.0004) and 24 weeks postpartum (EFV: aOR 1.81 [95% CI: 1.22-2.7], p= 0.003; LPV: aOR 1.53 [95% CI: 1.05-2.2], p=0.03).
Conclusions: We examined hair concentrations of ARVs in relation to virologic outcomes in pregnant and postpartum women for the first time. Hair concentrations of EFV and LPV were the strongest predictors of viral suppression at delivery and 24 weeks postpartum, surpassing self-reported adherence and pretreatment HIV-1 RNA. Hair concentrations are an innovative tool for measuring long-term ARV adherence and exposure and may be helpful to monitor women during the critical peripartum period.