Use of tenofovir diphosphate levels to predict viremia during the postpartum period in women living with HIV: a nested case-control study

Abstract

Abstract Background There are few data on the utility of tenofovir diphosphate (TFV-DP) in dried blood spots to predict future viral load (VL) in postpartum women with HIV on antiretroviral therapy (ART). Methods We conducted a nested case-control study within a trial of postpartum ART delivery strategies. Participants started ART containing tenofovir disoproxil fumarate (TDF) in pregnancy, were <10 weeks postpartum and had a VL <400 copies/mL. VL and TFV-DP samples were taken 3-6 monthly over 24 months. Cases had >1 VL >20 copies/mL; controls were randomly sampled from women with persistent viral suppression (VS; VL <20 copies/mL). Generalized estimating equations were used to calculate likelihood odds ratios (LORs) for future VL >20 copies/mL by TFV-DP concentration at the preceding visit. Results Sixty-one cases and 20 controls contributed 365 DBS-VL pairs (median ART duration 16 months). Sensitivity and specificity of TFV-DP <700 fmol/punch to detect future viremia were 62.9% (95% CI, 54.7%–70.6%) and 89.7% [95% CI, 84.9%–93.4%], respectively. Adjusting for age, ART duration, previous VL and duration between the TFV-DP and VL measures, LORs of viremia for TFV-DP concentrations 350–699 and <350 fmol/punch versus TFV-DP >1850 fmol/punch were 3.5 (95% CI, 1.1–10.8; P=0.033) and 12.9 (95% CI, 3.6–46.6; P<0.0001), respectively. Including only samples taken during VS, the LOR of future viremia for TFV-DP concentration <350 fmol/punch versus TFV-DP >1850 fmol/punch was 9.5 (95% CI, 1.9–47.0). Conclusions TFV-DP concentrations in DBS were strongly associated with future viremia and appear useful to identify non-adherence and predict future elevated VL.