Urine tenofovir and dried blood spot tenofovir diphosphate concentrations and viraemia in people taking efavirenz and dolutegravir-based antiretroviral therapy

Abstract

Objective: We aimed to determine whether urine tenofovir (TFV) and dried blood spot (DBS) tenofovir diphosphate (TFV-DP) concentrations are associated with concurrent HIV viraemia. Design: Cross-sectional study among people with HIV (PWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART). Methods: We used dual tandem liquid chromatography and mass spectrometry to measure urine TFV and DBS TFV-DP concentrations, and evaluated their associations with concurrent viraemia ≥1000 copies/mL using logistic regression models. In exploratory analyses, we used receiver operating curves to estimate optimal urine TFV and DBS TFV-DP thresholds to predict concurrent viraemia. Results: Among 124 participants, 68 (54.8%) were women, median age was 39 years (interquartile range [IQR] 34–45) and 74 (59.7%) were receiving efavirenz versus 50 (40.3%) receiving dolutegravir. Higher concentrations of urine TFV (1000 ng/mL increase, odds ratio [OR] 0.97 95%CI 0.94–0.99, p = 0.005) and DBS TFV-DP (100 fmol/punch increase, OR 0.76, 95%CI 0.67–0.86, p < 0.001) were associated with lower odds of viraemia. There was evidence that these associations were stronger among people receiving dolutegravir than among people receiving efavirenz (urine TFV p = 0.072, DBS TFV-DP p = 0.003). Nagelkerke Pseudo-R2 for the DBS TFV-DP models was higher than for the urine TFV models, demonstrating a stronger relationship between DBS TFV-DP and viraemia. Among people receiving dolutegravir, a DBS TFV-DP concentration of 483 fmol/punch had 88% sensitivity and 85% specificity to predict concurrent viraemia ≥1000 copies/ml. Conclusions: Among PWH receiving TDF-based ART, urine TFV concentrations, and in particular DBS TFV-DP concentrations, were strongly associated with concurrent viraemia, especially among people receiving dolutegravir.