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

Article scientifique 2023 Anglais

Résumé

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-R 2 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.

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Dorward, J., Govender, K., Moodley, P., Lessells, R., Samsunder, N., Sookrajh, Y., Fanshawe, T., Turner, P., Butler, C., Drain, P., Hayward, G., Garrett, N. (2023). Urine tenofovir and dried blood spot tenofovir diphosphate concentrations and viraemia in people taking efavirenz and dolutegravir based antiretroviral therapy. https://doi.org/10.1101/2023.09.27.23296217

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Auteur(s)

Jienchi Dorward Katya Govender Pravi Moodley Richard Lessells Natasha Samsunder Yukteshwar Sookrajh Thomas R. Fanshawe Philip J. Turner Christopher Butler Paul K. Drain Gail Hayward Nigel Garrett

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