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Renal mitochondrial toxicity: effects of thymidine analogues and tenofovir disoproxil fumarate in African people with HIV.

ABSTRACT: We investigated the contributions of thymidine analogue and tenofovir disoproxil fumarate (TDF) antiretroviral therapy on renal mitochondrial toxicity in Ghanaian people with HIV (PWH). Similar levels of renal biochemical and mitochondrial dysfunction were seen, and there was no increased risk in PWH who had sequenced from thymidine analogue to TDF. However, mild renal impairment was associated with mitochondrial DNA damage in TDF but not thymidine analogue-treated PWH. These data support the continued use of TDF in resource-limited settings.

SUBMITTER: Hunt M

PROVIDER: S-EPMC7612849 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Renal mitochondrial toxicity: effects of thymidine analogues and tenofovir disoproxil fumarate in African people with HIV.

Hunt Matthew M Phillips Richard R Hardy Yasmine Y Owusu Dorcas O DO Mitchelmore Rosa R Durrani Mehrab M Payne Brendan A I BAI Chadwick David R DR

AIDS (London, England) 20220304 7

We investigated the contributions of thymidine analogue and tenofovir disoproxil fumarate (TDF) antiretroviral therapy on renal mitochondrial toxicity in Ghanaian people with HIV (PWH). Similar levels of renal biochemical and mitochondrial dysfunction were seen, and there was no increased risk in PWH who had sequenced from thymidine analogue to TDF. However, mild renal impairment was associated with mitochondrial DNA damage in TDF but not thymidine analogue-treated PWH. These data support the co ...[more]

PMID: 35652677

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Project description:Safety of tenofovir disoproxil fumarate/emtricitabine (TDF-FTC) has been studied more extensively among HIV-infected patients than among HIV-uninfected people. Using data from a pre-exposure trial - FEM-PrEP -, we determined the cumulative probabilities of grade 1+ ALT, AST and creatinine and grade 2+ phosphorus toxicities; ALT/AST toxicities by baseline hepatitis B status; and change in mean creatinine, phosphorus, ALT and AST levels controlling for TDF-FTC adherence.FEM-PrEP was a randomized, blinded, placebo-controlled trial of daily TDF-FTC among women in Africa. Enrolled women were in general good health, HIV antibody negative, 18 to 35 years old, hepatitis B surface antigen negative, and had normal hepatic and renal function at baseline. AST, ALT, phosphorus and serum creatinine were measured regularly throughout the trial. TDF-FTC concentrations were measured to assess adherence to TDF-FTC. The cumulative probabilities of grade 1+ creatininemia and grade 2+ phosphatemia toxicities were not statistically different between TDF-FTC and placebo arms. The cumulative probabilities of grade 1+ ALT and AST toxicities were higher among participants in the TDF-FTC arm than in the placebo arm (p = 0.03 for both). The proportions of grade 1+ and grade 2+ ALT or AST toxicities were significantly higher in participants who were hepatitis B virus surface antibody (HBsAb) positive than in those who were HBsAb-negative. Women with good adherence had higher mean change from baseline to week 4 in their AST levels (2.90 (0.37, 5.42); p = 0.025) than women with less than good adherence.We did not observe a significant relationship between randomization to TDF-FTC and creatinine or phosphorus toxicities. Women randomized to TDF-FTC had higher rates of mild to moderate ALT/AST toxicities, especially women with prior hepatitis B virus exposure. We also observed a significant increase in AST from baseline to week 4 among women who had higher adherence to TDF-FTC during that interval.#NCT00625404, February 19, 2008.

Dataset Information

Renal mitochondrial toxicity: effects of thymidine analogues and tenofovir disoproxil fumarate in African people with HIV.

Publications

Renal mitochondrial toxicity: effects of thymidine analogues and tenofovir disoproxil fumarate in African people with HIV.

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