Tenofovir Disoproxil Fumarate-Lowering Lipid Effects Moderately Protect Liver during Long-Term Antiretroviral Therapy in HIV-Infected Patients

Background: Non-alcoholic fatty liver disease is prevalent in HIV-infected patients and dyslipidemia is the main cause of long-term toxicities of current antiretroviral therapy (ART). Tenofovir disoproxil fumarate (TDF) is a commonest antiretroviral of ART. It has been reported to have lipidlowering effects. Objectives: In this study, the influences of the lipid-lowering effects of TDF on fatty liver, liver function profiles and renal toxicity were further investigated in mono-HIV-infected patients during long-term ART up to five years. Methods: 115 and 38 HIV-infected, ART-naive patients who respectively received TDF- and zidovudine (AZT)-based regimens for 5 years were enrolled. The differences in lipid profiles, liver functions and renal toxicity between those two groups of patients and the correlations among these observed indicators were retrospectively analyzed. Results: After 5 years of ART, no increase in plasma triglyceride (TG) and only moderate increase in total cholesterol (TC) were found in TDF group. As for plasma TG and TC, the increments in the fifth year and the level changes over time in TDF group were all much less serious than those in AZT group. The new occurrence rates of hypercholesterolemia, fatty liver and abnormality of alanine aminotransferase (ALT) were significantly lower in TDF group. The mean estimated glomerular filtration rate (eGFR) was comparable between two groups except 4 patients who were excluded due to renal toxicity in TDF group. The further analyses showed that there were close correlations between TG and BMI, BMI and ALT, TC and ALT, and TC and AST, but no correlations between eGFR and TG or TC in patients treated with TDF-based regimen. Conclusion: The lipid-lowering effect of TDF had moderate protective effects on liver functions via reducing liver fat. In the era of tenofovir alafenamide fumarate and integrase inhibitors, TDF-based regimens may remain to be the first choice for young HIV-infection patients with dyslipidemia, fatty liver and obesity