Chapter 18 - Vitamin D, Oxidative Stress, and the Antiretroviral Tenofovir

Abstract

Tenofovir (TFV) is a nucleotide analogue of adenosine monophosphate used as a first-line medication in the treatment of acquired immune deficiency syndrome and chronic hepatitis B infection. Mitochondrial toxicity seems to be the main factor involved in the TFV toxicity. TFV inhibits DNA polymerase γ, leading to decreased mitochondrial DNA and increased oxidative stress. This has been related to mitochondrial structural changes and depletion. The most predominant kidney manifestations of TFV exposure include elevation in serum creatinine and proximal tubular dysfunction. In animal studies, oxidative stress inhibition reversed TFV nephrotoxicity and might represent a new therapeutic approach. Vitamin D deficiency (VDD) is prevalent among HIV-infected individuals. Superimposed VDD and TFV use aggravates nephrotoxicity due to changes in the redox state and involvement of renin–angiotensin–aldosterone system. Thus, it is important to monitor vitamin D levels, as well as to treat VDD, in HIV-infected patients under TFV therapy.