First-Line Therapy and Mitochondrial Damage: Different Nucleosides, Different Findings

Abstract

Background: Antiretroviral therapy has been associated with the development of morphologic body-shape changes and metabolic abnormalities, including dislipemia, insulin resistance, and hyperlactatemia. Mitochondrial damage secondary to the use of nucleoside analogue reverse transcriptase inhibitors (NRTIs) has been related to some of these complications, although the role of different NRTIs in their development is not well established. Objectives: To assess the incidence of hyperlactatemia and lipodystrophy body-shape changes in drug-na ve HIV-infected patients who began highly active antiretroviral therapy (HAART) based on a backbone of two different NRTI combinations. Method: Prospective, longitudinal, observational study of all consecutive drug-naïve HIV-infected individuals who started HAART with zidovudine (AZT) plus lamivudine (3TC) or didanosine (ddI) plus stavudine (d4T) between June 2000 and June 2003 at one single institution. Serum lactate levels and lipodystrophy body-shape changes were monitored periodically during 12 months. Results: At 1 year, mean lactate values remained p = .01). Conclusion: In drug-naïve HIV-infected patients who start antiretroviral therapy, ddI+d4T-based combinations produce a greater increase in serum lactate and lipoatrophy than therapies based on AZT+3TC within the first year of therapy. An increase in LDH, amylase, GGT, and AP levels may signal an increase in lactate, which may be harmful.