AEGiS-14IAC: Effects of different first-line HAART regimens on the content and function of lymphocyte mitochondria of HIV-infected patients without lipodystrophy.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Effects of different first-line HAART regimens on the content and function of lymphocyte mitochondria of HIV-infected patients without lipodystrophy.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. LbPeB9027)

Lopez S, Miro O, Martinez E, Rodriguez B, Milinkovic A, Predrol E, Casademont J, Nunes V, Gatell JM, Cardellach F
Hospital Clinic of Barcelona, IDIBAPS, University of Barcelona, Villarroel 170, 08036, Barcelona, Catalunya, Spain

BACKGROUND: Mitochondrial (mt) toxicity is supposed to be the deleterious effect of nucleoside reverse transcriptase inhibitors. We comprehensively assessed mt content and function in easy-to-obtain samples such as peripheral lymphocytes.

METHODS: Five groups of HIV-infected patients without clinically evident body fat changes were studied: one antiretroviral-naïve (control group) and the others receiving highly active antiretroviral therapy (HAART) consisting on AZT+3TC or d4T+ddI plus either nelfinavir (NFV) or nevirapine (NVP) for at least 6 months. The relative abundance of mtDNA respect to nuclear DNA was determined by real time PCR. Mt content was estimated by citrate synthase activity. Enzyme activity of complexes III and IV of the electron transport chain (ETC) was spectrophotometrically determined. Oxygen consumption was polarographically measured in intact lymphocytes and in the presence of complexes I and III substrates.

RESULTS: We included 25 untreated and 42 treated HIV-patients. Groups were comparable in age and gender. Only those groups receiving d4T+ddI exhibited significant mtDNA depletion. Mt content was significantly lower in all treated groups, showing NFV-containing HAART group the greatest decrease. Antiretroviral schedules containing either NFV or d4T+ddI were associated with a significant decrease of enzyme activity of complex IV, being the greatest decline found when NFV and d4T+ddI were combined in the same schedule. Despite previously mentioned differences, all oxidative activities remained normal.

CONCLUSIONS: Peripheral lymphocytes can be used to detect different degrees of mitochondrial toxicity of HAART regimens. Despite the abnormalities found, functional capacity of lymphocyte mitochondria remained normal. These results suggest caution on interpreting abnormal mitochondrial function test because it does not necessarily translate into an abnormal functional capacity. (FIPSE 3102/00, La Marato TV3 01/1710, SGR 00279).

Keywords: AEGIS, Antiretroviral Therapy, Highly Active, Lipodystrophy, HIV Infections, Stavudine, Reverse Transcriptase Inhibitors, Didanosine, Mitochondria, Nevirapine, Lamivudine, Zidovudine, Nelfinavir, DNA, Mitochondrial, Lymphocytes, HIV Seropositivity, Human, Physiology

020707
LbPeB9027