Improvement of mitochondrial toxicity in patients receiving a nucleoside reverse-transcriptase inhibitor-sparing strategy: results from the Multicenter Study with Nevirapine and Kaletra (MULTINEKA).

Full Abstract

BACKGROUND: Nucleoside reverse-transcriptase inhibitor (NRTI)-related mitochondrial toxicity has been suggested as a key factor in the induction of antiretroviral-related lipoatrophy. This study aimed to evaluate in vivo the effects of NRTI withdrawal on mitochondrial parameters and body fat distribution. METHODS: A multicenter, prospective, randomized trial assessed the efficacy and tolerability of switching to lopinavir-ritonavir plus nevirapine (nevirapine group; n = 34), compared with lopinavir-ritonavir plus 2 NRTIs (control group; n = 33) in a group of human immunodeficiency virus-infected adults with virological suppression. A subset of 35 individuals (20 from the nevirapine group and 15 from the control group) were evaluated for changes in the mitochondrial DNA (mtDNA) to nuclear DNA ratio and cytochrome c oxidase (COX) activity after NRTI withdrawal. Dual-energy X-ray absorptiometry (DEXA) scans were used to objectively quantify fat redistribution over time. RESULTS: The nevirapine group experienced a progressive increase in mtDNA content (a 40% increase at week 48; P = .039 for comparison between groups) and in the COX activity (26% and 32% at weeks 24 and 48, respectively; P = .01 and P = .09 for comparison between groups, respectively). There were no statistically significant between-group differences in DEXA scans at week 48, although a higher fat increase in extremities was observed in the nevirapine group. No virologic failures occurred in either treatment arm. CONCLUSIONS: Switching to a nucleoside-sparing regimen of nevirapine and lopinavir-ritonavir maintained full antiviral efficacy and led to an improvement in mitochondrial parameters, which suggests a reversion of nucleoside-associated mitochondrial toxicity. Although DEXA scans performed during the study only revealed slight changes in fat redistribution, a longer follow-up period may show a positive correlation between reduced mitochondrial toxicity and a clinical improvement of lipodystrophy.

Author information

Author/s: Negredo, Eugenia (E); Miró, Oscar (O); Rodríguez-Santiago, Benjamí (B); Garrabou, Glòria (G); Estany, Carla (C); Masabeu, Angels (A); Force, Lluís (L); Barrufet, Pilar (P); Cucurull, Josep (J); Domingo, Pere (P); Alonso-Villaverde, Carlos (C); Bonjoch, Anna (A); Morén, Constanza (C); Pérez-Alvarez, Núria (N); Clotet, Bonaventura (B); MULTINEKA Study Group;

Affiliation: Lluita contra la SIDA Foundation, Barcelona, Spain. enegredo(-atsign-)flsida.org

Journal and publication information

Publication Type: Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis), published in United States. (Language: eng)

Reference: 2009-Sep; vol 49 (issue 6) : pp 892-900

Dates: Created 2009/08/21; Completed 2009/11/05;

PMID: 19663689, status: MEDLINE (last retrieval date: 11/5/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Absorptiometry, Photon
Adult
Anti-HIV Agents - adverse effects; therapeutic use
Antiretroviral Therapy, Highly Active
Body Composition - drug effects
DNA, Mitochondrial - analysis
Drug Therapy, Combination
Electron Transport Complex IV - metabolism
Extremities
Female
Follow-Up Studies
HIV Infections - drug therapy; metabolism

HIV Infections - drug therapy; metabolism
HIV-Associated Lipodystrophy Syndrome - chemically induced; metabolism; pathology
Humans
Lipids - blood
Male
Middle Aged
Nevirapine - therapeutic use
Pyrimidinones - therapeutic use
Reverse Transcriptase Inhibitors - adverse effects; therapeutic use
Ritonavir - therapeutic use
Treatment Outcome
Viral Load

Associated Chemicals: Anti-HIV Agents (0) ; DNA, Mitochondrial (0) ; Lipids (0) ; Pyrimidinones (0) ; Reverse Transcriptase Inhibitors (0) ; Ritonavir (0) ; Nevirapine (129618-40-2) ; lopinavir (192725-17-0) ; Electron Transport Complex IV (EC 1.9.3.1)

These are the highest related articles currently in the database: