Improvement of mitochondrial toxicity in patients receiving a nucleoside reverse-transcriptase inhibitor - sparing strategy: Results from the multicenter study with nevirapine and kaletra (MULTTNEKA)

Eugenia Negredo, Óscar Miró, Benjamí Rodríguez-Santiago, Gloria Garrabou, Carla Estany, Angels Masabeu, Lluís Force, Pilar Barrufet, Josep Cucurull, Pere Domingo, Carlos Alonso-Villaverde, Anna Bonjoch, Constanza Morón, Nuria Pérez-Álvarez, Bonaventura Clotet, A. Alonso, V. Boix, J. A. Cartón, J. de la Torre, S. EchevarríaM. J. Galindo, F. Gutiérrez, V. Roca

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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 virologie 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 nucleosideassociated 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. © 2009 by the Infectious Diseases Society of America. All rights reserved.
Original languageEnglish
Pages (from-to)892-900
JournalClinical Infectious Diseases
Volume49
Issue number6
DOIs
Publication statusPublished - 15 Sep 2009

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