TY - JOUR
T1 - Improvement of mitochondrial toxicity in patients receiving a nucleoside reverse-transcriptase inhibitor - sparing strategy: Results from the multicenter study with nevirapine and kaletra (MULTTNEKA)
AU - Negredo, Eugenia
AU - Miró, Óscar
AU - Rodríguez-Santiago, Benjamí
AU - Garrabou, Gloria
AU - Estany, Carla
AU - Masabeu, Angels
AU - Force, Lluís
AU - Barrufet, Pilar
AU - Cucurull, Josep
AU - Domingo, Pere
AU - Alonso-Villaverde, Carlos
AU - Bonjoch, Anna
AU - Morón, Constanza
AU - Pérez-Álvarez, Nuria
AU - Clotet, Bonaventura
AU - Alonso, A.
AU - Boix, V.
AU - Cartón, J. A.
AU - de la Torre, J.
AU - Echevarría, S.
AU - Galindo, M. J.
AU - Gutiérrez, F.
AU - Roca, V.
PY - 2009/9/15
Y1 - 2009/9/15
N2 - 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.
AB - 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.
U2 - 10.1086/605440
DO - 10.1086/605440
M3 - Article
VL - 49
SP - 892
EP - 900
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
SN - 1058-4838
IS - 6
ER -