Improvement of Mitochondrial Toxicity in Patients Receiving a Nucleoside Reverse-Transcriptase Inhibitor-Sparing Strategy: Results from the Multicenter Study with Nevirapine and Kaletra (MULTINEKA)
Por:
Negredo, E, Miro, O, Rodriguez-Santiago, B, Garrabou, G, Estany, C, Masabeu, A, Force, L, Barrufet, P, Cucurull, J, Domingo, P, Alonso-Villaverde, C, Bonjoch, A, Moren, C, Perez-Alvarez, N, Clotet, B
Publicada:
15 sep 2009
Resumen:
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.
Filiaciones:
Negredo, E:
Univ Autonoma Barcelona, Germans Trias & Pujol Univ Hosp, Lluita SIDA Fdn, E-08193 Barcelona, Spain
Miro, O:
Univ Barcelona, Muscle Res Unit, Internal Med Dept,Inst Invest Biomed August Pi &, Mitochondrial Res Lab,Hosp Clin Barcelona, Barcelona, Spain
Rodriguez-Santiago, B:
Univ Autonoma Barcelona, Germans Trias & Pujol Univ Hosp, Lluita SIDA Fdn, E-08193 Barcelona, Spain
Ctr Biomed Res Rare Dis CIBERER, Inst Salud Carlos III, Barcelona, Spain
Univ Pompeu Fabra, Dept Expt & Hlth Sci, Genet Unit, Barcelona, Spain
Garrabou, G:
Univ Barcelona, Muscle Res Unit, Internal Med Dept,Inst Invest Biomed August Pi &, Mitochondrial Res Lab,Hosp Clin Barcelona, Barcelona, Spain
Estany, C:
Univ Autonoma Barcelona, Germans Trias & Pujol Univ Hosp, Lluita SIDA Fdn, E-08193 Barcelona, Spain
Masabeu, A:
Hosp Palamos, Girona, Spain
Force, L:
Hosp Mataro, Barcelona, Spain
Barrufet, P:
Hosp Mataro, Barcelona, Spain
Cucurull, J:
Hosp Figueres, Girona, Spain
Domingo, P:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Alonso-Villaverde, C:
Hosp St Joan de Reus, Tarragona, Spain
Bonjoch, A:
Univ Autonoma Barcelona, Germans Trias & Pujol Univ Hosp, Lluita SIDA Fdn, E-08193 Barcelona, Spain
Moren, C:
Univ Barcelona, Muscle Res Unit, Internal Med Dept,Inst Invest Biomed August Pi &, Mitochondrial Res Lab,Hosp Clin Barcelona, Barcelona, Spain
Perez-Alvarez, N:
Univ Autonoma Barcelona, Germans Trias & Pujol Univ Hosp, Lluita SIDA Fdn, E-08193 Barcelona, Spain
Clotet, B:
Univ Autonoma Barcelona, Germans Trias & Pujol Univ Hosp, Lluita SIDA Fdn, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Germans Trias & Pujol Univ Hosp, Irsicaixa Fdn, E-08193 Barcelona, Spain
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