Lopinavir/ritonavir plus nevirapine as a nucleoside-sparing approach in antiretroviral-experienced patients (NEKA study)

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 38; no. 1; p. 47
• Main Authors: Negredo, Eugènia, Moltó, José, Burger, David, Côté, Helene, Miró, Oscar, Ribalta, Josep, Martínez, Eva, Puig, Jordi, Ruiz, Lidia, Salazar, Juliana, López, Sònia, Montaner, Julio, Rey-Joly, Celestino, Clotet, Bonaventura
• Format: Journal Article
• Language: English
• Published: United States 01.01.2005
• Subjects: Adult; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Anti-HIV Agents - pharmacokinetics; Antiretroviral Therapy, Highly Active; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Drug Tolerance; Female; HIV Infections - drug therapy; HIV Infections - metabolism; HIV Infections - virology; HIV-Associated Lipodystrophy Syndrome - etiology; Humans; Lipids - blood; Lopinavir; Male; Middle Aged; Mitochondria - drug effects; Mitochondria - metabolism; Nevirapine - administration & dosage; Nevirapine - adverse effects; Nevirapine - pharmacokinetics; Prospective Studies; Pyrimidinones - administration & dosage; Pyrimidinones - adverse effects; Pyrimidinones - pharmacokinetics; Ritonavir - administration & dosage; Ritonavir - adverse effects; Safety
• ISSN: 1525-4135
• DOI: 10.1097/00126334-200501010-00009

To compare the efficacy and safety of a nucleoside-sparing approach with a conventional highly active antiretroviral therapy (HAART) regimen in antiretroviral-experienced patients with prolonged viral suppression. Pilot study including 31 antiretroviral-experienced patients with HIV RNA <80 copies/mL. Subjects were randomly assigned to lopinavir/ritonavir (LPV/rtv) 400/100 mg BID plus nevirapine (NVP) 200 mg BID (NVP group, n = 16) or LPV/rtv plus the 2 previous NRTIs (NRTI group, n = 15). The primary endpoint was the percentage of subjects who maintained viral suppression at week 48. Changes in lipid metabolism, mitochondrial parameters, and LPV trough levels were also assessed. All patients maintained viral suppression after 48 weeks. No subject discontinued therapy because of adverse events. HDL cholesterol increased by 28% at week 24 (P < 0.0001) and 10% after 48 weeks of follow-up (P = 0.319) in the NVP group. In the NRTI group, LDL cholesterol increased by 14% at week 48 (P = 0.076). Mitochondrial DNA/nuclear DNA ratio and mitochondrial respiratory chain complex IV activity showed a trend toward increasing in the NVP group. Mean (SD) LPV trough levels were 6340 (2129) ng/mL in the NRTI group and 5161 (2703) ng/mL in the NVP group (P = 0.140). In antiretroviral-experienced subjects with sustained viral suppression, dual therapy with NVP plus LPV/rtv at standard dosage was as potent and safe as standard-of-care HAART at 48 weeks of follow-up. This approach may reduce mitochondrial toxicity and improve LPV/rtv-associated lipid abnormalities. The results of this pilot study support the study of this approach in a larger, randomized trial.