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

J Acquir Immune Defic Syndr. 2005 Jan 1;38(1):47-52. doi: 10.1097/00126334-200501010-00009.

Abstract

Objectives: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Anti-HIV Agents
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Lipids
  • Pyrimidinones
  • Lopinavir
  • Nevirapine
  • Ritonavir