Seven-year efficacy of a lopinavir/ritonavir-based regimen in antiretroviral-naïve HIV-1-infected patients

Objective: Evaluate efficacy and tolerability of lopinavir/ritonavir (LPV/r) plus stavudine and lamivudine long term in antiretroviral-naïve patients. Design: Open-label follow-up of prospective, randomized, multicenter trial. Method: Antiretroviral-naïve HIV-1 -infected subjects (N = 100) received 1 of 3 doses of LPV/r plus stavudine and lamivudine for 48 weeks then received LPV/r soft-gel capsules 400/100 mg plus stavudine and lamivudine. After 6 years, subjects replaced stavudine with tenofovir. Results: At 7 years, by intent-to-treat analysis, 61% had plasma HIV-1 RNA <400 copies/mL and 59% had < 50 copies/mL. Thirty-nine subjects discontinued treatment due to adverse events (n = 16), personal/other reasons (10), loss to follow-up (9), and noncompliance (4). Among 28 subjects qualifying for drug resistance testing, no protease inhibitor or stavudine resistance was observed and 4 showed lamivudine resistance. Most common drug-related moderate or severe adverse events were diarrhea (28%), nausea (16%), and abdominal pain (11 %). Subjects who received stavudine (median 6.6 years) and switched to tenofovir demonstrated significant improvements in total cholesterol (p = .009), triglycerides (p = .023), apolipoprotein C-III (p < .001), adiponectin (p = .008), fasting insulin (p = .04), and leptin (p = .03). Conclusion: LPV/r-based therapy demonstrated sustained efficacy with no protease inhibitor or stavudine resistance through 7 years in antiretroviral-naïve patients. Switching from stavudine to tenofovir resulted in significant improvements in multiple metabolic parameters.