Nucleoside Analogs Plus Ritonavir in Stable Antiretroviral Therapy–Experienced HIV-Infected Children: A Randomized Controlled Trial

CONTEXT Although protease inhibitors are used routinely in adults with human immunodeficiency virus (HIV) infection, the role of these drugs in the treatment of clinically stable HIV-infected children is not clear. OBJECTIVE To evaluate the safety, tolerance, and virologic response produced by a change in antiretroviral therapy in HIV-infected children who were clinically and immunologically stable while receiving previous therapy. DESIGN The Pediatric AIDS Clinical Trials Group 338, a multicenter, phase 2, randomized, open-label controlled trial conducted from February 6 to April 30, 1997 (patient entry period); patients were followed up for 48 weeks. SETTING Pediatric HIV research clinics in the United States and Puerto Rico. PATIENTS Two hundred ninety-seven antiretroviral-experienced, protease inhibitor–naive, clinically stable HIV-infected children aged 2 to 17 years. INTERVENTIONS Children were randomized to receive zidovudine, 160 mg/m2 3 times per day, plus lamivudine, 4 mg/kg 2 times per day (n = 100); the same regimen plus ritonavir, 350 mg/m2 2 times per day (n = 100); or ritonavir, 350 mg/m2 2 times per day, and stavudine, 4 mg/kg 2 times per day (n = 97). MAIN OUTCOME MEASURE Plasma HIV-1 RNA levels at study weeks 12 and 48, compared among the 3 treatment groups. RESULTS At study week 12, 12% of patients in the zidovudine-lamivudine group had undetectable plasma HIV RNA levels (