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 huma n immunodeficiency virus (HIV) infection, the role of these drugs in the tr eatment of clinically stable HIV-infected children is not clear. Objective To evaluate the safety, tolerance, and virologic response produce d by a change in antiretroviral therapy in HIV-infected children who were c linically 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 Apri l 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 inhi bitor-naive, clinically stable HIV-infected children aged 2 to 17 years. Interventions Children were randomized to receive zidovudine, 160 mg/m(2) 3 times per day, plus lamivudine, 4 mg/kg 2 times per day (n = 100); the sam e regimen plus ritonavir, 350 mg/m(2) 2 times per day (n = 100); or ritonav ir, 350 mg/m(2) 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, comp ared among the 3 treatment groups. Results At study week 12, 12% of patients in the zidovudine-lamivudine grou p had undetectable plasma HIV RNA levels (<400 copies/mL) compared with 52% and 54% of patients in the 2- and 3-drug ritonavir-containing groups, resp ectively (P<.001). Through study week 48, 70% of children continued receivi ng their ritonavir-containing regimen. At study week 48, 42% of children re ceiving ritonavir plus 2 nucleosides compared with 27% of those receiving r itonavir and a single nucleoside had undetectable HIV RNA levels (P =.04); however, similar proportions in each group continuing initial therapy had H IV RNA levels of less than 10 000 copies/mL (58% vs 48%, respectively; P=.1 9). Conclusions In our study, change in antiretroviral therapy to a ritonavir-c ontaining regimen was associated with superior virologic response at study week 12 compared with change to a dual nucleoside analog regimen. More chil dren receiving ritonavir in combination with 2 compared with 1 nucleoside a nalog had undetectable HIV RNA levels at study week 48.