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 (<400 copies/mL) compared with 52%
and 54% of patients in the 2- and 3-drug ritonavir-containing groups, respectively
(P<.001). Through study week 48, 70% of children
continued receiving their ritonavir-containing regimen. At study week 48,
42% of children receiving ritonavir plus 2 nucleosides compared with 27% of
those receiving ritonavir and a single nucleoside had undetectable HIV RNA
levels (P = .04); however, similar proportions in
each group continuing initial therapy had HIV RNA levels of less than 10,000
copies/mL (58% vs 48%, respectively; P = .19).
Conclusions In our study, change in antiretroviral therapy to a ritonavir-containing
regimen was associated with superior virologic response at study week 12 compared
with change to a dual nucleoside analog regimen. More children receiving ritonavir
in combination with 2 compared with 1 nucleoside analog had undetectable HIV
RNA levels at study week 48.