Nucleoside analogs plus ritonavir in stable antiretroviral therapy-experienced HIV-infected children: a randomized controlled trial. Pediatric AIDS Clinical Trials Group 338 Study Team.

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 10000 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.