Nucleoside Analogs Plus Ritonavir in Stable Antiretroviral Therapy–Experienced HIV-Infected Children
A Randomized Controlled Trial
- Sharon A. Nachman, MD;
- Kenneth Stanley, PhD;
- Ram Yogev, MD;
- Stephen Pelton, MD;
- Andrew Wiznia, MD;
- Sophia Lee, MS;
- Lynne Mofenson, MD;
- Susan Fiscus, PhD;
- Mobeen Rathore, MD;
- Eleanor Jimenez, MD;
- William Borkowsky, MD;
- Jane Pitt, MD;
- Mary E. Smith, MD;
- Barbara Wells, BA;
- Kenneth McIntosh, MD;
- for the Pediatric AIDS Clinical Trials Group 338 Study Team
- Author Affiliations: Departments of Pediatrics, State University of New York at Stony Brook (Dr Nachman), Jacobi Medical Center, Albert Einstein College of Medicine (Dr Wiznia), New York University Medical Center (Dr Borkowsky), and Department of Pediatric Infectious Disease, College of Physicians and Surgeons, Columbia University (Dr Pitt), New York, NY; Center for Biostatistics in AIDS Research, School of Public Health, Harvard University (Dr Stanley and Ms Lee), Section of Pediatric Infectious Diseases, Boston Medical Center (Dr Pelton), and Department of Medicine, Division of Infectious Disease, Children's Hospital of Boston (Dr McIntosh), Boston, Mass; Division of Infectious Diseases, Children's Memorial Hospital, Chicago, Ill (Dr Yogev); Pediatric Adolescent and Maternal AIDS Branch, Center for Research for Mothers and Children, National Institute of Child Health and Human Development (Dr Mofenson) and Division of AIDS, National Institute of Allergy and Infectious Diseases (Dr Smith), National Institutes of Health, Bethesda, Md; Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill (Dr Fiscus); Department of Pediatrics, Health Science Center, University of Florida, Jacksonville (Dr Rathore); Department of Pediatrics, San Juan City Hospital, San Juan, Puerto Rico (Dr Jimenez); and Section of Pediatric Infectious Disease, Social and Scientific Systems, Rockville, Md (Ms Wells).
Abstract
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.
