Long-term follow-up of 414 HIV-infected Romanian children and adolescents receiving lopinavir/ritonavir-containing highly active antiretroviral therapy

BACKGROUND. There are no published reports of the long-term safety and effectiveness of highly active antiretroviral therapy for children and adolescents living in resource-limited settings or of large cohorts of HIV-infected children and adolescents treated long-term (> 48 weeks) with lopinavir/ritonavir-containing highly active antiretroviral therapy. OBJECTIVES. The purpose of this work was to evaluate the long-term outcomes of treatment of HIV-infected children and adolescents with lopinavir/ritonavir-containing highly active antiretroviral therapy in a resource-limited setting. METHODS. We studied an inception cohort of 414 HIV-infected children receiving lopinavir/ritonavir-containing highly active antiretroviral therapy between November 2001 and August 2006 at the Romanian-American Children's Center in Constanta, Romania. The center provides comprehensive primary and HIV specialty care and treatment to all known HIV-infected children and adolescents living in Constanta. We measured safety and effectiveness by the percentage of children remaining on treatment, rates of mortality, and changes in plasma HIV RNA concentrations and CD4(+) lymphocyte counts. RESULTS. The study population consisted predominantly of antiretroviral drug-experienced older children and adolescents with advanced HIV disease. Treatment was well tolerated, with 337 children (81%) remaining on therapy after a median duration of > 4 years. Thirty-seven deaths occurred; the death rate compared favorably to prospectively collected historical data. The most recent on-treatment plasma HIV RNA concentration was < 400 copies per milliliter in 192 of 265 children tested. The mean baseline CD4(+) lymphocyte count was 292 cells per microliter ( n = 299); the mean change from baseline was + 266 ( n = 284), + 317 (n = 260), + 343 ( n = 176), and + 270 cells per microliter ( n = 121) after 1, 2, 3, and 4 years of treatment, respectively. CONCLUSIONS. Highly active antiretroviral therapy can be administered safely and effectively to children and adolescents in resource-limited settings. Lopinavir/ritonavir-containing highly active antiretroviral therapy is a safe, effective, and durable treatment option for antiretroviral drug-experienced older children and adolescents with advanced HIV disease.