Drug resistance in the Chinese National Pediatric Highly Active Antiretroviral Therapy Cohort: implications for paediatric treatment in the developing world

Abstract

China's National Pediatric ART Program began in 2005, in which 32 ART-experienced and 51 antiretroviral therapy (ART)-naïve children received paediatric formulations of (zidovudine or stavudine) plus lamivudine plus (nevirapine or efavirenz). Reverse transcriptase sequencing and analysis was performed on plasma samples with >1000 HIV copies/mL after one year of treatment. Thirty-four samples were sequenced. Nearly all patients had nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor mutations. High/intermediate resistance was found to lamivudine/emtricitabine in 31 patients; to didanosine, abacavir, stavudine and zidovudine in 18 patients; and to tenofovir in 11 patients. All had high-level resistance to nevirapine; all but one had high/intermediate-level resistance to efavirenz. Viral load was the only cohort characteristic significantly associated with developing resistance. Resistance to zidovudine, stavudine and tenofovir was more common in ART-experienced versus ART-naïve patients ( P = 0.02–0.05). Drug resistance is high in this cohort. Second-line therapy will require additional ART strategies and options, which are currently unavailable in most developing settings.