Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital

Abstract

To assess long-term virological efficacy and the emergence of drug resistance in children who receive antiretroviral treatment (ART) in rural Tanzania. Haydom Lutheran Hospital has provided ART to HIV-infected individuals since 2003. From February through May 2009, a cross-sectional virological efficacy survey was conducted among children (<15 years) who had completed ≥6 months of first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Genotypic resistance was determined in those with a viral load of >200 copies/mL. Virological response was measured in 19 of 23 eligible children; 8 of 19 were girls and median age at ART initiation was 5 years (range 2–14 years). Median duration of ART at the time of the survey was 40 months (range 11–61 months). Only 8 children were virologically suppressed (≤40 copies/mL), whereas 11 children had clinically relevant resistance mutations in the reverse transcriptase gene. The most frequent mutations were M184V (n = 11), conferring resistance to lamivudine and emtricitabine, and Y181C (n = 4), G190A/S (n = 4) and K103N (n = 4), conferring resistance to NNRTIs. Of concern, three children had thymidine analogue mutations, associated with cross-resistance to all nucleoside reverse transcriptase inhibitors. Despite widespread resistance, however, only one child experienced a new WHO stage 4 event and none had a CD4 cell count of <200 cells/mm3. Among children on long-term ART in rural Tanzania, >50% harboured drug resistance. Results for children were markedly poorer than for adults attending the same programme, underscoring the need for improved treatment strategies for children in resource-limited settings.