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RESEARCH PRODUCT

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

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Drug resistance is widespread among children who receive long-term antiretroviral treatment in rural Tanzania. Objectives: Long-term virological response to pediatric antiretroviral treatment (ART) in rural Africa is poorly described. We examined virological efficacy and genotypic resistance in children who received first-line ART for up to 5 years in rural Tanzania. Methods: Haydom Lutheran Hospital has provided ART to HIV-infected children since 2003. A combination of stavudine or zidovudine with lamivudine and either nevirapine or efavirenz is the standard regimen; however, fixed-dose combinations for children have not been available until recently. From February through May 2009 we carried out a cross-sectional virological efficacy survey among children (200 copies/mL. Results: Virological response was measured in 18 children. Median age at ART initiation was 5 years (range 2-11), and median follow-up time on ART was 40 months (range 11-61). Virological suppression, defined as <40 copies/mL, was observed in only 6 individuals (33%). Ten (56%) children harbored clinically relevant resistance mutation in the reverse transcriptase gene. The most frequent mutations were M184V (n=10), conferring resistance to lamivudine, and Y181C (n=4), G190A (n=4) and K103N (n=3), conferring resistance to non-nucleoside reverse transcriptase inhibitors. Of concern, 3 children had thymidine analogue mutations (TAMs), associated with cross-resistance to all nucleoside reverse transcriptase inhibitors, and, hence, the WHO-recommended second-line regimen would not be fully active. Conclusions: Long-term virological suppression rates were poor in children who received first-line ART in rural Tanzania, and an alarmingly high prevalence of drug resistance was observed. Improved adherence strategies for children, such as fixed-dose combination drugs for all age groups, should be a priority in the global efforts to scale-up ART in resource-limited settings.