treatment failure

Clinical monitoring of pediatric HIV treatment remains a major challenge in settings where drug resistance genotyping is not routinely available. As a result, our understanding of drug resistance, and its impact on subsequent therapeutic regimens available in these settings, remains limited. We investigate the prevalence and correlates of HIV-1 drug resistance among 94 participants of the Ethiopia Pediatric HIV Cohort failing first-line combination antiretroviral therapy (cART) using dried blood spot-based genotyping. Overall, 81% (73/90) of successfully genotyped participants harbored resistance mutations. Strikingly, 42% of resistant participants harbored resistance to all four nucleoside reverse transcriptase inhibitors recommended for second-line use in this setting, meaning that there are effectively no remaining cART options for these children. Longer cART duration and prior regimen changes were significantly associated with detection of drug resistance mutations. Replicate genotyping increased the breadth of drug resistance detected in 34% of cases, and thus is recommended for consideration when typing from blood spots. Implementation of timely drug resistance testing and access to newer antiretrovirals and drug classes are urgently needed to guide clinical decision-making and improve outcomes for HIV-infected children on first-line cART in Ethiopia.

The Ethiopian Paediatric HIV Cohort was established to identify clinical and laboratory predictors of virological treatment failure to ultimately develop a clinical–immunological prediction rule with area under the curve of >0.80 for detecting first-line antiretroviral therapy failure (ARTF). It will also assess the performance of the current WHO guidelines for detection of first-line ARTF in children. Using a prospective cohort design, HIV-infected children and adolescents below the age of 18 years are followed every 6 months with a set of clinical and laboratory parameters at 6 hospitals in southern Ethiopia. From October 2015 through April 2016, 628 children have been enrolled. The cohort will be completed in September 2017. The successful completion of this study will allow for better targeting of viral-load testing to those at highest risk in resource-poor settings and provide clinicians and policymakers with a practical prediction rule.

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