Development of HIV drug resistance and therapeutic failure in children and adolescents in rural tanzania - an emerging public health concern.

OBJECTIVE To investigate the prevalence and determinants of virologic failure (VF) and acquired drug resistance-associated mutations (DRM) in HIV-infected children and adolescents in rural Tanzania. DESIGN Prospective cohort study with cross-sectional analysis. METHODS All children ≤18 years attending the paediatric HIV Clinic of Ifakara and on antiretroviral treatment (ART) for ≥12 months were enrolled. Participants with VF were tested for HIV-DRM. Pre-ART samples were used to discriminate acquired and transmitted resistances. Multivariate logistic regression analysis identified factors associated with VF and the acquisition of HIV-DRM. RESULTS Among 213 children on ART for a median of 4.3 years, 25.4% failed virologically. ART-associated DRM were identified in 90%, with multiclass resistances in 79%. Pre-ART data suggested that >85% had acquired key mutations during treatment. Suboptimal adherence [OR = 3.90; 95%CI 1.11-13.68], female sex [OR = 2.57; 95%CI 1.03-6.45], and current non-nucleoside reverse transcriptase inhibitor-based ART [OR = 7.32; 95%CI 1.51-35.46 compared to protease inhibitor-based] independently increased the odds of VF. CD4 T cell percentage [OR = 0.20; 0.10-0.40 per additional 10%] and older age at ART initiation [OR = 0.84per additional year-of-age; 95%CI 0.73 to 0.97] were protective (also in predicting acquired HIV-DRM). At the time of VF, less than 5% of the children fulfilled the WHO criteria for immunologic failure. CONCLUSION VF rates in children and adolescents were high, with the majority of ART-failing children harbouring HIV-DRM. The WHO criteria for immunologic treatment failure yielded an unacceptably low sensitivity. Viral load monitoring is urgently needed to maintain future treatment options for the millions of African children living with HIV.