Drug resistance profiles and influencing factors among HIV-infected children and adolescents receiving long-term ART: a multicentre observational study in China

Objectives To analyse the characteristics and determinants of drug resistance mutations (DRMs) in HIV-infected children and adolescents on long-term ART in China. Methods An observational cohort study was conducted in five centres. All participants younger than 15 years at ART initiation were screened, and those identified as having virological failure (VF) with viral load (VL) >= 400 copies/mL were included for genotypic resistance testing. Logistic regression analysis was performed and the accumulation of major mutations was analysed in a subgroup of resistant individuals with complete VL results since HIV diagnosis. Results Among 562 eligible participants, protease and RT regions were successfully amplified for 93 who failed treatment with a median of 10.0 years ART. Sixty-eight (73.1%) harboured >= 1 major mutations. NRTI, NNRTI and dual-class resistance accounted for 48.4%, 63.4% and 38.7%, respectively. Only 3.2% were resistant to PIs. Age at ART initiation [adjusted OR (aOR) = 0.813, 95% CI 0.690-0.957], subtype B (aOR = 4.378, 95% CI 1.414-13.560) and an initial NNRTI-based regimen (aOR = 3.331, 95% CI 1.180-9.402) were independently associated with DRMs. Among 40 resistant participants with additional VL data, 55.0% had continued VF on a suboptimal regimen and the estimated duration of VF was positively correlated with the total number of major mutations (r = 0.504, P = 0.001). Conclusions The development of DRMs was common in children and adolescents receiving long-term treatment, and continued VF was prevalent in those with resistance. Timely genotypic testing and new child-friendly formulations are therefore urgently required.