Dolutegravir in the long term in children and adolescents: frequent virological failure but rare acquired genotypic resistance.

Abstract

Although widely recommended, data about dolutegravir efficacy in HIV-1-infected children/adolescents are scarce, limited to short-term follow-up and mainly extrapolated from studies in adults with good adherence to treatment. This study aimed to provide long-term data about the risk of virological failure (VF) and acquired genotypic resistance in children and adolescents receiving dolutegravir. This retrospective monocentric study included 134 paediatric patients who received a dolutegravir-based regimen for ≥12months in 2014-2020. Virological failure was defined as not achieving a plasma viral load (pVL) <50 copies/mL within 3 months of dolutegravir initiation or as experiencing virological rebound ≥50 copies/mL. Most of the subjects were antiretroviral therapy-experienced (90.3%), naïve from integrase inhibitors (90.3%) and displayed virological suppression at baseline (63.4%). Their median (interquartile range, IQR) age was 12.0 (8.0-15.8)years. Genotypic susceptibility score of the new regimen was ≥2 in 96% of cases. Median (IQR) follow-up was 34(22-50) months. Virological failure occurred in 43 people (32.1%), more frequently where the baseline pVL was ≥50 copies/mL (67.4% vs. 22.0%, P<0.01). M184V/I mutations in the reverse transcriptase gene were newly detected in three people with VF. Resistance to dolutegravir (mutations G118R and E138A in the integrase gene) emerged in one adolescent (0.7% of subjects, 2.3% of those with VF). Whereas VF is relatively common on dolutegravir in the paediatric population, regimens associating dolutegravir with more than one fully active drug were associated with a low rate of emergent drug resistance. This result strengthens the recommendation of dolutegravir as part of preferred combinations in children/adolescents.