Dolutegravir in the Long Term in Children and Adolescents

Frequent Virological Failure But Rare Acquired Genotypic Resistance

Pierre Frange; Stephane Blanche; Florence Veber; Veronique Avettand-Fenoel

Disclosures

HIV Medicine. 2021;22(10):958-964. 

In This Article

Abstract and Introduction

Abstract

Objectives: 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.

Methods: This retrospective monocentric study included 134 paediatric patients who received a dolutegravir-based regimen for ≥ 12 months 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.

Results: 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).

Conclusions: 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.

Introduction

Achieving good adherence to treatment and viral suppression in the long term remains challenging in paediatric and young adult patients living with HIV. Overall, virological failure (VF) rates in this group are more than double those in adults, even in high-resource countries,[1,2] leading to a high risk of acquired genotypic resistance in paediatric patients.[3]

Dolutegravir is a powerful, easy-to-take, well-tolerated integrase inhibitor (INI), which has been placed as preferred choice for paediatric and adolescent antiretroviral therapy (ART) worldwide.[4] However, data on the efficacy of dolutegravir in these populations remain scarce, often limited by short-term follow-up,[5–10] and have mainly been extrapolated from adult trials in which the majority of participants were ≥ 30 years of age and had a high level of treatment adherence.[11–13] Thus, we aimed to provide data on the long-term follow-up and the emergence of resistance to dolutegravir in the paediatric population, which is of particular interest in settings where antiretroviral options are limited.

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