Outcomes of Integrase Inhibitor–based Antiretroviral Therapy in a Clinical Cohort of Treatment-experienced Children, Adolescents and Young Adults With HIV Infection

Abstract

Background: Data on integrase strand transfer inhibitor (INSTI) use in children, adolescents and young adults with HIV are limited. We evaluated virologic and safety outcomes following INSTI initiation among treatment-experienced children, adolescents and young adults. Methods: The DC Cohort is a multicenter observational study of individuals receiving HIV care in Washington, DC. This analysis included treatment-experienced participants 0–24 years of age who initiated an INSTI during 2011–2017. Viral suppression (VS) and safety outcomes were quantified. Differences in VS by age, sex and CD4 count were assessed using Kaplan-Meier curves. Results: Of 141 participants (median age 20 years; 35% <18 years; 60% male; 89% Black; 62% perinatally-infected), 35% had VS and 65% lacked VS on INSTI initiation. Dolutegravir was the most commonly prescribed INSTI (55%). Among participants without VS at INSTI initiation, 46% achieved VS after a median of 2.7 months. Participants 13–24 (vs. 0–12) years old (P = 0.011) and participants with CD4 counts <350 (vs. >500) cells/μL were less likely to achieve VS (P < 0.001). Among participants with VS at INSTI initiation, 51% sustained VS through a median of 11.0 months of follow-up; of the 49% with transient viremia, 77% later achieved VS again. There were no safety concerns associated with the use of INSTIs. Conclusions: More than half of treatment-experienced children, adolescents and young adults with detectable viremia at INSTI initiation did not achieve VS, while half of those with prior VS experienced transient viremia. Further evaluation of long-term outcomes associated with INSTI use among children, adolescents and young adults is warranted.

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

“…The virological status at baseline is another possible explanation. Indeed, we observed a higher risk of VF in subjects initiating dolutegravir with pVL > 50 copies/mL (mostly on ART) than in those with suppressed baseline viraemia, as previously described [6–10]. This result and the fact that VF was not associated with the GSS of the newly introduced regimen suggest that, at least in some children/adolescents, major adherence issues persist after switching ART and these cannot be definitely counterbalanced by the good efficacy and tolerance profile of dolutegravir‐based combinations.…”

“…Previous studies/cohorts described rates of VF on dolutegravir varying from 16% to 65% in children/adolescents [5–10]. Some factors may explain these differences, e.g.…”

“…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.…”

Adherence, Effectiveness and Safety of Dolutegravir Based Antiretroviral Regimens among HIV Infected Children and Adolescents in Tanzania

“…33 On 48 weeks follow-up, 5.7% of patients had rebound viremia. This observation has also been reported among patients using DTG regimens in previous studies 32 , 34 and requires further investigation to determine factors associated with rebound viremia.…”

“… 31 Patients with high baseline viral load (≥1000 copies/mL) were reported to be less likely to achieve virological suppression with INSTI-based ART. 32 …”