by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer

October 25, 2022

Featured Literature:
Torres-Fernandez D, Jiménez de Ory S, Fortuny C, et al. CoRIS and CoRISpe Spanish National Cohorts, CoRISpe and CoRISpe-FARO Cohort Working Group.  Integrase inhibitors in children and adolescents: clinical use and resistance.  J Antimicrob Chemother.  2022 Sept 30; 77(10): 2784-2792.  doi:10.1093/jac/dkac259.  PMID 35971971.  

Investigators in Spain retrospectively identified youth and adolescents who started an INI-based regimen between January 1, 2007 and November 30, 2019 to describe clinical outcomes related to INI exposure as well as development of INI-associated drug resistance mutations among those who experienced virological failure.  Data on 318 INI exposures involving 288 individuals (7.3% of whom were ARV naïve at time of INI initiation) were analyzed.  Almost 88% of patients had perinatally-acquired HIV, with prior receipt of several lines of treatment.  48.9% had viremia at INI initiation and 51% were switched onto INI-based therapy from a suppressive regimen.  Dolutegravir was the most frequently prescribed (42.1%), followed by raltegravir (34.6%), elvitegravir (23.0%), and bictegravir (0.3%).  Across the follow-up period (median: 2 years), investigators observed a notable reduction in VL for patients with viremia.  Slightly over half of patients were suppressed at the start of INI-based therapy: this proportion increased significantly to 83.7% at 6 months and 87.4% after 1 year.  Among 27 patients experiencing virological failure, sequences were available for 15 and 7 had major INI mutations; 5/7 had been receiving raltegravir-based therapy and 2/7 were on elvitegravir/cobicistat.  Of 5 patients experiencing virologic failure on dolutegravir, resistance information was not available for 2 and in another 2 no INI drug resistance mutations were detected.

Author’s Commentary:

Findings from this real world analysis of a single non-U.S. national cohort of youth/adolescents support current U.S. pediatric HIV infection treatment recommendations, which favor INIs for ARV-naïve youth as well as their consideration for ARV-experienced youth (this includes youth who have failed NNRTI/PI-based regimens as well as youth being considered for treatment simplification/optimization).  Given the proportion of patients in this cohort who had prior treatment experience involving multiple ARVs, the high rates of virologic suppression after INI initiation are especially encouraging.  Further, no patients discontinued INIs because of adverse events or tolerability concerns.  These observations highlight not only the potency of newer INI agents (i.e. dolutegravir), but also their overall tolerability profiles and availability in various fixed dose combinations and single tablet regimens – these considerations are important ones which may help mitigate adherence and pill fatigue challenges for youth and their caregivers. 

The author has no conflicts of interest to disclose.

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