Growing drug resistance (DR) in children living with HIV (CLHIV) on antiretroviral treatment (ART) threatens to undermine global HIV targets to achieve viral suppression and health outcomes for CLHIV with virologic failure (VF). We present DR testing results and outcomes among children with VF in the randomized controlled Opt4Kids trial.
CLHIV ages 1-14 years on ART were enrolled in the Opt4Kids study from five government facilities in Kisumu County, Kenya March to December 2019. Children were individually randomized 1:1 to control (standard-of-care) or intervention (point-of-care viral load testing every three months with targeted DR testing (DRT) for those with VF (> 1000 copies/ml]). A multidisciplinary clinical management committee (CMC) reviewed targeted DRT results and gave management recommendations. DR patterns are described and clinical outcomes compared by Fischer’s exact test.
A total of 704 CHIV were enrolled in the study with a median age 9 years (interquartile range [IQR] 7, 12) and median time on ART of 5.8 years (IQR 3.1, 8.6). Among 349 CHIV enrolled in the intervention arm, 89 (26%) had one or more episodes of viremia of which 84 (94%) had at least one DRT. All children with a DRT had DR mutations identified: 73(84%) had major DR; 70 (83%) NNRTI, 54 (64%) NRTI, 10 (12%) PI as well as 41 (49%) with dual class NRTI-NNRTI and 9 (11%) triple-class DR. The CMC recommended an ART regimen change for 38/84 (45%), and 35 (92%) of these changed regimens by end of study follow-up. Another 12 (14%) CHIV underwent ART regimen change per facility staff as part of the national programmatic transition to dolutegravir (DTG).The CMC did not recommend an ART regimen change for the remaining 34 CHIV, the majority of whom (29; 85%) were on protease inhibitor (PI)-based ART without any major PI DR. Excluding those with programmatic ART changes, the study viral suppression (VS) outcome at 12 months showed VS in 22/38 (58%) with recommendation to change ART and 11/34 (32%) without recommendation to change ART (p=0.0357). Additionally, ART-suppression was observed in 9/12 (75%) with programmatic switch to DTG.
Over 80% of CLHIV undergoing targeted DRT had major drug mutations detected and more than half required ART regimen change to address drug resistance and/or to optimize the regimen. Targeted use of DRT in CLHIV with VF may improve viral suppression, retention, and clinical outcomes.