Virologic response of treatmentexperienced HIV-infected Ugandan childrenand adolescents on NNRTI based first-lineregimen, previously monitored withoutviral load

Abstract

Background:Many HIV-infected African children gained access to antiretroviral treatment (ART) through expansionof PEPFAR programs since 2004 and introduction of“Test and Treat”WHO guidelines in 2015. As ART accessincreases and children transition from adolescence to adulthood, treatment failure is inevitable. Viral load (VL)monitoring in Uganda was introduced in 2016 replacing clinical monitoring. However, there’s limited data on thecomparative effectiveness of these two strategies among HIV-infected children in resource-limited settings (RLS).

Methods:HIV-infected Ugandan children aged 1–12 years from HIV-care programs with> 1 year of first-line ARTusing only immunologic and clinical criteria to monitor response to treatment were screened in 2010. Eligiblechildren were stratified by VL≤400 and > 400 copies/ml randomized to clinical and immunological (control) versusclinical, immunological and VL monitoring to determine treatment failure with follow-up at 12, 24, 36, and 48weeks. Plasma VL was analyzed retrospectively for controls. Mixed-effects logistic regression models were used tocompare the prevalence of viral suppression between study arms and identify factors associated with viralsuppression.

Results:At baseline all children (n= 142) were on NNRTI based ART (75% Nevirapine, 25% efavirenz). One third ofART-experienced children had detectable VL at baseline despite high CD4%. Median age was 6 years (interquartilerange [IQR]: 5–9) and 43% were female. Overall, the odds of viral suppression were not different between studyarms: (arm by week interaction,p= 0.63), adjusted odds ratio [aOR]: 1.07; 95%CI: 0.53, 2.17,p= 0.57) and did notchange over time (aOR: 0 vs 24 week: 1.15; 95% CI: 0.91, 1.46,p= 0.24 and 0 vs 48 weeks: 1.26; 95%CI: 0.92, 1.74,p= 0.15). Longer duration of a child’s ART exposure was associated with lower odds of viral suppression (aOR: 0.61;95% CI: 0.42, 0.87,p< .01). Only 13% (9/71) of children with virologic failure were switched to second-line ART, in spite of access to real-time VL.

Conclusion:With increasing ART exposure, viral load monitoring is critical for early detection of treatment failure inRLS. Clinicians need to make timely informed decisions to switch failing children to second-line ART.

Trial registration:ClinicalTrials.govNCT04489953, 28 Jul 2020. Retrospectively registered. (https://register.clinicaltrials.gov).