Virologic response of treatment experienced HIV-infected Ugandan children and adolescents on NNRTI based first-line regimen, previously monitored without viral load

BackgroundMany HIV-infected African children gained access to antiretroviral treatment (ART) through expansion of PEPFAR programs since 2004 and introduction of Test and Treat WHO guidelines in 2015. As ART access increases 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 the comparative effectiveness of these two strategies among HIV-infected children in resource-limited settings (RLS).MethodsHIV-infected Ugandan children aged 1-12years from HIV-care programs with >1year of first-line ART using only immunologic and clinical criteria to monitor response to treatment were screened in 2010. Eligible children were stratified by VL <= 400 and>400 copies/ml randomized to clinical and immunological (control) versus clinical, 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 to compare the prevalence of viral suppression between study arms and identify factors associated with viral suppression.ResultsAt baseline all children (n =142) were on NNRTI based ART (75% Nevirapine, 25% efavirenz). One third of ART-experienced children had detectable VL at baseline despite high CD4%. Median age was 6years (interquartile range [IQR]: 5-9) and 43% were female. Overall, the odds of viral suppression were not different between study arms: (arm by week interaction, p =0.63), adjusted odds ratio [aOR]: 1.07; 95%CI: 0.53, 2.17, p =0.57) and did not change over time (aOR: 0 vs 24week: 1.15; 95% CI: 0.91, 1.46, p =0.24 and 0 vs 48weeks: 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.ConclusionWith increasing ART exposure, viral load monitoring is critical for early detection of treatment failure in RLS. Clinicians need to make timely informed decisions to switch failing children to second-line ART.Trial registrationClinicalTrials.gov NCT04489953, 28 Jul 2020. Retrospectively registered. (https://register.clinicaltrials.gov).

Automated summary

This study in Uganda compared the effectiveness of treatment monitoring using only immunologic and clinical criteria versus adding viral load monitoring. The findings suggest that as the duration of ART exposure increases, viral load monitoring becomes critical for early detection of treatment failure.