Virologic Response Of Treatment Experienced HIV-Infected Ugandan Children And Adolescents On NNRTI Based First-Line Regimen, Previously Monitored Without Viral Load

Abstract
Many 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).HIV-infected Ugandan children aged 1–12 years from HIV-care programs with > 1 year 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 48 weeks. 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.At 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 6 years (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 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.With 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.
Description
Keywords
HIV, Antiretroviral therapy, Children and adolescents, Second-line, Switch, viral load, treatment failure, monitoring & response
Citation
Ssemambo, P. K., Nalubega-Mboowa, M. G., Owora, A., Serunjogi, R., Kironde, S., Nakabuye, S., ... & Barlow-Mosha, L. (2021). Virologic response of treatment experienced HIV-infected Ugandan children and adolescents on NNRTI based first-line regimen, previously monitored without viral load. BMC pediatrics, 21(1), 1-11.https://doi.org/10.1186/s12887-021-02608-0