Long-term virological outcome in children receiving first-line antiretroviral therapy

Abstract

Abstract Background Studies relating to long-term virological outcomes among children on first-line antiretroviral therapy (ART) from low and middle-income countries are limited. Methods Perinatally HIV infected, ART-naive children, between 2 and 12 years of age, initiating NNRTI-based ART during 2010–2015, with at least 12 months of follow-up, were included in the analysis. CD4 cell counts and plasma HIV-1 RNA were measured every 24 weeks post-ART initiation. Immunologic failure was defined as a decrease in the CD4 count to pre-therapy levels or below and virologic failure as HIV-RNA of > 1000 copies/ml at 48 weeks after ART initiation. Genotypic resistance testing was performed for children with virologic failure. Logistic regression analysis was done to identify predictors of virologic failure. Results Three hundred and ninety-three ART-naïve children living with HIV [mean (SD) age: 7.6 (3) years; mean (SD) CD4%: 16% (8); median (IQR) HIV-RNA: 5.1 (3.5–5.7) log10 copies/ml] were enrolled into the study. At 48 weeks, significant improvement occurred in weight-for-age and height-for-age z-scores from baseline (all p 90% adherence to ART. At the time of virologic failure, multiple NNRTI-associated mutations were observed: 80%—K103N and Y181C being the major NNRTI mutations—observed. Sensitivity (95% CI) of immunologic failure to detect virologic failure was 7% (2–12), specificity 97% (92.4–98.9), PPV 44% (13.7–78.8) and NPV was 72% (65–77.9). There were no statistically significant predictors to detect children who will develop virologic failure on treatment. Conclusions Considerable immunological improvement is seen in children with ART initiation, but may not be an effective tool to monitor treatment response in the long-term. There is a lack of correlation between immunologic and virologic response while on ART, which may lead to a delay in identifying treatment failures. Periodic viral load monitoring is, therefore, a priority.

Keywords

• Antiretroviral therapy
• Pediatrics
• First-line
• Treatment outcome
• Viral load