Long-term Virological Outcome in Children on First-line Antiretroviral Therapy in India

BACKGROUND: Long-term virologic data of children receiving antiretroviral therapy (ART) in India are limited. We examined the long-term virologic outcome of a pediatric cohort on non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART in south India. METHODS: Perinatally HIV infected children, between 2–12 years of age initiating NNRTI-based ART during 2010–2014 and with at least 12 months of follow-up, were included in analysis. CD4 cell counts and viral load measurements were performed at 24 and 48 weeks. Immunologic Failure (IF) was defined as decrease in CD4 count of > 30% from baseline; immunologic recovery (IR) as an increase in CD4 count of >25% from baseline while Virologic Failure (VF) was defined as HIV-RNA of >1,000 copies/ml at 48 weeks after ART initiation. Genotypic resistance testing was performed for children with VF. Logistic regression analysis was used to determine predictors of VF RESULTS: A total of 378 ART-naïve HIV infected children with mean age: 7.6 + 3 years, mean CD4%: 16% (8) and median HIV-RNA: 5.1 (3.5 – 5.7) log(10) copies/ml, were enrolled. 74 % were started on nevirapine and 24% on efavirenz-based ART. At 48 weeks, 331 of 378 (88%) children completed follow-up, 15 died, 3 transferred out and 29 were lost to follow up. Significant improvement occurred in weight-for-age and height-for-age z-scores from baseline (all P < 0.001). 79% of children showed IR. VF was seen in 29% (94 / 328), while IF was seen in only 3% (10 / 331) of children. 62% of children with VF reported >90% adherence to ART. Of the 94 children with VF, 5 children showed IF. Correlation between VF and IF was absent. Sensitivity (95% CI) of IF to VF was 6% (2.2–14.6), specificity 98% (94.9–99.5), PPV 56% (26.7–81.1) and NPV was 73.4% (67.8–78.4). At the time of VF, multiple NNRTI-associated mutations were observed in 80% (52/65) of children - K103N and Y181C were the major NNRTI DRMs onserved. M184V also was observed in 79% of children with VF. No definite predictors of VF could be determined. CONCLUSION: Though ART provides significant benefit to children in India, over a quarter of them had VF and developed major drug-resistance mutations after 48 weeks of ART. There is a lack of correlation between IF and VF, leading to delay in identifying treatment failure. Periodic plasma HIV-RNA testing should be performed to detect treatment failures early. DISCLOSURES: All authors: No reported disclosures.