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HIV-1 pol gene sequences were analyzed from 77 HIV-1 positive children infected perinatally and exhibiting virological failure (VF). Viral subtyping, phylogenetic analysis, and genotypic drug resistance analysis were carried out on samples collected before start of anti retroviral treatment (ART) (baseline, BL), and at 12 months post-ART initiation (M12). Subtype C was found to be most predominant, seen in 75 of the 77 (97.4%) children. The level of pretreatment drug resistance (PDR) was 14% among these children. At BL, K103N (5), E138A/G (4), and M184V (3) were the most common mutations. At M12 the prevalence of any resistance-associated mutation (RAM) (acquired drug resistance/ADR) was 81.8% (63/77). Dual class resistance mutations were seen in 64% (49/77) of children. M184V/I, K103N/S, and Y181C were the most commonly occurring mutations, seen in 76%, 51%, and 36% children. RAMs to the second-generation non-nucleoside reverse transcriptase inhibitors (NNRTI), etravirine (ETR) and rilpivirine (RPV), were seen in 40.2% (31/77) and 48.05% (37/77) of the children, respectively. Our findings reveal similar prevalence rates of PDR and ADR in children with VF as reported in other studies. Occurrence of ETR and RPV resistance associated mutations (RAMs) is of concern and highlights the need for timely switch of regimens guided by genotypic resistance testing in perinatally infected children from India.

Objectives: To study the predictors of mortality and mortality rate in a clinical cohort of Children Living with Human Immunodeficiency Virus infection (CLHIV) from India., Methods: This retrospective cohort analysis of CLHIV aged between 2 mo and 18 y registered during January 2004 through December 2014 at Pediatric Centre of Excellence (PCOE), Indira Gandhi Institute of Child Health (IGICH), was conducted using standard data collection sheet. Demographic and clinical characteristics of all eligible children were analyzed. The primary outcome measured was mortality. The authors also analyzed the cause of death and baseline parameters associated with death to study the predictors of mortality., Results: Out of 1289 CLHIV registered in the PCOE during the study period, 834 (64.7 %) CLHIV, with or without antiretroviral therapy (ART) care, were included. The total time contributed by the study participants was 2872.8 child-years. The mortality rate in these children was 4.9/100 child-years. A significantly higher mortality rate of 28.2 % was found in children < 5 y, 38.6 % in children with advanced WHO clinical staging, 35.2 % among severely immunosuppressed children and 22.3 % in severely malnourished children. Tuberculosis accounted for 28 % of deaths. Univariate Cox regression analysis showed treatment status, age <5 y, baseline WHO clinical stage 3 and 4, severe immune suppression and severe malnutrition were strongly associated with mortality., Conclusions: The mortality rate in the index study cohort was 4.9/100 child-years and tuberculosis was the major cause of death. Younger age, baseline advanced clinical and immunological staging were predictors of mortality. Even though mortality was significantly higher in Pre-ART children, treatment status was not found to be an independent predictor of mortality.

Adherence to ART, fundamental to treatment success, has been poorly studied in India. Caregivers of children attending HIV clinics in southern India were interviewed using structured questionnaires. Adherence was assessed using a visual analogue scale representing past-month adherence and treatment interruptions >48 h during the past 3 months. Clinical features, correlates of adherence and HIV-1 viral-load were documented. Based on caregiver reports, 90.9 % of the children were optimally adherent. In multivariable analysis, experiencing ART-related adverse effects was significantly associated with suboptimal adherence (p = 0.01). The proportion of children who experienced virological failure was 16.5 %. Virological failure was not linked to suboptimal adherence. Factors influencing virological failure included running out of medications (p = 0.002) and the child refusing to take medications (p = 0.01). Inclusion of drugs with better safety profiles and improved access to care could further enhance outcomes.

In this retrospective study, incidence of nevirapine (NVP) toxicity in children who were switched from efavirenz (EFV) to NVP (treatment experienced [TE] group) was compared with that of children who had started NVP-based antiretroviral therapy directly (treatment naïve [TN] group). This study also identified risk factors associated with development of NVP toxicity in children. The incidence and risk of developing NVP toxicities were significantly higher in TE when compared to TN group. Median duration of onset of NVP toxicity from the initiation was 2.14 and 3.84 weeks in TE and TN children, respectively. Mean CD4 count was found to be significantly higher in children who developed toxicity (577 ± 81 cells/µL) as compared to the children who did not develop toxicity (403 ± 29 cells/µL). Similarly, children in TE group who developed NVP toxicity had higher mean CD4 cell count than children in TN with NVP toxicity. The risk factors for the development of NVP toxicity include female gender with CD4 count >250 cells/μL and TE children especially girls with CD4% >15% and boys with CD4 count >400 cells/μL. To conclude, the higher incidence of NVP toxicity among TE group warrants a cautious approach while switching the NVP- from EFV-based therapy.