Impact of orphan status on HIV treatment outcomes and retention in care of children and adolescents in Asia

Abstract An analysis of the impact of orphanhood at antiretroviral therapy (ART) initiation on HIV outcomes in Asia included 4300 children; 51% were male. At ART initiation, 1805 (42%) were non-orphans (median age: 3 years), 1437 (33%) were single orphans (6 years) and 1058 (25%) were double orphans (7 years). Ten-year post-ART survival was 93.4–95.2% across orphan categories. Clinic transfers were higher among single and double orphans than non-orphans (41% vs 11%, P<0.001). On multivariate analysis, children ?3 years at ART initiation (hazard ratio 1.58 vs <3 years, 95% confidence interval: 1.11–2.24) were more likely to be lost to follow-up. Although post-ART mortality and retention did not differ by orphan status, orphans were at greater risk of starting ART at older ages, and with more severe immunosuppression and poorer growth. Key words: orphan, paediatric, HIV, Asia, antiretroviral, treatment Introduction An estimated 17.8 million children have lost one or both parents to the global HIV epidemic.[1] Orphaned children infected with HIV have been reported in multiple contexts to be at greater risk of delayed access to care, poor adherence and mental health issues [2–6]. As children age, they experience additional psychosocial stressors, including the need for HIV disclosure, fear of stigma and discrimination, managing antiretroviral therapy (ART) in the context of adolescent development, and impending transition to adult HIV care [7,8]. Orphanhood also puts social and financial strain on the remaining parent or non-parental caregivers [9–11]. We conducted an analysis of a regional paediatric HIV cohort in Asia to determine the impact of orphanhood on treatment outcomes and retention in care of children and adolescents. Methods Data were extracted from the TREAT Asia Pediatric HIV Observational Database (TApHOD), which is a member cohort of the International Epidemiology Databases to Evaluate AIDS (IeDEA) [12]. Data are collected from 16 participating clinical programmes in six countries comprising Cambodia, India, Indonesia, Malaysia, Thailand and Vietnam. Prospective data collection in TApHOD commenced in 2008 and retrospective clinical data were provided from the date of first entry into the clinic where available. For this analysis, the study population was restricted to children enrolled in TApHOD through September 2014, who initiated treatment at age <15 years for a duration >6 months, had at least one prospective follow-up visit after ART initiation (of any combination of antiretrovirals) and had recorded information on parental vital status. Institutional Review Board approvals were obtained at participating sites, the data management and analysis centre (Kirby Institute, UNSW Australia) and the coordinating centre (TREAT Asia/amfAR, Bangkok, Thailand). Definitions and statistical analysis The primary endpoint for this analysis was the proportion of children who stayed in care after ART initiation and the study factor of interest was orphan status. We used the following classification for orphan status of a child at the time of ART initiation: nonorphan (both parents were alive or were recorded as the primary caregivers); single orphan (one parent died or a child had only one parent involved in their care); and double orphan (both parents died or a child lived in an orphanage, group home or was homeless). If the vital status of both parents was unknown and there was no evidence of their involvement in care, the child was categorised as a double orphan. Children with insufficient data to make a determination on orphan status using these criteria were excluded from the analysis. The baseline CD4 cell count was the closest to the date of initiation of ART and within a window of 180 days before and 14 days after initiation of ART. Pre-ART HIV-RNA was the closest value to the initiation of ART, within a period of 365 days before or 14 days after ART initiation. For the most recent clinical data, we used the closest measurement within 12 months prior to the date of the last clinic visit. Patients were lost to follow-up (LTFU) if they did not have a recorded clinic visit or contact (e.g. lab test) for ?6 months and were not documented to have been transferred or have died. Those LTFU were censored at the date of their last known clinic visit. Children who were transferred to other care services also were censored at their most recent clinic visit. Demographic and clinical characteristics for different orphan groups were presented as proportions or median and interquartile ranges,