Growth failure is a common problem in HIV-infected children. The extent to which this growth failure could be reversed after the children receive antiretroviral therapy (ART) is not known. This study assessed the incidence of growth failure in HIV-infected Thai children, impact of ART on growth, and the predictors of growth reversal after initiating ART. Growth parameters and other characteristics were extracted from the database of a prospective cohort of HIV-infected children (age 15 years) who were enrolled to initiate non-nucleoside reverse transcriptase inhibitor-based ART between August 2002 and May 2007. Body weight and height measurements, CD4 cell counts, plasma HIV RNA levels were collected at baseline and 24-week intervals. A total of 225 HIV-infected children were included, 116 (51%) were males. The median age at baseline was 7.4 years (interquartile range [IQR] 5.2-9.8). Fifty-three percent were in Centers for Disease Control and Prevention (CDC) category C and 54% had CD4 percentage 5 or less. The mean (standard deviation [SD]) of baseline weight-for-age (WAZ) and height-forage (HAZ) z-scores were À2.02 (1.17) and À2.22 (1.51). The median follow-up time was 216 weeks (IQR 120-240). The cumulative probability of growth reversal among the 179 subjects with growth failure at entry was 58% (95% confidence interval [CI] 49-67) at week 240. In a multivariate Cox regression model, higher entry WAZ ( p < 0.001) and HAZ ( p < 0.001), use of a nevirapine-based regimen (compared to efavirenz, p ¼ 0.027) and larger CD4% gains to week 48 ( p < 0.001) were significant predictors of growth reversal after initiating ART. NNRTI-based ART leads to a substantial improvement in growth of HIV-infected children. Initiation of ART before the children developed growth failure should be encouraged.

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Background In multi-site HIV observational cohorts, clustering of observations often occur within sites. Ignoring clustering may lead to “Simpson's paradox” (SP) where the trend observed in the aggregated data is reversed when the groups are separated. This study aimed to investigate the SP in an Asian HIV cohort and the effects of site-level adjustment through various Cox-regression models. Methods Survival time from combination antiretroviral therapy (cART) initiation was analysed using four Cox models: (i) no site adjustment; (ii) site as a fixed effect; (iii) stratification through site; and (iv) shared frailty on site. Results A total of 6454 patients were included from 23 sites in Asia. SP was evident in the year of cART initiation variable. Model (i) shows the hazard ratio (HR) for years 2010-2014 was higher than the HR for 2006-2009, compared to 2003-2005 (HR = 0.68 vs 0.61). Models (ii)-(iv) consistently implied greater improvement in survival for those who initiated in 2010-2014 than 2006-2009 contrasting findings from Model (i). The effects of other significant covariates on survival were similar across four models. Conclusions Ignoring site can lead to SP causing reversal of treatment effects. Greater emphasis should be made to include site in survival models when possible.