Eleven sites in Cambodia, India, Indonesia, Malaysia, and Thailand contributed data to this analysis with complete retrospective data collected as far back as 1991. Of the 1655 children meeting inclusion criteria, 50.4% were male and 73% were from a single country (). Of the 94.3% of children who acquired their infection through mother-to-child transmission, >50% did not have documentation of receiving perinatal antiretroviral interventions to prevent HIV transmission. Other reported modes of transmission included blood transfusion (0.7%), sexual transmission (0.1%), sexual abuse (0.2%), other (0.3%), or were unknown/unconfirmed (4.4%). At baseline, the median age was 7.0 [interquartile range (IQR) 3.9–9.8] years, and the median CD4 percentage was 8 (IQR 2–15) percent. For the 996 children who were >6 years of age at cART initiation, the median CD4 count at baseline was 100.5 (IQR 23–291) cells/mm3. There were 628 children that had baseline HIV-RNA measured, the median viral load being 5.3 (IQR 4.8–5.8) log10 copies/mL. At least 50.2% of the children were at WHO stage III or IV before initiation of cART. Most children had either lost one parent (30%) or both parents (24%).
Baseline characteristics of patients at initiation of cART (N=1655 unless specified)
The first cART regimens were non-nucleoside reverse transcriptase inhibitors (NNRTI)-based (92.5%), and protease inhibitors (PI)-based (6%). The most common NNRTI-based regimens were stavudine (d4T) with lamivudine (3TC) and nevirapine (NVP), used in 38.6% of children, followed by zidovudine (AZT) with 3TC and NVP, used in 22.2% of children; 38.3% used fixed dose combinations in part or all of these regimens. Twelve percent had received mono- or dual-nucleoside reverse transcriptase inhibitor (NRTI) combinations before starting cART for a median duration of 2.1 (IQR 0.8–4.6) years.
The median duration of cART at the time of final data transfer was 2.9 (IQR 1.4–4.6) years, during which 121 (7.3%) children switched from an NNRTI- to PI-based regimen at the rate of 4.1 switches per 100 person-years (95% CI 3.4–4.8). The rate of change from PI-based regimens to NNRTI –based regimens was 3.8 switches per 100 person-years (95% CI 1.8–8.0).
The crude mortality rate at one year of cART was 5%, and 8% at five years of cART, with a mortality rate of 2.1 (95% CI 1.7–2.5) per 100 person-years (). LTFU increased from 4% at one year to 24% at five years, for an overall rate of 4.2 (3.7–4.8) per 100 person-years. The median WAZ gains after initiation of cART were 0.23 at one year, 0.3 at two years, and 0.43 at three years; HAZ gains were slower at 0.08 at one year and 0.32 at two years, but increased to 0.55 at three years (). The median CD4 percentage gain from baseline increased from 11 percentage points at one year, to 15 at two years, and 18 percentage points at three years after cART. The probabilities of achieving immunologic recovery, defined as CD4 percentage ≥25%, were 28% at one year of cART, and increased to 77% by four years (). The median duration from initiation of cART to CD4 recovery was 1.8 (IQR 0.9–3.5) years. In multivariate analysis, CD4 recovery to ≥25% was associated with starting cART at age <18 months, being female, lack of pre-cART mono- or dual-therapy exposure, and higher baseline CD4 percentage ().
Time to death and loss to follow-up after cART initiation
Growth recovery after cART as assessed by median weight-for-age and height-for-age z scores
Time to CD4 recovery to ≥25% after cART initiation, by baseline CD4% (A) and by age at cART initiation (B)
Univariate and multivariate analyses for factors associated with time to CD4 recovery to ≥25%
In 501 children who had HIV-RNA monitoring at 12 months of cART, factors independently associated with HIV-RNA >400 copies/mL at 12 months of cART included being male, pre-cART mono- or dual-therapy, and starting cART with NVP-based regimens as compared to EFV-based regimens (; Pearson chi-square for goodness-of-fit = 2.35, p=0.671). At 12 months of cART, 25% were >400 copies/ml. Of the 302 children with viral load at 36 months of cART, 19% were >400 copies/ml. Factors identified by univariate analysis to be associated with detectable viral load included starting cART with NVP-based regimens as compared to EFV-based regimens (OR 3.5; 95% CI 1.7–7.1, p= 0.001) and being a double orphan (OR 2.2; 95% CI 1.1–4.4, p=0.03). Multivariate analysis of detectable viral load at 36 months found that no variables were significantly associated after adjustment for NVP-based regimen.
Univariate and multivariate analyses for factors associated with HIV-RNA >400 copies/mL after 12 months of cART (N=501)