Background:  As infant diagnostic testing becomes more widely available in resource-limited settings, there is the opportunity for eligible children to initiate ART at a very young age. This study compared the response in CD4 cell percentage among 5 age groups and evaluated factors associated with immune response.

Methods:  We analyzed routine service delivery data from HIV-infected children who initiated ART at MTCT-Plus Initiative sites in 9 African countries. Change in CD4 percentage from baseline was analyzed using generalized linear modeling with random effects, adjusting for sex, nevirapine (NVP) exposure at birth, age, CD4 percentage, and CDC clinical stage at ART initiation, and time on ART.

Results:  Of 696 HIV-infected children, 437 (63%) initiated ART between February 2003 and March 2006. Analysis was restricted to 303 (69%) with baseline (–13 to +4 weeks) CD4 percentage. Median age at initiation was 19 months (range 2 months to 11 years) with the following distribution:  2 to 6 months = 64, 7 to 11 months = 53, 12 to 35 months = 82, 36 to 59 months = 43, and ≥5 years = 61; 51% were male. At initiation, median CD4 percentage was 13%; and 27% had CDC clinical stage C disease. Initial regimens included stavudine (d4T)/zidovudine (ZDV) + lamivudine (3TC), and non-nucleoside reverse transcriptase inhibitor (NNRTI) (84%), protease inhibitor (PI) (12%), NRTI (4%). Of 26 deaths occurring over 354 person-years, 12 (46%) were <6 months at ART initiation. The mean number of CD4 percentage measurements was 2.8 (range 1 to 6). Multivariate modeling was restricted to 229 children with baseline and ≥1 follow-up CD4 percentage. Overall, CD4 percentage increased after initiating ART:  the mean 6-month change in CD4 percentage from baseline was 9.8% (<6 months), 13.3 (7 to 11 months), 13.8 (12 to 35 months), 11.8 (36 to 59 months), and 11.6 (≥5 years). In linear modeling, age group (p <0.05), baseline CD4 percentage (p <0.01), and time on ART (p <0.001) were significantly associated with a positive change in CD4 prcentage. Within all age groups, except for <6 months, baseline values were significantly related to CD4 percentage change over time (p <0.05).

Conclusions:  Children initiating ART at MTCT-Plus sites demonstrated a robust immune response to treatment including those <6 months of age.  However, unlike in older children, baseline CD4 percentage was not a useful predictor of immune response in this age group.