Quantification of CD4 responses to combined antiretroviral therapy over 5 years among HIV-infected children in Kinshasa, Democratic Republic of Congo

Abstract

Background: The long-term effects of combined antiretroviral therapy (cART) on CD4 percentage in HIV-infected children are incompletely understood, with evidence from resource-deprived areas particularly scarce even though most children with HIV live in such settings. We sought to describe this relationship.

Methods: Observational longitudinal data from cART-naive children enrolled between December 2004 and May 2010 into an HIV care and treatment program in Kinshasa, Democratic Republic of Congo were analyzed. To estimate the effect of cART on CD4 percentage while accounting for time-dependent confounders affected by prior exposure to cART, a marginal structural linear mean model was used.

Results: Seven hundred ninety children were active for 2090 person-years and a median of 31 months; 619 (78%) initiated cART. At baseline, 405 children (51%) were in HIV clinical stage 3 or 4; 528 (67%) had advanced or severe immunodeficiency. Compared with no cART, the estimated absolute rise in CD4 percentage was 6.8% [95% confidence interval (CI), 4.7% to 8.9%] after 6 months of cART, 8.6% (95% CI, 7.0% to 10.2%) after 12 months, and 20.5% (95% CI, 16.1% to 24.9%) after 60 months. cART-mediated CD4 percentage gains were slowest but greatest among children with baseline CD4 percentage <15. The cumulative incidence of recovery to "not significant" World Health Organization age-specific immunodeficiency was lower if cART was started when immunodeficiency was severe rather than mild or advanced.

Conclusions: cART increased CD4 percentages among HIV-infected children in a resource-deprived setting, as previously noted among children in the United States. More gradual and protracted recovery in children with lower baseline CD4 percentages supports earlier initiation of pediatric cART.

FIGURE 1

Duration of cART (bars) and number of CD4 percentage measurements during each of the 6-month periods (lines) in 790 children initiating HIV care between December 2004 and May 2010 in Kinshasa, DRC.

FIGURE 2

Estimated effect of cART on CD4 percentage from marginal structural model,^a overall (Panel A) and by category of CD4 percentage at baseline (Panels B–E), and observed unadjusted CD4 percentage evolutions among children receiving cART and children not receiving cART (Panel F),^b 790 children initiating HIV care between December 2004 and May 2010 in Kinshasa, DRC. ^aEstimates are from repeated measures linear models, fit with generalized estimating equations, that include time modeled as a restricted cubic spline with 4 knots. To plot CD4 percentages among children not receiving cART, time was coded categorically (6-month periods). As there were no discernible upward or downward trends in CD4 percentage over time among children not receiving cART when spline terms were included as predictors in the stratum-specific models, it is assumed that the cumulative cART exposure parameters represent change from baseline. Error bars represent 95% CIs. ^bThe time scale for children not receiving cART is time since the start of follow-up, whereas the time scale for children receiving cART is time since cART initiation. Each box plot depicts the median and IQR, with the error bars marking the 10th and 90th percentiles. The most recent CD4 percentage was carried forward to each 6-month cut point.

FIGURE 3

Cumulative incidence curves of recovery to “not significant” WHO age-specific immunodeficiency, by category of suppression at the start of cART, 536 children initiating cART with mild, advanced, or severe immunodeficiency between December 2004 and May 2010 in Kinshasa, DRC.