Predictive value of absolute CD4 cell count for disease progression in untreated HIV-1-infected children

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Abstract
To describe the relationship between absolute CD4 cell count and the short-term risk of disease progression in HIV-1-infected children. A meta-analysis of individual longitudinal data on HIV-1-infected children enrolled in trials and cohort studies in Europe and the USA. The risks of progression to death and AIDS (or death) within 12 months, in terms of age and the most recent CD4 cell count, were estimated using parametric survival models. The analysis was restricted to measurements before the start of antiretroviral therapy except zidovudine monotherapy. The values of the absolute CD4 cell count and percentage predicting selected levels of disease progression risk were determined from this and previous models. A total of 566 deaths was observed over 9128 person-years of follow-up, and 992 children progressed to AIDS or death over 7309 person-years of follow-up. In children older than 4 or 5 years, the estimated risk of disease progression increased sharply when the CD4 cell count fell below 200-300 cells/microl. As with other immunological markers, CD4 cell count was less prognostic in younger children. The CD4 cell count values predicting a 12-month risk of death of 2-5% and of AIDS of 5-10% were much more strongly influenced by age than equivalent CD4 cell percentage values. This study suggests it may be appropriate to extend CD4 cell count criteria for initiating antiretroviral therapy in HIV-1-infected adults to children as young as 4 or 5 years. Monitoring by CD4 cell count in younger children is problematical because age is a highly influential variable.