Abstract
Total lymphocyte count has been proposed as an alternative to the percentage of CD4+ T-cells to indicate when antiretroviral therapy should be started in children with HIV in resource-poor settings. We aimed to assess thresholds of total lymphocyte count at which antiretroviral therapy should be considered, and compared monitoring of total lymphocyte count with monitoring of CD4-cell percentage. Longitudinal data on 3917 children with HIV infection were pooled from observational and randomised studies in Europe and the USA. The 12-month risks of death and AIDS by most recent total lymphocyte count and age were estimated by parametric survival models, based on measurements before antiretroviral therapy or during zidovudine monotherapy. Risks were derived and compared at thresholds of total lymphocyte count and CD4-cell percentage for starting antiretroviral therapy recommended in WHO 2003 guidelines. Total lymphocyte count was a powerful predictor of the risk of disease progression despite a weak correlation with CD4-cell percentage (r=0.08-0.19 dependent on age). For children older than 2 years, the 12-month risk of death and AIDS increased sharply at values less than 1500-2000 cells per mu L, with little trend at higher values. Younger children had higher risks and total lymphocyte count was less prognostic. Mortality risk was substantially higher at thresholds of total lymphocyte count recommended by WHO than at corresponding thresholds of CD4-cell percentage. When the markers were compared at the threshold values at which mortality risks were about equal, total lymphocyte count was as effective as CD4-cell percentage for identifying children before death, but resulted in an earlier start of antiretroviral therapy. In this population, total lymphocyte count was a strong predictor of short-term disease progression, being only marginally less predictive than CD4-cell percentage. Confirmatory studies in resource-poor settings are needed to identify the most cost-effective markers to guide initiation of antiretroviral therapy.
