Discordance between CD4 cell count and CD4 cell percentage: implications for when to start antiretroviral therapy in HIV-1 infected children

OBJECTIVE: Antiretroviral therapy (ART) guidelines for HIV-1-infected children specify both absolute CD4 cell count and CD4 percentage thresholds at which consideration should be given to initiating ART. This leads to clinical dilemma when one marker is below the threshold, whereas the other is above.DESIGN: Data were obtained on a large group of children followed longitudinally in trials and cohort studies in Europe and the USA. Follow-up was censored 6 months after the start of any antiretroviral drug other than zidovudine monotherapy.METHODS: Discordance between CD4 cell count and percentage was defined in relation to ART initiation thresholds in World Health Organization (WHO) and European paediatric treatment guidelines. The relative prognostic value of CD4 cell count and percentage for progression to AIDS/death was investigated using time-updated Cox proportional hazards models, stratified by age.RESULTS: Among 3345 children, with a total of 21,815 pairs of CD4 measurements analysed, 980 developed AIDS and/or died after a median follow-up of 1.7 years. Over one-half of children had discordant values of CD4 cell markers at the first visit when one or both treatment thresholds were crossed and approximately one-third had the same pattern of discordance at a subsequent measurement. Models suggested that CD4 percentage had little or no prognostic value over and above that contained in CD4 cell count, irrespective of age.CONCLUSIONS: More emphasis should be placed on CD4 cell count than on CD4 percentage in deciding when to start ART in HIV-1-infected children.