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

HIV Paediatric Prognostic Markers Collaborative Study

doi: 10.1097/QAD.0b013e3283389f41
Epidemiology and Social: CONCISE COMMUNICATION

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.

*See Acknowledgements section for details of Steering and Writing Committee.

Received 26 October, 2009

Revised 4 February, 2010

Accepted 11 February, 2010

Correspondence to Dr David Dunn, MRC Clinical Trials Unit, 222 Euston Road, London NW1 2DA, UK. Tel: +44 207 670 4739; fax: +44 207 670 4815; e-mail: d.dunn@ctu.mrc.ac.uk

© 2010 Lippincott Williams & Wilkins, Inc.