In developed countries the decision about when to start ART in adults and children with HIV is based on clinical symptoms, and assessment of the percentage of CD4 T-cells and HIV viral load. However, CD4 counting is too expensive to be made widely available in the countries most affected by the HIV/AIDS pandemic. Total lymphocyte count is a possible alternative. The World Health Organization (WHO) 2003 guidelines recommend total lymphocyte count thresholds for adults and children at which ART can be started in the absence of CD4 cell counts. However, the prognostic value of this marker has not been fully assessed until now.
David Dunn (Medical Research Council, UK) and colleagues combined data from 17 studies looking at total lymphocyte count and disease progression, involving over 3900 children with HIV infection in Europe and USA. The researchers found that total lymphocyte count could predict clinical progression almost as well as CD4 cell percentage. They also found inconsistency between the thresholds of CD4-cell percentage and total lymphocyte count recommended by WHO. The current CD4 threshold means that ART is initiated at a much lower mortality risk than the total lymphocyte count threshold.
Dr Dunn comments: "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."
He adds: "Our analysis showed an inconsistency between the thresholds of CD4-cell percentage and total lymphocyte count suggested by WHO, in that the former trigger therapy at a much lower mortality risk than the latter. To achieve consistency, either the total-lymphocyte-count thresholds should be increased or the CD4-cell percentage thresholds decreased."
In an accompanying Comment Julio Montaner (University of British Columbia, Vancouver, Canada) states: "Without CD4 testing, even an imperfect addition to clinical assessment will likely result in improved clinical management of paediatric and adult patients infected with HIV in low-income countries where access to ART is expanding relatively rapidly. The available evidence allows a compelling argument to be made for clinical trials and cost-effectiveness analysis to directly assess the performance of TLCs [total lymphocyte count] compared with CD4 counts in countries with limited resources."
Contact: David Dunn, Senior Statistician, HIV Group, MRC Clinical Trials Unit, 222 Euston Road, London NW1 2DA. T) +44 (0) 20 7670 4739
Comment: Professor Julio SG Montaner, AIDS Research Programme, St Paul's Hospital, University of British Columbia, 667-1081 Burrard Street, Vancouver BC, V6Z 1Y6, Canada. T) +1 604 806 8036 email@example.com