An Evaluation of Alternative Markers to Guide Initiation of Anti-retroviral Therapy in HIV-Infected Children in Settings where CD4 Assays are not Available

Objectives: In settings where CD4 testing is not available, alternative markers to start paediatric anti-retroviral therapy (ART) could be used. A comprehensive evaluation of these markers has not been performed. Methods: Prospective cross-sectional study of HIV-infected Malawian children not eligible for ART based on clinical criteria. Associations between CD4 and alternative markers [haemoglobin, total lymphocyte count (TLC), serum albumin, thrombocytes and growth parameters] were analysed, and accuracy of existing and new cut-offs were evaluated. Results: In all, 417 children were enrolled. Of 261 children aged >= 5 years, 155 (59%) qualified to start ART using CD4. In this group, only TLC was associated with CD4 (p<0.001). Sensitivity for TLC was 21% (95% CI: 15-29%), using World Health Organization cut-offs. Improved cut-offs increased sensitivity to 73% (95% CI: 65-80%), specificity 62% (95% CI: 52-72%). Conclusion: Clinical staging alone is an unreliable strategy to start ART in children. TLC is the only alternative marker for CD4, cut-offs need to be revised though.