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


CONCLUSIONS
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.
Global Child Health Group, Emma Children Hospital, Academic Medical Centre, University of Amsterdam, The Netherlands Mhw.huibers@gmail.com.
Minke H W
MH
Huibers
Department of Paediatrics, University of Malawi College of Medicine, Malawi.
Peter
P
Moons
Queen Elizabeth Central Hospital, Ministry of Health, Malawi.
Nelson
N
Maseko
Queen Elizabeth Central Hospital, Ministry of Health, Malawi.
Montfort B
MB
Gushu
Amsterdam Institute of Global Health Development (AIGHD), University of Amsterdam, The Netherlands.
Ferdinand W
FW
Wit
Centre for International Child Health, University of Melbourne, Department of Paediatrics and Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia.
Steve M
SM
Graham
Global Child Health Group, Emma Children Hospital, Academic Medical Centre, University of Amsterdam, The Netherlands Amsterdam Institute of Global Health Development (AIGHD), University of Amsterdam, The Netherlands.
Michael Boele
MB
van Hensbroek
Global Child Health Group, Emma Children Hospital, Academic Medical Centre, University of Amsterdam, The Netherlands Pediatric Intensive Care, Emma Children Hospital, Academic Medical Centre, University of Amsterdam, The Netherlands.
Job C
JC
Calis
D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D020000:Decision Support Systems, Clinical; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006679:HIV Seropositivity; D006801:Humans; D018655:Lymphocyte Count; D008295:Malawi; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014944:World Health Organization
D044966:Anti-Retroviral Agents; D015415:Biomarkers
CD4; HIV; total lymfocyte count