CD4 enumeration technologies: a systematic review of test performance for determining eligibility for antiretroviral therapy

Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational r...

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Bibliographic Details
Published in:PloS one 2015-03, Vol.10 (3), p.e0115019-e0115019
Main Authors: Peeling, Rosanna W, Sollis, Kimberly A, Glover, Sarah, Crowe, Suzanne M, Landay, Alan L, Cheng, Ben, Barnett, David, Denny, Thomas N, Spira, Thomas J, Stevens, Wendy S, Crowley, Siobhan, Essajee, Shaffiq, Vitoria, Marco, Ford, Nathan
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
AIDS
Anti-Retroviral Agents - therapeutic use
Antiretroviral agents
Antiretroviral drugs
Antiretroviral therapy
Assaying
Assessment centers
Bias
CD4 antigen
CD4 Lymphocyte Count - instrumentation
CD4 Lymphocyte Count - methods
Classification
Coefficient of variation
Drug therapy
Enumeration
Flow cytometry
Hematology
Highly active antiretroviral therapy
HIV
HIV Infections - blood
HIV Infections - drug therapy
HIV-1
Human immunodeficiency virus
Humans
Hygiene
Identification methods
Immunology
Infections
Laboratories
Lymphocytes
Lymphocytes T
Medicine
MEDLINE
Performance evaluation
Reproducibility
Sensitivity and Specificity
Systematic review
Technology
Test procedures
Thresholds
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Summary:Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts 350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0115019