Challenges in implementing CD4 testing in resource‐limited settings

Cytometry Part B (Clinical Cytometry) 74B (Suppl. 1):S123–S130 (2008)

Challenges in Implementing CD4 Testing in Resource-Limited Settings Trevor Peter,* Anne Badrichani, Emily Wu, Richard Freeman, Bekezela Ncube, Fabiana Ariki, Jennifer Daily, Yoko Shimada, and Maurine Murtagh Clinton Foundation HIV/AIDS Initiative, 225 Water Street, Quincy, Massachusetts 02169

The scale-up of HIV antiretroviral therapy in recent years has led to a rapid increase in CD4 and CD4% count capacity to meet the diagnostic needs of staging and monitoring disease progression and treatment efficacy in adults and infants. The speed of implementation of this technology has been unrivalled in recent years and has met challenges with technology selection, laboratory infrastructure development, human resource limitations, cost-effectiveness, instrument maintenance, and ensuring testing access and quality. The lessons learned from dealing with these challenges have helped strengthen existing laboratory systems for other diagnostics. They may also facilitate the implementation of new diagnostics in future. q 2008 Clinical Cytometry Society Key terms: CD4 count; HIV; AIDS; antiretroviral; laboratory; capacity building

How to cite this article: Peter T, Badrichani A, Wu E, Freeman R, Ncube B, Ariki F, Daily J, Shimada Y, Murtagh M. Challenges in implementing CD4 testing in resource-limited settings. Cytometry Part B 2008; 74B (Suppl. 1): S123–S130.

The CD4 count is the cornerstone of HIV diagnostics. Used for both staging and monitoring patients for HIV antiretroviral therapy (ART), CD4 testing has expanded dramatically in resource-limited countries initiating public ART programs in recent years. International and national guidelines have long recommended the use of CD4 count for treatment decisions, and recent experience reaffirms its utility as a predictor of disease progression, a criterion for treatment initiation, and as a marker of treatment outcome in both adults and children (1–10). CD4 testing is recommended at multiple points during the course of patient care. After a positive HIV diagnosis, a CD4 count is used to stage the disease so as to help determine whether the patient is eligible for ART. Most guidelines recommend ART in adults if the absolute CD4 count is under 200 or 350 cells per microliter and in infants under five years of age if the CD4% of lymphocytes is less than 15–25% (1,2). Once on ART, patients are scheduled to receive CD4 count tests routinely every 3– 6 months, while patients not yet eligible are usually monitored for disease progression with a CD4 count every 6–12 months. Clinical staging or the use of total lymphocyte count are recommended alternatives or adjuncts to CD4-staging, but the relative insensitivity of these methods and the ease with which highly accurate auto-

q 2008 Clinical Cytometry Society

mated CD4 machines can be obtained has limited the extensive use of these alternative approaches (7,11–13). All patients on ART will receive multiple CD4 counts, perhaps up to 50 tests or more, during the course of their lifelong treatment, and as a result, the demand for CD4 tests is high and will continue to increase for as long as ART programs grow. Prior to 2002, many resource-limited countries had limited CD4 capacity, commonly available only at a few central laboratories in the private sector or within research settings. The rapid expansion of public ART programs across multiple countries since 2002 highlighted this significant under-capacity and resulted in the The Cytometry Part B: Clinical Cytometry supplement (74B, Supplement 1, 2008) titled ‘‘The Global Health and Diagnostic (Flow) Cytometry—Breakthrough in HIV and Tuberculosis’’ is sponsored by Beckman Coulter, BD Biosciences, and Caltag-Medisystems. The contributing authors to this article have declared no conflict of interest. *Correspondence to: Trevor Peter, Clinton Foundation HIV/AIDS Initiative, 225 Water Street, Quincy, MA 02169, USA. E-mail: [email protected] Received 22 January 2008; Accepted 6 February 2008 Published online 17 March 2008 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/cyto.b.20416

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Table 1 Commercially Available CD4 Count Technology Capacity High throughput; 250–350 tests/day; 70,000 tests/year Low–intermediate throughout; 30–100 tests/day; 12,000 tests/year

Instrument (manufacturer)

Assay

FACSCalibur (Becton Dickinson) EPICS XL (Beckman Coulter) CyFlow SL 3 (Partec) FACSCount (Becton Dickinson)

Absolute CD4 count and CD4%

Flow cytometry; automated

Absolute CD4 count and CD4% Absolute CD4 count Absolute CD4 count and CD4% Absolute CD4 count and CD4%, white blood cell count Absolute CD4 count and CD4% Absolute CD4 count and CD4%

CyFlow Counter (Partec) Easy CD4 Analyzer (Guava) PointCare (PointCare Technologies) Apogee Auto40

Manual and semimanual assays;