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most reliable indicator of prognosis (Ann Intern Med 1997;126:946; Lancet 2002;360:119; Lancet 2003;362:679). An analysis of 13 cohorts with 16,214 patients found that the CD4 count was by far the most important predictor of death (Lancet 2004; 364:51). CD8 cell counts have not been found to predict outcome (NEJM 1990;322:166), but a prolonged time from HIV seroconversion to inversion of the CD4/CD8 ratio predicts slow progression (JAIDS 2006;42:620). HIV-specific CD8 cells (CD38 cells) are important for controlling HIV levels but cannot be routinely measured (Science 1999;283:857; JAIDS 2002;29:346).
- Technique: The standard method for determining CD4 count uses flow cytometers and hematology analyzers. The test requires fresh blood (<18 hours old) and generally costs $50 to $150. There is great need for rapid, simple, and affordable CD4 tests in resource-limited countries. This is being pursued with multiple methods, including Becton Dickinson FACSCount, Partec CyFlow, desktop instruments from Guava and PointCare Technologies, and microchip-based systems (Cytometry 2002;50:69; BMJ 2001;323: 809; J Immunol Methods 1999;222:209; J Clin Virol 2000;17:101; JAIDS 2006; 41: 607; J Transl Med 2006;4:33; Clin Diagn Lab Immu-nol 2005;12: 1416; PLoS 2005;2:e182). A status report for 2008 concluded that it will be possible to develop affordable portable flow cytometry and digital image cytometry was the predicted "winner" (Cytometry B Clin Cytom 2008;74:S27).
- Normal Values: Normal values for most laboratories are a mean of 800 to 1050 cells/mm3, with a range of two standard deviations of approximately 500 to 1400 cells/mm3 (Ann Intern Med 1993;119:55).
- Frequency of Testing: The CD4 count should be measured at baseline, and some recommend two measurements before levels starting treatment (DHHS guidelines 2008, www.aidsinfo.nih.gov/guidelines).The CD4 count should be repeated every 3 to 6 months. The test should be repeated when results are inconsistent with prior trends.
- Reproducibility: Both clinicians and patients must be aware of the variability in CD4 test results, especially if they will be used to make clinical decisions, such as initiation of antiretroviral therapy or opportunistic infection prophylaxis. The 95% confidence range for a true count of 200 cells/mm3, for example, is 118-337 cells/mm3 (JAIDS 1993;6:537). Results that are inconsistent with prior trends should be repeated. A 30% change in the absolute count or a 3% change in CD4 percentage is considered significant (DHHS Guidelines 2008, www.aidsinfo.nih.gov/guidelines).
- Factors that Influence CD4 Cell Counts: Factors include analytical variation, sea sonal and diurnal variations, some intercurrent illnesses, and corticosteroids. Substantial analytical
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