QUANTIFICATION OF THE VARIATION DUE TO LABORATORY AND PHYSIOLOGICAL SOURCES IN CD4 LYMPHOCYTE COUNTS OF CLINICALLY STABLE HIV-INFECTED INDIVIDUALS

We have conducted a study to quantify the amount of variation in the C D4 lymphocyte counts of HIV-infected individuals due to laboratory and physiological factors. Thirty HIV-infected male volunteers had blood drawn on six occasions: three times in each of 2 weeks, 4 weeks apart. Two tubes of blood were drawn at each visit, and duplicate measuremen ts were obtained from one of the tubes of blood, Differences between d uplicate measurements from a single tube of blood and between CD4 coun ts obtained from two tubes of blood drawn on the same day were attribu ted to laboratory factors. Differences between CD4 counts obtained on different days were attributed to a combination of laboratory factors and physiologic factors, which included the effects of exercise, tobac co, and the consumption of alcohol and caffeine, The mean absolute CD4 count at the first visit was 450 (range 86-1,081). The short-term coe fficient of variation of CD4 count was 13.7 (95% CI: 12.9, 14.6). Phys iologic and laboratory factors accounted for 85% and 15% of the variat ion in CD4 counts, respectively. Variation in the absolute white blood cell count, lymphocyte percentage, and CD4 percentage accounted for 5 2%, 29%, and 19% of the physiologic variation in CD4 counts, respectiv ely. Our results confirm a high degree of short-term variability of CD 4 counts among HIV-infected individuals, which can be largely attribut ed to physiological factors. This variability can be minimized more ef fectively by repeating CD4 counts over time than by repeating measurem ents at a single visit. Because 81% of the variation in CD4 counts is due to variation in the absolute lymphocyte count and because the cost of a lymphocyte count is similar to 10% of the cost of a CD4 fraction , a cost-effective strategy to reduce variation in CD4 counts is to co nsider a single CD4 fraction with repeated measurements of the lymphoc yte count over time.