Sources of variability in repeated t-helper lymphocyte counts from human immunodeficiency virus type 1-infected patients: Total lymphocyte count fluctuations and diurnal cycle are important

The study objective was to determine the causes and magnitude of absolute CD4 (T4) count variation in human immunodeficiency virus type 1 (HlV-l)-infected (+) adult males. We conducted a prospective, blinded, and controlled study of 22 adult military male outpatients, including 16 HIV(+) [12 in Walter Reed stage (WR-) 1 through 5, 4 in WR-6 (AIDS)], and 6 HIV seronegative (—) healthy controls. Ten CD4⁺ cell counts were drawn within a 3-day interval from each patient at the following times: 0800, 1200, 1600, and 2200 h on day 1; and 0800, 1200, and 1600 h on days 2 and 3. A significant CD4⁺ cell count diurnal increase of 59 cells/mm³ was detected between 0800 h and 2200 h from the WR-1-5 patients (p = 0.018), although this diurnal change was significantly blunted (p = 0.028) as compared with the 506 cells/mm³ CD4⁺ cell count diurnal increase observed from the HIV(-) healthy controls. The coefficients of variation [CV = (standard deviation/average) x 100] of the three daily 0800 h CD4 cell counts from each patient were 15 (median) and 19 (average) for the WR-1-5 patient group. Blood leukocyte counts, differential fractions of lymphocytes, and total lymphocyte counts contributed more to the observed CD4⁺ cell count variability than did the CD4% measurements [CV = 7.5 (median), 11 (average)] obtained from flow cytometry. We conclude that the large fluctuations that we observed in repeated CD4⁺ cell counts in HIV(+) patients can be explained in part by CD4⁺ cell count diurnal cycle and in part by high variability in total lymphocyte counts. Awareness of the causes and expected magnitude of CD4⁺ cell count variation should facilitate the interpretation of CD4⁺ cell count results from individual HIV(+) and HIV-seronegative individuals.