Effects of primary HIV-1 infection on subsets of CD4+ and CD8+ T lymphocytes.

Abstract

To analyse changes in T-lymphocyte subsets in patients with primary HIV infection and to determine their specificity (and therefore their diagnostic utility) by comparing these changes with those seen in other acute illnesses as well as in HIV-uninfected patients. T-lymphocyte subsets were analysed by two- and three-colour flow cytometry, and compared between HIV seroconverters (n = 16), HIV-infected (n = 18) and uninfected (n = 33) controls, patients with infectious mononucleosis (n = 7), and patients suspected clinically of having primary HIV infection but who were later found to be uninfected (referred to as HIV non-converters; n = 17). CD4+ lymphocyte counts were significantly lower in HIV seroconverters (mean, 444 x 10(6)/l) than in the HIV non-converters (793 x 10(6)/l; P = 0.003), HIV-seronegative controls (888 x 10(6)/l; P < 0.0001) and, to a lesser extent, those with mononucleosis (694 x 10(6)/l; P = 0.045). The reduction in CD4+ lymphocytes occurred in both the CD45RA+ (55%) and CD45R0+ (33%) subsets. CD8+ lymphocyte counts were significantly higher in HIV seroconverters (942 x 10(6)/l) than in HIV non-converters (570 x 10(6)/l; P = 0.003) and seronegative controls (467 x 10(6)/l; P < 0.0001), but significantly lower than in the mononucleosis group (3682 x 10(6)/l; P = 0.004). The CD8+ cells in the HIV seroconverters had increased coexpression of CD45R0, human leukocyte antigen (HLA)-DR, CD38 and CD11a/CD18. The mean CD4: CD8 ratio in the HIV seroconverters was 0.49, versus 1.52 in the non-converters (P < 0.0001), 2.08 in the seronegative patients (P < 0.0001) and 0.37 in the mononucleosis patients (P > 0.2). Primary HIV infection is characterized by a depletion of CD4+ lymphocytes, especially of the CD45RA+ phenotype, and by an increase in CD8+ lymphocytes with an activated phenotype; the latter was also seen in patients with infectious mononucleosis but not in HIV non-converters or HIV-seronegative patients. Patients suspected clinically of having primary HIV infection but with normal T-cell phenotype are less likely to have primary HIV infection. These phenotypic changes, as well as an inverted CD4: CD8 ratio, can readily distinguish patients with primary HIV infection from HIV-uninfected patients except those with infectious mononucleosis. Therefore, T-cell-subset enumeration may be useful in the diagnosis of primary HIV infection.