EARLY MARKERS OF HIV-INFECTION AND SUBCLINICAL DISEASE PROGRESSION

Human immunodeficiency virus (HIV) infection in US Air Force personnel between 1985 and 1989 was examined through a mandatory serological survey, and through annual examination of infected patients. CD4+ cell counts were determined by flow cytometry; beta2 microglobulin and neopterin were measured by immunoassay. During this period 933 cases were found, of which 161 were documented seroconversions, giving an incidence rate of 15.6/100 000 person-years. For patients with >400 CD4 cells mul-1, the rate of initial occurrence of opportunistic infection was 1 and 4% at 1 and 2 years, respectively. HIV-infected persons with <400 CD4+ cells mul-1, in contrast, had rates of 21% at 1 year and 36% at 2 years. In a cross-sectional study, beta2 microglobulin concentration was shown to increase in both the serum and spinal fluid of patients infected with HIV as their blood CD4 numbers declined. Neopterin levels in serum and spinal fluid showed a similar trend, with significantly lower neopterin concentrations in the group that had >1000 CD4+ T cells compared to the 0-600 CD4+ cell group. Longitudinal studies included correlation of HIV p24 antigen with CD4 counts over a 1 year period. The p24 antigen-positive group had a 21% decline in CD4+ T cells, while the antigen-negative group had a 14% decline. Specific helper T-cell subsets were also examined over a 6 month period. A significant decline was seen in the CD4+/CD29+, CD4+/CD45R+, and overall CD4+ subsets which was not seen in AZT(TM)-treated patients. A significant increase in the CD4+/CD29+ memory T-cell subset, which is responsible for response to recall antigens and is capable of gamma-interferon secretion, was noted in the AZT-treated group.