Background: HIV-infection results in progressive loss of CD4+ T helper cells over the course of disease, with a median time to progression to AIDS of 10 years. In a substantial proportion of patients a rapid decline of CD4+ T helper cells can be observed within two years (“rapid progressors”). A deeper understanding of factors that may be associated with a rapid decrease of CD4+ T helper cells in untreated patients with normal CD4+ T helper cell counts is important for risk assessment and for understanding the pathogenesis of the disease. We performed a longitudinal study over 24 months in which we analyzed lymphocyte subpopulations in a cohort of untreated HIV-infected subjects with more than 500 CD4+ T helper cells/ul at baseline.

Method: Lymphocyte subpopulations (CD4+ and CD8+ T cells, CD20/CD19+ B cells, CD56+/CD3- NK cells), viral load and demographic data have been assessed longitudinally in a cohort of 37 untreated HIV-infected subjects with CD4+ T helper cell counts above >500 cells/ul. Rapidly progressive HIV disease was defined as a loss of more than 50% of CD4+ T helper cells from baseline value within 24 months. Slowly progressive disease was defined as a decrease of less than 30% from baseline value within 24 months.

Results: 11 of 37 patients (29.72%) of subjects experienced a rapid loss of CD4+ T helper cells (> 50 % of baseline) within 24 months. 14 subjects (37.84%) had slowly progressive disease. Subjects with rapidly progressive disease had significantly lower absolute and relative numbers of NK-cells at baseline as compared to subjects with slowly progressive disease (149.60 ±77.90 versus 341.21 ±182.13 cells/ul; p<0.01 and 7.00 ±3.56 versus 14.07 ±6.19%; p<0.01). No significant difference between rapidly and slowly progressive disease at baseline was found for the other lymphocyte subpopulations, viral load or demographic data. 1 out of 16 subjects with absolute NK cell number >200/ul at baseline and 10 out of 21 patients with NK cell numbers <200/ul at baseline had rapid progression (p= 0.01). Conclusions: Our data indicate that untreated HIV-infected subjects with low numbers of natural killer cells may have a higher risk for rapid progression of HIV-disease. These data also indicate the prognostic value of NK cell numbers in HIV-infected patients with CD4+ T helper cell counts > 500/ul. Our findings support a role of the innate immune system in the pathogenesis of HIV-infection.

Keywords: lymphocyte subsets; natural killer cells; disease progression