Correlates of immune activation marker changes in human immunodeficiency virus (HIV)-seropositive and high-risk HIV-seronegative women who use illicit drugs

Abstract

The majority of natural history studies of human immunodeficiency virus (HIV) infection have immune and viral parameters in men. Data demonstrating that women have lower HIV-1 RNA levels than men at the same CD4 cell counts have raised the question of immunologic differences in HIV-seropositive women. This study describes levels and changes in phenotypic markers of immune maturity, function, and activation in the CD4 and CD8 cell subsets in HIV-seropositive and high-risk HIV-seronegative women. Our primary hypothesis was that activation levels would be significantly higher among illicit drug users. However, results showed that HIV-1 RNA level was the strongest predictor of marker level and that both HIV-1 RNA level and CD4 cell count were independently associated with CD4 activation, but illicit drug use was not. In summary, this study demonstrated that immune activation was a significant pathogenic feature in women and that activation was driven by HIV infection and not illicit drug use.

Figure 1

Scatter plots with nonlinear smooth curves of baseline percentage of HLADR⁺/CD38⁺ expressed in CD4 (dashed line) and CD8 (solid line) T cells over the range of baseline human immunodeficiency virus type 1 (HIV-1) RNA levels for 176 HIV-seropositive women. Curves were fitted with the S-PLUS lowess function (MathSoft). Open circles represent individual data points for CD4, and closed triangles represent data points for CD8. Vertical lines divide HIV-1 RNA levels into groups corresponding to those in table 2.

Figure 2

Scatter plots for percentage of CD4 T cell activation level vs. CD4 cell count in human immunodeficiency virus (HIV)–seronegative (left) and HIV-seropositive (center) women and for percentage of CD4 T cell activation level vs. HIV RNA level (right) for drug users (○) and non–drug users (▲). Regression lines from models including CD4 cell count or HIV-1 RNA level, drug use, and their interactions are shown for HIV-seropositive women; solid lines, drug users; dashed lines, non–drug users.