Background:  Immune activation is associated with HIV disease progression. Particularly, enhanced HLA-DR and CD38 expression on both CD4⁺ and CD8⁺ T cells is associated with CD4⁺ T cell decline in ART-naïve HIV⁺ patients, while increase in CD4 counts have been associated with post-HAART decrease in immune activation. Given >30% of HIV⁺ individuals are also co-infected with hepatitis C virus (HCV), we evaluated the influence of HCV on immune activation-driven CD4 decline in co-infected women.

Methods:  We investigated 251 HIV-infected women pre-HAART. Markers of immune activation including HLA-DR and CD38 expression on CD4⁺ and CD8⁺ cells were measured at baseline. For HCV antibody⁺ women, HCV RNA levels were determined at baseline and follow-up. Longitudinal measures of CD4⁺ cell count were tested for association with baseline immune activation using linear mixed effects analyses.

Results:  A total of 148 (59%) women were anti-HCV⁺ at baseline. Of those, 127 (86%) were viremic for HCV RNA and 21 (14%) non-viremic. Mean percentage of CD8⁺CD38⁺DR⁺ cells were higher in HCV⁺ than in HCV^– women at baseline (HCV⁺ viremic, 36.3; HCV⁺ non-viremic, 29.5; HCV^–, 19.5; p = 0.06). On the other hand, CD4 and CD8 counts, HIV RNA levels and CD4⁺CD38⁺DR⁺ levels were not significantly different across the 3 groups. Adjusted for age, ethnicity, education, current smoking, injection drug use, and anti-HCV status, CD8⁺CD38⁺DR⁺ and CD4⁺CD38⁺DR⁺ levels were significantly associated with CD4 decline (β estimates = –0.97, p = 0.002; –1.23, p = 0.07, respectively). However, stratified analyses by HCV status revealed that among HCV⁺ women CD4 decline was not significantly associated with baseline CD8⁺CD38⁺DR⁺ or CD4⁺CD38⁺DR⁺ levels in either viremic or non-viremic groups; whereas among HCV^– women, both the immune activation markers were significantly associated with CD4 decline (β estimates = –1.80, p = 0.001; –2.03, p = 0.04, respectively).

Conclusions:  Although HCV-co-infected women had higher levels of immune activation at baseline compared to HIV-only-infected women, immune activation was not associated with the rate of decline in CD4 among HIV⁺/HCV⁺ women. However, among women infected with HIV only, immune activation plays an important role in CD4 decline. These results are consistent with our previous report showing no effect of HIV⁺/HCV⁺ on CD4 and CD8 change and suggest that HCV co-infection may preserve CD4 counts, perhaps by reducing HIV-induced apoptosis.