Activation of CD8 T cells predicts progression of HIV infection in women coinfected with hepatitis C virus

Abstract

Background: Because activation of T cells is associated with human immunodeficiency virus (HIV) pathogenesis, CD4 and CD8 activation levels in patients coinfected with HIV and hepatitis C virus (HCV) may explain conflicting reports regarding effects of HCV on HIV disease progression.

Methods: Kaplan-Meier and multivariate Cox regression models were used to study the risk of incident clinical AIDS and AIDS-related deaths among 813 HCV-negative women with HIV infection, 87 HCV-positive nonviremic women with HIV coinfection, and 407 HCV-positive viremic women with HIV coinfection (median follow-up time, 5.2 years). For 592 women, the percentages of activated CD4 and CD8 T cells expressing HLA-DR (DR) and/or CD38 were evaluated.

Results: HCV-positive viremic women had a statistically significantly higher percentage of activated CD8 T cells (P < .001) and a statistically significantly higher incidence of AIDS compared with HCV-negative women (P < .001 [log-rank test]). The AIDS risk was greater among HCV-positive viremic women in the highest tertile compared with the lowest tertile (>43% vs <26%) of CD8(+)CD38(+)DR(+) T cells (hazard ratio, 2.94 [95% confidence interval, 1.50-5.77]; P = .001). This difference was not observed in the HCV-negative women (hazard ratio, 1.87 [95% confidence interval, 0.80-4.35]; P = .16). In contrast, CD4 activation predicted AIDS in both groups similarly. Increased percentages of CD8(+)CD38(-)DR(+), CD4(+)CD38(-)DR(-), and CD8(+)CD38(-)DR(-) T cells were associated with a >60% decreased risk of AIDS for HCV-positive viremic women and HCV-negative women.

Conclusion: HCV-positive viremic women with HIV coinfection who have high levels of T cell activation may have increased risk of AIDS. Earlier treatment of HIV and HCV infection may be beneficial.

Figure 1

AIDS development among AIDS-free women infected with human immunodeficiency virus (HIV) at baseline. HCV, hepatitis C virus; HCV+, HCV-positive; HCV−, HCV-negative; HIV+, HIV-positive; WIHS, Women’s Interagency HIV Study.

Figure 2

AIDS development among human immunodeficiency virus (HIV)–infected women with immune activation data. Baseline hepatitis C virus (HCV) data were missing for 11 of the 592 woman with immune activation data. HCV+, HCV-positive; HCV+RNA+, HCV-positive viremic; HCV+RNA−, HCV-positive nonviremic; HCV−, HCV-negative; HIV+, HIV-positive.

Figure 3

Kaplan-Meier estimates of the probability of remaining AIDS-free and of not dying of AIDS by hepatitis C virus (HCV) status at baseline. A, Probability of remaining AIDS-free by HCV status for 1307 women infected with human immunodeficiency virus (HIV). The number of women who developed AIDS-defining conditions was 495: 288 HCV-negative women; 31 HCV-positive nonviremic women; and 39, 40, 51, and 46 HCV-positive viremic women with RNA levels of ≤983,000, 983,001–2,395,000, 2,395,001–3,980,000, and >3,980,000 IU/mL, respectively (P < .001 [log-rank test]). B, Probability of not dying of AIDS by HCV status for these 1307 women. The number of women who died an AIDS-related death was 162: 97 HCV-negative women; 7 HCV-positive nonviremic women; and 11, 12, 13, and 22 HCV-positive viremic women with RNA levels of ≤983,000, 983,001–2,395,000, 2,395,001–3,980,000, and >3,980,000 IU/mL, respectively (P =.03 [log-rank test]). C, Probability of remaining AIDS-free by HCV status among 881 women who never had a CD4 T cell count of <200 cells/μL. Of these 881 women, the number of women who developed AIDS-defining conditions was 264: 145 HCV-negative women; 24 HCV-positive nonviremic women; and 25, 23, 27, and 20 HCV-positive viremic women with RNA levels of ≤983,000, 983,001–2,395,000, 2,395,001–3,980,000, and >3,980,000 IU/mL, respectively (P < .001 [log-rank test]). HCV−, HCV-negative; HCV+RNA−, HCV-positive nonviremic; HCV+RNA+, HCV-positive viremic.