Maternal, Child, and Adolescent, Center for Infectious Diseases and Virology, University of Southern California, Keck School of Medicine, HRA 300, 1640 Marengo St, Los Angeles, CA 90033, USA.
J Infect Dis. 2010 Mar 15;201(6):823-34. doi: 10.1086/650997.
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.
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.
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.
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.
由于 T 细胞的激活与人类免疫缺陷病毒(HIV)的发病机制有关,因此,HIV 和丙型肝炎病毒(HCV)合并感染患者的 CD4 和 CD8 激活水平可能可以解释关于 HCV 对 HIV 疾病进展影响的相互矛盾的报告。
我们使用 Kaplan-Meier 和多变量 Cox 回归模型研究了 813 例 HIV 阴性的 HCV 阴性妇女、87 例 HIV 合并感染的非病毒血症的 HCV 阳性妇女和 407 例 HIV 合并感染的病毒血症的 HCV 阳性妇女(中位随访时间为 5.2 年)中发生临床艾滋病和艾滋病相关死亡的风险。对于 592 名妇女,评估了表达 HLA-DR(DR)和/或 CD38 的活化的 CD4 和 CD8 T 细胞的百分比。
与 HCV 阴性妇女相比,HCV 阳性病毒血症妇女的 CD8 T 细胞的活化比例显著更高(P <.001),并且 AIDS 的发生率显著更高(P <.001[对数秩检验])。与 CD8(+)CD38(+)DR(+)T 细胞最低三分位数相比,HCV 阳性病毒血症妇女中最高三分位数(>43%与<26%)的 AIDS 风险更大(危险比,2.94[95%置信区间,1.50-5.77];P =.001)。在 HCV 阴性妇女中并未观察到这种差异(危险比,1.87[95%置信区间,0.80-4.35];P =.16)。相反,CD4 的激活在两组中均预测 AIDS。对于 HCV 阳性病毒血症妇女和 HCV 阴性妇女,CD8(+)CD38(-)DR(+)、CD4(+)CD38(-)DR(-)和 CD8(+)CD38(-)DR(-)T 细胞的百分比增加与 AIDS 的风险降低 60%以上相关。
HIV 和 HCV 合并感染的病毒血症妇女,如果 T 细胞激活水平较高,可能 AIDS 风险增加。早期治疗 HIV 和 HCV 感染可能有益。