aDepartment of Community Health Systems, School of Nursing, University of California San Francisco bDepartment of Epidemiology & Biostatistics, University of California San Francisco cDepartment of Medicine, University of California San Francisco dBlood Systems Research Institute, San Francisco, California, USA.
AIDS. 2013 Nov 13;27(17):2691-6. doi: 10.1097/01.aids.0000433242.86362.21.
HIV controllers demonstrate high rates of spontaneous clearance of hepatitis C virus (HCV) infection. The objective of this study was to evaluate the role of human leukocyte antigen (HLA) B*57 and other genetic polymorphisms on HCV clearance in HIV controllers.
This is a prospective cohort study.
Patients in the Study of the Consequences of Protease Inhibitor Era (SCOPE) were tested for anti-HCV using enzyme immunoassay (EIA3) and HCV RNA using discriminatory HCV transcription-mediated amplification assay (Norvatis). We compared the proportion of HIV controllers and noncontrollers demonstrating HCV clearance and fitted multivariable Poisson regression models with robust standard errors to estimate adjusted prevalence ratios (APRs) and assessed genetic and immunologic predictors of HCV clearance.
Of 279 HIV/HCV seropositive individuals, 48 were HIV controllers. HIV controllers compared to HIV noncontrollers, were significantly more likely to have HLA B57 (33 vs. 10%, P < 0.01). In multivariate analyses, adjusting for HLAB57, IL28B genotype, age, sex and race/ethnicity, HCV clearance was significantly more likely in HIV controllers than HIV noncontrollers [APR 1.78; 95% confidence interval (CI) 1.06-3.0; P = 0.03]. HLA B57 did not explain the increased proportion of HCV clearance in HIV controllers, but IL28B CC genotype was independently associated with spontaneous HCV clearance (APR 2.76; 95% CI 1.85-4.11; P < 0.001).
Although enriched in HIV controllers, HLA B*57 does not explain the increased HCV clearance. Further identification of host immunologic or genetic factors that contribute to control of HIV and HCV may support the development of novel treatments for and effective vaccines against both viruses.
HIV 控制者表现出高比例的自发性丙型肝炎病毒(HCV)感染清除。本研究的目的是评估人类白细胞抗原(HLA)B*57 和其他遗传多态性在 HIV 控制者中对 HCV 清除的作用。
这是一项前瞻性队列研究。
使用酶免疫测定法(EIA3)和 HCV RNA 检测试剂盒(诺华)对参加蛋白酶抑制剂时代后果研究(SCOPE)的患者进行抗 HCV 检测。我们比较了 HCV 清除的 HIV 控制者和非控制者的比例,并使用稳健标准误差拟合多变量泊松回归模型来估计调整后的患病率比(APR),并评估 HCV 清除的遗传和免疫预测因子。
在 279 例 HIV/HCV 血清阳性个体中,有 48 例为 HIV 控制者。与 HIV 非控制者相比,HIV 控制者更有可能携带 HLA B57(33%比 10%,P<0.01)。在多变量分析中,调整 HLA B57、IL28B 基因型、年龄、性别和种族/民族因素后,HIV 控制者比 HIV 非控制者更有可能发生 HCV 清除[APR 1.78;95%置信区间(CI)1.06-3.0;P=0.03]。HLA B*57 并不能解释 HIV 控制者中 HCV 清除比例的增加,但 IL28B CC 基因型与自发性 HCV 清除独立相关(APR 2.76;95%CI 1.85-4.11;P<0.001)。
尽管在 HIV 控制者中富集,但 HLA B*57 并不能解释 HCV 清除率的增加。进一步确定有助于控制 HIV 和 HCV 的宿主免疫或遗传因素,可能有助于开发针对这两种病毒的新治疗方法和有效疫苗。