Survival and HLA-B∗57 in HIV/HCV co-infected patients on highly active antiretroviral therapy (HAART)

Background and aims: HLA class I alleles, in particular HLA-B∗57, constitute the most consistent host factor determining outcomes in untreated HCV- and HIV-infection. In this prospective cohort study, we analysed the impact of HLA class I alleles on all-cause mortality in patients with HIV-, HCVand HIV/HCV-co-infection receiving HAART. Methods: In 2003 HLA-A and B alleles were determined and patients were prospectively followed in 3-month intervals until 2013 or death. HLA-A and B alleles were determined by strand-specific oligonucleotide hybridisation and PCR in 468 Caucasian patients with HCV-(n=120), HIV-(n=186) and HIV/HCV-infection (n=162). All patients with HIV-infection were on HAART. In each patient group, HLA class I-associated survival was analysed by Kaplan-Meier method and Cox regression analysis. Results: At recruitment the proportion of patients carrying a HLA-B∗57 allele differed between HIV-(12.9%) and HCV-infection (4.2%). Kaplan Meier analysis revealed significantly increased mortality in HLA-B∗57-positive patients with HIV-infection (p=0.032) and HIV/HCV-co-infection (p=0.004), which was apparently linked to non-viral infections. Cox logistic regression analysis confirmed HLA-B∗57 (p=0.001), serum gamma-glutamyltranspeptidase (p=0.003), serum bilirubin (p=0.022) and CD4 counts (p=0.041) as independent predictors of death in HIV-infected patients. Conclusion: Differences in the prevalence of HLA-B∗57 at study entry between HIV- and HCV-infected patients may reflect immune selection in the absence of antiviral therapy. When patients were treated with HAART, however, HLA-B∗57 was associated with increased mortality and risk to die from bacterial infections and sepsis, suggesting an ambiguous role of HLAB∗ 57 for survival in HIV/HCV infection depending on the circumstances.