Survival and HLA-B*57 in HIV/HCV Co-Infected Patients on Highly Active Antiretroviral Therapy (HAART).

Abstract

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-, HCV- and 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 HLA-B*57 for survival in HIV/HCV infection depending on the circumstances.

• Authors: Leona Dold, Golo Ahlenstiel, Eva Althausen, Carolin Luda, Carolynne Schwarze-Zander, Christoph Boesecke, Jan-Christian Wasmuth, Jürgen Kurt Rockstroh, Ulrich Spengler
• Journal: PloS one (PLoS One) Vol. 10 Issue 8 Pg. e0134158 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26241854 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• HLA-A Antigens
• HLA-B Antigens
• HLA-B57 antigen
• gamma-Glutamyltransferase

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Alleles
• Anti-HIV Agents (therapeutic use)
• Antiretroviral Therapy, Highly Active
• CD4 Lymphocyte Count
• Coinfection (immunology, mortality)
• Disease Progression
• Follow-Up Studies
• Gene Frequency
• Genes, MHC Class I
• Genes, MHC Class II
• Genotype
• HIV Infections (complications, drug therapy, immunology, mortality)
• HLA-A Antigens (analysis)
• HLA-B Antigens (analysis, genetics)
• Hepatitis C (complications, drug therapy, immunology, mortality)
• Humans
• Hyperbilirubinemia (etiology)
• Kaplan-Meier Estimate
• Middle Aged
• Proportional Hazards Models
• Prospective Studies
• T-Lymphocytes, Cytotoxic (immunology)
• Viral Load
• Young Adult
• gamma-Glutamyltransferase (blood)