Human leukocyte antigen B*57 does not fully explain hepatitis C clearance in HIV controllers

Area of Science:

• Immunogenetics
• Virology
• Hepatology

Background:

• HIV controllers exhibit higher rates of spontaneous hepatitis C virus (HCV) clearance.
• Understanding the genetic factors influencing HCV clearance in HIV-positive individuals is crucial for developing effective treatments and vaccines.

Purpose of the Study:

• To investigate the role of human leukocyte antigen (HLA) B*57 and other genetic polymorphisms in spontaneous HCV clearance among HIV controllers.
• To compare HCV clearance rates between HIV controllers and non-controllers.

Main Methods:

• Prospective cohort study involving 279 HIV/HCV seropositive individuals from the Study of the Consequences of Protease Inhibitor Era (SCOPE).
• HCV infection status was determined using enzyme immunoassay (EIA3) and HCV RNA transcription-mediated amplification.
• Multivariable Poisson regression models were used to analyze predictors of HCV clearance, adjusting for relevant covariates.

Main Results:

• HIV controllers were significantly more likely to possess HLA B*57 compared to non-controllers (33% vs. 10%, P < 0.01).
• HCV clearance was significantly more probable in HIV controllers (Adjusted Prevalence Ratio [APR] 1.78; P = 0.03), independent of HLA B*57, IL28B genotype, age, sex, and race/ethnicity.
• The IL28B CC genotype was independently associated with spontaneous HCV clearance (APR 2.76; P < 0.001), but HLA B*57 did not account for the higher clearance rates in HIV controllers.

Conclusions:

• While HLA B*57 is more prevalent in HIV controllers, it does not explain their enhanced capacity for HCV clearance.
• The IL28B CC genotype is a significant independent predictor of spontaneous HCV clearance.
• Further research into host genetic and immunologic factors controlling HIV and HCV is warranted for developing novel therapeutic and prophylactic strategies against both viruses.