CD4+ T-Cell-Dependent Reduction in Hepatitis C Virus-Specific Neutralizing Antibody Responses After Coinfection With...

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Human immunodeficiency virus (HIV) infection is known to worsen hepatitis C virus (HCV) outcomes.
• Mechanisms for accelerated HCV progression in HIV-coinfected individuals are not fully understood.
• HIV-induced immune dysfunction, particularly in humoral responses, may contribute to HCV progression.

Purpose of the Study:

• To investigate the impact of HIV coinfection on the anti-HCV antibody response.
• To define how HIV affects anti-HCV envelope binding antibodies and neutralizing antibodies (nAbs).

Main Methods:

• Longitudinal serum samples from HCV-infected individuals before and after HIV infection were analyzed.
• Measurements included anti-HCV envelope binding antibody titers and neutralizing antibody (nAb) titers and breadth.
• Analysis correlated antibody responses with CD4(+) T-cell counts.

Main Results:

• A significant decrease in anti-HCV envelope binding antibody and nAb titers was observed in subjects with CD4(+) T-cell counts below 350/mm(3) after HIV infection.
• Reduced nAb breadth was noted in subjects with CD4(+) T-cell counts below 200/mm(3).
• Individuals maintaining CD4(+) T-cell counts ≥350/mm(3) showed minimal decline in antibody levels.

Conclusions:

• HIV infection leads to a global decline in the anti-HCV envelope antibody response.
• This decline encompasses binding antibody titers, nAb titers, and nAb breadth.
• CD4(+) T-cell depletion by HIV is the primary driver of this impaired humoral immunity against HCV.