Persistent Low Anti-HIV Neutralizing Antibody Titers in HIV/HCV Coinfection Despite HCV Cure: A 5-Year Longitudinal Analysis

Abstract

Background: Anti-HIV neutralizing antibodies (anti-HIV-nAbs) play a critical role in the immune defense against HIV by preventing viral entry and limiting replication. This study longitudinally evaluated the titers and variability of anti-HIV-nAbs in individuals coinfected with HIV and HCV. Samples were collected at three time points: before starting HCV treatment, one year after completion, and five years post-treatment. Methods: A retrospective analysis was conducted on 71 HIV/HCV-coinfected patients who achieved a sustained virologic response following antiviral therapy for HCV. A control group of 41 HIV-monoinfected individuals was also included. Anti-HIV-nAb titers were evaluated by HIV neutralization assays using a panel of six recombinant HIV viruses representing multiple genetic subtypes. Generalized Linear Mixed Models and Generalized Linear Models were used for statistical analysis. p-values were adjusted using the Benjamini-Hochberg procedure (q-value). Results: HIV-neutralizing antibody responses in HIV/HCV-coinfected individuals remained stable over five years following HCV therapy without significant changes (q-value > 0.05). The mean neutralization scores remained stable, with baseline scores of 6.1 (95% CI: 5.4-6.7), 6.2 (95% CI: 5.5-6.8) at one year post-HCV therapy, and 6.0 (95% CI: 5.3-6.7) at five years post-HCV therapy. HIV/HCV-coinfected individuals consistently showed lower neutralization scores compared to the control group throughout the follow-up (q-value < 0.05). Regression analyses adjusted for age, gender, nadir CD4⁺, and baseline CD4⁺ counts confirmed that the observed differences between HIV-monoinfected and HIV/HCV-coinfected individuals persisted (q-value < 0.05) at both the baseline and after HCV therapy completion. Conclusions: Successful HCV eradication in HIV/HCV-coinfected individuals did not normalize anti-HIV-nAb titers, which remained consistently lower than those in HIV-monoinfected controls over five years.

Keywords: HCV cure; HIV; HIV neutralizing antibodies; HIV/HCV-coinfection; humoral immunity.

Figure 1

Comparison of the neutralization scores for antibody responses against HIV in HIV/HCV-coinfected individuals. Abbreviations: EOT = end-of-treatment; Yr = year.

Figure 2

Comparison of the neutralization scores for antibody responses against HIV in HIV/HCV-coinfected individuals stratified by variables related to HIV/HCV coinfection: (A) HCV therapy (IFN-based therapy vs. IFN-free therapy); (B) LSM (≤20 kPa vs. >20 kPa); (C) HCV-RNA (≤850,000 IU/mL vs. >850,000 IU/mL); (D) HCV Gt1 (Non-HCV Gt1 vs. HCV Gt1); (E) Nadir CD4+ (≤200 cells/mm³ vs. >200 cells/mm³); (F) Baseline CD4+ (≤500 cells/mm³ vs. >500 cells/mm³). Abbreviations: EOT = end-of-treatment; Yr = year; HIV = Human Immunodeficiency Virus; HCV = Hepatitis C Virus; IFN = Interferon; HCV-RNA = Hepatitis C Virus Ribonucleic Acid.