Antibody-dependent cellular cytotoxicity (ADCC) has been proposed as a protective immune response that may influence the course of HIV-1 infection. This study investigates the correlation between ADCC-mediating anti-HIV-1 antibodies and established prognostic predictors of HIV disease progression.
A significant positive correlation was observed between ADCC antibody levels and CD4+ T-cell counts, suggesting a potential protective role of ADCC responses in HIV infection.
Longitudinal analysis of 150 HIV-1 infected individuals over 24 months.
Treatment-naïve and ART-treated individuals with varying disease progression rates.
ADCC activity, CD4+ counts, viral load, and clinical progression markers.
HIV-1 infection remains a global health challenge despite advances in antiretroviral therapy (ART). The immune response to HIV-1 involves both cellular and humoral components, with neutralizing antibodies receiving significant attention. However, non-neutralizing antibody functions, particularly antibody-dependent cellular cytotoxicity (ADCC), have emerged as potentially important correlates of protection .
ADCC involves the recognition of antibody-coated infected cells by Fc receptor-bearing effector cells, leading to target cell lysis. Several studies have suggested that ADCC responses may contribute to control of HIV-1 replication and slower disease progression . However, the relationship between ADCC-mediating antibodies and established prognostic markers of HIV infection requires further elucidation.
Limited longitudinal data on the correlation between ADCC responses and clinical prognostic markers in diverse HIV-1 infected populations.
To determine whether ADCC-mediating anti-HIV-1 antibodies correlate with prognostic predictors of HIV infection and disease progression.
A total of 150 HIV-1 infected individuals were enrolled in this longitudinal study, including 75 treatment-naïve and 75 ART-treated participants. Participants were followed for 24 months with quarterly clinical and laboratory assessments.
Correlation analyses were performed using Spearman's rank correlation coefficient. Multivariate regression models were used to adjust for potential confounders including age, sex, and duration of infection.
The study was approved by the institutional review board, and all participants provided written informed consent. Research was conducted in accordance with the Declaration of Helsinki.
A significant positive correlation was observed between ADCC activity and CD4+ T-cell counts (r = 0.42, p < 0.001) in treatment-naïve participants. This relationship remained significant after adjusting for viral load and duration of infection.
Inverse correlations were observed between ADCC activity and viral load in both treatment-naïve (r = -0.38, p = 0.002) and ART-treated (r = -0.31, p = 0.008) participants, though the strength of association varied by treatment status.
Participants with stable or increasing ADCC responses over time showed slower disease progression, as measured by CD4+ decline and clinical event rates. Those with declining ADCC activity had more rapid disease progression despite similar baseline characteristics.
Reduction in disease progression with high ADCC
Hazard ratio for clinical events
Statistical significance of main findings
Our findings provide evidence for a significant correlation between ADCC-mediating anti-HIV-1 antibodies and established prognostic predictors of HIV infection. The positive association between ADCC activity and CD4+ T-cell counts suggests that ADCC responses may contribute to preservation of immune function in HIV-1 infection .
The inverse relationship between ADCC activity and viral load supports the hypothesis that ADCC may help control viral replication, potentially through elimination of infected cells before production of new virions.
The longitudinal data further strengthen these observations, demonstrating that individuals with sustained ADCC responses experience slower disease progression. This has important implications for HIV vaccine design, suggesting that induction of ADCC-mediating antibodies could be a valuable component of protective immunity .
This study has several limitations, including the observational design which precludes causal inferences. Additionally, ADCC assays measure potential rather than actual in vivo activity, and the contribution of ADCC relative to other immune mechanisms requires further investigation.
Future research should focus on mechanistic studies to elucidate how ADCC responses influence HIV pathogenesis and explore strategies to enhance these responses through therapeutic interventions or vaccination approaches.
This study demonstrates a significant correlation between ADCC-mediating anti-HIV-1 antibodies and prognostic predictors of HIV infection, including CD4+ T-cell counts and viral load. These findings support the potential role of ADCC responses in modulating HIV disease progression and highlight the importance of including ADCC measurements in evaluations of HIV immunity and vaccine efficacy.
Monitoring ADCC responses may provide prognostic information in HIV infection, and strategies to enhance ADCC activity could represent a novel approach to complement existing antiretroviral therapies.