Background: Biological pathways mediating the link between intimate partner violence (IPV) and increased HIV risk remain unexplored. We hypothesized that IPV-induced stress negatively affects HIV systemic immune defenses and aimed to evaluate whether IPV was associated with immune profiles linked to HIV susceptibility: CD4 activation and diminished regulatory T-cell (Treg) frequency.
Methods: Seventy-five HIV-negative high-risk women were surveyed regarding their IPV experience. They provided blood, urine, and (if present) genital ulcer samples for cortisol, immune assays, and STI testing. Using flow cytometry, we assessed activated CD4+ T-cell (%HLA-DR+/CD38+) and Treg (%CD4+CD25+FoxP3+) frequencies and phenotyping. Nonparametric tests evaluated the association between IPV and immune outcomes. Multivariate regression explored confounding and moderation of the IPV-CD4 activation pathway.
Results: Lifetime IPV was associated with increased CD4+ activation (r = 0.331, P = 0.004), a shift in CD4+ phenotype from naïve to effector memory (r = 0.343, P = 0.003), and a decrease in naive (%HLA-DR+/CD45RA-) Treg frequency (r = -0.337, P = 0.003). Experiencing IPV over the past year had similar trends. After controlling for sexual IPV, lifetime physical and psychological abuse remained significantly associated with CD4+ activation (P = 0.004 and P = 0.033, respectively). After controlling for race (the only covariate linked to activation), the lifetime IPV-CD4 activation association remained significant (P = 0.012). Alcohol use and depression were identified as potential pathway moderators.
Conclusion: Our data is the first to suggest an immune link between IPV and HIV, and may help explain differences at the individual level in HIV susceptibility and response to biological HIV prevention strategies. The association of psychological and physical abuse with CD4 activation independent of sexual abuse further supports the existence of a stress-induced immune pathway.
Keywords: CD4-positive T-lymphocytes; HIV infections; gender-based violence; humans; intimate partner violence; lymphocyte activation; regulatory T-lymphocytes; risk; spouse abuse.