Higher Body Mass Index Is Associated with Greater Proportions of Effector CD8⁺ T Cells Expressing CD57 in Women Living with HIV

Background: A low proportion of CD28^- CD8⁺ T cells that express CD57 is associated with increased mortality in HIV infection. The effect of increasing body mass index (BMI) changes in the proportion of CD57⁺ CD28^- CD8⁺ T cells among HIV-infected individuals on antiretroviral therapy is unknown. Setting: In a US cohort of HIV-infected women, we evaluated associations of BMI and waist circumference with 3 distinct CD8⁺ T cell phenotypes: % CD28^- CD57⁺ CD8⁺ T cells, % CD57⁺ of CD28^- CD8⁺ T cells, and % CD28^- of all CD8⁺ T cells. Methods: Multivariable linear regression analysis was used to estimate beta coefficients for each of 3 T-cell phenotypes. Covariates included HIV parameters (current and nadir CD4, current viral load), demographics (age, race, income, and study site), and lifestyle (tobacco and alcohol use) factors. Results: Of 225 participants, the median age was 46 years and 50% were obese (BMI >30 m²/kg). Greater BMI and waist circumference were both associated with higher % CD28^- CD57⁺ CD8⁺ T cells and % CD57⁺ of all CD28^- CD8⁺ T cells in multivariable analysis, including adjustment for HIV viral load (all P < 0.05). The association between greater BMI and the overall proportion of CD28^- CD8⁺ cells in fully adjusted models (0.078, 95% confidence interval: -0.053 to 0.209) was not significant. Conclusions: In this analysis, greater BMI and waist circumference are associated with greater expression of CD57 on CD28^- CD8⁺ T cells and a greater proportion of CD57⁺ CD28^- CD8⁺ T cells. These findings may indicate that increasing BMI is immunologically protective in HIV-infected women. Future research is needed to understand the prognostic importance of these associations on clinical outcomes.