Sex Differences in the Association of Fat and Inflammation Among People with Treated HIV Infection

Introduction: Ectopic fat deposition may contribute to chronic inflammation in people with HIV (PWH). To provide information for future mechanistic studies of metabolic risk in this population, we sought to determine which fat measures relate more strongly to inflammation and whether the fat-inflammation relationship is modified by sex or HIV status.

Methods: We conducted a cross-sectional study of 105 PWH and 20 age- and sex-matched HIV-negative controls. Interleukin-6 (IL-6) and high-sensitivity C reactive protein (hs-CRP) levels were measured from plasma. Pericardial fat (PCF) and thoracic periaortic adipose tissue (TAT) volumes and peri-right coronary artery (RCA), left atrium (LA) roof, and liver densities were measured from cardiac CT scans. Unadjusted and multivariate adjusted linear regression models were used to determine the relationship between ectopic fat measures and inflammation biomarkers.

Results: Forty participants had BMI < 25, 33 had BMI 25 to 30, and 52 had BMI > 30. Systolic blood pressure and insulin resistance increased with BMI. Participants with higher BMI had a higher CD4+ count. In models adjusted for demographics, HIV status, and metabolic risk factors, BMI was positively associated with IL-6 and hs-CRP. Ectopic PCF and TAT volumes were positively associated with IL-6 and hs-CRP; however, these relationships were somewhat attenuated in adjusted models. LA roof (but not peri-RCA) fat radiodensity was inversely associated with hs-CRP in fully adjusted models, and the association with IL-6 was borderline statistically signifi-cant ( = 0.054). IL-6 was more strongly associated with BMI and LA roof density in women than in men ( for interaction = 0.05).

Conclusions: Among PWH receiving antiretroviral therapy, higher BMI and excessive ectopic fat burden were associated with circulating markers of systemic inflammation. Because these measures appear to be more strongly related to inflammation among women than men, future clinical studies of metabolic risk and inflammation among PWH should include sex-stratified analyses.