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

Abstract

Introduction: Ectopic fat deposition may contribute to chronic inflammation in people with HIV (PWH). To inform 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 subjects had BMI <25, 33 had BMI 25-30, and 52 had BMI >30. Systolic blood pressure and insulin resistance increased with BMI. Subjects with higher BMI had 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 significant. IL-6 was more strongly associated with BMI and LA roof density in women than in men (p for interaction=0.05).Conclusions: Among PWH on antiretroviral therapy, higher BMI and excessive visceral fat burden were associated with circulating markers of systemic inflammation, and this relationship appears to be stronger in women compared to men.

A Meta‐Analysis of Different Types of Cardiac Adipose Tissue in HIV Patients

“…Meanwhile, EAT is associated with CVD risk in HIV patients, independent of traditional CVD risk factors [ 44 ]. The clinicians could measure EAT to identify the phenotype of adiposopathy (i.e., “sick fat”) among treated patients with HIV infection; then, targeting these patients with lifestyle interventions and metabolic therapies may reduce the levels of chronic inflammation and immune activation that are thought to contribute to a wide range of HIV chronic comorbidities such as CVD [ 30 ].…”

Sex Differences in Non-AIDS Comorbidities Among People With Human Immunodeficiency Virus

“…Women vs men may be at heightened risk of inflammatory consequences associated with metabolically unhealthy fat including HIV-related adipocyte hypertrophy [ 76 , 77 ] and ectopic fat accumulation [ 78 , 79 ]. A cross-sectional study of PWH and age-/sex-matched HIV-negative persons found that HIV did not significantly modify the association of chronic inflammatory markers and ectopic adipose tissue; however, there was a statistically significant sex difference in correlations between interleukin 6 (IL-6) and BMI [ 80 ] ( Table 4 ).…”

Cardiac adiposity as a modulator of cardiovascular disease in HIV

“…Increased EAT volume, is associated with HIV infection, ART duration, and subclinical coronary atherosclerosis. Specifically, cardiac ectopic fat burden in PLWH appears to be correlated with HIV infection and ART, independently of traditional risk factors [28‐32,37]. A clear association between EAT volume and CD4 T‐cell count was first reported in two studies conducted by Guaraldi et al and Zona et al [28,29].…”

“…Inflammation and immune markers were significantly related to PAT volume and/or density, while their changes over 96 weeks were weakly but positively associated with PAT volume/density. Subsequently, the same group found that left atrium roof density was more strongly associated with systemic inflammation than peri‐right coronary artery fat in PLWH, highlighting that there may be regional vascularity differences in the association of PAT with the adiposopathy phenotype [37]. Interestingly, the fat‐inflammation relationship was stronger for women than for men, but did not differ by HIV status, indicating that future clinical studies of metabolic risk and inflammation among PLWH should include sex‐stratified analyses.…”