 |
|
|
| |
HIV Immune Dysregulation Predicts Lean Tissue &
Fat Changes During Chronic Disease
|
| |
| |
Reported by Jules Levin
CROI 2018 March 4-7 Boston MA
Louie Mar A. Gangcuangco, Dominic C. Chow, Scott A. Souza, Glen M. Chew, Brooks I. Mitchell, Michelle L D'Antoni, Jason T. Huynh, LishomwaC. Ndhlovu, and Cecilia M. Shikuma
University of Hawaii, Honolulu, Hawaii, USA
Program abstract:
Changes in body composition such as fat accumulation and lean tissue loss may impact physical function and mortality. We investigated the association between various HIV-associated immune parameters and 2-year body composition changes assessed by dual-energy x-ray absorptiometry (DXA) among HIV patients on stable ART.
Longitudinal analysis of HIV+ individuals ≥40 years old on stable ART ≥3 months in the Hawaii Aging with HIV cohort. Multiparametric flow cytometry was performed on cryopreserved year 1 peripheral blood mononuclear cells to quantitate the percentages of monocyte (MO) phenotypes, and T cells expressing activation (HLA-DR/CD38) and exhaustion markers (PD-1/TIM-3/TIGIT). Select plasma soluble biomarkers were measured by Luminex technology. Among subjects not on zidovudine and stavudine, multivariate linear regression analyses were performed to assess the association between T cell subsets with DXA changes.
Of 97 subjects, median age at enrollment was 52 (48, 57) years, BMI 26.5 kg/m2, CD4 count 502 cells/uL, and nadir CD4 count 150 cells/uL. Majority were males (87.6%), Caucasian (56.7%), and 82.5% had undetectable HIV RNA < 50 copies/mL. Median (Q1, Q3) body composition changes: total fat 10.0 (-86.5, 11.4) mg/m2, peripheral fat 10.0 (-29.7, 46.7) mg/m2, truncal fat 10.0 (-48.1, 62.3) mg/m2, and lean tissue -33.0 (-86.8, 23.7) mg/m2. Multivariable linear regression adjusted for age, gender, and undetectable plasma HIV RNA showed that percent lean tissue change [(year3-year1)/year1] was associated with IL-10 (β=0.24, p=0.04), sE-selectin (β=-0.31, p=0.008), percentage of the inflammatory intermediate (CD14+CD16+) MO (β=-0.24, p=0.04), and TIGIT+TIM-3+ CD8+ T cell (β=-0.52, p=0.03). Total fat change was associated with TIGIT+ CD4+ T cell (β=-0.58, p=0.01), PD-1+ CD4+ T cell (β=-0.46, p=0.04), and TIGIT+PD-1+ CD4+ T cell (β=-0.61, p=0.008). Peripheral fat change was associated with TIGIT+ CD4+ T cell (β=-0.61, p=0.007), PD-1+ CD4+ T cell (β=-0.54, p=0.01), and TIGIT+PD-1+ CD4+ T cell (β=-0.67, p=0.004). Truncal fat change was associated with TIGIT+ CD4+ T cell (β=-0.56, p=0.02) and TIGIT+PD-1+ CD4+ T cell (β=-0.58, p=0.01).
Over two years, modest changes in body composition was seen in our patients with chronic HIV. HIV-associated immune dysregulation, including higher T cell exhaustion, higher intermediate MO subset levels as well as a pro-inflammatory cytokine profile were associated with lean tissue and fat loss.
|
| |
|
|
|
|
|
