Adipose tissue (AT) disturbances are common in people living with HIV (PLWH), and changes in AT quality may occur independently of changes in AT quantity. Decreases in AT density, a marker of AT quality, suggest disrupted adipocyte function and lipid accumulation. We previously reported that subcutaneous AT (SAT) density on computed tomography (CT) reflects biopsy-quantified SAT adipocyte size in PLWH, and that AT quantity increases on antiretroviral therapy (ART). In this exploratory analysis, we assessed changes in AT density after ART initiation and associations with immuno-metabolic parameters.
ACTG A5257 randomized ART-naïve, adult PLWH to raltegravir (RAL) or ritonavir-boosted atazanavir (ATV/r) or darunavir (DRV/r), each with tenofovir disoproxil fumarate and emtricitabine, for 96 weeks. The subset with Weeks 0 and 96 (W0 and W96) abdominal CT scans and W96 HIV-1 RNA <50 copies/mL were included. Linear regression models compared W0, W96 and 96-week changes in SAT and visceral AT (VAT) density (in Hounsfield units, HU), adjusting for AT area and clinical/demographic parameters. Partial Spearman’s correlations adjusting for AT area assessed relationships between AT density and immuno-metabolic parameters.
Median age was 36 years, CD4+ T cell count 344 cells/μL and BMI 24.5 kg/m2; 89% were male and 56% non-white. W0 median SAT and VAT density were -99 and -80 HU, respectively. Over 96 weeks, SAT and VAT HU decreased in all arms (Table). In adjusted models, female sex and higher W0 HIV-1 RNA were independently associated with greater declines in AT density (women: SAT -4.8 and VAT -4.0 HU greater than men; per log10 HIV-1 RNA copies/mL: SAT -2.3 and VAT -2.7 HU). Statistically different effects of ART type were not seen (p>0.13), though variability was high. W96 SAT and VAT HU correlated (p<0.05) positively with HDL cholesterol and adiponectin levels (r=0.19 to 0.30) and negatively with IL-6, non-HDL cholesterol, triglyceride, leptin and HOMA-IR (r=-0.23 to -0.68) even after adjusting for baseline CD4+ T cell count, HIV-1 RNA and AT area.
VAT and SAT density decreased following ART initiation. Women and PLWH with higher HIV-1 RNA had greater decreases. Following virologic suppression, lower AT density was associated with greater systemic inflammation, lipid parameter disruption and insulin resistance independent of AT area. These findings suggest that changes in fat tissue during ART may have adverse health consequences.