(P06-21-26) Inflammatory and Metabolic Biomarker Changes in Relation to Body Composition Following INSTI Initiation Among Women With HIV

Objectives: Integrase strand transfer inhibitor (INSTI) based antiretroviral therapy (ART) is associated with weight gain in some women with human immunodeficiency virus (HIV; WWH). We hypothesized that anthropometric changes after INSTI initiation would be differentially associated with serum inflammatory and metabolic biomarker changes compared with women on non-INSTI ART and to women without HIV (WWOH).

Methods: We analyzed longitudinal data (2007–2020) from 195 women enrolled in the MACS/WIHS Combined Cohort Study, including virally suppressed WWH ( < 200 copies/mL) who initiated an INSTI, WWH on non-INSTI ART, and WWOH. Biomarkers such as adiponectin (Acrp30), high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, soluble CD14, soluble CD163, retinol-binding protein 4 (RBP4), fatty acid–binding protein 4 (FABP4), and chemerin were measured 6-12 months before and 1-2 years after INSTI initiation, and at comparable timepoints among controls. Absolute change was calculated for weight, waist, hip, and arm circumferences, waist-to-hip ratio (WHR), and biomarker levels. General linear models assessed associations between anthropometric and biomarker changes, including interaction terms for study group, adjusting for baseline age and body mass index (BMI).

Results: Participants mean age was 46 years, mean BMI 32 kg/m², and 70% were Black. Acrp30 (µg/mL) (β = −0.10; p = 0.0063) and RBP4 (ng/mL) (β = −636.40; p = 0.0002) were significantly associated with weight decrease, whereas sCD163 (ng/mL) (β = 9.71;

p = 0.0001) was associated with weight increase. INSTI-specific associations were observed for sCD14 (ng/mL) in relation to regional adiposity (n = 83), including stronger relationships with waist change (β = −69.28; p = 0.034) and hip change (β = −85.23; p = 0.0006). FABP4 (ng/mL) also demonstrated INSTI-specific associations with hip change (β = −3.61; p = 0.031), WHR change (β = 345.71;p = 0.025), and arm change (β = −8.83; p = 0.0033).

Conclusions: INSTI initiation is associated with distinct inflammatory, metabolic, and body compositional changes. Associations of sCD14 and FABP4 with regional adiposity suggest immune and adipocyte mechanisms may contribute to INSTI-related weight gain in WWH. Larger cohorts are needed to validate these associations and explore strategies to mitigate metabolic risk.

Funding Sources: No external funding