S2080 Antiretroviral Therapy Enhances the Cardioprotective Benefit of GLP-1 Receptor Agonists in People With HIV

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) provide cardiovascular protection in individuals with type 2 diabetes (T2DM) and obesity. However, their benefit in people with HIV (PWH)—a population at elevated cardiovascular risk—remains understudied. Moreover, whether antiretroviral therapy (ART) modifies this cardioprotective association is unclear. We evaluated the association between GLP-1 RA use and major adverse cardiovascular events (MACE) in PWH and tested for interaction by ART exposure. Methods: We analyzed data from the All of Us Research Program (2016–2022), a nationwide EHR-based cohort, to identify adults (≥18 years) living with HIV and without prior MACE. Eligible participants had T2DM and/or obesity and ≥3 months of GLP-1 RA use. We excluded individuals with pancreatitis, chronic kidney disease (CKD) stage 3–5, or personal/family history of multiple endocrine neoplasia. ART use was defined as ≥3 months of continuous exposure. The primary outcome was new-onset MACE, including myocardial infarction, stroke, or cardiovascular death. Propensity score matching (2:1 nearest-neighbor; caliper 0.1) was performed on age, gender, race/ethnicity, and income. Adjusted logistic regression estimated odds of MACE, controlling for CKD, hypertension, hyperlipidemia, metabolic dysfunction-associated steatotic liver disease, smoking, CD4 count, and body mass index. Interaction by ART was tested, and models were stratified by ART status. Results: Among 2,712 eligible PWH, 14.7% (n = 398) used GLP-1 RAs. The matched cohort included 1,194 individuals (398 users; 796 non-users); mean age was 58.9 ± 10.6 years, 40% were women, 48% Black, and 25% Hispanic. During follow-up, 130 MACE events occurred. GLP-1 use was associated with 87% lower odds of MACE (adjusted odds ratio [aOR]: 0.13; 95% confidence interval [CI]: 0.03–0.39; P = 0.001). A significant interaction was observed between GLP-1 use and ART (P = 0.020). In stratified models, GLP-1 RA use remained protective among ART users (aOR: 0.28; 95% CI: 0.15–0.48; P< 0.001) but was attenuated and nonsignificant among non-ART users (aOR: 0.42; 95% CI: 0.15–1.04; P = 0.080). Among ART users, CKD (aOR: 1.70; 95% CI: 1.06–2.71; P = 0.026) and hyperlipidemia (aOR: 5.04; 95% CI: 2.72–10.2; P < 0.001) were also associated with MACE. Conclusion: GLP-1 RA use was associated with significantly lower cardiovascular risk among PWH with T2DM and/or obesity, particularly in those receiving ART. These findings suggest that ART may enhance the cardioprotective effects of GLP-1 RAs and highlight the importance of integrated HIV-metabolic care to reduce cardiovascular risk.