Weight and mortality in people living with HIV and heart failure: Obesity paradox in the era of glucagon‐like peptide 1 (GLP‐1) receptor agonists and sodium‐glucose cotransporter‐2 (SGLT‐2) inhibitors

Abstract Background Obesity is a recognized risk factor for heart failure (HF) in people living with HIV. However, among patients with HF, being overweight or having mild to moderate obesity has been associated with significantly improved survival rates compared with those at normal weight—a phenomenon known as the obesity paradox. This paradox has not yet been evaluated in patients with both HIV and HF in the era of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2is). Our study aimed to assess the mortality risk associated with body mass index (BMI) in patients with both HIV and HF and evaluate the impact of GLP‐1 RAs and SGLT‐2is on mortality across different weight categories. Method This study analyzed data from the New York City Health + Hospitals Corporation (NYC HHC) cohort (NYC 4H), which included records from 11 major New York City Health + Hospitals facilities. The dataset combined retrospective baseline data with ongoing prospective follow‐up. The cohort consisted of adults with confirmed HIV and HF who had inpatient or clinic visits between July 2017 and June 2022. HIV infection and HF were initially identified using relevant International Classification of Diseases and Related Health Problems, 10th Revision codes and were further confirmed through laboratory results and echocardiograms. Medication data were verified through electronic health records and cross‐referenced with pharmacy records. The primary outcome was the hazard ratio (HR) of overall mortality across different BMI categories in patients with both HIV and HF, assessed using proportional hazard regression models adjusted for age, sex, race, comorbidities, smoking status, and functional status. Secondary analyses included re‐hospitalization within 6 months of discharge and the association between GLP‐1 RAs/SGLT‐2is and overall mortality in patients with HIV and HF. Additional analyses were conducted to assess the efficacy of these medications within different BMI categories. Results A total of 1044 patients were analyzed, including 657 males (62.9%) and 387 females (37.1%), with an average age of 61.6 years at baseline and an average follow‐up of 3.8 years. A low BMI (<18.5) was associated with a 57% increase in mortality (HR 1.57; 95% confidence interval [CI] 1.03–2.39; p = 0.04), whereas class I obesity (BMI 30.0–35.9) was associated with a 35% reduction in mortality (HR 0.65; 95% CI 0.42–0.99; p = 0.04) compared with normal BMI, after adjusting for covariates. Class II obesity was associated with a lower rate of re‐hospitalization within 6 months of discharge. No significant differences were observed in cardiovascular mortality across different BMI categories. The use of GLP‐1 RAs was associated with a 46% reduction in overall mortality risk (HR 0.54; 95% CI 0.30–0.97; p = 0.04), and SGLT‐2is were associated with a 77% reduction in overall mortality risk (HR 0.23; 95% CI 0.11–0.46; p < 0.001) after adjusting for BMI and comorbidities. For both medications, the greatest mortality benefit was observed in patients with the highest BMI categories. Conclusion Our study found that overall mortality was higher among underweight individuals with both HIV and HF. Among patients with both conditions, GLP‐1 RAs and SGLT‐2is significantly reduced mortality, with the greatest survival benefit observed in users within the highest BMI categories.