Tesamorelin as an Adjunct to Exercise for Improving Physical Function in HIV

Inclusion Criteria: 1. Men and women, 50-80 years old 2. Documented HIV infection on suppressive antiretroviral therapy for at least 1 year with HIV-1 RNA \<200 copies/mL and CD4+ T cell count \>200/µL 3 3. Sedentary lifestyle, defined as self-reported physical activity that breaks a sweat \<3 days/week with no regular resistance exercise in the past 3 months 4. ≥1 Fried frailty criterion (weakness, slow gait speed, exhaustion, decreased physical activity, or unintentional weight loss as defined by specific thresholds) 5. Excess abdominal adiposity as indicated by at least one of the following elevated anthropometric measures assessed at Screen: (1) waist circumference ≥102 cm in non-Asian males (≥90 cm in Asian males) or ≥88 cm in non-Asian females (≥80 cm in Asian females); (2) waist-to-hip ratio ≥0.9 in males or ≥0.85 in females; (3) waist-to-height ratio ≥0.5 in males and females 6. Normal mammogram within 2 years (females ≤74 years old) or prostate specific antigen \<4 ng/mL (males ≤70 years old) per U.S. Preventive Services Task Force (USPSTF) age-appropriate cancer screening guidelines 7. For females, postmenopausal defined as no menses for ≥12 months and anti-müllerian hormone (AMH) \<20 pg/mL or history of bilateral oophorectomy at least 3 months ago 8. Provider approval to participate Exclusion Criteria: 1. Use of tesamorelin or other growth hormone (GH)-based therapy within 6 months 2. Insulin-like growth factor 1 (IGF-1) z-score \>2.0 3. HbA1c \>8% 4. Active or suspected malignancy (with the exception of non-melanoma skin cancer) within 24 months 5. Supraphysiologic testosterone or corticosteroid exposure, or change in exogenous testosterone or corticosteroid dose within 3 months 6. Change in glucose-lowering medication (e.g., glucagon-like peptide-1 receptor agonists) within 3 months 7. Active or unstable coronary artery disease, chest pain suspicious for angina, or serious arrythmia 8. History of hypopituitarism, head irradiation, or other conditions known to affect the GH/IGF-1 axis 9. Known hypersensitivity to tesamorelin or mannitol 10. Acute or chronic illness judged by the investigator to represent a contraindication to study participation