Effects of Semaglutide in HIV-Associated Lipohypertrophy

Inclusion Criteria: 1. Male or female, aged ≥18 years. 2. HIV-1 infection as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test. 3. Body mass index ≥25 kg/m2. 4. Waist circumference and waist-to-hip ratio \>95 cm and \>0.94 cm, respectively, for men, and \>94 cm and \>0.88 cm, respectively, for women occurring in the context of HIV treatment. 5. Subjective evidence of increased abdominal girth occurring after initiation of HIV treatment. 6. HIV-1 RNA \<400 copies/mL for ≥6 months. 7. Receiving a stable antiretroviral regimen for at least the last 12 weeks prior to study entry with cumulative duration of 1 year of treatment at the time of study entry. 8. Provision of signed and dated informed consent form and is capable of reading and comprehending the informed consent. 9. Stated willingness to comply with all study procedures and availability for the duration of the study. 10. All women of child-bearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to start of study medication. WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), who is not postmenopausal (defined as amenorrhea 12 consecutive months), or is on hormone replacement therapy (HRT) with documented plasma follicle-stimulating hormone level 35 mIU/mL. Women who are using oral, implanted, or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered of child-bearing potential. 11. Female subjects who are not of reproductive potential (have reached menopause or undergone hysterectomy, bilateral oophorectomy or tubal ligation) or whose male partner has undergone successful vasectomy with resulting azoospermia or has azoospermia for any other reason, are eligible without requiring the use of contraception. Patient-reported history of menopause, sterilization, and azoospermia is considered acceptable documentation. 12. All subjects must not participate in a conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the female subject/male partner must use condoms (male or female) in addition to one of the following forms of contraception while on study: either a spermicidal agent, diaphragm, cervical cap, IUD, or hormonal-based contraception. 13. Have no plans to alter antiretroviral therapy, or to undergo any weight loss program, formal exercise training or surgery during the study period, or initiate structured/strategic antiretroviral treatment interruptions. Exclusion Criteria: 1. Known cardiovascular disease or diagnosed diabetes. If on metformin without a diabetes diagnoses metformin use has to be constant, uninterrupted for 6 months prior to entry. 2. Any active or chronic uncontrolled inflammatory condition, infection or cancer. 3. Women who are pregnant or breastfeeding. 4. Women with a positive pregnancy test on enrollment or prior to study drug administration. 5. A clinically-relevant illness within 14 days prior to study entry not explicitly excluded by the protocol, a physical or psychiatric disability, or a laboratory abnormality that might place the subject at increased risk by being exposed to the medications in this study or which might confound the interpretation of this investigation. 6. Active gastrointestinal symptom Grade \>1 within the last month. 7. Regular use of immunomodulators/agents which could impact inflammation. Regular use of NSAIDS allowed if constant, uninterrupted for 6 months and no plans to alter. Statin use must also be constant, uninterrupted for 6 months prior to study entry. Thyroid medication allowed unless diagnosed with uncontrolled thyroid disease. 8. Inability to communicate effectively with study personnel. 9. Use of megestrol acetate, testosterone, or any steroid use beyond normal amounts found in the body within 6 months of study, or intend to start. 10. Glomerular filtration rate \<50 cc/min/1.73 m2. 11. Hemoglobin \<10 g/dL. 12. Elevated lipase level \>1.5 upper limit of normal 13. AST AND ALT \>2.5x upper limit of normal. 14. Use of growth hormone or growth hormone-releasing hormone in the last year, or intent to start. 15. History of excessive alcohol use (on average 2 or more drinks a day) , pancreatitis, thyroid cancer, or a diagnosis of multiple endocrine neoplasia (MEN) syndrome type 2. 16. History of lactose intolerance or inability to consume milk products will be exclusionary for participation in the mixed-meal tolerance test portion of the study.