The SLIM LIVER Study (SLIM LIVER)

Inclusion Criteria: Two separate reports of HIV-1 RNA measurements <50 copies/mL, and no HIV-1 RNA measurement >500 copies/mL, during the 48 weeks prior to entry. No change in ART in 24 weeks prior to entry or plans to change during study. Not meeting criteria for diabetes but with central adiposity (i.e., minimum waist circumference of ≥95 cm for individuals assigned male sex at birth or ≥94 cm for individuals assigned female sex at birth), ≥5% IHTG content, plus at least one of the following indicators of insulin resistance or pre-diabetes: fasting plasma glucose 100-125 mg/dL, HbA1c between 5.7% and <6.5%, or HOMA-IR >3.0. Documented evidence of immunity to hepatitis A virus (HAV) or documented history of HAV vaccination within 30 days prior to entry. CD4+ T-cell count ≥200 cells/mm3 within 30 days prior to pre-entry. The following laboratory values obtained within 30 days prior to pre-entry: Absolute neutrophil count (ANC) >750 cells/mm3. Hemoglobin >10 g/dL for individuals assigned male sex at birth and >9 g/dL for individuals assigned female sex at birth. Creatinine clearance (CrCl) ≥50 mL/min, as calculated by the CKD-Epi equation. Aspartate aminotransferase (AST) (SGOT) ≤3 x ULN on at least two measures. Alanine aminotransferase (ALT) (SGPT) ≤3 x ULN on at least two measures. Fasting triglyceride level ≤500 mg/dL. For individuals prescribed daily medications with anti-inflammatory properties, the doses must be stable. For individuals taking daily lipid-lowering medications, the doses must be stable. Agree to use contraception if able to become pregnant. For individuals taking vitamin E (any dose), the dose must be stable. Exclusion Criteria: Pregnant, breastfeeding, or plans to become pregnant. Known active hepatitis C virus (HCV) infection. Active/chronic hepatitis B virus (HBV). Known retinopathy (excluding remote history of cotton wool spots). Known active severe delayed gastric emptying. Gain or loss of >5% body weight within 12 weeks prior to study entry. Any plans to change diet or exercise regimen significantly, except for the adoption of study-provided suggestions for diet and exercise, within the study period. Known acute or chronic liver disease with cirrhosis or portal hypertension. History of liver transplant. Current diagnosis of diabetes mellitus or current use of diabetes medications, or a laboratory measurement of hemoglobin A1c ≥6.5% at screening. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2). History of unexplained hypercalcemia corrected for albumin that is >10.5 mg/dL. Use of any immunomodulatory (including prednisone equivalent of ≥10 mg), HIV vaccine, investigational therapy, or TNF-α therapy within 3 months prior to study entry. Use of human growth hormone, tesamorelin, supraphysiologic testosterone to achieve therapeutic blood levels, or any use of other anabolic steroids within 3 months prior to study entry or plans to start these while on study. Use of estrogens or progesterones at supraphysiologic doses within 3 months prior to study entry. Known allergy/sensitivity or any hypersensitivity to components of study drug or its formulation. Current serious illness requiring systemic treatment and/or hospitalization. Use of GLP-1 agonists within 24 weeks prior to study entry. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements. Excessive consumption of alcohol of ≥3 months within 90 days prior to screening. Known chronic pancreatitis or more than one episode of pancreatitis ever in the past. Intent to use any medication likely to cause significant changes in weight during the study period. Use of stavudine within 12 months prior to study entry. Prior bariatric surgery (e.g., lap band, gastric sleeve, or Roux-en-Y bypass surgery) or major gastric surgery or plans to undergo weight reduction surgery while on study. Individuals with any metal, implantable devices (e.g., pacemakers, prosthetics), or shrapnel, per standard MRI exclusion criteria.