Study of Semaglutide for Non-Alcoholic Fatty Liver Disease (NAFLD), a Metabolic Syndrome With Insulin Resistance, Increased Hepatic Lipids, and Increased Cardiovascular Disease Risk (The SLIM LIVER Study)

Inclusion Criteria: * HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load. * NOTE: The term "licensed" refers to a US Food and Drug Administration (FDA)-approved kit, which is required for all investigational new drug (IND) studies, or for sites located in countries other than the United States, a kit that has been certified or licensed by an oversight body within that country and validated internally. Non-US sites are encouraged to use US FDA-approved methods for IND studies. * WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load. * 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. One of the HIV-1 RNA values must be the screening visit value, and the other value obtained between 24 and 48 weeks prior to entry. * NOTE: All values must have been reported from a US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or at any network-approved non-US laboratory that is Virology Quality Assurance (VQA) certified. * No change in antiretroviral therapy (ART) in the 24 weeks prior to entry. * NOTE A: Modifications of ART formulation (e.g., from standard formulation to fixed dose combination or single tablet regimen) will be permitted. * NOTE B: Within-class substitutions are not permitted. * No plan to change ART for the study duration. * Within 30 days prior to pre-entry, a minimum WC measurement of ≥95 cm for individuals assigned male sex at birth or ≥94 cm for individuals assigned female sex at birth. * NOTE: For transgender study participants, sites should use the parameter that matches sex assigned at birth. * At least one of the following drawn within 30 days prior to pre-entry by any US laboratory that has a CLIA certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs: * Fasting plasma glucose 100-125 mg/dL (refer to the study protocol for a definition of fasting). * HbA1c between ≥5.7 and \<6.5% * Homeostatic model assessment of insulin resistance (HOMA-IR) \>3.0 (Refer to calculator: https://www.mdcalc.com/homa-ir-homeostatic-model-assessment-insulin-resistance) * Documentation of negative hepatitis A virus (HAV) immunoglobulin M (IgM) or HAV vaccination prior to study entry. * NOTE: If documentation is not available prior to screening, this should be obtained through routine clinical care within 30 days prior to entry. * Hepatic fat content (i.e., IHTG) ≥5%, as determined by liver magnetic resonance imaging-proton density fat fraction (MRI-PDFF) within 14 days prior to entry (and between 1-30 days after screening). * NOTE: Refer to the study protocol for more details. * CD4+ T-cell count ≥200 cells/mm\^3 within 30 days prior to pre-entry (may be from standard of care) at any US laboratory that has a CLIA certification or its equivalent, or at any network-approved non-US laboratory that is Immunology Quality Assurance (IQA) certified. * The following laboratory values obtained within 30 days prior to pre-entry by any US laboratory that has a CLIA certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with GCLP and participates in appropriate external quality assurance programs: * Absolute neutrophil count (ANC) \>750 cells/mm\^3 * Hemoglobin \>10 g/dL for individuals assigned male at birth and \>9 g/dL for individuals assigned female at birth * Creatinine clearance (CrCl) ≥50 mL/min, as calculated by the CKD-Epi equation. * NOTE: Please refer to A5371 protocol-specific web page (PSWP) for the website link to calculate CrCl using the CKD-Epi calculator. * NOTE: Calculations will be done without using cystatin C. Please refer to the A5371 Manual of Operating Procedures (MOPS) for further details. * Aspartate aminotransferase (AST) (SGOT) ≤3 x ULN on at least two measurements, with at least one within 30 days prior to pre-entry. Participants must also have no evidence of AST \>3 x ULN within the 3 months prior to entry, from routine clinical monitoring, if available. If no additional monitoring is available in the 3 months prior to entry, additional testing should be obtained within the screening interval (2-4 weeks apart) to ensure stability. * Alanine aminotransferase (ALT) (SGPT) ≤3 x ULN on at least two measurements, with at least one within 30 days prior to pre-entry. Participants must also have no evidence of ALT \>3 x ULN within the 3 months prior to entry, from routine clinical monitoring, if available. If no additional monitoring is available in the 3 months prior to entry, additional testing should be obtained within the screening interval (2-4 weeks apart) to ensure stability. * Fasting triglyceride level ≤500 mg/dL. * NOTE A: See the study protocol for a definition of fasting. * NOTE B: If level is \>500 mg/dL, level may be rechecked within the screening window. * For individuals taking daily medications with anti-inflammatory properties, including but not limited to, statins and chronic corticosteroids (inhaled corticosteroids exempt), the doses must be stable as determined by the site investigator for ≥3 months prior to study entry, and the individual should have no active plans to change dosing during the study period. * For individuals taking daily lipid-lowering medications (such as statins, fibrates, niacin, fish oil), the doses must be stable as determined by the site investigator for ≥3 months prior to study entry, and the individual should have no active plans to change dosing during the study period. * NOTE: Lipid-lowering equivalents for niacin and fish oil are ≥1 g and ≥3 g daily, respectively. * Ability and willingness of participant to provide informed consent * Willingness and ability to use auto-inject pen weekly for 24 weeks. * Willingness and ability to undergo MRI scans. * NOTE: Anxiolytics will not be provided through the study but may be provided at site expense. * For persons able to become pregnant, a negative serum or urine pregnancy test (urine test must have a sensitivity of \<25 mIU/mL) both 1) at screening (within 30 days prior to pre-entry MRI) and 2) within 3 days before or at entry (prior to registration into study) by any US clinic or laboratory that has a CLIA certification or its equivalent, or is using a point of care (POC)/ CLIA-waived test, or at any network-approved non-US laboratory or clinic that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs. * NOTE: Individuals able to become pregnant are defined as individuals who have reached menarche and who have not been post-menopausal for at least 24 consecutive months (i.e., have had menses within the preceding 24 months), and have not undergone surgical sterilization such as hysterectomy, bilateral oophorectomy, tubal ligation, or salpingectomy. * If participating in sexual activity that could lead to the participant becoming pregnant, the participant must agree to use contraception while on study drug (24 weeks) and for 2 months following the last dose of study drug. At least one of the following must be used: * Intrauterine device (IUD) * Hormone-based contraceptive * Partner sterilization (i.e., vasectomy) and is the sole partner for the participant. * NOTE: Participant self-report of partner sterilization is acceptable. * For individuals taking Vitamin E (any dose), the dose must be stable as determined by the site investigator for more than 1 year prior to entry. * Willingness to be contacted by telephone or e-mail by study staff throughout the study. Exclusion Criteria: * Known active hepatitis C virus (HCV) infection, defined as a detectable HCV RNA within 24 weeks prior to study entry. * NOTE A: Individuals with HCV RNA below the limit of quantitation for \>24 weeks prior to study entry are eligible, i.e., individuals who have been treated for hepatitis C are eligible if they have completed therapy \>24 weeks prior to study entry, and/or individuals who spontaneously cleared hepatitis C virus are eligible as long as they have had undetectable HCV RNA for \>24 weeks. HCV RNA testing is not provided by the study. * NOTE B: If HCV antibody testing has not been performed in the 5 years prior to screening and the participant does not have history of cured HCV infection, HCV antibody testing should be repeated at screening. If screening HCV antibody is positive or reactive, the individual is not eligible and should be referred for clinical evaluation through routine care. * Active/chronic hepatitis B (HBV), defined as a positive hepatitis B surface antigen (HBsAg) at screening. * NOTE A: HBsAg testing is only required at screening if HBV laboratory results are not available within the last 5 years prior to screening and individual does not have documented immunity. * NOTE B: If HBsAg positive, individual is not eligible and should be referred for clinical evaluation through routine care. * Known active severe delayed gastric emptying, as determined by the site investigator. * Gain or loss of \>5% body weight within 12 weeks prior to study entry. * NOTE: Self-report recall is acceptable. * 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. * NOTE: "Significantly" refers to intent to join a weight-loss program such as Weight Watchers, or start a specific diet (such as ketogenic or very low carbohydrate). * Known acute or chronic liver disease with cirrhosis or portal hypertension. * History of liver transplant. * Breastfeeding or plans to become pregnant. * Current diagnosis of diabetes mellitus or current use of diabetes medications, or a laboratory measurement of hemoglobin A1c ≥6.5% at screening. * NOTE: Stable use of metformin (i.e., for ≥12 weeks) for indication other than diabetes (e.g., polycystic ovarian syndrome or pre-diabetes/impaired fasting glucose) may be permitted with approval of the Clinical Management Committee (CMC). * Known retinopathy (excluding remote history of cotton wool spots). * Personal or family (first-degree relative) history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2). * Untreated, poorly controlled, or previously undiagnosed thyroid disease defined as the presence of abnormal thyroid-stimulating hormone (TSH) at screening with no clear explanation. * Unexplained hypercalcemia corrected for albumin that is \>10.5 mg/dL at screening. Please refer to the A5371 MOPS for the calculation. * 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. * NOTE: Chronic, stable hormone replacement therapy ≥3 months prior to entry in men with diagnosed hypogonadism or transgender person on masculinizing hormonal therapy is permitted. * Use of estrogens or progesterones at supraphysiologic doses within 3 months prior to study entry. * NOTE: Stable doses used for contraception, post-menopausal hormone replacement or feminizing hormone therapy for transgender persons ≥3 months prior to entry is permitted. * Known allergy/sensitivity or any hypersensitivity to components of study drug or its formulation. * Current serious illness requiring systemic treatment and/or hospitalization. * NOTE: The individual can be rescreened when they complete therapy or are clinically stable as determined by the site investigator. * 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, defined as: * Consuming ≥5 alcoholic drinks for men or consuming ≥4 alcoholic drinks for women during a single occasion (i.e., at the same time or within a couple of hours of each other), or * ≥3 drinks on 4 or more days of the week on average for men or ≥2 drinks on 4 or more days of the week on average for women. * NOTE: For transgender study participants, sites should use the parameter that matches sex assigned at birth. * Known chronic pancreatitis or more than one episode of pancreatitis ever in the past. * Inability to keep study product at 36°F to 46°F (2°C to 8°C) prior to first use, or to maintain the study product at a controlled room temperature between 59°F and 86°F (15°C to 30°C) following first use. * Intent to use any medication likely to cause significant changes in weight during the study period. * NOTE: Refer to the study protocol for a list of medications in this category. * 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. * Any condition that the site investigator believes would make the individual unsuitable for participation.