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 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 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 assuranc