Evaluation of Semaglutide for Weight Reduction in Patients with HIV and Obesity: A Randomized, Controlled, Open-Label Trial

The primary objective of this study is to assess the efficacy of **GLP-1 analogue** therapy, specifically subcutaneous semaglutide, as an adjunct to diet and exercise in achieving greater weight loss in people living with HIV and obesity (PLWHO) compared to diet and exercise alone. This is clinically relevant as obesity is a significant comorbidity in individuals with HIV, potentially exacerbating health complications and impacting the effectiveness of antiretroviral therapy.

Secondary objectives include exploring the effect of GLP-1 analogue therapy on markers of inflammation, immune function, and HIV viral reservoirs in PLWHO. Additionally, the study aims to investigate the impact on markers of glucose and lipid metabolism, as well as gut microbial translocation. Furthermore, the safety of semaglutide therapy in PLWHO on stable antiretroviral therapy (ART) will be assessed. These secondary objectives are crucial for understanding the broader metabolic and immunological effects of semaglutide in this population, which may inform future therapeutic strategies.

The clinical trial involves participants living with **HIV** and **obesity**, aiming to evaluate the efficacy of GLP-1 analogue therapy as an adjunct to diet and exercise. The study population includes both male and female subjects, aged 18 years and older. Participants are required to be HIV-1 antibody positive, on stable antiretroviral therapy for at least two years, and have a CD4 count of at least 200 cells/mm³ for a minimum of one year. Additionally, participants must have a body mass index (BMI) of 30 kg/m² or higher, or a BMI of 27 kg/m² with associated conditions such as hypertension, dyslipidemia, or type 2 diabetes mellitus. The trial population was selected based on these criteria, and participants are expected to adhere to a regimen of diet and exercise. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed as a **randomized**, controlled, parallel group, open-label study to evaluate the impact of treatment with the GLP-1 analogue **semaglutide** on weight loss in individuals living with **HIV** and **obesity**. The trial aims to assess the efficacy of semaglutide, administered as a subcutaneous injection, as an adjunct to diet and exercise compared to diet and exercise alone. The study will involve participants who meet specific inclusion criteria, such as being over 18 years old, having a confirmed HIV-1 antibody positive status, and maintaining a stable antiretroviral therapy (ART) regimen for at least two years. Participants must also have a body mass index (BMI) of 30 kg/m² or higher, or a BMI of 27 kg/m² with additional conditions like hypertension, dyslipidemia, or type 2 diabetes mellitus.

The trial will span approximately four years, with an estimated recruitment start date of June 1, 2022, and an expected end date of October 31, 2026. Participants will be involved in the study for a maximum treatment period of 20 weeks. The study visits will include an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor progress and collect data on primary and secondary endpoints. The primary endpoint is the change in total body weight from baseline at week 28. Secondary endpoints include changes in total and subcutaneous fat, markers of immune function, inflammation, and metabolic parameters, as well as health-related quality of life and ECG changes.

Participants will be required to attend scheduled visits throughout the study duration, including an end-of-study visit to assess final outcomes. Conditions that may lead to early termination from the study include non-compliance with study procedures, adverse events, or withdrawal of consent. The trial is conducted in accordance with ethical guidelines, and participants are required to provide written informed consent before enrollment. The study is not classified as a low-intervention trial and is categorized as a Phase 4 clinical trial.

The clinical trial involves the administration of **semaglutide**, a GLP-1 analogue, in various dosages to evaluate its efficacy in weight loss among individuals living with HIV and obesity. The experimental medication is provided in the form of a **solution for injection** in pre-filled pens, manufactured by Novo Nordisk A/S. The trial includes three different dosages of semaglutide: 0.25 mg, 0.5 mg, and 1 mg. Each dosage is administered via subcutaneous injection.

Ozempic 0.25 mg solution for injection in a pre-filled pen is administered with a maximum daily dose of 0.25 mg. The treatment period for this dosage is set at a maximum of 4 weeks. The administration route is subcutaneous injection, and the pharmaceutical form is a solution for injection.

Ozempic 0.5 mg solution for injection in a pre-filled pen is administered with a maximum daily dose of 0.5 mg. The treatment period for this dosage is also set at a maximum of 4 weeks. The administration route remains subcutaneous injection, and the pharmaceutical form is a solution for injection.

Ozempic 1 mg solution for injection in a pre-filled pen is administered with a maximum daily dose of 1 mg. The treatment period for this dosage extends to a maximum of 20 weeks. The administration route is subcutaneous injection, and the pharmaceutical form is a solution for injection.

Throughout the trial, participant compliance with the dosing schedule is monitored to ensure adherence to the treatment regimen. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. The primary objective is to assess the efficacy of semaglutide as an adjunct to diet and exercise in achieving greater weight loss compared to diet and exercise alone.

The efficacy of the GLP-1 analogue therapy, specifically subcutaneous **semaglutide**, will be assessed in a clinical trial aimed at evaluating its impact on weight loss in individuals living with HIV and obesity. The primary endpoint for efficacy evaluation is the change from baseline in total body weight at week 28. Secondary endpoints include changes from baseline in total and subcutaneous fat as measured by DXA at week 28, as well as changes in markers of B-cell function, T-cell function, innate immunity, inflammation, gut microbiome composition, adipose tissue function, cholesterol and glucose metabolism, and HIV RNA and viral reservoir. Additionally, the proportion of subjects not achieving at least 5% weight loss from baseline at week 16 will be assessed, along with changes in health-related quality of life and PR interval on ECG from baseline to week 4, stratified by class of antiretrovirals.

Data collection will occur at specified timepoints, including week 4, week 16, and week 28, using validated scales and laboratory tests. The analysis will focus on comparing the efficacy of semaglutide as an adjunct to diet and exercise against diet and exercise alone. The trial is designed as a randomised, controlled, parallel group, open-label study, ensuring a robust evaluation of the treatment's efficacy in achieving greater weight loss in the target population.