Optimizing metabolic management for people with HIV on integrase-based therapy

A Phase III/IV Factorial Randomized Double-blind Trial to Compare the Addition of Dapagliflozin vs Placebo and Rosuvastatin/Ezetimibe Versus Pitavastatin in Patients With HIV on Integrase Strand Transfer Inhibitor-based Antiretrovirals With Elevated Metabolic Risk

This study is testing if a diabetes medication can help people with HIV who are at risk for metabolic issues feel better while they are on specific HIV treatments.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 40 Years to 75 Years
• Sex: All
• Sponsor: Kirby Institute (Government)
• Locations: 3 sites (Sydney, New South Wales and 2 other locations)
• Trial ID: NCT06317051 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effects of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on metabolic parameters in individuals with HIV who are at high metabolic risk and currently on integrase strand transfer inhibitors (INSTIs). Participants will be randomly assigned to receive either dapagliflozin or a placebo, alongside either pitavastatin or a combination of rosuvastatin and ezetimibe. The study aims to assess both the efficacy and safety of these treatments over a 48-week period, with primary endpoints evaluated at 24 weeks. A total of 300 participants will be enrolled, with follow-up assessments at multiple time points.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 40-75 with HIV who have experienced significant weight gain or have a high BMI while on INSTI-based ART.

Not a fit: Patients currently taking protease inhibitors or those with severe renal or hepatic impairment may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved metabolic health and reduced cardiovascular risks for patients living with HIV.

How similar studies have performed: Previous studies have shown promising results with SGLT2 inhibitors in reducing cardiovascular risks, suggesting potential success for this approach.

Eligibility criteria

Inclusion Criteria:

1. Age 40-75 years and at least one of the following risk factors:

   1. BMI \> 7% increase or \> 5kg weight gain since INSTI commencement, or
   2. BMI ≥ 30 kg/m2
2. BMI ≥18 kg/m2 prior to INSTI commencement
3. Currently taking INSTI-based ART
4. Sustained virologic response, defined as viral load \<200 copies/mL for at least 12 months
5. Current CD4 \>250 cells/mm3
6. Informed consent for trial participation

Exclusion Criteria:

1. Currently taking a protease inhibitor
2. Indicated to take or already taking high intensity statin
3. estimated glomerular filtration rate (eGFR) \< 30 ml/min/1.73m2
4. Currently taking an SGLT-2 inhibitor or glucagon-like peptide 1 (GLP-1) agonist
5. Absolute contraindication or absolute indication to SGLT2 inhibitor therapy
6. Absolute contraindication to pitavastatin, rosuvastatin, ezetimibe or combination of rosuvastatin/ezetimibe
7. Pregnant or breast feeding
8. Severe hepatic impairment (Child Pugh B or C)
9. Participants receiving any excluded/contraindicated medication
10. Participants who are enrolled into an additional interventional study.
11. Expected inability or unwillingness to participate in study procedures.
12. In the opinion of the investigator, participation in a trial is not in the best interest of the patient.

Where this trial is running

Sydney, New South Wales and 2 other locations

• St Vincent's Hospital — Sydney, New South Wales, Australia (Recruiting)
• Austin Health — Melbourne, Victoria, Australia (Recruiting)
• Cart-Crs — Chennai, Tamil Nadu, India (Recruiting)

Study contacts

• Principal investigator: Gail Matthews, MD — Kirby Institute
• Study coordinator: Hila Haskelberg, PhD

Conditions HIV Infections; Weight Gain; HIV