CTN 345: RESTART Trial

About the Study

RESTART is a randomized controlled trial that is investigating whether treatment with fostemsavir can reduce inflammation and comorbidities like cardiovascular disease in people living with HIV. Fostemsavir is an antiretroviral therapy (ART) medication currently approved by Health Canada for treatment-resistant HIV. The results of CTN 345 will allow the researchers to identify who could benefit most from this treatment, potentially resulting in a significant shift in personalized, HIV-specific approaches for people aging with HIV.

Background

Although ART has greatly improved quality of life and health outcomes for people living with HIV, they still develop comorbidities like heart disease 15 years earlier than their HIV-negative, ageing counterparts. A primary cause of this gap is persistent chronic, low-level inflammation experienced by some people living with HIV. This inflammation can accelerate the ageing process and impact multiple organ systems.

CTN 345 builds on findings from CTNPT 052, which showed how small fragments of HIV, known as soluble glycoprotein 120 (gp120), can remain in the bloodstream of people living with HIV even when they have an undetectable viral load, contributing to inflammation and immune dysfunction. Nearly 30 per cent of participants in CTNPT 052 had detectable levels of gp120. People with higher levels of gp120 were at higher risk of heart disease.

Earlier research by Dr. Durand and collaborators also found that fostemsavir, a type of ART medication known as an entry inhibitor, may prevent gp120 from negatively affecting the immune system. However, fostemsavir now needs to be tested in a large group of people living with HIV to confirm that it can reduce their risk of comorbidities.

Study Approach

The research team is conducting a randomized controlled trial of 150 participants, split into two even groups. The trial aiming to have at least half of the participants be women. One study group will receive 600mg of fostemsavir daily for 24 months in addition to their standard regimen, and the other will stick to their usual standard of care regimen.

A screening visit will occur in the first month to establish baseline measurements via blood tests and non-invasive cardiovascular imaging to assess the presence and extent of cardiovascular disease. Follow-up visits will take place at 6, 12, and 18 months. During study visits, medication will be dispensed, vitals will be recorded, and blood samples will be collected for biobanking. An end-of-treatment visit will occur at 24 months where imaging will be repeated. A post-treatment visit at 27 months will collect a final blood sample for biobanking purposes. The imaging and biomarkers measured during the visits will allow the team to determine the impact of fostemsavir on heart disease risk, inflammation, and immune dysfunction.