About the study (objectives)
This short-term pilot trial will test the safety, tolerance, and efficacy of vedolizumab, a monoclonal antibody, as a functional cure for chronic HIV infection. A functional cure refers to an intervention that would allow people living with HIV to stop taking antiretroviral therapy (ART) without experiencing viral rebound, progressive infection, and health consequences. Vedolizumab, also called anti-α4β7 integrin mAb, is a safe, licensed treatment for inflammatory bowel disease.
About the disease/condition (background/context)
In most cases, interruption of regular ART adherence results in viral rebound and the spread of HIV throughout the body. A recently published study showed that, after treatment with vedolizumab, viral load suppression and preserved CD4 count were maintained in monkeys with SIV (the primate equivalent of HIV) who were previously on stable ART. In the context of HIV, vedolizumab’s mechanism of action is not well understood. The drug may work by preventing a specific type of immune cell (one that is often targeted by HIV) from entering into the tissue of the gut, an area of significant inflammation and viral activity during infection.
Study Approach (methodology)
This study will enroll 12 participants. Each participant will receive a total of seven doses via injection over a period of twenty-six weeks. Four participants will receive 300 mg per dose, four will receive 150 mg, and four will receive 75 mg. Following the third dose, participants will stop taking their ART and will be monitored during physician visits every three to four weeks for up to one year. Researchers will collect blood samples at regular intervals to understand if the drug can prevent a significant increase or promote suppression of viral load without the use of ART.
If a significant or persistent viral rebound occurs, or if CD4 count falls too low, participants will be reinitiated on ART. If this occurs, researchers will see how the immune system responds and if the effectiveness of ART retreatment is modified by vedolizumab.
- Adult (≥ 18 to 65 years) with HIV infection
- Nadir CD4 T cell count ≥ 200 and current CD4 T cell count > 500 cells/mcL
- Adherent on ART 2 to 9 years with sustained pVL ≤ 50 copies/mL
- Ability to comprehend English and provided informed consent
- Past AIDS-defining or AIDS-related immune deficiency diseases
- Past drug-resistant HIV or ART-refractory pVL response
- Current hepatitis B or C virus infection, or untreated latent TB infection
- Clinically significant concurrent health condition
- Pregnancy, lactation, or non-adherence with contraception if fertile.
The Ottawa Hospital — General Campus
501 Smyth Rd, Ottawa
ON K1H 8L6
If you would like more information on this clinical study, please refer to the principal investigator or to clinicialtrials.gov.
Fellow, Infectious Diseases, uOttawa
Professor of Medicine, Division of Infectious Diseases, uOttawa
Co-Principal and Qualified Investigator