Vedolizumab treatment across antiretroviral treatment interruption in chronic HIV infection: the HAVARTI protocol for a pilot dose-ranging clinical trial to assess safety, tolerance, immunological and virological activity
| Autor: | D. William Cameron, Sanjay K. Murthy, Jonathan B. Angel, Ashok Kumar, Nancy Tremblay, Michelle Dennehy, Siddappa N. Byrareddy, Curtis Cooper, Juthaporn Cowan, Paul MacPherson, Michaeline McGuinty, Richmond Sy |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male medicine.medical_specialty Adolescent HIV & AIDS HIV Infections Antibodies Monoclonal Humanized Vedolizumab immunology 03 medical and health sciences Young Adult 0302 clinical medicine Acquired immunodeficiency syndrome (AIDS) inflammatory bowel disease Internal medicine medicine Humans 030212 general & internal medicine Dosing Immunodeficiency Aged clinical trials Dose-Response Relationship Drug business.industry General Medicine Middle Aged Viral Load medicine.disease 3. Good health Discontinuation Clinical trial Regimen Tolerability Anti-Retroviral Agents HIV/AIDS Medicine 030211 gastroenterology & hepatology Female business medicine.drug |
| Zdroj: | BMJ Open, Vol 10, Iss 10 (2020) BMJ Open |
| ISSN: | 2044-6055 |
| Popis: | IntroductionContinuous antiretroviral therapy (ART) suppresses HIV plasma viral load (pVL) to very low levels, which allows for some immune recovery. Discontinuation of ART leads to pVL rebound from reservoirs of persistence and latency, and progressive immunodeficiency. One promising but controversial strategy targeting CD4+ T lymphocytes with a monoclonal antibody (mAb) against α4β7 integrin has shown promise through sustained virological remission of pVL (SVR) in SIV239-infected rhesus macaques. We propose to assess the safety and tolerability of vedolizumab, a licensed humanised mAb against human α4β7 integrin, in healthy HIV-infected adults on ART. This study will also assess, by analytical treatment interruption (ATI), whether vedolizumab treatment can induce SVR beyond ART and vedolizumab treatment.Methods and analysisThe HIV-ART-vedolizumab-ATI (HAVARTI) trial is a single-arm, dose-ranging pilot trial in healthy HIV-positive adult volunteers receiving ART. Twelve consenting persons will be enrolled in sequential groups of 4 to each serial dosing vedolizumab regimen (300 mg, 150 mg, 75 mg). The primary outcomes are: (1) to assess the safety and tolerability of seven serial infusions of vedolizumab at each of three doses; (2) to identify the immunovirological measures, including pVL and T-cell kinetics, that characterise HIV/ART cases before, during, after vedolizumab treatment and ATI; and (3) to seek SVR of pVL after ATI. Secondary outcomes will include immune reconstitution and pVL suppression as well as immune reconstitution and long-term safety following re-initiation of ART in the absence of SVR.Ethics and disseminationThe study protocol was approved by the Ottawa Health Science Network-REB and by the Health Canada Therapeutic Products Directorate. A Data Safety Monitor will review safety information at regular intervals. The final manuscript will be submitted to an open access journal within a year of study completion.Trial registration numberClinicalTrials.gov NCT03147859; https://clinicaltrials.gov/ct2/show/NCT03147859 |
| Databáze: | OpenAIRE |
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