Vedolizumab (Anti-alpha4beta7) in Subjects With HIV Infection Undergoing Analytical Treatment Interruption

HIV Clinical Trial

Official title: An Exploratory, Open-Label Study of Vedolizumab (Anti-alpha4beta7 Antibody) in Subjects With HIV Infection Undergoing Analytical Treatment Interruption

Status Completed

Clinical Trial Summary

Background:

In most people infected with human immunodeficiency virus (HIV), their immune system cannot control HIV infection. They need drugs called combination antiretroviral therapy (cART) to control the HIV. When people stop cART treatment, their immune system cannot control the infection again. They can also become resistant to cART and have lasting side effects. Researchers want to test if the drug vedolizumab is effective at controlling HIV infection without the need for cART.

Objective:

To test if vedolizumab is safe and can control the amount of HIV in the blood when cART is not taken.

Eligibility:

People ages 18-65 who have HIV and are being treated with cART

Design:

Participants will be screened with:

Physical exam

Medical history

Electrocardiogram: Soft, sticky patches on the chest, arms, and legs measure heart activity.

Blood and urine tests

Participants will have a baseline visit. This will be 2-5 hours each day for 1-2 days. It will include repeats of the screening tests and:

Leukapheresis: Blood is removed through a needle in the arm. A machine separates the white blood cells from the blood. The rest of the blood is returned to the participant.

Neurologic exam: The nerves and reflexes are tested.

First vedolizumab infusion through an arm vein

Participants will have visits every 4 weeks for 30 weeks. These will include:

Vedolizumab infusions

Repeats of baseline tests

Participants will have more visits for blood draws.

Participants will keep taking cART until after the week 22 infusion.

After discontinuing cART at study week 22, participants will be seen every two weeks to monitor the CD4 count and the level of HIV in the blood. Some of these visits will occur in between infusion visits and will only take about 1 hour to complete. cART will be restarted if a participant's HIV levels go up to high, or if their CD4 cell counts decreases by too much.

For the follow-up phase, participants will have visits every 4 weeks for 24 weeks. These will include blood tests and a physical exam.

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Clinical Trial Description

While combination antiretroviral therapy (cART) has improved the clinical outcome for HIV-infected individuals, persistence of viral reservoirs in the peripheral blood and lymphoid tissues remains a hurdle to complete eradication of virus and cure of the infection. The concept that HIV preferentially infects discrete subsets of CD4+ T cells underscores the need to develop therapeutics that exploit specific cell-virus interactions. T cells expressing integrin alpha4beta7 not only regulate migration into the gut associated lymphoid tissue (GALT), but also concomitantly bind HIV, placing them in a prime position to disseminate HIV throughout the tissue. Previously, it has been shown that the HIV envelope protein gp120 binds to alpha4beta7 on CD4+ T cells in vitro, alpha4beta7high CD4+ T cells are highly susceptible to productive HIV infection in vitro, and the administration of anti-alpha4beta7 monoclonal antibody (mAb) prevents and/or delays transmission of SIV upon repeated challenges and preserves CD4+ T cells in rhesus macaques. Furthermore, it has been demonstrated that administration of anti-alpha4beta7 mAb in SIV-infected rhesus macaques receiving cART suppresses plasma viremia for extended periods following discontinuation of cART, collectively suggesting that sustained virologic remission in the absence of cART may be achieved via direct targeting of alpha4beta7 integrin. It is well established that the vast majority of HIV-infected individuals treated with cART experience plasma viral rebound within weeks of cessation of therapy. Considering that current research on the treatment of HIV-infected individuals has been heavily focused on developing strategies aimed at achieving sustained virologic remission in the absence of cART, it is of great interest to investigate whether administration of anti-alpha4beta7 mAb can prevent plasma viral rebound and allow durable suppression of viral replication in HIV infected individuals after discontinuation of cART. We propose to examine the effect of vedolizumab, an FDA approved anti-alpha4beta7 mAb for the treatment of ulcerative colitis and Crohn's disease, on plasma viral rebound in HIV-infected individuals following analytical treatment interruption (ATI). ;

Related Conditions & MeSH terms

• HIV
• HIV Infections

• NCT number: NCT02788175
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: May 28, 2016
• Completion date: March 4, 2019