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Protease Inhibitor vs. Raltegravir-based ART and Inflammation in HIV Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02691065
Recruitment Status : Unknown
Verified September 2016 by Jean-Pierre Routy, McGill University Health Centre/Research Institute of the McGill University Health Centre.
Recruitment status was:  Not yet recruiting
First Posted : February 25, 2016
Last Update Posted : September 14, 2016
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Jean-Pierre Routy, McGill University Health Centre/Research Institute of the McGill University Health Centre

Brief Summary:

Human immunodeficiency virus (HIV) infection damages body defence mainly by affecting two important white blood cells called cluster of differentiation (CD4) T cells and monocytes. This immune dysfunction leads to persistent inflammation, which is partially resolved with long-term anti-HIV therapy. Importantly, such inflammation increases risk for cardiovascular, diabetes, and kidney diseases. The causes of this inflammation are largely unknown and include HIV itself, presence of other infections, lifestyle characteristics like increased cholesterol levels, obesity, smoking and alcohol abuse. In addition, inflammation can be driven by certain type of anti-HIV therapy called protease inhibitor (PI). PI has been associated with an increase of cholesterol and may contribute to inflammation. A new class of medication that is now available in Canada called integrase inhibitor (II) may have a lesser or no effect on cholesterol levels. Therefore, it is important to study the effect of II on cholesterol levels and inflammation.

The purpose of this study is to assess the inflammatory changes, in the blood of persons treated with PI that will switch to the II or may remain on their PI-containing regimen. By comparing persons continuing their current PI-based regimen with those who switch to II-based regimen, we will know if the change from PI to raltegravir (Isentress), a type of II, decreases lipids and inflammatory markers.

The adult persons living with HIV, who are on PI-based therapy for more than a year, with any CD4 T cell count and plasma viral load below level of detection, will be invited to participate in the study. 40 study participants will be selected by randomization (like a toss of a coin) to either continue PI-based regimen (20 participants) or switch to raltegravir-based regimen (20 participants) for a period of 12 months. Blood samples of the study participants will be drawn before, during and at the end of study to evaluate changes in markers of inflammation, cholesterol level and CD4 T cell and monocyte function. No experimental anti-HIV medication will be used; change of therapy will include raltegravir which is one of currently recommended medications to treat HIV in Canada.

This study will be able to answer this important question whether inflammation can be decreased by switching therapy from PI-based therapy to raltegravir-based therapy. Ultimately, information provided by this study will contribute to the health of persons living with HIV.

Condition or disease Intervention/treatment Phase
HIV Drug: Integrase Inhibitor Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of a Treatment Switch From Protease Inhibitor to Raltegravir-based ART on Myeloid Cell Inflammation in HIV-infected Patients.
Study Start Date : October 2016
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : February 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Integrase Inhibitor
Switch from protease inhibitor-based regimen to raltegravir-based regimen
Drug: Integrase Inhibitor
No Intervention: Protease inhibitor
Continuation of protease-inhibitor based regimen

Primary Outcome Measures :
  1. Reduction in the frequency of inflammatory monocytes [ Time Frame: 12 months ]
    Phenotypic assessment of peripheral blood monocytes by flow cytometry to determine the percentage of CD14+ CD16+ monocytes. This will be compared between two arms to determine the effect of Raltegravir-based therapy vs protease inhibitor-based therapy.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

  1. HIV-1 infected male or female adults greater than or equal to 18 years of age
  2. Participants who are on protease-inhibitor-based ART for more than a year
  3. Participants with any CD4 T-cell count.
  4. Participants with plasma viral load below level of detection (40 copies/mL)
  5. Able to understand and sign the informed consent form prior to screening
  6. Women of child-bearing potential must have a negative pregnancy test at screening and at Day 1 and agree to use the following approved methods of birth control while on study:

    • Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide);
    • Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion);
    • Male partner sterilization confirmed prior to the female subject's entry into the study; this male is the sole partner for that subject;
    • Approved hormonal contraception;
    • Any other method with published data showing that the expected failure rate is <1% per year.

    Any contraception method must be used consistently, in accordance with the approved product label, and for at least 2 weeks after discontinuation of metformin.

  7. Women of non-child-bearing potential as defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy.
  8. Men who are using at least one barrier method of contraception (e.g. condom).

Exclusion Criteria

  1. Individuals with a known hypersensitivity/allergy to the Raltegravir.
  2. Individuals who are actively participating in an experimental therapy study or who have received experimental therapy within the last three months.
  3. Individuals who are suffering from severe systemic diseases (uncontrolled hypertension, chronic renal failure), or active uncontrolled infections
  4. Patients who are currently on any integrase inhibitor-based ART.
  5. Individuals with a history of congestive heart failure (NYHA I-IV) or individuals having a cardiac pacemaker
  6. Severe liver or kidney disease based on physician evaluation
  7. Elevated AST or ALT 3-fold above the upper normal limit
  8. Elevated alkaline phosphatase 2-fold above upper normal limit
  9. Elevated creatinine (above 150 µmol/l)
  10. Current use of oral steroids
  11. A systemic infection within the last month
  12. Women who are pregnant or breastfeeding.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02691065

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Contact: Natacha Cotta-Grand, PhD (514) 934 -1934 ext 32547

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Canada, Quebec
Chronic Viral Illness Service, McGill University Health Centre
Montreal, Quebec, Canada, H4A 3J1
Sponsors and Collaborators
McGill University Health Centre/Research Institute of the McGill University Health Centre
Merck Sharp & Dohme Corp.
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Principal Investigator: Jean-Pierre Routy, MD; FRCPC McGill University Health Centre/Research Institute of the McGill University Health Centre

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Responsible Party: Jean-Pierre Routy, Professor, McGill University Health Centre/Research Institute of the McGill University Health Centre Identifier: NCT02691065    
Other Study ID Numbers: 15-579-MUHC
First Posted: February 25, 2016    Key Record Dates
Last Update Posted: September 14, 2016
Last Verified: September 2016
Additional relevant MeSH terms:
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Pathologic Processes
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents