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

Effect of a Treatment Switch From Protease Inhibitor to Raltegravir-based ART on Myeloid Cell Inflammation in HIV-infected Patients.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • Chronic Viral Illness Service, McGill University Health Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Integrase Inhibitor
Switch from protease inhibitor-based regimen to raltegravir-based regimen
Raltegravir
No Intervention: Protease inhibitor
Continuation of protease-inhibitor based regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Jean-Pierre Routy, MD; FRCPC, McGill University Health Centre/Research Institute of the McGill University Health Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 20, 2017

Primary Completion (Actual)

March 31, 2021

Study Completion (Actual)

March 31, 2021

Study Registration Dates

First Submitted

February 17, 2016

First Submitted That Met QC Criteria

February 19, 2016

First Posted (Estimate)

February 25, 2016

Study Record Updates

Last Update Posted (Actual)

March 21, 2023

Last Update Submitted That Met QC Criteria

March 17, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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