CCR5 Inhibitor Treatment Intensification on CD4+ T-cell Recovery

• Status: Completed
• Trial end date: 2014-04-11
• Target enrollment: 0
• Participant gender: All

Summary

CCTG 590 is a open-label study to evaluate the impact of therapy intensification with Maraviroc (MVC) (a CCR5 inhibitor) to a stable suppressive HIV antiretroviral regimen on the rate of CD4+ T-cell recovery and gene expression profiles. Patients on a stable first-line HIV regimen with continued viral suppression and sub-optimal CD4+ T-cell counts will be eligible for this study. Those who are found to be eligible will have MVC (dose-adjusted to background HIV regimen) added to their current HIV regimen for 24 weeks. After the 24 week intensification, the MVC will be discontinued, the original antiretroviral regimen will be continued and the subjects will be followed for an additional 12 weeks.

The investigators hypothesize that MVC will improve the rate of CD4 recovery. This improved CD4 recovery will be associated with favorable changes in gene expression profiles of genes involved with CD4 maintenance and circulation.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: California Collaborative Treatment Group; University of California, San Diego
• Collaborators: California HIV/AIDS Research Program; Pfizer; University of California, Los Angeles; University of Southern California
• Treatments: Maraviroc

Criteria

Inclusion Criteria:

1. HIV-1 infection

2. All available CD4+ T cell counts within the last 12 months of screening below 350 cells/mm3 (minimum of 3 values obtained > 30 days apart).

3. HIV treatment with a stable (for at least 6 months) antiretroviral regimen consisting of at least 2 NRTIs and either a protease inhibitor boosted with low dose ritonavir or an NNRTI. A stable regimen is defined as no additions or deletions for more than 14 cumulative days.

4. Patient considered to be receiving initial HIV regimen (history of medication substitution for toxicity is allowed).

5. All available plasma HIV RNA levels within the last 12 months are below the level of detection. Isolated values that are detectable but < 1000 copies will be allowed as long as the plasma HIV RNA levels before and after this detectable time point are undetectable - The subject should have a minimum of 3 values obtained > 30 days apart.

6. Females of childbearing potential must have a negative serum pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period.

7. Men and women age ≥ 18 years.

Exclusion Criteria:

1. Current antiretroviral regimen contains tenofovir disoproxil fumarate AND didanosine in combination.

2. History of chronic hepatitis C (defined as HCV antibody positive and HCV RNA detectable).

3. History of chronic active hepatitis B (defined as surface antibody negative, surface antigen positive and HBV DNA detectable).

4. Concurrent use of G-CSF or GM-CSF.

5. Prior or concurrent use of IL-2.

6. Prior or concurrent use of a CCR5 inhibitor.

7. Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.

8. Use of any immunomodulator, HIV vaccine, or investigational therapy within 30 days of study entry.

9. Use of human growth hormone within 30 days prior to study entry.

10. Initiation of testosterone or anabolic steroids within 30 days prior to study entry. (Exception: Chronic replacement dosages in patient's with diagnosed hypogonadism is allowed).

11. Evidence of splenic sequestration or suppressed bone marrow function:

• Clinical or radiographic evidence of significant splenomegaly.

• History of leukemia or lymphoma.

• History of myelosuppressive chemotherapy or irradiation