CCR5 Inhibitor Treatment Intensification on CD4+ T-cell Recovery
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Maraviroc
Intervention description: Maraviroc will be given dose-adjusted to background HIV treatment (150 mg, 300 mg, or 600 mg twice daily)
Intervention MeSH terms: Maraviroc
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV; low CD4 recovery; Low CD4 recovery despite HIV control; Treatment experienced

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.
    

Eligibility 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