Maraviroc as an Immunomodulatory Drug for Antiretroviral-treated HIV Infected Patients Exhibiting Immunologic Failure
Condition: HIV Infection
MeSH terms: HIV Infections
Intervention: Placebo; Maraviroc
Intervention description: Dose based on current medications in regimen: 150mg PO BID for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens.; Dose based on current medications in regimen: 150mg orally (PO) twice daily (BID) for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens.
Intervention MeSH terms: Maraviroc
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV infection; T cell activation; Antiretroviral Therapy; CCR5; Maraviroc

Summary:

      Many people with HIV fail to regain normal CD4 counts despite effectively suppressing HIV
      replication with medications. Blocking the "co-receptor" for HIV might decrease inflammation
      of the immune system, potentially providing an immune benefit. The goal of the current trial
      is to determine whether adding maraviroc, a new CCR5 "co-receptor" blocker, decreases
      inflammation, providing an immune benefit for patients with low CD4 counts despite
      undetectable viral loads on HIV medications.

      In this study, HIV-infected patients who are receiving antiretroviral therapy for HIV will
      receive either maraviroc or a placebo (sugar pill) each day for 24 weeks. After 24 weeks, the
      study medication will be stopped and all subjects will be followed for 12 more weeks. Blood
      tests measuring the extent of inflammation, low-level viremia, and immune function will be
      measured throughout the trial and compared between treatment arms.
    

Eligibility criteria:

        Inclusion Criteria:

          1. HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by Western
             blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA,
             or a second antibody test by a method other than ELISA is acceptable as an alternative
             confirmatory test.

          2. Stable antiretroviral therapy for at least 12 months

          3. Screening CD4+ T cell count below 350 cells/mm3

          4. All available CD4+ T cell counts in the last year and at screening < 350 cells/mm3

          5. Screening plasma HIV RNA levels below level of detection (< 50 copies RNA/mL using
             Roche Amplicor or < 75 copies/mL using Bayer bDNA)

          6. All available plasma HIV RNA levels within past year below the level of detection.
             Isolated values that are detectable but < 500 copies will be allowed as long as the
             plasma HIV RNA levels before and after this time point are undetectable.

          7. > 90% adherence to therapy within the preceding 30 days, as determined by self-report.

          8. Both male and female subjects are eligible. 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.

          9. Ability and willingness of subject or legal guardian/representative to provide
             informed consent

        Exclusion Criteria:

          1. Increase in CD4 count of > 100 cells/mm3 in past year.

          2. Patients who are intending to modify antiretroviral therapy in the next 24 weeks for
             any reason.

          3. Serious illness requiring hospitalization or parental antibiotics within preceding 3
             months.

          4. Concurrent treatment with immunomodulatory drugs, or exposure to any immunomodulatory
             drug in past 16 weeks.

          5. HBVsAg+ or active hepatitis C or hepatitis B which will require treatment in the
             subsequent 24 weeks.

          6. Prior exposure to CCR5 inhibitors

          7. Screening absolute neutrophil count <1,000 cells/mm3, platelet count <50,000
             cells/mm3, hemoglobin < 8mg/dL, estimated creatinine clearance <40 mL/minute.

          8. Pregnant or breastfeeding women

          9. Use of both Tenofovir and Didanosine in current antiretroviral therapy regimen.