Study of the Antiviral and Immunological Effects of Intensification of Suppressive Antiretroviral Therapy With Maraviroc

• Status: Completed
• Trial end date: 2011-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Hypothesis: Intensification of current ARV regimens with maraviroc will result in more complete suppression of viral replication, particularly in the gastrointestinal mucosa with resultant reduction in markers of immune activation and improved GI immune reconstitution.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rockefeller University
• Collaborators: Aaron Diamond AIDS Research Center; Pfizer
• Treatments: Abacavir; Antiviral Agents; Maraviroc; Protease Inhibitors; Tenofovir

Criteria

Inclusion Criteria:

• Documented treatment with combination antiviral therapy (ARV) during acute and early HIV-1 infection defined as:

• Negative ELISA/Western Blot or indeterminate Western Blot in the presence of HIV-1 RNA>5,000 copies/ml

• Positive HIV-1 serology with a detuned ELISA O.D. value below 1.0

• A documented negative serology within 180 days of screening and a positive HIV-1 serology at screening

• Treatment for at least one year with ARVs

• Plasma HIV-1 RNA levels below detection for at least 6 months

• CCR5 tropic virus pretreatment using the Monogram assay

• GI biopsy at study entry

• Agree to subsequent GI biopsy at 12 and 24 weeks

• Laboratory values obtained within 45 days prior to study entry.

• Absolute neutrophil count (ANC) ≥500/mm³

• Hemoglobin ≥9.0 g/dL

• Platelet count ≥80,000/mm³

• AST (SGOT), ALT (SGPT), and alkaline phosphatase < 5.0 x ULN

• Total bilirubin ≤ 2.5 X ULN if not on atazanavir containing regimen

• PT/PTT within 1.5 control

• Calculated creatinine clearance ≥60 mL/min as estimated by the Cockcroft Gault equation:

• For men, (140 - age in years) x (body weight in kg) / (serum creatinine in mg/dL x 72) = CrCl (mL/min)

• For women, multiply the result by 0.85 = CrCl (mL/min) NOTE: A program to assist in calculations is available on the DMC web site at: http://www.fstrf.org/ACTG/ccc.html

• For women of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to initiating study medications unless otherwise specified by product labeling.

• Female candidates of reproductive potential is defined as girls who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months) or have not undergone surgical sterilization (e.g., hysterectomy, or bilateral oophorectomy, or bilateral tubal ligation).

• Contraception requirements:

• Female candidates of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree that they will use at least one reliable method of contraception while receiving the protocol-specified drugs and for 6 weeks after stopping the medications.

• Male Candidates: If you are a heterosexual male, you and your sexual partner must agree to use acceptable methods of birth control during the entire study. Acceptable methods of birth control include intrauterine device (IUD), diaphragm with spermicide,condoms or not having sex. Oral contraceptives alone are not an acceptable method of birth control.

• Men and women age ≥18 years.

• Participants must be HLA-B5701 negative if not taking abacavir as part of their regimen.

• Ability and willingness of subject to give written informed consent.

Exclusion Criteria:

• Currently breast-feeding.

• Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry. NOTE: Subjects receiving stable physiologic glucocorticoid doses, defined as prednisone ≤ 10 mg/day, will not be excluded.

• Known allergy/sensitivity to study drugs or their formulations.

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

• Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry.

• Pretreatment viral population that is either dual mixed tropic or X4 tropic using the Monogram assay

• Current imprisonment or involuntary incarceration in a medical facility for psychiatric or physical (e.g., infectious disease) illness.

• Any other clinical conditions or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the requirements.