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

NCT00703586 | Completed Phase 1

• 1 other identifier: MMA-0612
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV Infections

Keywords

Maraviroc; Treatment Experienced

Outcome Measures

Primary Outcomes (1)

• MMC HIV RNA

  24 weeks

Study Arms (2)

1

EXPERIMENTAL

ARM A: Intensification with maraviroc for 24 weeks at one of the following doses: * 150 mg orally BID when coadministered with a ritonavir-boosted protease inhibitor * 600 mg orally BID when coadministered with efavirenz or nevirapine

Drug: Maraviroc

2

ACTIVE COMPARATOR

ARM B Intensification with an additional NRTI for 12 weeks then cross over to maraviroc intensification for an additional 12 weeks as above: * Addition of abacavir 600 mg orally once daily to a tenofovir containing regimen for 12 weeks then replacing the abacavir with maraviroc * Addition of an alternate FDA approved NRTI \[such as zidovudine (AZT) or didanosine (ddi)\] at standard oral dosing to a tenofovir containing regimen for 12 weeks (if the participant declines abacavir therapy) then replacing the alternate NRTI with maraviroc.

Drug: Maraviroc

Interventions

Maraviroc DRUG

ARM A: Addition of maraviroc to baseline ARV medications for 24 weeks at one of the following doses: * 150 mg orally BID when coadministered with a ritonavir-boosted protease inhibitor * 600 mg orally BID when coadministered with efavirenz or nevirapine ARM B: Addition of an additional NRTI to baseline ARV medications for 12 weeks then cross over to maraviroc intensification for an additional 12 weeks as above: * Addition of abacavir 600 mg orally once daily to a tenofovir containing regimen for 12 weeks then replacing the abacavir with maraviroc. * Addition of an alternate FDA approved NRTI \[such as zidovudine (AZT) or didanosine (ddi)\] at standard oral dosing to a tenofir containing regimen for 12 weeks (if the participant declines abacavir therapy) then replacing the alternate NRTI with maraviroc. * Addition of tenofovir 300 mg daily to an abacavir containing regimen for 12 weeks then replacing the tenofovir with maraviroc.

1; 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rockefeller University: lead
• Aaron Diamond AIDS Research Center: collaborator
• Pfizer: collaborator

Study Sites (1)

Rockefeller University Hospital

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Maraviroc

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Martin Markowitz, MD

  Rockefeller University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2008
• First Posted: June 23, 2008
• Study Start: September 1, 2007
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: October 23, 2012

Record last verified: 2012-10

Locations

US (1)