Bone, Immunologic, and Virologic Effects of a Antiretroviral Regimen

NCT ID: NCT01400412

Last Updated: 2024-10-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 262 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-17
• Study Completion Date: 2014-06-30

Brief Summary

The main purpose of this study was to compare the effects on bones of the following two drug combinations:

• maraviroc (MVC), emtricitabine (FTC), plus darunavir/ritonavir (DRV/r)
• tenofovir (TDF) plus emtricitabine (FTC) plus darunavir/ritonavir (DRV/r)

Additional study objectives were the following:

• To see how the drug combinations affect the brain and kidneys.
• To see how well the drug combinations lower the HIV viral load.
• To see how safe the drug combinations are, how well people are able to take the study drug combinations, and how well their immune systems respond to the study drugs.

Detailed Description

There are now several HIV treatment options for a person with HIV infection who has not yet been treated. Most people who receive treatment and take their medications as directed have a good result. This is usually determined by measuring the amount of HIV in the blood (viral load). The best response is when HIV cannot be found (less than 50 copies/mL) in the blood. However, it has recently become clear that some people with HIV who are receiving effective HIV drugs continue to have more health problems than people without HIV infection. Sometimes, there is damage to organs in the body, including bone, kidneys, and the brain.

Conditions

HIV-1 Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

MVC Arm: DRV/r + MVC + FTC + TDF placebo

Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD

Group Type: EXPERIMENTAL

Darunavir

Intervention Type: DRUG

Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet.

Ritonavir

Intervention Type: DRUG

Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food.

Emtricitabine

Intervention Type: DRUG

Emtricitabine was administered orally once a day as one 200 mg capsule.

Placebo for Tenofovir disoproxil fumarate

Intervention Type: DRUG

Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.

Maraviroc

Intervention Type: DRUG

Maraviroc was administered orally once a day as one 150 mg tablet.

TDF Arm: DRV/r + TDF + FTC + MVC placebo

Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD

Group Type: EXPERIMENTAL

Darunavir

Intervention Type: DRUG

Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet.

Ritonavir

Intervention Type: DRUG

Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food.

Tenofovir disoproxil fumarate

Intervention Type: DRUG

Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day.

Emtricitabine

Intervention Type: DRUG

Emtricitabine was administered orally once a day as one 200 mg capsule.

Placebo for Maraviroc

Intervention Type: DRUG

Placebo for maraviroc was administered orally once a day as one tablet.

Interventions

Darunavir

Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet.

Intervention Type: DRUG

Ritonavir

Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food.

Intervention Type: DRUG

Tenofovir disoproxil fumarate

Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day.

Intervention Type: DRUG

Emtricitabine

Emtricitabine was administered orally once a day as one 200 mg capsule.

Intervention Type: DRUG

Placebo for Tenofovir disoproxil fumarate

Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.

Intervention Type: DRUG

Placebo for Maraviroc

Placebo for maraviroc was administered orally once a day as one tablet.

Intervention Type: DRUG

Maraviroc

Maraviroc was administered orally once a day as one 150 mg tablet.

Intervention Type: DRUG

Other Intervention Names

Prezista; TMC-114; DRV; Norvir; RTV; Viread; TDF; Emtriva; FTC; Coviracil; Celesentri; Selzentry

Eligibility Criteria

Inclusion Criteria

• HIV-1 infection
• No evidence of exclusionary resistance mutations defined as evidence of any major NRTI mutation according to the current IAS list of HIV-1 Resistance Mutations Associated with Drug Resistance, or any DRV RAMs (refer to the A5303 PSWP for a list of these mutations) on any genotype; or evidence of significant NRTI or DRV resistance on any phenotype performed at any time prior to study entry. NNRTI-associated resistance mutations were not exclusionary.
• ARV drug-naïve, defined as </=10 days of ART at any time prior to study entry, except in the instances defined in section 4.1.3 of the protocol.
• R5-only tropism based on Trofile testing performed within 90 days prior to study entry.
• Screening HIV-1 RNA >1000 copies/mL obtained within 90 days prior to study entry by any FDA-approved test for quantifying HIV-1 RNA at any laboratory that has a CLIA certification or its equivalent.
• Known hepatitis C virus (HCV) antibody status (performed at any laboratory that had a CLIA certification or its equivalent).
• Certain laboratory values obtained within 60 days prior to study entry, as defined in section 4.1.7 of the protocol.
• For women of reproductive potential, negative serum or urine pregnancy test with a sensitivity of ≤25 mIU/mL within 72 hours prior to study entry.
• Female subjects of reproductive potential, who were participating in sexual activity that could lead to pregnancy, must agree to use at least one reliable method of contraception (as defined in section 4.1.9.1 of the protocol) while receiving the study drugs and for 6 weeks after stopping the medications.
• Female subjects who were not of reproductive potential or whose male partner(s) had azoospermia were eligible to take study drugs without the use of contraceptives.
• Ability and willingness of subject or legal guardian/representative to give written informed consent.
• Willingness to undergo neuropsychological testing.
• DXA scan performed after confirmation of the subject's eligibility by Trofile testing but no more than 4 weeks prior to randomization.

Exclusion Criteria

• Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry.
• New use of hormonal therapies within 6 months prior to study entry. (Stable therapy for ≥6 months was permitted.)
• New use of oral contraceptive pills (OCPs) in the past 3 months. (Stable therapy for ≥3 months was permitted.)
• Any oral, intravenous, or inhaled steroids within 30 days prior to study entry. (Intranasal steroids and topical corticosteroids were allowed.)
• Known allergy/sensitivity to study drugs or their formulations. (A history of sulfa allergy was not an exclusionary condition.)
• Known hypersensitivity to soy lecithin.
• Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or was clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry. (Oral candidiasis, vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses (as judged by the site investigator) were not exclusionary conditions.)
• Requirement for any current medications that were prohibited with any study drugs. (Prohibited medications must be discontinued at least 30 days prior to entry. Refer to the A5303 PSWP for a list of prohibited medications.)
• The presence of decompensated cirrhosis.
• A history of or current, active HBV infection defined as positive hepatitis B surface antigen test (or positive HBV DNA in subjects with isolated HBcAb positivity, defined as negative HBsAg, negative HBsAb, and positive HBcAb) at screening.
• Current or prior use of biphosphonates, teriparatide, raloxifene, or denosumab.
• Weight >300 lbs (exceeds weight limit of DXA scanners).
• History after 18 years of age of fracture of the spine, hip, wrist, or other site thought to be related to osteoporosis or bone fragility.
• Currently breastfeeding.
• Any active psychiatric illness including schizophrenia, severe depression, or severe bipolar affective disorder that, in the opinion of the investigator, could confound the analysis of the neurological examination or neuropsychological test results.
• Active drug or alcohol abuse that, in the investigator's opinion, could prevent compliance with study procedures or confound the analysis of study endpoints.
• Active brain infection (except for HIV-1), fungal meningitis, toxoplasmosis, central nervous system (CNS) lymphoma, brain neoplasm, or space-occupying brain lesion requiring acute or chronic therapy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Babafemi Taiwo, MBBS, MD

Role: STUDY_CHAIR

Northwestern University CRS

Locations

31788 Alabama CRS

Birmingham, Alabama, United States

University of Southern California (1201)

Los Angeles, California, United States

UCLA CARE Center CRS (601)

Los Angeles, California, United States

Ucsd, Avrc Crs (701)

San Diego, California, United States

Ucsf Aids Crs (801)

San Francisco, California, United States

University of Colorado Hospital CRS (6101)

Aurora, Colorado, United States

University of Colorado Denver ATN CRS (33022)

Denver, Colorado, United States

Georgetown University CRS (GU CRS) (1008)

Washington D.C., District of Columbia, United States

Children's National Med. Ctr. ATN CRS (33003)

Washington D.C., District of Columbia, United States

Univ. of Miami AIDS CRS (901)

Miami, Florida, United States

Univ. of South Florida (USF) College of Medicine ATN CRS (33001)

Tampa, Florida, United States

The Ponce de Leon Center CRS (5802)

Atlanta, Georgia, United States

Northwestern University CRS (2701)

Chicago, Illinois, United States

Rush Univ. Med. Ctr. ACTG CRS (2702)

Chicago, Illinois, United States

IHV Baltimore Treatment CRS (4651)

Baltimore, Maryland, United States

201 Johns Hopkins University CRS

Baltimore, Maryland, United States

Massachusetts General Hospital ACTG CRS (101)

Boston, Massachusetts, United States

Brigham and Women's Hosp. ACTG CRS (107)

Boston, Massachusetts, United States

Washington U CRS (2101)

St Louis, Missouri, United States

Cooper Univ. Hosp. CRS (31476)

Camden, New Jersey, United States

Columbia Physicians and Surgeons CRS (30329)

New York, New York, United States

Trillium Health ACTG CRS (1108)

Rochester, New York, United States

University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)

Rochester, New York, United States

Unc Aids Crs (3201)

Chapel Hill, North Carolina, United States

Moses H. Cone Memorial Hospital CRS (3203)

Greensboro, North Carolina, United States

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, United States

Case CRS (2501)

Cleveland, Ohio, United States

Metro Health CRS (2503)

Cleveland, Ohio, United States

The Ohio State Univ. AIDS CRS (2301)

Columbus, Ohio, United States

Hops. of Univ. of Pennsylvania CRS (6201)

Philadelphia, Pennsylvania, United States

The Miriam Hospital ACTG CRS (2951)

Providence, Rhode Island, United States

St. Jude Children's Research Hosp. ATN CRS (33016)

Memphis, Tennessee, United States

Vanderbilt Therapeutics CRS (3652)

Nashville, Tennessee, United States

Peabody Health Center CRS (31443)

Dallas, Texas, United States

Houston AIDS Research Team CRS (31473)

Houston, Texas, United States

Texas Childrens Hospital ATN CRS (33018)

Houston, Texas, United States

University of Washington AIDS CRS (1401)

Seattle, Washington, United States

Puerto Rico-AIDS CRS (5401)

San Juan, , Puerto Rico

Countries

United States; Puerto Rico

References

Taiwo BO, Chan ES, Fichtenbaum CJ, Ribaudo H, Tsibris A, Klingman KL, Eron JJ, Berzins B, Robertson K, Landay A, Ofotokun I, Brown T; AIDS Clinical Trials Group A5303 Study Team. Less Bone Loss With Maraviroc- Versus Tenofovir-Containing Antiretroviral Therapy in the AIDS Clinical Trials Group A5303 Study. Clin Infect Dis. 2015 Oct 1;61(7):1179-88. doi: 10.1093/cid/civ455. Epub 2015 Jun 9.

Reference Type: DERIVED

PMID: 26060295 (View on PubMed)

Other Identifiers

1U01AI068636

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ACTG A5303

Identifier Type: -

Identifier Source: org_study_id