Bone, Immunologic, and Virologic Effects of a Antiretroviral Regimen

NCT01400412 | Completed Phase 2 Results DMC

• 2 other identifiers: ACTG A53031U01AI068636
• Study Type: interventional
• Target: 262
• Locations: 2 countries
• Sites: 38

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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Total Hip Bone Mineral Density (BMD)

  The primary endpoint is the percent change in bone mineral density (BMD) at total hip (as measured by DXA scan) from baseline (week 0) to week 48.

  Week 0, week 48

Secondary Outcomes (19)

• Percent Change in Lumbar Spine Bone Mineral Density (BMD)

  Week 0, week 48

• Change in CD4 Count From Baseline to Week 24

  Week 0, week 24

• Change in CD4 Count From Baseline to Week 48

  Week 0, week 48

• CD8+ T-cell Change From Baseline to Week 48

  At weeks 0 and 48

• Percentage Change in Expression of CD38+/HLA-DR+ on CD4+ T Cells From Baseline to Week 48

  At weeks 0 and 48

Study Arms (2)

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

EXPERIMENTAL

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

Drug: Darunavir; Drug: Ritonavir; Drug: Emtricitabine; Drug: Placebo for Tenofovir disoproxil fumarate; Drug: Maraviroc

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

EXPERIMENTAL

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

Drug: Darunavir; Drug: Ritonavir; Drug: Tenofovir disoproxil fumarate; Drug: Emtricitabine; Drug: Placebo for Maraviroc

Interventions

Darunavir 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.

Also known as: Prezista, TMC-114, DRV

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

Ritonavir DRUG

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

Also known as: Norvir, RTV

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

Tenofovir disoproxil fumarate DRUG

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

Also known as: Viread, TDF

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

Emtricitabine DRUG

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

Also known as: Emtriva, FTC, Coviracil

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

Placebo for Tenofovir disoproxil fumarate DRUG

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

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

Placebo for Maraviroc DRUG

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

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

Maraviroc DRUG

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

Also known as: Celesentri, Selzentry

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

Eligibility Criteria

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

You may qualify if:

• HIV-1 infection
• 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.

You may not qualify if:

• 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 hypersensitivity to soy lecithin.
• 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.

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (38)

31788 Alabama CRS

Birmingham, Alabama, 35294, United States

Location

University of Southern California (1201)

Los Angeles, California, 90033-1079, United States

Location

UCLA CARE Center CRS (601)

Los Angeles, California, 90095, United States

Location

Ucsd, Avrc Crs (701)

San Diego, California, 92103, United States

Location

Ucsf Aids Crs (801)

San Francisco, California, 94110, United States

Location

University of Colorado Hospital CRS (6101)

Aurora, Colorado, 80045, United States

Location

University of Colorado Denver ATN CRS (33022)

Denver, Colorado, 80262, United States

Location

Georgetown University CRS (GU CRS) (1008)

Washington D.C., District of Columbia, 20007, United States

Location

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

Washington D.C., District of Columbia, 20010, United States

Location

Univ. of Miami AIDS CRS (901)

Miami, Florida, 33136, United States

Location

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

Tampa, Florida, 33606, United States

Location

The Ponce de Leon Center CRS (5802)

Atlanta, Georgia, 30308, United States

Location

Northwestern University CRS (2701)

Chicago, Illinois, 60611, United States

Location

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

Chicago, Illinois, 60612, United States

Location

IHV Baltimore Treatment CRS (4651)

Baltimore, Maryland, 21201, United States

Location

201 Johns Hopkins University CRS

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital ACTG CRS (101)

Boston, Massachusetts, 02114, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

Washington U CRS (2101)

St Louis, Missouri, 63110, United States

Location

Cooper Univ. Hosp. CRS (31476)

Camden, New Jersey, 08103, United States

Location

Columbia Physicians and Surgeons CRS (30329)

New York, New York, 10032, United States

Location

Trillium Health ACTG CRS (1108)

Rochester, New York, 14642, United States

Location

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

Rochester, New York, 14642, United States

Location

Unc Aids Crs (3201)

Chapel Hill, North Carolina, 27516, United States

Location

Moses H. Cone Memorial Hospital CRS (3203)

Greensboro, North Carolina, 27401, United States

Location

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, 45267, United States

Location

Case CRS (2501)

Cleveland, Ohio, 44106, United States

Location

Metro Health CRS (2503)

Cleveland, Ohio, 44109, United States

Location

The Ohio State Univ. AIDS CRS (2301)

Columbus, Ohio, 43210, United States

Location

Hops. of Univ. of Pennsylvania CRS (6201)

Philadelphia, Pennsylvania, 19104, United States

Location

The Miriam Hospital ACTG CRS (2951)

Providence, Rhode Island, 02906, United States

Location

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

Memphis, Tennessee, 38105, United States

Location

Vanderbilt Therapeutics CRS (3652)

Nashville, Tennessee, 37232, United States

Location

Peabody Health Center CRS (31443)

Dallas, Texas, 75215, United States

Location

Houston AIDS Research Team CRS (31473)

Houston, Texas, 77030, United States

Location

Texas Childrens Hospital ATN CRS (33018)

Houston, Texas, 77030, United States

Location

University of Washington AIDS CRS (1401)

Seattle, Washington, 98104, United States

Location

Puerto Rico-AIDS CRS (5401)

San Juan, 00935, Puerto Rico

Location

Related Publications (1)

• 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.

  PMID: 26060295 DERIVED

MeSH Terms

Interventions

Darunavir; Ritonavir; Tenofovir; Emtricitabine; Maraviroc

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Organophosphonates; Organophosphorus Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems

ACTGCT.Gov@s-3.com

301-628-3313

Study Officials

• Babafemi Taiwo, MBBS, MD

  Northwestern University CRS

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2011
• First Posted: July 22, 2011
• Study Start: January 17, 2012
• Primary Completion: June 30, 2014
• Study Completion: June 30, 2014
• Last Updated: October 15, 2024
• Results First Posted: July 15, 2015

Record last verified: 2024-10

Locations

US (37); PR (1)