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HIV-1 InfectionPhase 2NCT01400412

Bone, Immunologic, and Virologic Effects of a Antiretroviral Regimen

A Phase 2 study testing Darunavir, Ritonavir and Tenofovir disoproxil fumarate in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 38 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV-1 Infection
What is being tested?
Darunavir, Ritonavir and Tenofovir disoproxil fumarate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
262 participants
Where
38 sitesin 2 countries
Study dates
17 Jan 2012to 30 Jun 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

38 sites in 2 countries.

38 sites in 2 countries

United States37 sites

  • The Ponce de Leon Center CRS (5802)

    Atlanta, Georgia, 30308

  • University of Colorado Hospital CRS (6101)

    Aurora, Colorado, 80045

  • IHV Baltimore Treatment CRS (4651)

    Baltimore, Maryland, 21201

  • 201 Johns Hopkins University CRS

    Baltimore, Maryland, 21205

  • 31788 Alabama CRS

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital ACTG CRS (101)

    Boston, Massachusetts, 02114

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

    Boston, Massachusetts, 02115

  • Cooper Univ. Hosp. CRS (31476)

    Camden, New Jersey, 08103

  • Unc Aids Crs (3201)

    Chapel Hill, North Carolina, 27516

  • Northwestern University CRS (2701)

    Chicago, Illinois, 60611

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

    Chicago, Illinois, 60612

  • Univ. of Cincinnati CRS (2401)

    Cincinnati, Ohio, 45267

  • Case CRS (2501)

    Cleveland, Ohio, 44106

  • Metro Health CRS (2503)

    Cleveland, Ohio, 44109

  • The Ohio State Univ. AIDS CRS (2301)

    Columbus, Ohio, 43210

  • Peabody Health Center CRS (31443)

    Dallas, Texas, 75215

  • University of Colorado Denver ATN CRS (33022)

    Denver, Colorado, 80262

  • Moses H. Cone Memorial Hospital CRS (3203)

    Greensboro, North Carolina, 27401

  • Houston AIDS Research Team CRS (31473)

    Houston, Texas, 77030

  • Texas Childrens Hospital ATN CRS (33018)

    Houston, Texas, 77030

  • University of Southern California (1201)

    Los Angeles, California, 90033-1079

  • UCLA CARE Center CRS (601)

    Los Angeles, California, 90095

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

    Memphis, Tennessee, 38105

  • Univ. of Miami AIDS CRS (901)

    Miami, Florida, 33136

  • Vanderbilt Therapeutics CRS (3652)

    Nashville, Tennessee, 37232

  • Columbia Physicians and Surgeons CRS (30329)

    New York, New York, 10032

  • Hops. of Univ. of Pennsylvania CRS (6201)

    Philadelphia, Pennsylvania, 19104

  • The Miriam Hospital ACTG CRS (2951)

    Providence, Rhode Island, 02906

  • Trillium Health ACTG CRS (1108)

    Rochester, New York, 14642

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

    Rochester, New York, 14642

  • Ucsd, Avrc Crs (701)

    San Diego, California, 92103

  • Ucsf Aids Crs (801)

    San Francisco, California, 94110

  • University of Washington AIDS CRS (1401)

    Seattle, Washington, 98104

  • Washington U CRS (2101)

    St Louis, Missouri, 63110

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

    Tampa, Florida, 33606

  • Georgetown University CRS (GU CRS) (1008)

    Washington D.C., District of Columbia, 20007

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

    Washington D.C., District of Columbia, 20010

Other trials in United States

Puerto Rico1 site

  • Puerto Rico-AIDS CRS (5401)

    San Juan, 00935

Other trials in Puerto Rico

About this study

Official title: A Phase 2b, Double-Blind, Placebo-Controlled, Exploratory Randomized Trial to Determine the Bone, Immunologic, Virologic, and Neurocognitive Effects of a Novel Maraviroc-Containing Antiretroviral Regimen in Treatment-Naïve Patients Infected With R5-Tropic HIV-1

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.
Read the 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
Being tested
Darunavir, Ritonavir, Tenofovir disoproxil fumarate, Emtricitabine, Placebo for Tenofovir disoproxil fumarate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DarunavirDrug

    Also called Prezista, TMC-114, DRV

    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.

  • RitonavirDrug

    Also called Norvir, RTV

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

  • Tenofovir disoproxil fumarateDrug

    Also called Viread, TDF

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

  • EmtricitabineDrug

    Also called Emtriva, FTC, Coviracil

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

  • Placebo for Tenofovir disoproxil fumarateDrug

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

  • Placebo for MaravirocDrug

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

  • MaravirocDrug

    Also called Celesentri, Selzentry

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

Study groups in NCT01400412
Study groupRoleWhat they receive
MVC Arm: DRV/r + MVC + FTC + TDF placeboExperimentalDarunavir 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
Receives: Drug: Darunavir; Drug: Ritonavir; Drug: Emtricitabine; Drug: Placebo for Tenofovir disoproxil fumarate; Drug: Maraviroc
TDF Arm: DRV/r + TDF + FTC + MVC placeboExperimentalDarunavir 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
Receives: Drug: Darunavir; Drug: Ritonavir; Drug: Tenofovir disoproxil fumarate; Drug: Emtricitabine; Drug: Placebo for Maraviroc

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Week 0, week 48

Secondary outcomes (19)

  1. Percent Change in Lumbar Spine Bone Mineral Density (BMD)

    The percent change in bone mineral density (BMD) at lumbar spine (as measured by DXA scan) from baseline (week 0) to week 48.

    Measured: Week 0, week 48

  2. Change in CD4 Count From Baseline to Week 24

    Change in CD4 count from baseline (week 0) to week 24

    Measured: Week 0, week 24

  3. Change in CD4 Count From Baseline to Week 48

    Change in CD4 count from baseline (week 0) to week 48

    Measured: Week 0, week 48

  4. CD8+ T-cell Change From Baseline to Week 48

    CD8+ T-cell change from baseline to week 48

    Measured: At weeks 0 and 48

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

    percentage change is define as [ (week 48 - week 0) / week 0 ] * 100%

    Measured: At weeks 0 and 48

  6. Percentage Change in Expression of CD38+/HLA-DR+ on CD8+ T Cells From Baseline to Week 48

    percentage change is defined as [ (week 48 - week 0) / week 0 ] * 100%

    Measured: At weeks 0 and 48

  7. Percent Change in Expression of CD28+/CD57+ on CD8+ T Cells From Baseline to Week 48

    percentage change is define as [ (week 48 - week 0) / week 0 ] * 100%

    Measured: At weeks 0 and 48

  8. Percent Change in Expression of CD57+ on CD8+ T Cells From Baseline to Week 48

    percentage change is define as [ (week 48 - week 0) / week 0 ] * 100%

    Measured: At weeks 0 and 48

  9. Percent Change in Expression of CD28+ on CD8+ T Cells From Baseline to Week 48

    percentage change is define as [ (week 48 - week 0) / week 0 ] * 100%

    Measured: At weeks 0 and 48

  10. Percent Change in Expression of RANKL+ on CD8+ T Cells From Baseline to Week 48

    percentage change is defined as [ (week 48 - week 0) / week 0 ] * 100%

    Measured: At weeks 0 and 48

  11. Change in Levels of IL-6 From Baseline to Week 48

    Change in levels of Interleukin 6 (IL-6) from baseline to week 48

    Measured: At weeks 0 and 48

  12. Change in Level of IP-10 From Baseline to Week 48

    Change in level of Interferon gamma-induced protein 10 (IP-10) from baseline to week 48

    Measured: At weeks 0 and 48

  13. Change in Levels of sCD163 From Baseline to Week 48

    Change in levels of soluble CD163 from baseline to week 48

    Measured: At weeks 0 and 48

  14. Change in Levels of sCD14 From Baseline

    Change in levels of soluble CD14 from baseline

    Measured: At weeks 0 and 48

  15. Change in Levels of D-dimer From Baseline

    Change in levels of D-dimer from baseline

    Measured: At weeks 0 and 48

  16. Cumulative Probability of Virologic Failure by Week 48

    Confirmed virologic failure is defined as confirmed plasma HIV-1 RNA levels > 1000 copies/mL at or after week 16 and before week 24, or confirmed HIV-1 RNA levels> 200 copies/mL at or after week 24. Participants who discontinued the study with an unconfirmed virologic failure (HIV-1 RNA > 1000 copies at 16 weeks or HIV-1 RNA level > 200 copies/mL at or after week 24) are considered as virologic failures at the study visit week of the unconfirmed value. Time to virologic failure is defined as the time from study entry to the planned visit week of the initial failure.

    Product-limit estimates for the survival function were used to estimate the cumulative probability of virologic failure over time and its corresponding 95% confidence interval for each treatment group.

    Measured: From study treatment initiation to week 48

  17. Number of Participants Who Experienced Bone Fractures

    Number of participants who experienced bone fractures during the study

    Measured: From study treatment initiation to week 48

  18. Number of Participants Who Died During the Study

    Number of participants who died during the study

    Measured: From study treatment initiation to week 48

  19. Number of Participants Who Developed Grade 3 or 4 Primary Adverse Events

    Grade 3 or 4 primary adverse events includes primary signs/symptoms, primary laboratory abnormalities, or primary diagnoses.

    See DAIDS AE Grading Table Version 1.0, Dec 2004 (Clarification, Aug 2009)

    Measured: From study treatment initiation to week 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jul 2011 (estimated)
  2. Study start17 Jan 2012
  3. Primary completion30 Jun 2014
  4. Study completion30 Jun 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
262 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01400412
Sponsor's protocol ID
ACTG A5303
Other IDs
1U01AI068636
Status last verified
Oct 2024
First submitted
21 Jul 2011
Last updated
15 Oct 2024
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 26060295

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Darunavir, Ritonavir and Tenofovir disoproxil fumarate in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 38 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jul 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) (time frame: Week 0, week 48). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01400412, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2024.

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