HIV InfectionsNCT00709111

Adding Maraviroc to Antiretroviral Therapy for Suboptimal CD4 T-Cell Recovery Despite Sustained Virologic Suppression

A study testing Maraviroc in people with HIV Infections, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 29 sites in United States.

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

Despite viral suppression, antiretroviral therapy (ART) does not restore CD4+ T-cell counts in some subjects. The purpose of this study is to assess whether adding maraviroc (MVC) to a suppressive ART will result in a significant CD4+ T-cell count increase over 24 weeks in subjects with suboptimal CD4+ T-cell recovery… Read more about this study

Who is it for?: Ages 16 years and older
Conditions the study is for: HIV Infections
What is being tested?: Maraviroc
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 34 participants
Where: 29 sitesUnited States
Study dates: Jan 2009to Apr 2010
Phase: Interventional
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 16 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

HIV-1 infection
On ART for at least 48 weeks prior to study entry with a regimen that includes three or more antiretroviral medications
No change in ART regimen for at least 24 weeks prior to study entry
Screening CD4+ T-cell count less than 250 obtained within 60 days prior to study entry
Stable CD4+ T-cell count for at least 48 weeks prior to study entry (as assessed by an estimated CD4+ T-cell count slope between -20 and +20 cells/year)
Screening HIV-1 RNA below the limit of detection using an FDA-approved assay obtained within 60 days prior to study entry

Show all 16Show fewer

All other plasma HIV-1 RNA measurements in the 48 weeks prior to study entry must be below the limit of detection
Laboratory values obtained within 60 days prior to study entry:
Absolute neutrophil count (ANC) >=750/µL
Hemoglobin >=9.0 g/dL for female subjects and >=10.0 g/dL for male subjects
Platelet count >=50,000/ µL
Calculated creatinine clearance (CrCl) >=30 mL/min
Aspartate aminotransferase (serum glutamic oxaloacetic transaminase), alanine aminotransferase (serum glutamic pyruvic transaminase), and alkaline phosphatase <=5 X Upper Limit of Normal (ULN)
Direct bilirubin <=2.5 X ULN
Females of reproductive potential will need a negative serum or urine pregnancy test within 48 hours prior to study entry
Agree not to participate in the conception process, and if participating in sexual activity that could lead to pregnancy, the subject/partner must use at least two reliable forms of contraceptives while receiving study treatment and for 6 weeks after stopping study treatment.

Who cannot join

Unstable clinical condition
Currently breast-feeding or pregnant
Use of immunomodulators or cancer chemotherapy or radiation treatment within 12 months prior to study entry
An acute AIDS-defining illness within 60 days prior to study entry
Known allergy/sensitivity or hypersensitivity to components of MVC, including allergy or hypersensitivity to soya lecithin, soya or peanuts
Active drug or alcohol abuse that, in the opinion of the investigator, would interfere with adherence to study regimens

Show all 11Show fewer

Serious illness requiring systemic treatment and/or hospitalization within 60 days prior to study entry
Receipt of a vaccine within 30 days prior to study entry
Current or previous use of a CCR5 inhibitor
Plan to change background ART regimen within 24 weeks after study entry
Receipt of experimental or non-experimental medications for the purpose of raising CD4+ T-cell counts within 6 months prior to study entry

Trial locations and contacts

29 sites in 1 country.

City, postcode or hospital

29 sites in 1 country

United States29 sites

The Ponce de Leon Ctr. CRS (5802)
Atlanta, Georgia, 30308
IHV Baltimore Treatment CRS (4651)
Baltimore, Maryland, 21201
Johns Hopkins Adult AIDS CRS (201)
Baltimore, Maryland, 21205
Alabama Therapeutics CRS (5801)
Birmingham, Alabama, 35294
Massachusetts General Hospital ACTG CRS (101)
Boston, Massachusetts, 02114
Brigham and Women's Hosp. ACTG CRS (107)
Boston, Massachusetts, 02115
Boston Medical Center ACTG CRS (104)
Boston, Massachusetts, 02118
Unc Aids Crs (3201)
Chapel Hill, North Carolina, 27516
Northwestern University CRS (2701)
Chicago, Illinois, 60611
Univ. of Cincinnati CRS (2401)
Cincinnati, Ohio, 45267
MetroHealth CRS (2503)
Cleveland, Ohio, 44109
The Ohio State Univ. AIDS CRS (2301)
Columbus, Ohio, 43210
Peabody Health Ctr. CRS (31443)
Dallas, Texas, 75215
Duke Univ. Med. Ctr. Adult CRS (1601)
Durham, North Carolina, 27710
Houston AIDS Research Team CRS (31473)
Houston, Texas, 77030
UCLA CARE Center CRS (601)
Los Angeles, California, 90035
Univ. of Miami AIDS CRS (901)
Miami, Florida, 33136
Vanderbilt Therapeutics CRS (3652)
Nashville, Tennessee, 37204
Cornell CRS (7804)
New York, New York, 10011
NY Univ. HIV/AIDS CRS (401)
New York, New York, 10016
Stanford CRS (501)
Palo Alto, California, 94304
Hosp. of the Univ. of Pennsylvania CRS (6201)
Philadelphia, Pennsylvania, 19104
Pittsburgh CRS (1001)
Pittsburgh, Pennsylvania, 15213
AIDS Care CRS (1108)
Rochester, New York, 14642
Univ. of Rochester ACTG CRS (1101)
Rochester, New York, 14642
Ucsd, Avrc Crs (701)
San Diego, California, 92103
Ucsf Aids Crs (801)
San Francisco, California, 94110
Washington University CRS (2101)
St Louis, Missouri, 63110
Georgetown University CRS (GU CRS) (1008)
Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: A Pilot Trial of Maraviroc for Treatment of Subjects on Antiretroviral Therapy With Suboptimal CD4 T-cell Count Recovery Despite Sustained Virologic Suppression

Read the detailed description

The majority of HIV-infected subjects with virologic suppression on antiretroviral therapy (ART) have a marked increase in CD4+ T-cell counts over the first year on treatment. However, a portion of these individuals show a suboptimal immune response and remain at an elevated risk for disease progression. The use of the CCR5 inhibitor maraviroc (MVC) is associated with enhanced CD4+ T-cell recovery in subjects who initiate ART. AIDS Clinical Trials Group (ACTG) A5256 studied the effect of ART intensification with MVC on CD4+ T-cell counts in subjects with suboptimal CD4 recovery despite sustained virologic suppression. Eligible subjects added MVC to their ART regimen, and continued MVC for 24 weeks. At week 24, subjects discontinued MVC and were followed for an additional 24 weeks off MVC.

Subjects were seen through week 48 for clinical and laboratory evaluations, including plasma HIV-1 RNA, CD4+ T-cell count, and safety laboratories. Subjects had 2 baseline visits prior to starting MVC. Study visits were scheduled at weeks 4, 8, 12, 16, 22, 24, 36, 46, and 48. CD4+ T-cell counts were measured at every study visit and HIV-1 RNA at weeks 12, 24, 36, and 48, regardless of treatment status. Measures of activation, T-cell maturation, and apoptosis were performed at all weeks except 4, 8, and 16. At the end of the study, the pre-entry, entry, week 12, 22, 24, and 36 samples for the HIV-1 RNA by single-copy assay (SCA) were run. The week 46 and 48 samples were not run.

Conditions: HIV Infections
Being tested: Maraviroc
Keywords: CCR5 antagonist, CD4 T-cell count, immune activation, treatment experienced
Medical subject headings: HIV Infections

What participants receive

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

MaravirocDrug
Also called MVC, Selzentry
The maraviroc doses were 150 mg orally twice daily, 300 mg orally twice daily, or 600 mg orally twice daily, depending on the pharmacokinetic interaction with a subject's pre-study ART and non-ART drug regimen according to the package insert.

Study groups in NCT00709111
Study group	Role	What they receive
Maraviroc	Experimental	Maraviroc (MVC) was taken for 24 weeks, in addition to the subject's current antiretroviral therapy (ART) drug regimen. At week 24, subjects discontinued MVC and were followed for an additional 24 weeks off MVC, but still on current ART drug regimen. Receives: Drug: Maraviroc

What is being measured

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

Change in CD4+ T-cell Count
Change was calculated as the week 24 CD4+ T-cell count (average of the week 22 and week 24 values) minus the baseline CD4+ T-cell count (average of pre-entry and entry values).
Measured: From baseline to week 24

Secondary outcomes (34)

Proportion of Participants Achieving a 50-cell Increase in CD4+ T-cell Count
Baseline was defined as the average of pre-entry and entry values. Week 24 was defined as the average of the week 22 and week 24 values.
Measured: From baseline to week 24
Within-subject CD4+ T-cell Count Slopes
The estimated mean slope was summarized across the population by using generalized estimating equations. Baseline was defined as the average of pre-entry and entry values. Week 24 was defined as the average of the week 22 and week 24 values.
Measured: From baseline through week 24
Change From Within-subject Pre-treatment CD4+ T-cell Count Slopes to Corresponding Within-subject CD4+ T-cell Count Slopes From Baseline Through Week 24
The estimated mean change in slopes was summarized across the population by using generalized estimating equations. Pre-treatment CD4+ T-cell counts (from at least 48 weeks prior to study entry) were recorded at screening from patient source documentation. Baseline was defined as the average of pre-entry and entry values. Week 24 was defined as the average of the week 22 and week 24 values.
Measured: From pre-treatment through week 24
Change in CD4+ T-cell Count
Change was calculated as week 36 CD4+ T-cell count minus the week 24 CD4+ T-cell count (average of the week 22 and week 24 values).
Measured: From week 24 to week 36
Change in CD4+ T-cell Count
Change was calculated as week 48 CD4+ T-cell count (average of week 46 and week 48) minus the week 24 CD4+ T-cell count (average of the week 22 and week 24 values).
Measured: From week 24 to week 48
Change in CD4 Percentage
Change was calculated as the week 24 CD4 percentage (average of the week 22 and week 24 values) minus the baseline CD4 percentage (average of pre-entry and entry values).
Measured: From baseline to week 24
Within-subject CD4 Percentage Slopes
The estimated mean slope was summarized across the population by using generalized estimating equations. Baseline was defined as the average of pre-entry and entry values. Week 24 was defined as the average of the week 22 and week 24 values.
Measured: From baseline through week 24
Change From Within-subject Pre-treatment CD4 Percentage Slopes to Corresponding Within-subject CD4 Percentage Slopes From Baseline Through Week 24
The estimated mean change in slopes was summarized across the population by using generalized estimating equations. Pre-treatment CD4 percentage (from at least 48 weeks prior to study entry) were recorded at screening from patient source documentation. Baseline was defined as the average of pre-entry and entry values. Week 24 was defined as the average of the week 22 and week 24 values.
Measured: From pre-treatment through week 24
Change in CD4 Percentage
Change was calculated as week 36 CD4 percentage minus the week 24 CD4 percentage (average of the week 22 and week 24 values).
Measured: From week 24 to week 36
Change in CD4 Percentage
Change was calculated as week 48 CD4 percentage (average of week 46 and week 48) minus the week 24 CD4 percentage (average of the week 22 and week 24 values).
Measured: From week 24 to week 48
Number of Subjects Who Experience a Grade 2, 3 or 4 Signs and Symptoms, Grade 3 or 4 Laboratory Abnormalities, or Death.
Events with date of onset or specimen date prior to first dose of MVC or after the last dose of MVC were excluded. Signs and symptoms with a date of onset the same as the first dose of MVC were excluded if confirmed by the site to be before the first dose. Lab abnormalities with the date of specimen the same as the date of the first dose of MVC were excluded on the assumption that the specimen was drawn before the first dose. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables, where Grade 1=Mild, 2=Moderate, 3=Severe, 4=Potentially life-threatening.
Measured: From baseline through week 24
Change in Percentage of CD4+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
Measured: From baseline to week 24
Change in Percentage of CD8+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
Measured: From baseline to week 24
Change in Percentage of CD4+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
Measured: From week 24 to week 36
Change in Percentage of CD8+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
Measured: From week 24 to week 36
Change in Percentage of CD4+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
Measured: From week 24 to week 48
Change in Percentage of CD8+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
Measured: From week 24 to week 48
Change in Soluble CD14
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values). Soluble CD14 is a marker of gut microbial translocation.
Measured: From baseline to week 24
Change in Soluble CD14
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values). Soluble CD14 is a marker of gut microbial translocation.
Measured: From week 24 to week 36
Change in Soluble CD14
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values). Soluble CD14 is a marker of gut microbial translocation.
Measured: From week 24 to week 48
Change in High Sensitivity C-reactive Protein (Hs-CRP)
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
Measured: From baseline to week 24
Change in Interleukin (IL)-6, Monocyte Chemoattractant Protein (MCP)-1, MCP-2, and Plasma CD40 Ligand (CD40L)
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
Measured: From baseline to week 24
Change in Intercellular Cell Adhesion Molecule (ICAM)-1, Plasma P-selectin, Soluble TNFRII (sTNFRII), and Matrix Metalloproteinase (MMP)-9
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
Measured: From baseline to week 24
Change in D-dimer
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
Measured: From baseline to week 24
Change in Hs-CRP
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
Measured: From week 24 to week 36
Change in IL-6, MCP-1, MCP-2, and Plasma CD40L
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
Measured: From week 24 to week 36
Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
Measured: From week 24 to week 36
Change in D-dimer
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
Measured: From week 24 to week 36
Change in Hs-CRP
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
Measured: From week 24 to week 48
Change in IL-6, MCP-1, MCP-2, and Plasma CD40L
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
Measured: From week 24 to week 48
Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
Measured: From week 24 to week 48
Change in D-dimer
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
Measured: From week 24 to week 48
Proportion of Participants With Detectable HIV-1 Viremia as Measured by Single Copy Assay (SCA)
A subject was considered detectable at a specific week if HIV-1 RNA by SCA >=1 copy/ml.
Measured: At weeks -1 (pre-entry), 0 (entry), 12, 22, 24, and 36
Drug Adherence Assessed as Number of Missed Doses Over a 4-day Recall
Self-reported MVC adherence data were based on a four-day (8 expected doses) recall. Based on the wording of the Self Report case report form (CRF), participants reporting that they were currently taking MVC that then failed to complete the record of the number of missed doses were assumed to have no missed doses to report. Missing adherence assessments at a time point of interest were ignored and only those participants completing an adherence assessment at least one time point of interest were included.
Measured: At weeks 4, 12, and 24

Timeline

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

Jan 2009Apr 2010

First posted3 Jul 2008 (estimated)
Study startJan 2009
Primary completionOct 2009
Study completionApr 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (6)Papers the sponsor has linked to this study.
Other trials for HIV InfectionsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 N/A
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 34 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00709111
Sponsor's protocol ID: ACTG A5256
Other IDs: 1U01AI068636
Status last verified: Sep 2018
First submitted: 1 Jul 2008
Last updated: 12 Oct 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Fadel H, Temesgen Z. Maraviroc. Drugs Today (Barc). 2007 Nov;43(11):749-58. doi: 10.1358/dot.2007.43.11.1131763.
PubMed 18174962
MacArthur RD, Novak RM. Reviews of anti-infective agents: maraviroc: the first of a new class of antiretroviral agents. Clin Infect Dis. 2008 Jul 15;47(2):236-41. doi: 10.1086/589289.
PubMed 18532888
Wilkin T, Lalama C, Tenorio A, Landay A, Ribaudo H, McKinnon J, Gandhi R, Mellors J, Currier J, and Gulick R. Maraviroc Intensification for Suboptimal CD4+ Cell Response Despite Sustained Virologic Suppression: ACTG 5256. 17th Conference on Retroviruses and Opportunistic Infections, San Francisco, CA, February 16-19, 2010.
Wilkin T, Lalama C, Tenorio A, Landay A, Fox L, McKinnon J, Gandhi R, Mellors J, Currier J, Gulick R. ACTG 5256: Effect of adding and removing maraviroc (MVC) on immune activation in participants on suppressive antiretroviral therapy (ART). 18th Conference on Retroviruses and Opportunistic Infections, Boston, MA, February 27-March 02, 2011.
Hilldorfer B, Lalama C, McKinnon J, Coombs B, Tenorio A, Fox L, Gandhi R, Ribaudo H, Currier J, Gulick R, Wilkin TJ, Mellors J. Effects of Maraviroc (MVC) on Residual Low-Level Viremia in Patients on Suppressive Antiretroviral Therapy (ART): Results from ACTG 5256. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Rome, Italy, July 17-20, 2011.
Wilkin TJ, Lalama CM, McKinnon J, Gandhi RT, Lin N, Landay A, Ribaudo H, Fox L, Currier JS, Mellors JW, Gulick R, Tenorio AR. A pilot trial of adding maraviroc to suppressive antiretroviral therapy for suboptimal CD4(+) T-cell recovery despite sustained virologic suppression: ACTG A5256. J Infect Dis. 2012 Aug 15;206(4):534-42. doi: 10.1093/infdis/jis376. Epub 2012 Jun 27.
PubMed 22740718

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 12 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Trial of Maraviroc for Treatment of Subjects on Antiretroviral Therapy With Suboptimal CD4 T-cell Count Recovery Despite Sustained Virologic Suppression
ClinicalTrials.gov ID: NCT00709111
Acronym / sponsor ID: ACTG A5256
Conditions: HIV Infections
Keywords: CCR5 antagonist, CD4 T-cell count, immune activation, treatment experienced
Study type: Interventional
Recruitment status: Completed
Enrolment: 34 participants (actual)
Lead sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other InfectionsResearch network
Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Study start: Jan 2009
Primary completion: Oct 2009 (actual)
Study completion: Apr 2010 (actual)
First posted: 3 Jul 2008 (estimated)
Results: Posted 24 Feb 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Maraviroc	Experimental	Drug: MaravirocMaraviroc (MVC) was taken for 24 weeks, in addition to the subject's current antiretroviral therapy (ART) drug regimen. At week 24, subjects discontinued MVC and were followed for an additional 24 weeks off MVC, but still on current ART drug regimen.

Who may qualify

Ages: 16 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (16 listed)

HIV-1 infection
On ART for at least 48 weeks prior to study entry with a regimen that includes three or more antiretroviral medications
No change in ART regimen for at least 24 weeks prior to study entry
Screening CD4+ T-cell count less than 250 obtained within 60 days prior to study entry
Stable CD4+ T-cell count for at least 48 weeks prior to study entry (as assessed by an estimated CD4+ T-cell count slope between -20 and +20 cells/year)

Key exclusion criteria (11 listed)

Unstable clinical condition
Currently breast-feeding or pregnant
Use of immunomodulators or cancer chemotherapy or radiation treatment within 12 months prior to study entry
An acute AIDS-defining illness within 60 days prior to study entry
Known allergy/sensitivity or hypersensitivity to components of MVC, including allergy or hypersensitivity to soya lecithin, soya or peanuts

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MaravirocAlso: MVC, SelzentryThe maraviroc doses were 150 mg orally twice daily, 300 mg orally twice daily, or 600 mg orally twice daily, depending on the pharmacokinetic interaction with a subject's pre-study ART and non-ART drug regimen according to the package insert.	Drug	Maraviroc

Primary outcome

Change in CD4+ T-cell Count
Time frame: From baseline to week 24
Change was calculated as the week 24 CD4+ T-cell count (average of the week 22 and week 24 values) minus the baseline CD4+ T-cell count (average of pre-entry and entry values).

34 secondary outcomes

Proportion of Participants Achieving a 50-cell Increase in CD4+ T-cell Count
Time frame: From baseline to week 24
Within-subject CD4+ T-cell Count Slopes
Time frame: From baseline through week 24
Change From Within-subject Pre-treatment CD4+ T-cell Count Slopes to Corresponding Within-subject CD4+ T-cell Count Slopes From Baseline Through Week 24
Time frame: From pre-treatment through week 24
Change in CD4+ T-cell Count
Time frame: From week 24 to week 36
Change in CD4+ T-cell Count
Time frame: From week 24 to week 48
Change in CD4 Percentage
Time frame: From baseline to week 24
Within-subject CD4 Percentage Slopes
Time frame: From baseline through week 24
Change From Within-subject Pre-treatment CD4 Percentage Slopes to Corresponding Within-subject CD4 Percentage Slopes From Baseline Through Week 24
Time frame: From pre-treatment through week 24
Change in CD4 Percentage
Time frame: From week 24 to week 36
Change in CD4 Percentage
Time frame: From week 24 to week 48
Number of Subjects Who Experience a Grade 2, 3 or 4 Signs and Symptoms, Grade 3 or 4 Laboratory Abnormalities, or Death.
Time frame: From baseline through week 24
Change in Percentage of CD4+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+
Time frame: From baseline to week 24
Change in Percentage of CD8+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+
Time frame: From baseline to week 24
Change in Percentage of CD4+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+
Time frame: From week 24 to week 36
Change in Percentage of CD8+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+
Time frame: From week 24 to week 36
Change in Percentage of CD4+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+
Time frame: From week 24 to week 48
Change in Percentage of CD8+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+
Time frame: From week 24 to week 48
Change in Soluble CD14
Time frame: From baseline to week 24
Change in Soluble CD14
Time frame: From week 24 to week 36
Change in Soluble CD14
Time frame: From week 24 to week 48
Change in High Sensitivity C-reactive Protein (Hs-CRP)
Time frame: From baseline to week 24
Change in Interleukin (IL)-6, Monocyte Chemoattractant Protein (MCP)-1, MCP-2, and Plasma CD40 Ligand (CD40L)
Time frame: From baseline to week 24
Change in Intercellular Cell Adhesion Molecule (ICAM)-1, Plasma P-selectin, Soluble TNFRII (sTNFRII), and Matrix Metalloproteinase (MMP)-9
Time frame: From baseline to week 24
Change in D-dimer
Time frame: From baseline to week 24
Change in Hs-CRP
Time frame: From week 24 to week 36
Change in IL-6, MCP-1, MCP-2, and Plasma CD40L
Time frame: From week 24 to week 36
Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9
Time frame: From week 24 to week 36
Change in D-dimer
Time frame: From week 24 to week 36
Change in Hs-CRP
Time frame: From week 24 to week 48
Change in IL-6, MCP-1, MCP-2, and Plasma CD40L
Time frame: From week 24 to week 48
Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9
Time frame: From week 24 to week 48
Change in D-dimer
Time frame: From week 24 to week 48
Proportion of Participants With Detectable HIV-1 Viremia as Measured by Single Copy Assay (SCA)
Time frame: At weeks -1 (pre-entry), 0 (entry), 12, 22, 24, and 36
Drug Adherence Assessed as Number of Missed Doses Over a 4-day Recall
Time frame: At weeks 4, 12, and 24

Results and safety

Results posted to the registry on 24 Feb 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Maraviroc	34	32

Primary outcome: Change in CD4+ T-cell Count

Time frame: From baseline to week 24. Median (90% Confidence Interval). Unit: cells/mm^3

Measure	Maraviroc n = 32
Value	12 (1 to 22)

Maraviroc: p = 0.97, Wilcoxon signed-rank, 1-sided

Population analysed: As-treated: Only participants with either a week 22 CD4+ T-cell count or a week 24 CD4+ T-cell count obtained while receiving MVC without change in background regimen were included.

34 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose of MVC until off-study. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Maraviroc	4 of 34 (11.8%)	22 of 34 (64.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 18174962Fadel H, Temesgen Z. Maraviroc. Drugs Today (Barc). 2007 Nov;43(11):749-58. doi: 10.1358/dot.2007.43.11.1131763.
Background: PubMed 18532888MacArthur RD, Novak RM. Reviews of anti-infective agents: maraviroc: the first of a new class of antiretroviral agents. Clin Infect Dis. 2008 Jul 15;47(2):236-41. doi: 10.1086/589289.
Results publicationWilkin T, Lalama C, Tenorio A, Landay A, Ribaudo H, McKinnon J, Gandhi R, Mellors J, Currier J, and Gulick R. Maraviroc Intensification for Suboptimal CD4+ Cell Response Despite Sustained Virologic Suppression: ACTG 5256. 17th Conference on Retroviruses and Opportunistic Infections, San Francisco, CA, February 16-19, 2010.
Results publicationWilkin T, Lalama C, Tenorio A, Landay A, Fox L, McKinnon J, Gandhi R, Mellors J, Currier J, Gulick R. ACTG 5256: Effect of adding and removing maraviroc (MVC) on immune activation in participants on suppressive antiretroviral therapy (ART). 18th Conference on Retroviruses and Opportunistic Infections, Boston, MA, February 27-March 02, 2011.
Results publicationHilldorfer B, Lalama C, McKinnon J, Coombs B, Tenorio A, Fox L, Gandhi R, Ribaudo H, Currier J, Gulick R, Wilkin TJ, Mellors J. Effects of Maraviroc (MVC) on Residual Low-Level Viremia in Patients on Suppressive Antiretroviral Therapy (ART): Results from ACTG 5256. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Rome, Italy, July 17-20, 2011.
Derived from this study: PubMed 22740718Wilkin TJ, Lalama CM, McKinnon J, Gandhi RT, Lin N, Landay A, Ribaudo H, Fox L, Currier JS, Mellors JW, Gulick R, Tenorio AR. A pilot trial of adding maraviroc to suppressive antiretroviral therapy for suboptimal CD4(+) T-cell recovery despite sustained virologic suppression: ACTG A5256. J Infect Dis. 2012 Aug 15;206(4):534-42. doi: 10.1093/infdis/jis376. Epub 2012 Jun 27.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Timothy J. Wilkin, MD, MPH study chair

Cornell Clinical Research Site

Roy Gulick, MD, MPH study chair

Cornell HIV Clinical Trials Unit

29 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Maraviroc in people with HIV Infections, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 29 sites in United States.

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 16 inclusion and 11 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 12 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in United States. 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Feb 2012). 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?

Change in CD4+ T-cell Count (time frame: From baseline to week 24). 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 NCT00709111, which also lists 6 linked publications.

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 12 Oct 2018.