Skip to main content
OpenTrials
Completed

NCT Number: NCT00709111

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

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 despite sustained virologic suppression.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

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

Age range

16 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Alabama Therapeutics CRS (5801), Birmingham, Alabama, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • 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.

Exclusion criteria

  • 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
  • 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

Treatment and study plan

Maraviroc

Drug

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.

Other names: MVC, Selzentry

Primary outcomes

  1. 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).

Secondary outcomes

  1. Proportion of Participants Achieving a 50-cell Increase in CD4+ T-cell Count

    Time frame: From baseline to week 24

    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.

  2. Within-subject CD4+ T-cell Count Slopes

    Time frame: From baseline through week 24

    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.

  3. 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

    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.

  4. Change in CD4+ T-cell Count

    Time frame: From week 24 to week 36

    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).

  5. Change in CD4+ T-cell Count

    Time frame: From week 24 to week 48

    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).

  6. Change in CD4 Percentage

    Time frame: From baseline to week 24

    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).

  7. Within-subject CD4 Percentage Slopes

    Time frame: From baseline through week 24

    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.

  8. 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

    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.

  9. Change in CD4 Percentage

    Time frame: From week 24 to week 36

    Change was calculated as week 36 CD4 percentage minus the week 24 CD4 percentage (average of the week 22 and week 24 values).

  10. Change in CD4 Percentage

    Time frame: From week 24 to week 48

    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).

  11. 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

    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.

  12. 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 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).

  13. 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 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).

  14. 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 was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).

  15. 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 was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).

  16. 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 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).

  17. 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 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).

  18. Change in Soluble CD14

    Time frame: From baseline to week 24

    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.

  19. Change in Soluble CD14

    Time frame: From week 24 to week 36

    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.

  20. Change in Soluble CD14

    Time frame: From week 24 to week 48

    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.

  21. Change in High Sensitivity C-reactive Protein (Hs-CRP)

    Time frame: From baseline to week 24

    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).

  22. 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 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).

  23. 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 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).

  24. Change in D-dimer

    Time frame: From baseline to week 24

    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).

  25. Change in Hs-CRP

    Time frame: From week 24 to week 36

    Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).

  26. Change in IL-6, MCP-1, MCP-2, and Plasma CD40L

    Time frame: From week 24 to week 36

    Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).

  27. Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9

    Time frame: From week 24 to week 36

    Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).

  28. Change in D-dimer

    Time frame: From week 24 to week 36

    Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).

  29. Change in Hs-CRP

    Time frame: From week 24 to week 48

    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).

  30. Change in IL-6, MCP-1, MCP-2, and Plasma CD40L

    Time frame: From week 24 to week 48

    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).

  31. Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9

    Time frame: From week 24 to week 48

    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).

  32. Change in D-dimer

    Time frame: From week 24 to week 48

    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).

  33. 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

    A subject was considered detectable at a specific week if HIV-1 RNA by SCA >=1 copy/ml.

  34. Drug Adherence Assessed as Number of Missed Doses Over a 4-day Recall

    Time frame: At weeks 4, 12, and 24

    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.

Sponsors and collaborators

Lead sponsor

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

Network

Collaborators

  • National Institute of Allergy and Infectious Diseases (NIAID)

Registry information

Official study title

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

Important dates

Study start
2009
Primary completion
2009
Study completion
2010
First posted
Jul 3, 2008
Registry last updated
Oct 12, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.