Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
JF003
Study information
Scientific title
Investigating the effect of maraviroc on Microbial Translocation in HIV infected individuals who are receiving antiretroviral therapy: a phase IV, prospective, intervention study
Acronym
MT Study
Study hypothesis
This is a proof of concept study investigating a novel mechanism for the impact of maraviroc on clinical outcome
Ethics approval
St. Thomas' REC approval pending as of 20/04/2011
Study design
Phase IV prospective intervention study
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Human immunodeficiency virus (HIV)
Intervention
In this non-randomised study, maraviroc will be given according to the Summary of Product Characteristics (SmPC) for 24 weeks.
Maraviroc (dose based on current medications in regimen as per SmPC):
1.150 mg orally two times a day (PO BID) for those on a protease inhibitor-based regimen other than Tipranavir
2. 600 mg PO BID for efavirenz-containing regimens
3. 300 mg PO BID for all other regimens
Total duration of study is 24 weeks, plus screening period.
Intervention type
Drug
Phase
Phase IV
Drug names
Maraviroc
Primary outcome measure
Microbial translocation: soluble CD14a level
Measured at baseline, wk 2, wk 4, wk 12 and wk 24
Secondary outcome measures
1. Level of gut permeability/microbial translocation: bacterial 16s DNA will be quantified by polymerase chain reaction (PCR)
2. Th17 Tc17/MAIT cell quantification: Flow cytometry will quantify CD161+ T cells (CD4+ and CD8+) expressing IL17, Il22 and IFNg
3. Natural killer cell (NK) function: As markers of NK function, CD3-, CD161+ NK cell subset frequencies will be quantified and their secretion of IFNg, (also IL17 and IL22) analysed
4. Immune activation: As markers of CD8 T-cell activation, the percentage of CD3+ CD8+ cells expressing CD38+ and HLA-DR and PD-1 will be analysed
5. Clinical outcome: CD4+ T cell count change, HIV plasma viral load
6. Biomarkers of inflammation: Inflammatory cytokines will be analysed using a cytometric bead array (CBA) assay (IL-6, TNF and D-dimer) will be evaluated and their relationship to gut permeability and immune activation investigated
7. Low copy viral quantification of cell associated plasma and tissue cell-associated HIV DNA and HIV RNA by real-time polymerase chain reaction (PCR) and/or in situ hybridisation
8. Neurocognitive function: formal neurocognitive tests will be carried out to investigate the relationship between microbial translocation and neurocognitive function
9. Immune reconstitution/HIV specific immune function will be evaluated using intracellular cytokine staining (TNFa, IFNg, IL2, IL17) following in vitro HIV-derived antigenic stimulation by co-culture of peripheral blood mononuclear cell (PBMC) with gag peptides
10. Immunohistochemistry (gut only) will investigate the distribution of GALT (CD3, CD4, CD8), immune activation (CD38, Ki67), innate cells (T reg cells (FoxP3), dendritic cells (CD23), macrophages (CD68), gut permeability (ZO-1, occludin, claudins 1, 2, 5 and 8) and epithelial apoptosis (TUNEL)
11. Gut derived lymphocytes: Paired blood and gut derived lymphocyte samples will be analysed for the frequencies of CD3+ CD4+ or CD3+ CD8+ T cells expressing CD161 and secreting IL17
Measured at baseline, wk 2, wk 4, wk 12 and wk 24
Overall trial start date
01/09/2011
Overall trial end date
01/09/2012
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Males and females aged between 18-70 with confirmed human immunodeficiency virus (HIV)-1 infection
2. Patients on stable antiretroviral therapy for at least 12 months
3. Screening CD4+ T cell count below 350 cells/mm3
4. All available CD4+ T cell counts in the last year and at screening < 350 cells/mm3
5. Screening plasma HIV ribonucleic acid (RNA) levels below 100copies RNA/mL
6. All available plasma HIV RNA levels within past 6-months below the level of detection. Isolated values that are detectable but < 500 copies will be allowed as long as the plasma HIV RNA levels before and after this time point are undetectable.
7. Females of childbearing potential must have a negative serum pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period and at least 28 days after last dose of study drug. Effective methods include condoms in combination with a female condom, diaphragm, intrauterine device, hormonal contraceptives (oral, implants, injectable), abstinence, vasectomy or tubal ligation.
8. Ability and willingness of subject to provide informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
10
Participant exclusion criteria
1. Patient unlikely to comply with protocol, and in particular adhere to therapeutic regimen
2. Patient likely to use narcotics during the study period
3. Increase in CD4 count of > 100 cells/mm3 in past year
4. Patients who are intending to modify antiretroviral therapy in the next 24 weeks for any reason
5. Serious illness requiring hospitalization or parental antibiotics within preceding 3 months
6. Concurrent treatment with immunomodulatory drugs, or exposure to any immunomodulatory drug in past 16 weeks
7. Hepatitis B surface antigen (HBVsAg+) or active hepatitis C or hepatitis B which will require treatment in the subsequent 24 weeks
8. Prior exposure to chemokine (C-C motif) receptor 5 (CCR5) inhibitors
9. Estimated creatinine clearance < 40 mL/minute
10. Pregnant or breastfeeding women
11. Use of both tenofovir and didanosine in current antiretroviral therapy regimen
Recruitment start date
01/09/2011
Recruitment end date
01/09/2012
Locations
Countries of recruitment
United Kingdom
Trial participating centre
St. Thomas' Hospital
London
SE1 7EH
United Kingdom
Funders
Funder type
Industry
Funder name
Viiv Healthcare (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list