HIV-1 InfectionPhase 2NCT01466595
Rifaximin as a Modulator of Microbial Translocation and Immune Activation
A Phase 2 study testing Rifaximin in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 32 sites in 2 countries.
Trial summary
This study is being done to see whether rifaximin, an antibiotic that works in the intestines, can lower the amount of germs in the intestines of HIV infected persons. It is possible that when the amount of these germs is lowered, an HIV-infected person's immune system will become less active and will have a better… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV-1 Infection
- What is being tested?
- Rifaximin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 73 participants
- Where
- 32 sitesin 2 countries
- Study dates
- Sep 2011to Nov 2012
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infection
- On ART for at least 96 weeks prior to study entry with a regimen that includes three or more antiretroviral medications. (Ritonavir ≤ 400 mg/day will not be considered a separate antiretroviral agent.)
- No plans to change the antiretroviral regimen at least in the next 3 months after study entry.
- CD4+ cell count < 350 cells/mm3 obtained within 120 days prior to study entry at any laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.
- All previous CD4+ cell counts should be < 350 cells/mm3 for at least 96 weeks prior to study entry while subjects were on ART. (A single CD4+ cell count ≥ 350 cells/mm3 is permitted within 96 weeks prior to study entry while subjects were on ART.)
- Documentation of HIV-1 RNA below the limit of detection (e.g., < 50 copies/mL on Roche Amplicor HIV-1 Monitor assay, < 75 copies/mL on the Versant HIV-1 RNA assay by branched DNA, < 400 copies/mL on a standard Roche Amplicor assay, < 40 copies/mL on the Abbott m2000sp/m2000rt real-time PCR test, < 48 copies/mL on the COBAS AmpliPrep/TAQMAN HIV-1 assay) verified by at least two measurements prior to study entry, one of which must be at least 48 weeks prior to study entry and one measurement that was obtained between 121 days and 48 weeks prior to study entry.
Show all 14Show fewer
- Screening HIV-1 RNA below the limit of detection obtained within 120 days prior to study entry using a FDA -approved assay (e.g., < 50 copies/mL on Roche Amplicor HIV-1 Monitor assay, < 75 copies/mL on the Versant HIV-1 RNA assay by branched DNA, < 40 copies/mL on the Abbott m2000sp/m2000rt real-time PCR test, < 48 copies/mL on the COBAS AmpliPrep/TAQMAN HIV-1 assay). (The virologic assay must have a lower limit of detection of ≤ 75 copies/mL.)
- All other plasma HIV-1 RNA measurements in the 48 weeks prior to study entry must be below the limit of detection. (A single detectable measurement of ≤ 200 copies/mL is permitted if RNA levels immediately before and after are below the limits of detection for the assay.)
- Certain fasting laboratory values obtained within 45 days prior to entry as indicated in Section 4.1.9 of the protocol.
- Pre-entry peripheral blood mononuclear cell (PBMC) specimen for assay of the primary immune activation endpoint (change in CD8+ T-cells activation (%HLA-DR+CD38+CD8+ T-cells) has been obtained. Sites must receive confirmation from the processing lab via phone, e-mail, or fax, that this specimen has been entered into the ACTG's Laboratory Data Management System (LDMS).
- Female subjects of reproductive potential must have a negative serum or urine β-HCG pregnancy test with a sensitivity of at least 50 mIU/mL performed within 24 hours prior to study entry.
- If participating in sexual activity that could lead to pregnancy, the female subject must agree to use one form of contraceptive as listed in section 4.1.11 of the protocol while receiving protocol-specified treatment and for 4 weeks after stopping the treatment.
- If the female subject is not of reproductive potential, she is eligible without requiring the use of a contraceptive. Self report is acceptable documentation of sterilization, other contraceptive methods, and menopause.
- Ability and willingness of subject or legally authorized representative to provide informed consent.
Who cannot join
- Active diarrhea (3 or more unformed stools per day) within 28 days prior to study entry (except if site investigator or primary care provider attributes diarrhea to antiretroviral or azithromycin use).
- History of or active inflammatory bowel disease.
- History of or active Clostridium difficile colitis.
- History of significant liver disease, defined as having chronic liver disease (including chronic alcoholic liver disease, hepatitis B or C), plus either: a) ascites, b) encephalopathy, or c) a Child-Pugh Score of > 7.
- Receipt of antimicrobial therapy within 30 days prior to study entry. (NOTE: Antimicrobial use for prophylaxis of opportunistic infections, e.g., azithromycin or trimethoprim-sulfamethoxazole, is allowed.)
- Active infection requiring the use of antibiotics within 30 days prior to study entry.
Show all 18Show fewer
- Known allergy/sensitivity or any hypersensitivity to components of study drug or their formulation (e.g., allergy to rifampin).
- Serious illness requiring systemic treatment and/or hospitalization within 14 days prior to entry.
- Use of any of the following medications for more than 3 consecutive days within the 60 days prior to study entry:
- Immunosuppressives
- Immune modulators
- Antineoplastic agents
- Probiotics
- Anticoagulants
- Vaccinations within 1 week prior to the pre-entry or study entry visits. (NOTE: Subjects are encouraged to get the flu vaccine prior to study pre-entry visit.)
- Participation on any HIV immunotherapy/therapeutic vaccination trials within 6 months prior to study entry.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Breastfeeding.
Trial locations and contacts
32 sites in 2 countries.
32 sites in 2 countries
United States31 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
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
Beth Israel Deaconess Med. Ctr., ACTG CRS (103)
Boston, Massachusetts, 02215
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
Duke Univ. Med. Ctr. Adult CRS (1601)
Durham, North Carolina, 27710
UCLA CARE Center CRS (601)
Los Angeles, California, 90095
Univ. of Miami AIDS CRS (901)
Miami, Florida, 33136
Cornell CRS (7804)
New York, New York, 10011
NY Univ. HIV/AIDS CRS (401)
New York, New York, 10016
HIV Prevention & Treatment CRS (30329)
New York, New York, 10032
New Jersey Medical School-Adult Clinical Research Ctr. CRS (31477)
Newark, New Jersey, 07103
Stanford CRS (501)
Palo Alto, California, 94304
Hosp. of the Univ. of Pennsylvania CRS (6201)
Philadelphia, Pennsylvania, 19104
Pittsburgh CRS (1001)
Pittsburgh, Pennsylvania, 15213
The Miriam Hosp. ACTG CRS (2951)
Providence, Rhode Island, 02906
AIDS Care CRS (1108)
Rochester, New York, 14642
Univ. of Rochester ACTG CRS (1101)
Rochester, New York, 14642
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
Georgetown University CRS (GU CRS) (1008)
Washington D.C., District of Columbia, 20007
About this study
Official title: A Pilot Study of Rifaximin as a Modulator of Gut Microbial Translocation and Systemic Immune Activation in HIV-Infected Individuals With Incomplete CD4+ T-cell Recovery on Antiretroviral Therapy
This study is being done to see whether rifaximin, an antibiotic that works in the intestines, can lower the amount of germs in the intestines of HIV infected persons. It is possible that when the amount of these germs is lowered, an HIV-infected person's immune system will become less active and will have a better chance of recovering. Also, the study will evaluate the safety of using rifaximin in HIV-infected subjects.
Read the detailed description
A5286 is a randomized, open-label, two-arm, pilot (phase II) study that evaluated whether 4 weeks of treatment with rifaximin, a non-absorbable antibiotic, decreases markers of immune activation and levels of translocated gut microbial products in HIV-1 infected subjects virally suppressed on ART with CD4+ T-cells < 350 cells/mm^3. Rifaximin were admistered to subjects for 3 weeks. Follow-up continued to week 12. The total sample size was 73 subjects. Subjects were randomized at a 2:1 ratio (rifaximin: no study treatment), using permuted blocks, without institutional balancing.
Subjects were seen through week 12 for clinical and laboratory evaluations, including plasma HIV-1 RNA, CD4+ T-cell count, and safety laboratories. Subjects had 2 baseline visits -- at pre-entry and entry. Study visits were scheduled at weeks 2, 4, 8, and 12. CD4+ T-cell counts and HIV-1 RNA were measured at all weeks; measures of activations, gut-homing markers, and soluble biomarkers were also performed at all weeks.
- Conditions
- HIV-1 Infection
- Being tested
- Rifaximin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RifaximinDrug
Participant were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Treatment with rifaximin | Experimental | Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks. Receives: Drug: Rifaximin |
| Arm B: No study treatment | No intervention | No study treatment for 4 weeks |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in CD8+ T-cell Activation From Baseline to Week 4
Change in CD8+ T-cell activation percent co-expressing HLA-DR and CD38 from baseline to week 4, where the baseline value is the average of pre-entry and entry values.
Measured: At baseline and 4 weeks
Secondary outcomes (42)
Change in D-dimer From Baseline to Week 4
Change in D-dimer from baseline to week 4, where baseline value is the average of pre-entry and entry.
D-dimer is a fibrin degradation product (FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis.
Measured: At baseline and 4 weeks
Change in IL-6 From Baseline to Week 4
Change in Interleukin (IL)-6 from baseline to week 4, where baseline value is the average of pre-entry and entry
Measured: At baseline and 4 weeks
Change in LPS From Baseline to Week 4
Change in Lipopolysaccharide (LPS) from baseline to week 4, where baseline value is the average of pre-entry and entry
Measured: At baseline and 4 weeks
Change in hsCRP From Baseline to Week 4
Change in High Sensitivity C-reactive Protein (Hs-CRP) from baseline to week 4, where baseline value is the average of pre-entry and entry
Measured: At baseline and 4 weeks
Change in sCD14 From Baseline to Week 4
Change in soluble CD14 (sCD14) from baseline to week 4, where baseline value is the average of pre-entry and entry
Measured: At baseline and 4 weeks
Change in Peripheral B7hi CD4+ T-cell From Baseline to Week 4
Change in gut-homing percent B7hi+ of CD4+ from baseline to week 4, where baseline value is the average of pre-entry and entry
Measured: At baseline and 4 weeks
Change in %CD38+ of CD4+ From Baseline to Week 4
Change in advanced flow percent CD38+ of CD4+ from baseline to week 4, where baseline value is the average of pre-entry and entry
Measured: At baseline and 4 weeks
Change in %CD38+ of CD8+ From Baseline to Week 4
Change in advanced flow percent CD38+ of CD8+ from baseline to week 4, where baseline value is the average of pre-entry and entry
Measured: At baseline and 4 weeks
Change in %Ki67+ of CD4+ From Baseline to Week 4
Change in advanced flow percent Ki67+ of CD4+ from baseline to week 4, where baseline value is the average of pre-entry and entry
Measured: At baseline and 4 weeks
Change in %Ki67+ of CD8+ From Baseline to Week 4
Change in advanced flow percent Ki67+ of CD8+ from baseline to week 4, where baseline value is the average of pre-entry and entry
Measured: At baseline and 4 weeks
Change in %HLA-DR+/CD38+ of CD4+ From Baseline to Week 4
Change in CD4 activation percent co-expressing HLA-DR and CD38 from baseline to week 4, where baseline value is the average of pre-entry and entry
Measured: At baseline and 4 weeks
Change in CD38+ of CD8+ MFI From Baseline to Week 4
Change in CD38+ of CD8+ MFI (Median Fluorescence Intensity) from baseline to week 4, where baseline value is the average of pre-entry and entry.
MFI measures the shift in fluorescence intensity of a population of cells. MFI values are based on control to demonstrate an increase or decrease in expression of the marker. MFI in this study was automatically calculated in FlowJo. The median is the relative intensity value below which 50% of the events are found. MFI is an arbitrary unit of relative intensity.
Measured: At baseline and 4 weeks
Change in CD4 Count From Baseline to Week 4
Change in total CD4 T-cell from baseline to week 4, where baseline value is the average of pre-entry and entry
Measured: At baseline and 4 weeks
Change in CD8+ T-cell Activation From Week 4 to Week 8
Change in CD8+ T-cell activation percent co-expressing HLA-DR and CD38 from week 4 to week 8
Measured: At weeks 4 and 8
Change in D-dimer From Week 4 to Week 8
D-dimer is a fibrin degradation product (FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis.
Measured: At weeks 4 and 8
Change in IL-6 From Week 4 to Week 8
Change in IL-6 from week 4 to week 8.
Measured: At weeks 4 and 8
Change in LPS From Week 4 to Week 8
Change in LPS from week 4 to week 8.
Measured: At weeks 4 and 8
Change in hsCRP From Week 4 to Week 8
Change in hsCRP from week 4 to week 8.
Measured: At weeks 4 and 8
Change in sCD14 From Week 4 to Week 8
Change in soluble CD14 from week 4 to week 8
Measured: At weeks 4 and 8
Change in Peripheral B7hi CD4+ T-cells From Week 4 to Week 8
Change in gut homing percent B7hi+ of CD4+ from week 4 to week 8
Measured: At weeks 4 and 8
Change in %CD38+ of CD4+ From Week 4 to Week 8
Change in advanced flow percent CD38+ of CD4+ from week 4 to week 8
Measured: At weeks 4 and 8
Change in %CD38+ of CD8+ From Week 4 to Week 8
Change in advanced flow percent CD38+ of CD8+ from week 4 to week 8
Measured: At weeks 4 and 8
Change in %Ki67+ of CD4+ From Week 4 to Week 8
Change in advanced flow percent Ki67+ of CD4+ from week 4 to week 8
Measured: At weeks 4 and 8
Change in %Ki67+ of CD8+ From Week 4 to Week 8
Change in advanced flow percent Ki67+ of CD8+ from week 4 to week 8
Measured: At weeks 4 and 8
Change in CD4 Activation Percent From Week 4 to Week 8
Change in CD4 activation percent co-expressing HLA-DR and CD38 from week 4 to week 8
Measured: At weeks 4 and 8
Change in CD38+ of CD8+ MFI From Week 4 to Week 8
Change in CD38+ of CD8+ median fluorescence intensity (MFI) from week 4 to week 8.
MFI measures the shift in fluorescence intensity of a population of cells. MFI values are based on control to demonstrate an increase or decrease in expression of the marker. MFI in this study was automatically calculated in FlowJo. The median is the relative intensity value below which 50% of the events are found. MFI is an arbitrary unit of relative intensity.
Measured: At weeks 4 and 8
Change in CD4 Count From Week 4 to Week 8
Change in total CD4 T-cell count from week 4 to week 8
Measured: At weeks 4 and 8
Change in CD8+ T-cell Activation From Week 4 to Week 12
Change in CD8+ T-cell activation percent co-expressing HLA-DR and CD38 from week 4 to week 12
Measured: At weeks 4 and 12
Change in D-dimer From Week 4 to Week 12
D-dimer is a fibrin degradation product (FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis.
Measured: At weeks 4 and 12
Change in IL-6 From Week 4 to Week 12
Change in IL-6 from week 4 to week 12.
Measured: At weeks 4 and 12
Change in LPS From Week 4 to Week 12
Change in LPS from week 4 to week 12.
Measured: At weeks 4 and 12
Change in hsCRP From Week 4 to Week 12
Change in hsCRP from week 4 to week 12.
Measured: At weeks 4 and 12
Change in sCD14 From Week 4 to Week 12
Change in soluble CD14 from week 4 to week 12
Measured: At weeks 4 and 8
Change in Peripheral B7hi CD4+ T-cells From Week 4 to Week 12
Change in gut homing percent B7hi+ of CD4+ from week 4 to week 12
Measured: At weeks 4 and 12
Change in %CD38+ of CD4+ From Week 4 to Week 12
Change in advanced flow percent CD38+ of CD4+ from week 4 to week 12
Measured: At weeks 4 and 12
Change in %CD38+ of CD8+ From Week 4 to Week 12
Change in advanced flow percent CD38+ of CD8+ from week 4 to week 12
Measured: At weeks 4 and 12
Change in %Ki67+ of CD4+ From Week 4 to Week 12
Change in advanced flow percent Ki67+ of CD4+ from week 4 to week 12
Measured: At weeks 4 and 12
Change in %Ki67+ of CD8+ From Week 4 to Week 12
Change in advanced flow percent Ki67+ of CD8+ from week 4 to week 12
Measured: At weeks 4 and 12
Change in CD4 Activation Percent From Week 4 to Week 12
Change in CD4 activation percent co-expressing HLA-DR and CD38 from week 4 to week 12
Measured: At weeks 4 and 12
Change in CD38+ of CD8+ MFI From Week 4 to Week 12
Change in CD38+ of CD8+ median fluorescence intensity (MFI) from week 4 to week 12.
MFI measures the shift in fluorescence intensity of a population of cells. MFI values are based on control to demonstrate an increase or decrease in expression of the marker. MFI in this study was automatically calculated in FlowJo. The median is the relative intensity value below which 50% of the events are found. MFI is an arbitrary unit of relative intensity.
Measured: At weeks 4 and 12
Change in CD4 Count From Week 4 to Week 12
Change in total CD4 T-cell count from week 4 to week 12
Measured: At weeks 4 and 12
Primary Adverse Events
Primary adverse events include all SAEs, defined according to ICH guidelines and targeted protocol events (grade 2 or higher signs and symptoms, grade 2 or higher laboratory abnormality, all diagnoses identified by the ACTG criteria for clinical events, and all events that led to a change in treatment regardless of grade).
Measured: from study enrollment until study completion at 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2011 (estimated)
- Study startSep 2011
- Primary completionSep 2012
- Study completionNov 2012
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 (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1 InfectionStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Allan R. Tenorio, M.D., Study chair, Rush University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01466595
- Sponsor's protocol ID
- ACTG A5286
- Other IDs
- 1U01AI068636
- Status last verified
- Aug 2018
- First submitted
- 6 Oct 2011
- Last updated
- 10 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Tenorio AR, Chan ES, Bosch RJ, Macatangay BJ, Read SW, Yesmin S, Taiwo B, Margolis DM, Jacobson JM, Landay AL, Wilson CC; A5286 Team. Rifaximin has a marginal impact on microbial translocation, T-cell activation and inflammation in HIV-positive immune non-responders to antiretroviral therapy - ACTG A5286. J Infect Dis. 2015 Mar 1;211(5):780-90. doi: 10.1093/infdis/jiu515. Epub 2014 Sep 11.
PubMed 25214516
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Rifaximin as a Modulator of Gut Microbial Translocation and Systemic Immune Activation in HIV-Infected Individuals With Incomplete CD4+ T-cell Recovery on Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT01466595
- Acronym / sponsor ID
- ACTG A5286
- Conditions
- HIV-1 Infection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 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
- Sep 2011
- Primary completion
- Sep 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 8 Nov 2011 (estimated)
- Results
- Posted 7 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being done to see whether rifaximin, an antibiotic that works in the intestines, can lower the amount of germs in the intestines of HIV infected persons. It is possible that when the amount of these germs is lowered, an HIV-infected person's immune system will become less active and will have a better chance of recovering. Also, the study will evaluate the safety of using rifaximin in HIV-infected subjects.
Detailed description
A5286 is a randomized, open-label, two-arm, pilot (phase II) study that evaluated whether 4 weeks of treatment with rifaximin, a non-absorbable antibiotic, decreases markers of immune activation and levels of translocated gut microbial products in HIV-1 infected subjects virally suppressed on ART with CD4+ T-cells < 350 cells/mm^3. Rifaximin were admistered to subjects for 3 weeks. Follow-up continued to week 12. The total sample size was 73 subjects. Subjects were randomized at a 2:1 ratio (rifaximin: no study treatment), using permuted blocks, without institutional balancing.
Subjects were seen through week 12 for clinical and laboratory evaluations, including plasma HIV-1 RNA, CD4+ T-cell count, and safety laboratories. Subjects had 2 baseline visits -- at pre-entry and entry. Study visits were scheduled at weeks 2, 4, 8, and 12. CD4+ T-cell counts and HIV-1 RNA were measured at all weeks; measures of activations, gut-homing markers, and soluble biomarkers were also performed at all weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Treatment with rifaximin | Experimental | Drug: RifaximinParticipants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks. |
| Arm B: No study treatment | No intervention | –No study treatment for 4 weeks |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- HIV-1 infection
- On ART for at least 96 weeks prior to study entry with a regimen that includes three or more antiretroviral medications. (Ritonavir ≤ 400 mg/day will not be considered a separate antiretroviral agent.)
- No plans to change the antiretroviral regimen at least in the next 3 months after study entry.
- CD4+ cell count < 350 cells/mm3 obtained within 120 days prior to study entry at any laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.
- All previous CD4+ cell counts should be < 350 cells/mm3 for at least 96 weeks prior to study entry while subjects were on ART. (A single CD4+ cell count ≥ 350 cells/mm3 is permitted within 96 weeks prior to study entry while subjects were on ART.)
Key exclusion criteria (18 listed)
- Active diarrhea (3 or more unformed stools per day) within 28 days prior to study entry (except if site investigator or primary care provider attributes diarrhea to antiretroviral or azithromycin use).
- History of or active inflammatory bowel disease.
- History of or active Clostridium difficile colitis.
- History of significant liver disease, defined as having chronic liver disease (including chronic alcoholic liver disease, hepatitis B or C), plus either: a) ascites, b) encephalopathy, or c) a Child-Pugh Score of > 7.
- Receipt of antimicrobial therapy within 30 days prior to study entry. (NOTE: Antimicrobial use for prophylaxis of opportunistic infections, e.g., azithromycin or trimethoprim-sulfamethoxazole, is allowed.)
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 |
|---|---|---|
| RifaximinParticipant were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks. | Drug | Arm A: Treatment with rifaximin |
Primary outcome
Change in CD8+ T-cell Activation From Baseline to Week 4
Time frame: At baseline and 4 weeks
Change in CD8+ T-cell activation percent co-expressing HLA-DR and CD38 from baseline to week 4, where the baseline value is the average of pre-entry and entry values.
42 secondary outcomes
Change in D-dimer From Baseline to Week 4
Time frame: At baseline and 4 weeks
Change in IL-6 From Baseline to Week 4
Time frame: At baseline and 4 weeks
Change in LPS From Baseline to Week 4
Time frame: At baseline and 4 weeks
Change in hsCRP From Baseline to Week 4
Time frame: At baseline and 4 weeks
Change in sCD14 From Baseline to Week 4
Time frame: At baseline and 4 weeks
Change in Peripheral B7hi CD4+ T-cell From Baseline to Week 4
Time frame: At baseline and 4 weeks
Change in %CD38+ of CD4+ From Baseline to Week 4
Time frame: At baseline and 4 weeks
Change in %CD38+ of CD8+ From Baseline to Week 4
Time frame: At baseline and 4 weeks
Change in %Ki67+ of CD4+ From Baseline to Week 4
Time frame: At baseline and 4 weeks
Change in %Ki67+ of CD8+ From Baseline to Week 4
Time frame: At baseline and 4 weeks
Change in %HLA-DR+/CD38+ of CD4+ From Baseline to Week 4
Time frame: At baseline and 4 weeks
Change in CD38+ of CD8+ MFI From Baseline to Week 4
Time frame: At baseline and 4 weeks
Change in CD4 Count From Baseline to Week 4
Time frame: At baseline and 4 weeks
Change in CD8+ T-cell Activation From Week 4 to Week 8
Time frame: At weeks 4 and 8
Change in D-dimer From Week 4 to Week 8
Time frame: At weeks 4 and 8
Change in IL-6 From Week 4 to Week 8
Time frame: At weeks 4 and 8
Change in LPS From Week 4 to Week 8
Time frame: At weeks 4 and 8
Change in hsCRP From Week 4 to Week 8
Time frame: At weeks 4 and 8
Change in sCD14 From Week 4 to Week 8
Time frame: At weeks 4 and 8
Change in Peripheral B7hi CD4+ T-cells From Week 4 to Week 8
Time frame: At weeks 4 and 8
Change in %CD38+ of CD4+ From Week 4 to Week 8
Time frame: At weeks 4 and 8
Change in %CD38+ of CD8+ From Week 4 to Week 8
Time frame: At weeks 4 and 8
Change in %Ki67+ of CD4+ From Week 4 to Week 8
Time frame: At weeks 4 and 8
Change in %Ki67+ of CD8+ From Week 4 to Week 8
Time frame: At weeks 4 and 8
Change in CD4 Activation Percent From Week 4 to Week 8
Time frame: At weeks 4 and 8
Change in CD38+ of CD8+ MFI From Week 4 to Week 8
Time frame: At weeks 4 and 8
Change in CD4 Count From Week 4 to Week 8
Time frame: At weeks 4 and 8
Change in CD8+ T-cell Activation From Week 4 to Week 12
Time frame: At weeks 4 and 12
Change in D-dimer From Week 4 to Week 12
Time frame: At weeks 4 and 12
Change in IL-6 From Week 4 to Week 12
Time frame: At weeks 4 and 12
Change in LPS From Week 4 to Week 12
Time frame: At weeks 4 and 12
Change in hsCRP From Week 4 to Week 12
Time frame: At weeks 4 and 12
Change in sCD14 From Week 4 to Week 12
Time frame: At weeks 4 and 8
Change in Peripheral B7hi CD4+ T-cells From Week 4 to Week 12
Time frame: At weeks 4 and 12
Change in %CD38+ of CD4+ From Week 4 to Week 12
Time frame: At weeks 4 and 12
Change in %CD38+ of CD8+ From Week 4 to Week 12
Time frame: At weeks 4 and 12
Change in %Ki67+ of CD4+ From Week 4 to Week 12
Time frame: At weeks 4 and 12
Change in %Ki67+ of CD8+ From Week 4 to Week 12
Time frame: At weeks 4 and 12
Change in CD4 Activation Percent From Week 4 to Week 12
Time frame: At weeks 4 and 12
Change in CD38+ of CD8+ MFI From Week 4 to Week 12
Time frame: At weeks 4 and 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25214516Tenorio AR, Chan ES, Bosch RJ, Macatangay BJ, Read SW, Yesmin S, Taiwo B, Margolis DM, Jacobson JM, Landay AL, Wilson CC; A5286 Team. Rifaximin has a marginal impact on microbial translocation, T-cell activation and inflammation in HIV-positive immune non-responders to antiretroviral therapy - ACTG A5286. J Infect Dis. 2015 Mar 1;211(5):780-90. doi: 10.1093/infdis/jiu515. Epub 2014 Sep 11.
Related trials for HIV-1 Infection
RecruitingObservational study
Cohort of Women Living With HIV-1 and Receiving Bictegravir/Emtricitabine/Tenofovir Alafenamide
HIV (Human Immunodeficiency Virus), Pregnancy
RecruitingPhase 4
A Study to Provide Continued Access to Study Drug to Children and Adolescents Who Have Completed Clinical Studies Involving Gilead HIV Treatments
HIV-1-infection
RecruitingObservational study
Leukapheresis Procedures to Obtain Plasma and Lymphocytes for Research Studies on Antiretroviral Naive HIV-1 Research Participants
HIV
Active, not recruitingPhase 3
Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Treated With Biktarvy
HIV-1-infection
Active, not recruitingPhase 2/3
Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Treated With a Complicated Regimen (ARTISTRY-1)
HIV-1-infection
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.
Allan R. Tenorio, M.D. study chair
Rush University Medical Center
32 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rifaximin in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 32 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 14 inclusion and 18 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 10 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 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 7 Nov 2013). 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 CD8+ T-cell Activation From Baseline to Week 4 (time frame: At baseline and 4 weeks). 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 NCT01466595, 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 10 Sep 2018.