Rifaximin as a Modulator of Microbial Translocation and Immune Activation

• Sponsor: AIDS Clinical Trials Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT01466595
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Enrollment: 73
• Locations: 32
• Arms: 2
• Duration (Months): 14
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief 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 chance of recovering. Also, the study will evaluate the safety of using rifaximin in HIV-infected subjects.

Condition or Disease	Intervention/Treatment	Phase
HIV-1 Infection	Drug: Rifaximin	Phase 2

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

• Study Type: Interventional
• Actual Enrollment: 73 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Treatment with rifaximin Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Drug: Rifaximin; Participant were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.
No Intervention: Arm B: No study treatment No study treatment for 4 weeks

Outcome Measures

Primary Outcome Measures

1. Change in CD8+ T-cell Activation From Baseline to Week 4 [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.

Secondary Outcome Measures

1. Change in D-dimer From Baseline to Week 4 [At baseline and 4 weeks]

   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.

2. Change in IL-6 From Baseline to Week 4 [At baseline and 4 weeks]

   Change in Interleukin (IL)-6 from baseline to week 4, where baseline value is the average of pre-entry and entry

3. Change in LPS From Baseline to Week 4 [At baseline and 4 weeks]

   Change in Lipopolysaccharide (LPS) from baseline to week 4, where baseline value is the average of pre-entry and entry

4. Change in hsCRP From Baseline to Week 4 [At baseline and 4 weeks]

   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

5. Change in sCD14 From Baseline to Week 4 [At baseline and 4 weeks]

   Change in soluble CD14 (sCD14) from baseline to week 4, where baseline value is the average of pre-entry and entry

6. Change in Peripheral B7hi CD4+ T-cell From Baseline to Week 4 [At baseline and 4 weeks]

   Change in gut-homing percent B7hi+ of CD4+ from baseline to week 4, where baseline value is the average of pre-entry and entry

7. Change in %CD38+ of CD4+ From Baseline to Week 4 [At baseline and 4 weeks]

   Change in advanced flow percent CD38+ of CD4+ from baseline to week 4, where baseline value is the average of pre-entry and entry

8. Change in %CD38+ of CD8+ From Baseline to Week 4 [At baseline and 4 weeks]

   Change in advanced flow percent CD38+ of CD8+ from baseline to week 4, where baseline value is the average of pre-entry and entry

9. Change in %Ki67+ of CD4+ From Baseline to Week 4 [At baseline and 4 weeks]

   Change in advanced flow percent Ki67+ of CD4+ from baseline to week 4, where baseline value is the average of pre-entry and entry

10. Change in %Ki67+ of CD8+ From Baseline to Week 4 [At baseline and 4 weeks]

    Change in advanced flow percent Ki67+ of CD8+ from baseline to week 4, where baseline value is the average of pre-entry and entry

11. Change in %HLA-DR+/CD38+ of CD4+ From Baseline to Week 4 [At baseline and 4 weeks]

    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

12. Change in CD38+ of CD8+ MFI From Baseline to Week 4 [At baseline and 4 weeks]

    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.

13. Change in CD4 Count From Baseline to Week 4 [At baseline and 4 weeks]

    Change in total CD4 T-cell from baseline to week 4, where baseline value is the average of pre-entry and entry

14. Change in CD8+ T-cell Activation From Week 4 to Week 8 [At weeks 4 and 8]

    Change in CD8+ T-cell activation percent co-expressing HLA-DR and CD38 from week 4 to week 8

15. Change in D-dimer From Week 4 to Week 8 [At weeks 4 and 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.

16. Change in IL-6 From Week 4 to Week 8 [At weeks 4 and 8]

    Change in IL-6 from week 4 to week 8.

17. Change in LPS From Week 4 to Week 8 [At weeks 4 and 8]

    Change in LPS from week 4 to week 8.

18. Change in hsCRP From Week 4 to Week 8 [At weeks 4 and 8]

    Change in hsCRP from week 4 to week 8.

19. Change in sCD14 From Week 4 to Week 8 [At weeks 4 and 8]

    Change in soluble CD14 from week 4 to week 8

20. Change in Peripheral B7hi CD4+ T-cells From Week 4 to Week 8 [At weeks 4 and 8]

    Change in gut homing percent B7hi+ of CD4+ from week 4 to week 8

21. Change in %CD38+ of CD4+ From Week 4 to Week 8 [At weeks 4 and 8]

    Change in advanced flow percent CD38+ of CD4+ from week 4 to week 8

22. Change in %CD38+ of CD8+ From Week 4 to Week 8 [At weeks 4 and 8]

    Change in advanced flow percent CD38+ of CD8+ from week 4 to week 8

23. Change in %Ki67+ of CD4+ From Week 4 to Week 8 [At weeks 4 and 8]

    Change in advanced flow percent Ki67+ of CD4+ from week 4 to week 8

24. Change in %Ki67+ of CD8+ From Week 4 to Week 8 [At weeks 4 and 8]

    Change in advanced flow percent Ki67+ of CD8+ from week 4 to week 8

25. Change in CD4 Activation Percent From Week 4 to Week 8 [At weeks 4 and 8]

    Change in CD4 activation percent co-expressing HLA-DR and CD38 from week 4 to week 8

26. Change in CD38+ of CD8+ MFI From Week 4 to Week 8 [At weeks 4 and 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.

27. Change in CD4 Count From Week 4 to Week 8 [At weeks 4 and 8]

    Change in total CD4 T-cell count from week 4 to week 8

28. Change in CD8+ T-cell Activation From Week 4 to Week 12 [At weeks 4 and 12]

    Change in CD8+ T-cell activation percent co-expressing HLA-DR and CD38 from week 4 to week 12

29. Change in D-dimer From Week 4 to Week 12 [At weeks 4 and 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.

30. Change in IL-6 From Week 4 to Week 12 [At weeks 4 and 12]

    Change in IL-6 from week 4 to week 12.

31. Change in LPS From Week 4 to Week 12 [At weeks 4 and 12]

    Change in LPS from week 4 to week 12.

32. Change in hsCRP From Week 4 to Week 12 [At weeks 4 and 12]

    Change in hsCRP from week 4 to week 12.

33. Change in sCD14 From Week 4 to Week 12 [At weeks 4 and 8]

    Change in soluble CD14 from week 4 to week 12

34. Change in Peripheral B7hi CD4+ T-cells From Week 4 to Week 12 [At weeks 4 and 12]

    Change in gut homing percent B7hi+ of CD4+ from week 4 to week 12

35. Change in %CD38+ of CD4+ From Week 4 to Week 12 [At weeks 4 and 12]

    Change in advanced flow percent CD38+ of CD4+ from week 4 to week 12

36. Change in %CD38+ of CD8+ From Week 4 to Week 12 [At weeks 4 and 12]

    Change in advanced flow percent CD38+ of CD8+ from week 4 to week 12

37. Change in %Ki67+ of CD4+ From Week 4 to Week 12 [At weeks 4 and 12]

    Change in advanced flow percent Ki67+ of CD4+ from week 4 to week 12

38. Change in %Ki67+ of CD8+ From Week 4 to Week 12 [At weeks 4 and 12]

    Change in advanced flow percent Ki67+ of CD8+ from week 4 to week 12

39. Change in CD4 Activation Percent From Week 4 to Week 12 [At weeks 4 and 12]

    Change in CD4 activation percent co-expressing HLA-DR and CD38 from week 4 to week 12

40. Change in CD38+ of CD8+ MFI From Week 4 to Week 12 [At weeks 4 and 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.

41. Change in CD4 Count From Week 4 to Week 12 [At weeks 4 and 12]

    Change in total CD4 T-cell count from week 4 to week 12

42. Primary Adverse Events [from study enrollment until study completion at 12 weeks]

    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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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.

• 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.

Exclusion Criteria:

• 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.

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Therapeutics CRS (5801)	Birmingham	Alabama	United States	35294
2	UCLA CARE Center CRS (601)	Los Angeles	California	United States	90095
3	Stanford CRS (501)	Palo Alto	California	United States	94304
4	Ucsf Aids Crs (801)	San Francisco	California	United States	94110
5	University of Colorado Hospital CRS (6101)	Aurora	Colorado	United States	80045
6	Georgetown University CRS (GU CRS) (1008)	Washington	District of Columbia	United States	20007
7	Univ. of Miami AIDS CRS (901)	Miami	Florida	United States	33136
8	The Ponce de Leon Center CRS (5802)	Atlanta	Georgia	United States	30308
9	Northwestern University CRS (2701)	Chicago	Illinois	United States	60611
10	Rush Univ. Med. Ctr. ACTG CRS (2702)	Chicago	Illinois	United States	60612
11	IHV Baltimore Treatment CRS (4651)	Baltimore	Maryland	United States	21201
12	Massachusetts General Hospital ACTG CRS (101)	Boston	Massachusetts	United States	02114
13	Brigham and Women's Hosp. ACTG CRS (107)	Boston	Massachusetts	United States	02115
14	Beth Israel Deaconess Med. Ctr., ACTG CRS (103)	Boston	Massachusetts	United States	02215
15	Washington U CRS (2101)	Saint Louis	Missouri	United States	63110
16	New Jersey Medical School-Adult Clinical Research Ctr. CRS (31477)	Newark	New Jersey	United States	07103
17	Cornell CRS (7804)	New York	New York	United States	10011
18	NY Univ. HIV/AIDS CRS (401)	New York	New York	United States	10016
19	HIV Prevention & Treatment CRS (30329)	New York	New York	United States	10032
20	AIDS Care CRS (1108)	Rochester	New York	United States	14642
21	Univ. of Rochester ACTG CRS (1101)	Rochester	New York	United States	14642
22	Unc Aids Crs (3201)	Chapel Hill	North Carolina	United States	27516
23	Duke Univ. Med. Ctr. Adult CRS (1601)	Durham	North Carolina	United States	27710
24	Univ. of Cincinnati CRS (2401)	Cincinnati	Ohio	United States	45267
25	Case CRS (2501)	Cleveland	Ohio	United States	44106
26	Metro Health CRS (2503)	Cleveland	Ohio	United States	44109
27	The Ohio State Univ. AIDS CRS (2301)	Columbus	Ohio	United States	43210
28	Hosp. of the Univ. of Pennsylvania CRS (6201)	Philadelphia	Pennsylvania	United States	19104
29	Pittsburgh CRS (1001)	Pittsburgh	Pennsylvania	United States	15213
30	The Miriam Hosp. ACTG CRS (2951)	Providence	Rhode Island	United States	02906
31	University of Washington AIDS CRS (1401)	Seattle	Washington	United States	98104
32	Puerto Rico-AIDS CRS (5401)	San Juan		Puerto Rico	00935

Sponsors and Collaborators

• AIDS Clinical Trials Group
• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Chair: Allan R. Tenorio, M.D., Rush University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AIDS Clinical Trials Group
• ClinicalTrials.gov Identifier: NCT01466595
• Other Study ID Numbers: ACTG A5286; 1U01AI068636
• First Posted: Nov 8, 2011
• Last Update Posted: Sep 10, 2018
• Last Verified: Aug 1, 2018

• Additional relevant MeSH terms: Rifaximin

Study Results

Participant Flow

Recruitment Details	A5286 opened under version 2.0 on 09/01/11, and the first subject was randomized on 10/03/11. Accrual to the study closed on 07/30/12, with a total of 73 subjects enrolled from 32 sites within the US.
Pre-assignment Detail	Subjects were randomized with a 2:1 ratio (Rifaximin : no study treatment) at enrollment.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Period Title: Overall Study
STARTED	49	24
COMPLETED	49	23
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment	Total
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks	Total of all reporting groups
Overall Participants	49	24	73
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	46 93.9%	24 100%	70 95.9%
>=65 years	3 6.1%	0 0%	3 4.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.5 (8.1)	49.7 (9.7)	49.6 (8.6)
Sex: Female, Male (Count of Participants)
Female	4 8.2%	2 8.3%	6 8.2%
Male	45 91.8%	22 91.7%	67 91.8%
Region of Enrollment (participants) [Number]
United States	49 100%	24 100%	73 100%
Number of participants with HIV-1 RNA below assay lower limit (participants) [Number]
Number [participants]	49 100%	24 100%	73 100%
CD4 count (cells/mm^3) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cells/mm^3]	240	223	236

Outcome Measures

1. Primary Outcome

Title	Change in CD8+ T-cell Activation From Baseline to Week 4
Description	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.
Time Frame	At baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

The primary analysis is as-treated, limited to subjects who had data for both baseline and week 4, and (for the rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change antiretroviral therapy (ART) or use prohibited medications or have virologic failure during this time period.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [percentage HLA-DR+/CD38+ of CD8+]	0.00	0.64

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Treatment With Rifaximin, Arm B: No Study Treatment
	Comments	Null hypothesis: There is no difference between the two arms in the change in T-cell activation from baseline to week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.028
	Comments	not adjusted for multiple comparisons
	Method	Wilcoxon (Mann-Whitney)
	Comments	no other adjustments

2. Secondary Outcome

Title	Change in D-dimer From Baseline to Week 4
Description	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.
Time Frame	At baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [log10 ng/mL]	0.00	-0.03

3. Secondary Outcome

Title	Change in IL-6 From Baseline to Week 4
Description	Change in Interleukin (IL)-6 from baseline to week 4, where baseline value is the average of pre-entry and entry
Time Frame	At baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [log10 pg/mL]	-0.03	0.05

4. Secondary Outcome

Title	Change in LPS From Baseline to Week 4
Description	Change in Lipopolysaccharide (LPS) from baseline to week 4, where baseline value is the average of pre-entry and entry
Time Frame	At baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [log10 pg/mL]	0.00	-0.01

5. Secondary Outcome

Title	Change in hsCRP From Baseline to Week 4
Description	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
Time Frame	At baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [log10 ng/mL]	-0.08	-0.09

6. Secondary Outcome

Title	Change in sCD14 From Baseline to Week 4
Description	Change in soluble CD14 (sCD14) from baseline to week 4, where baseline value is the average of pre-entry and entry
Time Frame	At baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [log10 ng/mL]	-0.03	-0.03

7. Secondary Outcome

Title	Change in Peripheral B7hi CD4+ T-cell From Baseline to Week 4
Description	Change in gut-homing percent B7hi+ of CD4+ from baseline to week 4, where baseline value is the average of pre-entry and entry
Time Frame	At baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [percentage B7hi+ of CD4+]	-0.40	0.00

8. Secondary Outcome

Title	Change in %CD38+ of CD4+ From Baseline to Week 4
Description	Change in advanced flow percent CD38+ of CD4+ from baseline to week 4, where baseline value is the average of pre-entry and entry
Time Frame	At baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [percentage CD38+ of CD4+]	0.89	0.91

9. Secondary Outcome

Title	Change in %CD38+ of CD8+ From Baseline to Week 4
Description	Change in advanced flow percent CD38+ of CD8+ from baseline to week 4, where baseline value is the average of pre-entry and entry
Time Frame	At baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [percentage CD38+ of CD8+]	0.21	0.66

10. Secondary Outcome

Title	Change in %Ki67+ of CD4+ From Baseline to Week 4
Description	Change in advanced flow percent Ki67+ of CD4+ from baseline to week 4, where baseline value is the average of pre-entry and entry
Time Frame	At baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [percentage Ki67+ of CD4+]	-0.17	0.05

11. Secondary Outcome

Title	Change in %Ki67+ of CD8+ From Baseline to Week 4
Description	Change in advanced flow percent Ki67+ of CD8+ from baseline to week 4, where baseline value is the average of pre-entry and entry
Time Frame	At baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [percentage Ki67+ of CD8+]	-0.12	0.12

12. Secondary Outcome

Title	Change in %HLA-DR+/CD38+ of CD4+ From Baseline to Week 4
Description	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
Time Frame	At baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [percentage HLA-DR+/CD38+ of CD4+]	-0.15	0.15

13. Secondary Outcome

Title	Change in CD38+ of CD8+ MFI From Baseline to Week 4
Description	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.
Time Frame	At baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [MFI (relative intensity)]	0.00	0.03

14. Secondary Outcome

Title	Change in CD4 Count From Baseline to Week 4
Description	Change in total CD4 T-cell from baseline to week 4, where baseline value is the average of pre-entry and entry
Time Frame	At baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [cells/mm3]	-3.00	11.25

15. Secondary Outcome

Title	Change in CD8+ T-cell Activation From Week 4 to Week 8
Description	Change in CD8+ T-cell activation percent co-expressing HLA-DR and CD38 from week 4 to week 8
Time Frame	At weeks 4 and 8

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who had data for both week 4 and week 8, and (for the rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	41	21
Median (Inter-Quartile Range) [percentage HLA-DR+/CD38+ of CD8+]	0.08	-0.71

16. Secondary Outcome

Title	Change in D-dimer From Week 4 to Week 8
Description	D-dimer is a fibrin degradation product (FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis.
Time Frame	At weeks 4 and 8

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	42	21
Median (Inter-Quartile Range) [log10 ng/mL]	-0.02	0.03

17. Secondary Outcome

Title	Change in IL-6 From Week 4 to Week 8
Description	Change in IL-6 from week 4 to week 8.
Time Frame	At weeks 4 and 8

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	42	21
Median (Inter-Quartile Range) [log10 pg/mL]	-0.03	0.06

18. Secondary Outcome

Title	Change in LPS From Week 4 to Week 8
Description	Change in LPS from week 4 to week 8.
Time Frame	At weeks 4 and 8

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	42	21
Median (Inter-Quartile Range) [log10 pg/mL]	-0.01	0.00

19. Secondary Outcome

Title	Change in hsCRP From Week 4 to Week 8
Description	Change in hsCRP from week 4 to week 8.
Time Frame	At weeks 4 and 8

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	42	21
Median (Inter-Quartile Range) [log10 ng/mL]	-0.05	0.23

20. Secondary Outcome

Title	Change in sCD14 From Week 4 to Week 8
Description	Change in soluble CD14 from week 4 to week 8
Time Frame	At weeks 4 and 8

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	42	21
Median (Inter-Quartile Range) [log10 ng/mL]	-0.05	0.02

21. Secondary Outcome

Title	Change in Peripheral B7hi CD4+ T-cells From Week 4 to Week 8
Description	Change in gut homing percent B7hi+ of CD4+ from week 4 to week 8
Time Frame	At weeks 4 and 8

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	41	21
Median (Inter-Quartile Range) [percentage B7hi+ of CD4+]	0.26	-0.02

22. Secondary Outcome

Title	Change in %CD38+ of CD4+ From Week 4 to Week 8
Description	Change in advanced flow percent CD38+ of CD4+ from week 4 to week 8
Time Frame	At weeks 4 and 8

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	41	21
Median (Inter-Quartile Range) [percentage CD38+ of CD4+]	-0.84	1.00

23. Secondary Outcome

Title	Change in %CD38+ of CD8+ From Week 4 to Week 8
Description	Change in advanced flow percent CD38+ of CD8+ from week 4 to week 8
Time Frame	At weeks 4 and 8

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	41	21
Median (Inter-Quartile Range) [percentage CD38+ of CD8+]	-0.12	-1.20

24. Secondary Outcome

Title	Change in %Ki67+ of CD4+ From Week 4 to Week 8
Description	Change in advanced flow percent Ki67+ of CD4+ from week 4 to week 8
Time Frame	At weeks 4 and 8

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	41	21
Median (Inter-Quartile Range) [percentage Ki67+ of CD4+]	0.21	-0.01

25. Secondary Outcome

Title	Change in %Ki67+ of CD8+ From Week 4 to Week 8
Description	Change in advanced flow percent Ki67+ of CD8+ from week 4 to week 8
Time Frame	At weeks 4 and 8

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	41	21
Median (Inter-Quartile Range) [percentage Ki67+ of CD8+]	0.11	-0.08

26. Secondary Outcome

Title	Change in CD4 Activation Percent From Week 4 to Week 8
Description	Change in CD4 activation percent co-expressing HLA-DR and CD38 from week 4 to week 8
Time Frame	At weeks 4 and 8

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	41	21
Median (Inter-Quartile Range) [percentage HLA-DR+/CD38+ of CD4+]	0.17	-0.53

27. Secondary Outcome

Title	Change in CD38+ of CD8+ MFI From Week 4 to Week 8
Description	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.
Time Frame	At weeks 4 and 8

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	41	21
Median (Inter-Quartile Range) [MFI (relative intensity)]	0.08	-0.71

28. Secondary Outcome

Title	Change in CD4 Count From Week 4 to Week 8
Description	Change in total CD4 T-cell count from week 4 to week 8
Time Frame	At weeks 4 and 8

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	42	21
Median (Inter-Quartile Range) [cells/mm3]	-9.50	-13.00

29. Secondary Outcome

Title	Change in CD8+ T-cell Activation From Week 4 to Week 12
Description	Change in CD8+ T-cell activation percent co-expressing HLA-DR and CD38 from week 4 to week 12
Time Frame	At weeks 4 and 12

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who had data for both week 4 and week 12, and (for the rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	42	22
Median (Inter-Quartile Range) [percentage HLA-DR+/CD38+ of CD8+]	-0.05	-0.77

30. Secondary Outcome

Title	Change in D-dimer From Week 4 to Week 12
Description	D-dimer is a fibrin degradation product (FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis.
Time Frame	At weeks 4 and 12

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [log10 ng/mL]	-0.01	0.07

31. Secondary Outcome

Title	Change in IL-6 From Week 4 to Week 12
Description	Change in IL-6 from week 4 to week 12.
Time Frame	At weeks 4 and 12

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [log10 pg/mL]	0.02	0.02

32. Secondary Outcome

Title	Change in LPS From Week 4 to Week 12
Description	Change in LPS from week 4 to week 12.
Time Frame	At weeks 4 and 12

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [log10 pg/mL]	0.00	0.03

33. Secondary Outcome

Title	Change in hsCRP From Week 4 to Week 12
Description	Change in hsCRP from week 4 to week 12.
Time Frame	At weeks 4 and 12

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [log10 ng/mL]	0.09	0.04

34. Secondary Outcome

Title	Change in sCD14 From Week 4 to Week 12
Description	Change in soluble CD14 from week 4 to week 12
Time Frame	At weeks 4 and 8

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	43	22
Median (Inter-Quartile Range) [log10 ng/mL]	0.03	0.02

35. Secondary Outcome

Title	Change in Peripheral B7hi CD4+ T-cells From Week 4 to Week 12
Description	Change in gut homing percent B7hi+ of CD4+ from week 4 to week 12
Time Frame	At weeks 4 and 12

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	41	22
Median (Inter-Quartile Range) [percentage B7hi+ of CD4+]	-0.07	-0.19

36. Secondary Outcome

Title	Change in %CD38+ of CD4+ From Week 4 to Week 12
Description	Change in advanced flow percent CD38+ of CD4+ from week 4 to week 12
Time Frame	At weeks 4 and 12

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	42	22
Median (Inter-Quartile Range) [percentage CD38+ of CD4+]	-0.67	-0.54

37. Secondary Outcome

Title	Change in %CD38+ of CD8+ From Week 4 to Week 12
Description	Change in advanced flow percent CD38+ of CD8+ from week 4 to week 12
Time Frame	At weeks 4 and 12

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	42	22
Median (Inter-Quartile Range) [percentage CD38+ of CD8+]	-0.93	-1.96

38. Secondary Outcome

Title	Change in %Ki67+ of CD4+ From Week 4 to Week 12
Description	Change in advanced flow percent Ki67+ of CD4+ from week 4 to week 12
Time Frame	At weeks 4 and 12

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	42	22
Median (Inter-Quartile Range) [percentage Ki67+ of CD4+]	0.14	-0.22

39. Secondary Outcome

Title	Change in %Ki67+ of CD8+ From Week 4 to Week 12
Description	Change in advanced flow percent Ki67+ of CD8+ from week 4 to week 12
Time Frame	At weeks 4 and 12

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	42	22
Median (Inter-Quartile Range) [percentage Ki67+ of CD8+]	0.13	-0.09

40. Secondary Outcome

Title	Change in CD4 Activation Percent From Week 4 to Week 12
Description	Change in CD4 activation percent co-expressing HLA-DR and CD38 from week 4 to week 12
Time Frame	At weeks 4 and 12

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	42	22
Median (Inter-Quartile Range) [percentage HLA-DR+/CD38+ of CD4+]	-0.14	-0.50

41. Secondary Outcome

Title	Change in CD38+ of CD8+ MFI From Week 4 to Week 12
Description	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.
Time Frame	At weeks 4 and 12

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	42	22
Median (Inter-Quartile Range) [MFI (relative intensity)]	-0.02	-0.02

42. Secondary Outcome

Title	Change in CD4 Count From Week 4 to Week 12
Description	Change in total CD4 T-cell count from week 4 to week 12
Time Frame	At weeks 4 and 12

Outcome Measure Data

Analysis Population Description

This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	42	22
Median (Inter-Quartile Range) [cells/mm3]	0.00	-5.50

43. Secondary Outcome

Title	Primary Adverse Events
Description	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).
Time Frame	from study enrollment until study completion at 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: Treatment With Rifaximin	Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	No study treatment for 4 weeks
Measure Participants	49	24
Number [participants]	27 55.1%	9 37.5%

Adverse Events

Time Frame	AEs reported from study enrollment until study completion at 12 weeks
Adverse Event Reporting Description	AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Arm/Group Title	Arm A: Treatment With Rifaximin		Arm B: No Study Treatment
Arm/Group Description	Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.		No study treatment for 4 weeks
All Cause Mortality
	Arm A: Treatment With Rifaximin		Arm B: No Study Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A: Treatment With Rifaximin		Arm B: No Study Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/49 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Arm A: Treatment With Rifaximin		Arm B: No Study Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/49 (73.5%)		19/24 (79.2%)
Gastrointestinal disorders
Diarrhoea	3/49 (6.1%)		0/24 (0%)
Flatulence	3/49 (6.1%)		0/24 (0%)
Nausea	4/49 (8.2%)		0/24 (0%)
Vomiting	3/49 (6.1%)		0/24 (0%)
General disorders
Fatigue	4/49 (8.2%)		1/24 (4.2%)
Pyrexia	3/49 (6.1%)		1/24 (4.2%)
Investigations
Blood bilirubin increased	7/49 (14.3%)		2/24 (8.3%)
Blood cholesterol increased	18/49 (36.7%)		12/24 (50%)
Blood creatinine increased	2/49 (4.1%)		2/24 (8.3%)
Blood glucose increased	7/49 (14.3%)		5/24 (20.8%)
Blood phosphorus decreased	2/49 (4.1%)		3/24 (12.5%)
Blood sodium decreased	4/49 (8.2%)		2/24 (8.3%)
Blood uric acid increased	1/49 (2%)		4/24 (16.7%)
Lipase abnormal	0/49 (0%)		2/24 (8.3%)
Lipase increased	2/49 (4.1%)		2/24 (8.3%)
Low density lipoprotein increased	11/49 (22.4%)		9/24 (37.5%)
Neutrophil count decreased	6/49 (12.2%)		0/24 (0%)
Platelet count decreased	1/49 (2%)		2/24 (8.3%)
White blood cell count decreased	4/49 (8.2%)		0/24 (0%)
Metabolism and nutrition disorders
Decreased appetite	3/49 (6.1%)		0/24 (0%)
Nervous system disorders
Headache	4/49 (8.2%)		1/24 (4.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.