Rifaximin as a Modulator of Microbial Translocation and Immune Activation
Condition: HIV-1 Infection
Intervention: Rifaximin
Intervention description: Participant were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.
Intervention MeSH terms: Rifaximin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 73.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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.