Telmisartan to Reduce AIDS-Related Fibrotic and Inflammatory Contributors (TRAFIC Study)
Condition: HIV-1 Infection
Intervention: Telmisartan
Intervention description: Participants received Telmisartan 40 mg daily during weeks 0-4 followed by telmisartan 80 mg daily during weeks 5-48.
Intervention MeSH terms: Telmisartan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 58.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The main goal of this study was to see if a drug called telmisartan would decrease fibrosis
      (scarring) and inflammation (irritation) in people who are infected with HIV and doing well
      on their HIV medications. The study was also done to see what effects telmisartan has on
      other signs of disease and inflammation in the body, and to see whether people who have HIV
      can take telmisartan safely and without side effects that make them want to stop the drug.
      Telmisartan is FDA-approved for treating high blood pressure and decreasing the chance of
      heart attacks and strokes in people over the age of 55 years of age who are at high risk for
      these events.
    

Eligibility criteria:

        Step 1 Inclusion Criteria:

          -  HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or
             chemiluminescence immunoassay (E/CIA) test kit at any time prior to Step 1 entry and
             confirmed by a licensed Western blot or a second antibody test by a method other than
             the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, or plasma HIV-1 RNA viral
             load >2000 copies/mL on two occasions.

          -  On antiretroviral therapy (ART) continuously for ≥48 weeks prior to Step 1 entry.

          -  Documentation of HIV-1 RNA <50 copies/mL at screening, performed by any US laboratory
             that has a CLIA certification or its equivalent.

          -  At least one HIV-1 RNA level <200 copies/mL in the 48 weeks prior to Step 1 entry (not
             including the screening).

          -  No change in ART regimen in the 12 weeks prior to Step 1 entry (except as noted
             below).

        NOTE: Modifications of ART dosing during the 12 weeks prior to Step 1 entry are permitted.
        In addition, the change in formulation (eg, from standard formulation to fixed dose
        combination or single tablet regimen) is allowed within 12 weeks of Step 1 entry. A
        within-class single drug substitution (eg, switch from nevirapine to efavirenz or from
        atazanavir to darunavir) is allowed within 12 weeks of Step 1 entry, with the exception of
        a switch from any other NRTI to abacavir. No other changes in ART in the 12 weeks prior to
        Step 1 entry are permitted.

          -  No active plan to change ART for the 48-week study duration.

          -  Body mass index (BMI) 20-35 kg/m^2.

          -  For females of reproductive potential, negative serum or urine pregnancy test within 3
             days prior to Step 1 entry.

          -  Ability and willingness of subject or legal guardian/representative to provide
             informed consent.

          -  Willingness to undergo the Step 1 entry and week 48 lymphoid and adipose tissue
             biopsies.

        Step 2 Inclusion Criteria:

          -  Entry lymphoid tissue and adipose tissue specimen for assay of the primary endpoint
             has been obtained. (Prior to Letter of Amendment #2, 11/19/14)

          -  (Letter of Amendment #2, 11/19/14) Entry lymphoid tissue and adipose tissue specimens
             for assay of the primary endpoint have been obtained, entered into the ACTG's
             Laboratory Data Management System (LDMS), and confirmed by the protocol team as
             adequate for endpoint determination.

        NOTE: If the lymph node specimen is determined by the protocol team to be inadequate for
        endpoint determination despite the interventions summarized in LOA #2, the participant will
        be permitted to enroll if adequate adipose tissue is obtained. However, as change in lymph
        node fibrosis remains one of the primary endpoints of this study, it is critical that every
        effort be made to obtain an adequate sample while still trying to minimize complication
        rates.

          -  Willingness to undergo the week 48 lymphoid and adipose tissue biopsies. (Prior to
             Letter of Amendment #2, 11/19/14)

          -  (Letter of Amendment #2, 11/19/14) Willingness to undergo the week 48 lymphoid and
             adipose tissue biopsies.

        NOTE: A week 48 lymph node biopsy is not required if the Step 1 lymph node specimen was
        deemed inadequate as noted in 4.3.1. Week 48 adipose tissue biopsies will still be required
        for these participants.

        Step 1 Exclusion Criteria:

          -  More than one HIV-1 RNA >200 copies/mL in the 48 weeks prior to Step 1 entry.

          -  One HIV-1 RNA 200-500 copies/mL in the 24 weeks prior to Step 1 entry that is not
             immediately preceded and followed by HIV-1 RNA <50 copies/mL.

        NOTE: The preceding viral load <50 copies/mL may be >24 weeks prior to Step 1 entry.

          -  Confirmed systolic blood pressure >160 mmHg or <100 mmHg or diastolic blood pressure
             >100 mmHg.

          -  Known untreated renal artery stenosis.

          -  Known cirrhosis or severe liver disease (eg, ascites, encephalopathy, history of
             variceal bleeding).

        NOTE: Potential subjects with chronic hepatitis B or C virus infection with no known
        cirrhosis or severe liver disease may participate in the study, provided there are no plans
        to start therapy for hepatitis C infection during the 48-week study duration.

          -  Unstable coronary artery disease/angina or decompensated congestive heart failure.

          -  Either breastfeeding or pregnant within 24 weeks prior to Step 1 entry.

          -  Use of thiazolidinediones or any angiotensin receptor blocker (ARB) or angiotensin
             converting enzyme inhibitor (ACEi) in the 24 weeks prior to Step 1 entry. If the
             subject took either of these classes of medications for less than 2 weeks in the 24
             weeks prior to Step 1 entry, the subject may enroll if 30 days have passed since the
             last dose. If the subject is diabetic and/or has a calculated glomerular filtration
             rate (GFR) <60mL/min, aliskiren-containing medications are also prohibited.

          -  History of intolerance, other than cough, to any ARB or ACEi.

          -  Use of anticoagulants other than aspirin 81 mg or 325 mg daily. NOTE: If the subject
             is on aspirin 81 mg or 325 mg daily and is willing/able to stop therapy for 7 days
             prior to the biopsy procedures, the subject may enroll.

          -  Any known bleeding disorder or coagulopathy.

          -  Projected need for daily potassium supplementation for ≥2 weeks during the study
             period.

          -  The following laboratory values obtained within 30 days prior to Step 1 entry by any
             US laboratory that has a CLIA certification or its equivalent:

               -  Absolute neutrophil count (ANC) ≤750 cells/mm^3

               -  Hemoglobin ≤10 g/dL

               -  Platelet count ≤75,000/mm^3

               -  Calculated creatinine clearance (CrCl) <50 mL/min, as estimated by the
                  Cockcroft-Gault equation

               -  Aspartate aminotransferase (AST) (SGOT) >/=3x ULN (upper limit of normal)

               -  Alanine aminotransferase (ALT) (SGPT) >/=3x ULN

               -  Partial thromboplastin time (PTT) >1.2x ULN

               -  Prothrombin time (PT) >1.2x ULN

          -  Heritable connective tissue disorders (eg Ehlers-Danlos syndrome, osteogenesis
             imperfecta, Stickler syndrome, Marfan's syndrome).

        NOTE: Subjects with acquired/autoimmune chronic inflammatory diseases/connective tissue
        disorders who are clinically stable (in the opinion of the site investigator) and not on a
        prohibited medication may enroll with approval of the A5317 study chairs.

          -  Serious illness requiring systemic treatment and/or hospitalization until subject
             either completes therapy or is clinically stable on therapy, in the opinion of the
             site investigator, for at least 7 days prior to Step 1 entry.

          -  Active drug or alcohol use or dependence that, in the opinion of the site
             investigator, would interfere with adherence to study requirements.

          -  Any condition that, in the opinion of the site investigator, would compromise the
             subject's ability to participate in the study.

        Step 2 Exclusion Criteria:

        - Any AE associated with the Step 1 entry biopsy that would exclude the subject from
        undergoing follow-up biopsy at week 48.