Evaluating the Effectiveness of Pentoxifylline at Improving Blood Vessel Function in HIV-infected People Not Receiving Antiretroviral Medications
Condition: HIV; Cardiovascular Diseases; Atherosclerosis
MeSH terms: Cardiovascular Diseases; Atherosclerosis
Intervention: Pentoxifylline; Placebo
Intervention description: 400 mg three times a day for 8 weeks; One pill three times a day for 8 weeks
Intervention MeSH terms: Pentoxifylline
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Endothelial Function; Inflammation

Summary:

      People infected with HIV have a greater risk of developing cardiovascular disease than people
      not infected with HIV. This may be due to increased inflammation brought on by either the HIV
      infection itself or the use of antiretroviral medications to treat HIV infection. This study
      will evaluate an anti-inflammatory drug, pentoxifylline, to determine whether it improves
      blood vessel function and reduces inflammation in people infected with HIV who are not
      currently receiving antiretroviral medications.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Documentation of HIV infection with a positive HIV enzyme-linked immunosorbent assay
             (ELISA) test and confirmatory western blot test

          -  CD4 cell count greater than 350/µL at the time of screening

          -  Has not received any antiretroviral therapies in the 6 months before screening

          -  No anticipated need for any antiretroviral therapies during the course of this study,
             as determined by the principal investigator or by the participant's HIV caregiver

        Note: There is no HIV-1 RNA level eligibility criterion.

        Exclusion Criteria:

          -  Incarceration at the time of screening or at any study visit

          -  Diagnosed vascular disease, including history of angina pectoris, coronary disease,
             peripheral vascular disease, cerebrovascular disease, aortic aneurysm, or otherwise
             known atherosclerotic disease

          -  Diagnosed disease or process, other than HIV infection, associated with increased
             systemic inflammation (including, but not limited to, systemic lupus erythematosis,
             inflammatory bowel diseases, or other collagen vascular diseases). Hepatitis B or C
             co-infections are NOT exclusionary.

          -  History of bleeding diathesis, gastrointestinal ulceration or bleeding,
             cerebrovascular aneurysm or bleeding, or retinal hemorrhage

          -  Known or suspected cancer requiring systemic treatment in the 6 months before
             screening

          -  History of American Diabetes Association (ADA)-defined diabetes mellitus. History of
             gestational diabetes is not exclusionary if the potential participant does not have
             current ADA-defined diabetes.

          -  History of migraine headaches

          -  History of Raynaud's phenomenon

          -  History of cardiac arrhythmias or cardiomyopathy

          -  History of hypothyroidism or hyperthyroidism, even if treated

          -  Known allergy or intolerance to pentoxifylline or other methylxanthines (e.g.,
             theophylline, caffeine, theobromine). Use of caffeinated products, except on the
             mornings of the study visits, is not exclusionary.

          -  Known allergy or intolerance to nitroglycerin

          -  History of carotid bruits

          -  Creatinine clearance less than 50 mL/min, using the Cockcroft-Gault equation and a
             serum creatinine level measured in the 28 days before screening or at the screening
             visit

          -  Hemoglobin less than 9.0 mg/dL in the 28 days before screening or at the screening
             visit

          -  Alanine aminotransferase (ALT) level or aspartate aminotransferase (AST) greater than
             three times the upper limit of normal (ULN) in the 28 days before screening or at the
             screening visit

          -  Total bilirubin greater than 2.5 times the ULN in the 28 days before screening or at
             the screening visit

          -  Fever, defined as a temperature greater than or equal to 38.0 C in the 48 hours before
             screening. Fever in the 48 hours before each study visit will require postponement of
             that study visit until the participant's temperature has been lower than 38.0 C for at
             least 48 hours; fevers continuing past the allowed study visit timeframe will result
             in study discontinuation.

          -  Therapy for acute infection or other serious medical illnesses in the 14 days before
             screening. Therapy for acute infection or other serious medical illnesses that
             overlaps with a study visit will result in postponement of that study visit until the
             course of therapy is completed; postponement outside of the allowed study visit
             timeframe will result in study discontinuation.

          -  Pregnant or breastfeeding

          -  Hypotension, defined as systolic blood pressure less than 90 mm Hg, at time of
             screening. Hypotension noted prior to brachial artery reactivity testing at each study
             visit will result in study visit postponement of at least 1 day until systolic
             pressure is greater than or equal to 90 mm Hg the morning of brachial reactivity
             testing; postponement outside of the allowed study visit timeframe will result in
             study discontinuation.

          -  Hypertension, defined as the receipt of any antihypertensive medication in the 28 days
             before screening or systolic blood pressure greater than 160 mm Hg at the screening
             visit

          -  Receipt of anti-inflammatory agents (including, but not limited to, plaquenil,
             infliximab, etanercept, mycophenolate mofetil, sirolimus, tacrolimus, cyclosporine,
             pentoxifylline, or thalidomide) in the 28 days before screening

          -  Receipt of investigational agents, cytotoxic chemotherapy, systemic or topical
             glucocorticoids (of any dose), or anabolic steroids in the 28 days before screening.
             Physiologic testosterone replacement therapy is not exclusionary.

          -  Receipt of lipid-lowering drugs, aspirin, other non-steroidal anti-inflammatory drugs
             (NSAIDS), acetazolamide, anticoagulants, anticonvulsants, or thyroid replacements in
             the 28 days before screening

          -  Use of sildenafil, vardenafil, or tadalafil in the 72 hours before or after each study
             visit

          -  Active drug or alcohol use or dependence that, in the opinion of the investigator,
             would interfere with adherence to study requirements