Pentoxifylline and Combination Antiretroviral Therapy to Improve Blood Vessel Function in HIV-Infected People
Condition: HIV; Vascular Diseases; Cardiovascular Diseases; Atherosclerosis; HIV Infections
MeSH terms: Cardiovascular Diseases; Atherosclerosis; Vascular Diseases
Intervention: Combination antiretroviral therapy (cART); Pentoxifylline; Placebo
Intervention description: Participants will receive the appropriate cART medications, as prescribed by their primary HIV doctor for 48 weeks. (cART medications may be prescribed beyond the length of this study.); Participants will receive 400 mg of pentoxifylline three times per day for 48 weeks.; Participants will receive placebo three times per day for 48 weeks.
Intervention MeSH terms: Anti-Retroviral Agents; 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: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Endothelial Function; Pentoxifylline; Antiretroviral Therapy; 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 in the blood vessels. This
      study will determine whether an anti-inflammatory drug, pentoxifylline, in combination with
      antiretroviral medications, is more effective at improving blood vessel function and reducing
      inflammation than antiretroviral medications alone in people infected with HIV.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Documentation of HIV infection with a positive HIV enzyme-linked immunosorbent assay
             (ELISA) test and confirmatory western blot test

          -  Has not received any antiretroviral therapies in the 6 months before screening

          -  Participant is planning to initiate cART, per the primary HIV caregiver (there is no
             CD4 or HIV-1 RNA level criteria)

        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.

          -  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 ULN in the 28 days before screening or at the
             screening visit

          -  Fever, defined as a temperature greater than or equal to 38.0 degrees Celsius (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 (besides HIV infection)
             within 14 days prior to screening.

        Note: Therapy for acute infection or other serious medical illnesses that overlaps with a
        main 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.

          -  Pregnancy or breastfeeding during the course of the study.

          -  Hypotension, defined as systolic blood pressure < 90mmHg, at time of screening.

        Note: Hypotension noted prior to brachial artery reactivity testing on each main study
        visit will result in study visit postponement of at least one day until systolic pressure
        is ≥ 90mmHg the morning of brachial reactivity testing; postponement outside of the allowed
        study visit timeframe will result in study discontinuation.

          -  Uncontrolled hypertension, defined as a confirmed systolic blood pressure > 160mmHg at
             screening (regardless of use of antihypertensive medications).

          -  Receipt of anti-inflammatory agents (including, but not limited to, plaquenil,
             infliximab, etanercept, mycophenylate mofetil, sirolimus, tacrolimus, cyclosporine,
             pentoxifylline, thalidomide).

          -  Receipt of investigational agents, cytotoxic chemotherapy, systemic or topical
             glucocorticoids (of any dose), or anabolic steroids within 28 days of screening.

        Note: Physiologic testosterone replacement therapy is not exclusionary.

          -  Receipt of lipid-lowering drugs, acetazolamide, anticoagulants, anticonvulsants, or
             thyroid replacements within 28 days prior to screening.

          -  Receipt of aspirin or other NSAIDS within 7 days of screening.

          -  Use of sildenafil, vardenafil, or tadalafil within 72 hours (before or after) of each
             main study visit.

          -  Active drug or alcohol use or dependence that, in the opinion of the investigator,
             would interfere with adherence to study requirements.