Efavirenz Versus Rilpivirine on Vascular Function, Inflammation, and Oxidative Stress
Condition: Cardiovascular Disease
MeSH terms: Cardiovascular Diseases
Intervention: Efavirenz; Rilpivirine
Intervention description: 600mg orally every evening; 25mg orally once daily
Intervention MeSH terms: Efavirenz; Rilpivirine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: endothelium; inflammation; oxidative stress; HIV-1

Summary:

      The purpose of this study is to compare the cardiovascular profiles of efavirenz and
      rilpivirine, which are two drugs used to treat HIV infection.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 18 years of age or older

          2. Negative ELISA for HIV-1 or HIV-2 at screening

          3. Negative hepatitis B surface antigen at screening

          4. Negative hepatitis C antibody at screening

          5. For women of reproductive potential, a negative urine pregnancy test at screening and
             willingness to use two forms of birth control during the course of the study

          6. For men who are capable of impregnating a female sexual partner, a willingness to use
             condoms with spermicidal gel for all sexual contacts during the course of the study

          7. No documented history of or receipt of medications being used to treat any psychiatric
             disorder, including (but not limited to) depression, dysthymia, mania, bipolar
             disease, schizophrenia, or previous suicidal ideation/attempts

          8. No anticipated changes or additions to other medical therapies during the course of
             the study

          9. No documented history of seizure disorder

        Exclusion Criteria:

          1. Inability to provide written, informed consent

          2. Known allergy/intolerance to rilpivirine, efavirenz, or nitroglycerin

          3. Absolute neutrophil count < 750cell/mL at screening

          4. Hemoglobin < 11g/dL at screening

          5. Platelet count < 100,000/mL at screening

          6. Estimated creatinine clearance (per Cockcroft-Gault equation) < 55 mL/min at screening

          7. Liver transaminases (AST or ALT) > 100 IU/mL or total bilirubin > 1.5mg/dL at
             screening

          8. Serum glucose > 200mg/dL at screening

          9. Serum total cholesterol > 190mg/dL at screening

         10. Breastfeeding at screening or during the course of the study

         11. Hypotension, defined as SBP < 90mmHg at time of each main study visit before brachial
             artery ultrasound measurements

         12. Hypertension, defined as SBP > 160mmHg at time of screening

         13. Receipt of investigational agents within 30 days of each screening visit or
             anticipated use during the trial

         14. Receipt of cytotoxic chemotherapy within 30 days of each screening visit or
             anticipated use during the trial

         15. Receipt of systemic glucocorticoids (> 10mg/day of prednisone or the equivalent),
             inhaled/nasal/topical fluticasone, or anabolic steroids within 30 days of each
             screening visit or anticipated use during the trial

         16. Use of sildenafil (Viagra or Silagra), vardenafil (Levitra), or tadalafil (Cialis),
             within 72 hours (before or after) of brachial artery reactivity testing

         17. Indwelling vascular catheters within any upper body vessel at time of brachial artery
             reactivity testing

         18. Active drug or alcohol use or dependence that, in the opinion of the investigator or
             study personnel, would interfere with adherence to study requirements

         19. Acute therapy for serious infection or other serious medical illnesses (in the
             judgment of the site investigator) requiring systemic treatment and/or hospitalization
             within 14 days prior to each screening and study visit

         20. History of migraine headaches

         21. History of Raynaud's phenomenon

         22. History of cardiac arrythmias

         23. History of hypothyroidism or hyperthyroidism that is untreated (defined as a TSH
             outside the normal range on most recent testing during normal clinical care)

         24. History of carotid bruits

         25. History of any tobacco use (cigarette smoking, cigar smoking, chewing tobacco) or
             nicotine replacement treatments (patch, gum) within 45 days of screening

         26. Drugs/therapies with significant CYP 450 induction or inhibition potential at
             screening

         27. Use of antacids, H2-blockers, or proton pump inhibitors within 30 days of screening or
             anticipated use of these drugs during the trial

         28. Any history of injection or illicit drug use

         29. Presence of fever, defined as an oral or tympanic temperature > 100.3F, at either the
             Entry or Closeout Visits

         30. On the PHQ-9 depression questionnaire at screening, a total score of more than 9 or
             any score over 0 on question 9.