Effects of Etravirine on Endothelial Function in HIV-uninfected Adults: A Pilot Study
Condition: Endothelial Function; Lipids; Insulin Resistance; Inflammation; HIV Infections
MeSH terms: Insulin Resistance; Inflammation
Intervention: Etravirine
Intervention description: Two one-hundred mg tablets orally twice daily for four weeks
Intervention MeSH terms: Etravirine
Phase: Phase 1
Study type: Interventional
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: HIV; Endothelial function; Etravirine

Summary:

      The purpose of this study is to determine the safety and effects of etravirine, an HIV
      antiretroviral medication, on vascular function.
    

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. No history of diabetes, hypertension, or dyslipidemia

          7. No anticipated changes or additions to other medical therapies during the course of
             the study

        Exclusion Criteria:

          1. Inability to provide written, informed consent

          2. Known allergy/intolerance to etravirine 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. Breastfeeding at screening and during the course of the study

          9. Hypotension, defined as SBP<90mmHg at time of each main study visit before brachial
             artery ultrasound measurements

         10. Receipt of investigational agents, cytotoxic chemotherapy, systemic glucocorticoids
             (>10mg/day of prednisone or the equivalent), or anabolic steroids within 30 days of
             each screening visit or each main study visit

         11. Use of sildenafil (Viagra or Silagra), vardenafil (Levitra), or tadalafil (Cialis),
             within 72 hours (before or after) of brachial artery reactivity testing

         12. Indwelling vascular catheters within any upper body vessel at time of brachial artery
             reactivity testing

         13. Active drug or alcohol use or dependence that, in the opinion of the investigator,
             would interfere with adherence to study requirements

         14. 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

         15. History of migraine headaches

         16. History of Raynaud's phenomenon

         17. History of cardiac arrythmias

         18. History of hypothyroidism or hyperthyroidism that is untreated (defined as a TSH
             outside the normal range on most recent testing during normal clinical care)

         19. History of carotid bruits.

         20. History of any tobacco use (cigarette smoking, cigar smoking, chewing tobacco) or
             nicotine replacement treatments (patch, gum) within one year of screening.