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

We hypothesize that in HIV-uninfected subjects, etravirine 200mg twice daily for four weeks will have no effect on endothelial function. The primary objective of this study is to determine the effects of etravirine 200mg twice daily given for four weeks on endothelial function, measured as flow-mediated dilation (FMD) of the brachial artery, in HIV-uninfected subjects. Secondary objectives include determination of the effects of etravirine 200mg twice daily given for four weeks on safety measures, lipid fractions, HOMA-IR, blood pressure, inflammatory parameters, and endothelial activation parameters.

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.

Six weeks