Intervention: Efavirenz
Trial phase: Phase 4
ATC code: J05AG03 | J05AR06 | J05AR11
SMILES: O=C1Nc2ccc(Cl)cc2[C@@](C#CC2CC2)(C(F)(F)F)O1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 20
Group description: Efavirenz 600mg given nightly without food for 30 days

Efavirenz: 600mg orally every evening
Eligibility criteria:
Inclusion Criteria:

18 years of age or older
Negative ELISA for HIV-1 or HIV-2 at screening
Negative hepatitis B surface antigen at screening
Negative hepatitis C antibody at screening
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
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
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
No anticipated changes or additions to other medical therapies during the course of the study
No documented history of seizure disorder

Exclusion Criteria:

Inability to provide written, informed consent
Known allergy/intolerance to rilpivirine, efavirenz, or nitroglycerin
Absolute neutrophil count < 750cell/mL at screening
Hemoglobin < 11g/dL at screening
Platelet count < 100,000/mL at screening
Estimated creatinine clearance (per Cockcroft-Gault equation) < 55 mL/min at screening
Liver transaminases (AST or ALT) > 100 IU/mL or total bilirubin > 1.5mg/dL at screening
Serum glucose > 200mg/dL at screening
Serum total cholesterol > 190mg/dL at screening
Breastfeeding at screening or during the course of the study
Hypotension, defined as SBP < 90mmHg at time of each main study visit before brachial artery ultrasound measurements
Hypertension, defined as SBP > 160mmHg at time of screening
Receipt of investigational agents within 30 days of each screening visit or anticipated use during the trial
Receipt of cytotoxic chemotherapy within 30 days of each screening visit or anticipated use during the trial
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
Use of sildenafil (Viagra or Silagra), vardenafil (Levitra), or tadalafil (Cialis), within 72 hours (before or after) of brachial artery reactivity testing
Indwelling vascular catheters within any upper body vessel at time of brachial artery reactivity testing
Active drug or alcohol use or dependence that, in the opinion of the investigator or study personnel, would interfere with adherence to study requirements
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
History of migraine headaches
History of Raynaud's phenomenon
History of cardiac arrythmias
History of hypothyroidism or hyperthyroidism that is untreated (defined as a TSH outside the normal range on most recent testing during normal clinical care)
History of carotid bruits
History of any tobacco use (cigarette smoking, cigar smoking, chewing tobacco) or nicotine replacement treatments (patch, gum) within 45 days of screening
Drugs/therapies with significant CYP 450 induction or inhibition potential at screening
Use of antacids, H2-blockers, or proton pump inhibitors within 30 days of screening or anticipated use of these drugs during the trial
Any history of injection or illicit drug use
Presence of fever, defined as an oral or tympanic temperature > 100.3F, at either the Entry or Closeout Visits
On the PHQ-9 depression questionnaire at screening, a total score of more than 9 or any score over 0 on question 9.