Effect of Genetics on Metabolism of Efavirenz

* ELIGIBILITY CRITERIA: Healthy Volunteers: Inclusion Criteria: 1. Males and females between the ages of 18 and 55 years. 2. Healthy by medical history and physical exam 3. Laboratory values within established guidelines for participation in clinical studies: AST less than 1.25 x ULN; SCr less than or equal to ULN; hemoglobin equal to or greater than 11 g/dL (for males and females). 5.) Ability to abstain from eating grapefruit or drinking grapefruit juice during EFV administration and EFV PK sampling periods. 6.) Negative serum pregnancy test for females of child-bearing potential (within 1 day before starting EFV). 7.) Females of child-bearing potential who are able and willing to either practice abstinence or use two non-hormonal forms of birth control (such as condoms, diaphragms, IUDs, etc.) while taking EFV and up to the 28th day after their last EFV dose. 8.) Non-smokers for at least 1 month prior to study participation. Exclusion Criteria: 1. Concomitant routine therapy with any prescription, over-the-counter, herbal, or holistic medications, including oral contraceptives and hormonal IUDs, for 14 days prior to study participation. * Intermittent use of acetaminophen and non-steroidal anti-inflammatory medications (i.e. ibuprofen) will be allowed during the study, but should not be taken on the days of pharmacokinetic blood sampling. Intermittent use of the non-sedating antihistamines fexofenadine and cetirizine and topical hydrocortisone cream will be allowed during the study under the supervision of and with the approval of the study team; however, fexofenadine and cetirizine should not be taken on the days of pharmacokinetic blood sampling. * A daily multivitamin with minerals will be allowed during the study. 2. Inability to obtain venous access for blood sample collection. 3. The presence or history of any of the following: HIV infection, active tuberculosis, renal disease (chronic or acute renal failure or insufficiency), diabetes, hepatitis B or C infection (as assessed by patient interview) or hepatic impairment, pancreatitis, peptic ulcer disease requiring maintenance pharmacologic therapy, injection drug use, epilepsy or seizure disorders, history of head trauma, any psychiatric illness or symptoms (including, but not limited to depression, bipolar disorder, a history of suicide attempts or suicidal ideation, psychosis, schizophrenia, and bulimia or anorexia nervosa) as assessed by patient interview and through clinician evaluation using the Beck Depression Index, or any other condition that may interfere with the interpretation of the study results or not be in the best interest of the subject in the opinion of the investigators. 4. Positive pregnancy test or breastfeeding female. 5. A previously documented history of persistent diarrhea or malabsorption that would interfere with the subject's ability to absorb drugs. 6. Drug or alcohol abuse that may impair safety or adherence or interfere with the study results (more than 3 alcoholic drinks per day on a regular basis). 7. History of intolerance or allergic reaction to efavirenz (Sustiva® (Registered Trademark)) or bupropion (Wellbutrin® (Registered Trademark)). HIV-infected volunteers: Inclusion Criteria 1. HIV-positive males and females at least 18 years old. 2. On a standard EFV-containing regimen (EFV + 2 or 3 NRTIs) for at least 1 month prior to study participation. 3. Laboratory values within established guidelines for participation in clinical studies53: AST less than or equal to 1.25 x ULN; SCr less than or equal to ULN; hemoglobin equal to or greater than 11 g/dL (for both males and females). 4. Ability to abstain from eating grapefruit or drinking grapefruit juice during the EFV PK sampling period and for 3 days prior. 5. A negative pregnancy test for women of child-bearing potential. Exclusion Criteria 1.) Concomitant therapy with a PI or any NNRTI other than EFV for 30 days prior to study participation. 2,) Concomitant therapy with any prescription, over-the-counter, herbal, or holistic medications that are known to interact with EFV or modulate CYP2B6 activity for 14 days prior to study participation. 3.) Inability to obtain venous access for blood sample collection. 4.) The presence of any of the following: Any active opportunistic infection (including, but not limited to tuberculosis, Mycobacterium avium complex, cytomegalovirus, Pneumocystis jiroveci, Cryptococcus neoformans, and esophageal candidiasis), renal disease (chronic or acute renal failure or insufficiency), hepatic impairment, pancreatitis, or any other condition that may interfere with the interpretation of the study results or not be in the best interest of the subject in the opinion of the investigators. 5.) A previously documented history of persistent diarrhea or malabsorption that would interfere with the subject's ability to absorb drugs. 6.) Drug or alcohol abuse that may impair safety or adherence or interfere with the study results. 7.) Non-adherence to efavirenz therapy (regularly misses greater than 1 dose/week) 8.) Positive pregnancy test or breastfeeding female. 9.) Severe or potentially life-threatening adverse event/toxicitiy from efavirenz, such that administration of an additional dose of efavirenz would be unsafe and is deemed unwarranted by the study personnel or the patient's primary physician.