Effect of Galantamine on Inflammation and Cognition

Inclusion Criteria: Eligible subjects will be males and females: 1. At least 30 years old 2. Diagnosed with HIV-1 infection 3. On stable ART regimens (no changes to treatment within 4 weeks of Intake visit) 4. Viral load of less than or equal to 200 copies/mL 5. Current cluster of differentiation (CD4) counts greater than 200 6. If current or past diagnosis of bipolar disorder, eligible if: 1. No psychotic features 2. Montgomery-Asberg Depression Rating Scale (MADRS): total score less than 8 (past 4 weeks), suicidal item score less than 1 (past 4 weeks) 3. Young Mania Rating Scale (Y-MRS): total score less than 8 (past 4 weeks), irritability, speech content, disruptive or aggressive behavior items score less than 3 (past 4 weeks) 4. No psychiatric hospitalization or Emergency Room visits for psychiatric issues in the past 6 months 5. No aggressive or violent acts or behavior in the past 6 months 7. Able to communicate in English and provide written informed consent 8. Will be residing in the geographic area for at least 7 months 9. Not currently trying to quit smoking 10. Smoking Status 1. Smokers (HIV+S) will report at least 5 instances of smoking per day, on average for the past year and provide a breath carbon monoxide (CO) sample greater than 5 ppm at Intake and at the beginning of each treatment period 2. Non-smokers (HIV+NS) will report smoking fewer than 100 cigarettes in their lifetime, or less than 5 pack years of smoking and no cigarettes in the last year. They will self-report no current use of any tobacco or nicotine product and will provide a CO sample of less than 3 ppm at Intake and at the beginning of each treatment period. If CO sample does not reflect self-report, the PI will be consulted to determine eligibility. Exclusion Criteria: Subjects who present with and/or self-report the following criteria will not be eligible to participate in the study. Smoking Behavior 1. Current enrollment or plans to enroll in another smoking cessation program in the next 7 months. 2. Regular (daily) use of electronic cigarettes, chewing tobacco, snuff, snus, cigars, cigarillos, or pipes. 3. Current use or plans to use nicotine substitutes (gum, patch, lozenge, e-cigarette) or smoking cessation treatments in the next 7 months. Alcohol/Drug Use 1. Current untreated and unstable diagnosis of substance abuse or dependence (if past use and if receiving treatment and stable for at least 30 days, eligible) 2. Positive urine drug screen for cocaine, methamphetamines, phencyclidine (PCP), barbiturates, ecstasy (MDMA), at Intake or Lab visits. Those who screen positive for amphetamines, benzodiazepines, methadone, oxycodone, and/or opiates (low level cut-off 300 ng/mL) and who are prescribed these medications will be reviewed on a case-by-case basis by the study physician and PIs (see Measures and Table 1 for details). Participants believed to have a false-positive result on the drug screen may continue in the study, with investigator approval. Medical/Psychiatric Conditions 1. Women who are pregnant, planning a pregnancy or lactating 2. Current diagnosis of unstable and untreated major depression (if stable for at least 30 days, eligible) 3. Current or past diagnosis of psychotic disorder 4. Cancer diagnosis within the past 6 months (except basal cell carcinoma) 5. Major heart disease or stroke within the past 6 months 6. Uncontrolled hypertension (systolic blood pressure greater than 160 or diastolic blood pressure greater than 100). 7. Medical conditions contraindicated for use with galantamine: 1. Diagnosis of Alzheimer's disease or dementia 2. Epilepsy or other seizure disorder 8. Bladder outflow obstruction 9. Active HCV co-infection (if cured, requires study physician approval) 10. Liver function tests more than 20% outside of the normal range; Gamma-glutamyl transpeptidase (GGT) values more than 20% outside of the normal range. If Albumin/Globulin ratios are 20% outside of normal range the abnormal value will be evaluated for clinical significance by the Study Physician and eligibility will determined on a case-by-case basis. 11. Renal disease or renal dysfunction (e.g., serum creatinine levels greater than 1.5 X upper limit of normal). Those with moderate hepatic impairment or creatinine clearance 9 to 59 mL/min shall not exceed the 16 mg/day dose. 12. Peptic ulcer disease (requires study physician approval) 13. Suicide risk as indicated by at least one of the following on the Columbia Suicide Severity Rating Scale (the PI and/or study psychologist will be consulted to assess safety and determine eligibility in cases close to the eligibility cutoffs): 1. Current suicidal ideation (within 30 days of enrollment) 2. Two or more lifetime suicide attempts or episodes of suicidal behavior 3. Any suicide attempt or suicidal behavior within 2 years of enrollment Medication 1. Current use or discontinuation within the last 14 days of: 1. Quit smoking medications including varenicline (Chantix), bupropion (Wellbutrin) 2. Anti-psychotic medications (e.g., Zyprexa, Clozaril, Seroquel, Risperdal). If used to treat psychotic symptoms. Other uses may be eligible pending physician approval). 3. Systemic Steroids (e.g., Prednisone). 4. Alzheimer's disease medications (e.g., Acetylcholinesterase inhibitors (ACIs), Aricept/donepezil, Exelon/rivastigmine, Tacrine, or memantine) 5. Irritable bowel syndrome medication (e.g., Dicyclomine/Bentyl) 6. Heart medications (e.g., quinidine). 7. Muscle relaxants (e.g., Anectine/succinylcholine) 8. Anti-seizure medications (e.g. Ativan, Banzel, Carbatrol, Dilantin, Lamictal, Gabitril, Lyrica, Neurontin, Tegretol, Topomax) if used to treat a seizure disorder or epilepsy. Other uses may be eligible. 9. Urinary retention medications (e.g., Duvoid/bethanechol, Proscar/finasteride, Avodart/dutasteride, Dibenzyline/ phenoxybenzamine, Regitine/phentolamine) 2. Daily use of: 1. Opiate-containing medications for chronic pain (Duragesic/fentanyl patches, Percocet, Oxycontin). Smokers who report taking opiate-containing medications on an "as-needed" basis will be instructed to refrain from use until their study participation is over and that they will be tested to ensure they have complied with this requirement. 2. Chronic obstructive pulmonary disease (COPD) medication (e.g., Atrovent/Ipratropium Bromide) 3. Known allergy to study medication. Subjects will be instructed to refrain from using any study prohibited drugs/medications (both recreational and prescription) throughout their participation in the study.