Inclusion Criteria:
1. Willing and able to provide written informed consent
2. Male or female, age ≥ 18 and ≤ 65 years
3. HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load.
4. Continuous therapy with a Department of Health and Human Services (DHHS) recommended/alternative combination ART for least 24 months (at least 3 agents) at study entry with no regimen changes in the preceding 12 weeks
5. Maintenance of undetectable plasma HIV-1 RNA (\<40 copies/ml) for at least 12 months. Episodes of single HIV plasma RNA 50-500 copies/ml will not exclude participation if subsequent HIV plasma RNA is \<40 copies/ml.
6. No plans to modify ART during the study period (146 days, or approximately 5 months)
7. Screening CD4+ (cluster of differentiation 4) T-cell count ≥ 350 cells/mm3
8. Screening hemoglobin ≥ 12.5 g/dL
9. No current or prior history of methamphetamine (MA) use disorder by DSM-5 diagnostic criteria. Participants may have a prior history of taking prescription medications containing amphetamines-type stimulants such as Adderall® or Dexedrine® or Ritalin for the treatment of conditions such as attention deficit hyperactivity disorder as long as the participant has not taken these medications in the last 12 months or plans to take these medications during the entire study period.
10. Willingness to use two forms of contraception throughout the study period as well as up to 30 days after the last day of study completion.
11. Ability and availability to participate in the full 146 days of the study (approximately 5 month) and maintain the inclusion/exclusion criteria.
Exclusion Criteria:
1. History of methamphetamine ("meth") use disorder by DSM-5 diagnostic criteria.
2. Evidence of MA use other than due to the administered oral methamphetamine study drug, based on urine, hair, or serum MA measurements collected at baseline and follow-up study visits.
3. Current use of prescription medications containing amphetamine-type stimulants (e.g., Adderall®, Dexedrine®, Ritalin, etc.) within the last 1 year.
4. Sensitivity or allergy to amphetamine-type stimulants
5. Current use of any other "psychoactive" drug within the last 1 year. These include cocaine, ecstasy, lysergic acid diethylamide (LSD), mushrooms, or other recreational drugs - but nicotine or caffeine use is ok.
6. Marijuana use in the last 30 days; marijuana may influence the interpretation of the study drug's effect on viral transcription, inflammation, and/or gene expression.
7. Current use of opioids (heroin, methadone) or prescription opioid agonists such as hydrocodone (Norco®), buprenorphine/naloxone (Suboxone®), oxycodone (Oxycontin®), hydromorphone (Dilaudid®) within the last 1 year by self-report and/or urine qualitative screening.
8. Current use of alcohol use disorder (DSM-5 criteria) within the last 1 year as this might put patient at risk of withdrawal during the study.
9. Significant physical or psychiatric illness that might impair the ability to safely complete the study or that might be complicated by the study drugs, including prior seizures (after age 8) or other active neurological disease.
10. Clinically significant abnormalities on physical examination or screening laboratory values
11. History of serious adverse event or hypersensitivity to MA or corn starch (the latter is used in the placebo).
12. Recent use within the last month of the following medications given potential interactions with oral methamphetamine: acebrophylline, iobenguane, isocarboxazid, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine, asunaprevir, buproprion, topical cocaine, fluoxetine, iohexol, linezolid, paroxetine, potassium citrate, quinidine, sodium bicarbonate, sodium citrate, sodium lactate, tipranavir, and tromethamine.
13. Recent hospitalization in the last 90 days.
14. Recent infection in the last 90 days requiring systemic antibiotics.
15. Screening hemoglobin below 12.5 g/dL.
16. Prior diagnosis or abnormal screening labs consistent with a diagnosis of hyperthyroidism or hypothyroidism.
17. Poorly controlled hypertension with systolic blood pressure \> 160 on more than one occasion.
18. History of glaucoma.
19. Significant myocardial disease (current myocarditis or reduced left ventricular ejection fraction below the lower limit of normal) or diagnosed coronary artery disease.
20. History of psychotic symptoms (e.g., hallucinations, delusional thinking).
21. History of bipolar disorder.
22. Significant respiratory disease requiring oxygen.
23. A history of hypersensitivity to sympathomimetic amines (e.g., epinephrine, norepinephrine, or dopamine).
24. Diabetes or current hypothyroidism.
25. Participants of reproductive potential or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test at screening. All participants of childbearing potential must agree to use a double-barrier method of contraception throughout the study period and up to 90 days after the last dose of MA.
26. Exposure to any immunomodulatory drug (including maraviroc) in the 16 weeks prior to study.
27. Prior or current use of experimental agents used with the intent to perturb the HIV-1 viral reservoir.
28. History of seizures, psychosis, abnormal electroencephalogram or brain damage with significant persisting neurological deficit
29. Recent vaccination within the last 2 weeks prior to study baseline visit. Routine or standard of care vaccinations (such as influenza, pneumococcal, and meningococcal vaccinations) are allowed but must be administered greater than 14 days prior to baseline study visit.
