This study employs novel methods to identify key determinants and consequences of concurrent HIV infection and regular cannabis use. This study will acquire extensive phenotype data from peripheral and brain markers of immune activation, brain structure, and neuropsychological performance (NP) in persons living with HIV (PLWH) receiving combination anti-retroviral therapy (cART) (80 regular cannabis users and 80 non-users) and HIV uninfected (HIV-) controls (80 regular cannabis users and 80 non-users). This study will provide key insights into the effects of regular cannabis and HIV on peripheral and brain markers of immune function and NP in PLWH and HIV- controls. These insights are critical for cure strategies and ongoing HIV treatment initiatives.

Inclusion Criteria:

1. Participants must be 18-70 years old.
2. PLWH must have documented HIV infection for approximately 1 year, be on a cART regimen for approximately ≥3 months, and be virally well-controlled (< 200 copies/mL).
3. HIV- controls must have confirmed HIV- serostatus.
4. Participants must complete at least 9 years of education.
5. Participants must be able to provide informed consent.
6. Female participants must have a negative pregnancy test or written documentation of tubal ligation, hysterectomy, post-menopausal status, etc. and cannot be breastfeeding.
7. Participants should have no contraindications to an MRI scan.
8. Participants should be willing to have cannabis use history confirmed via clinical interview and urine analysis .
9. All inclusion criteria at PI discretion.

Exclusion Criteria:

1. History of neurological disorder (e.g., stroke, head injury with loss of consciousness for >5 minutes, developmental learning disability, etc.).
2. Uncontrolled major affective disorder; history of bipolar disorder or schizophrenia. Major depression controlled with no hospitalizations or suicidal ideation in the past year is allowed.
3. Current substance use disorder (SUD) as defined by DSM-5 criteria besides cannabis use disorder (CUD) (though a past SUD > 1 year before the time of study enrolment will be allowed).
4. currently prescribed anti-coagulants (only exclusionary if participant will engage in optional LP).
5. an allergy to lidocaine or similar anesthetic (only exclusionary if participant will engage in optional LP).
6. a history of a bleeding disorder (only exclusionary if participant will engage in optional LP).
7. claustrophobia or a pacemaker that would prevent magnetic resonance imaging (MRI) scanning.
8. all exclusion criteria at PI discretion.

A total of 160 PLWH (80 regular cannabis users and 80 non-users) and 160 demographically similar healthy HIV- controls (80 regular cannabis users and 80 non-users) may undergo multimodal neuroimaging, immunophenotyping (including blood and cerebrospinal fluid), and neuropsychological testing to address the specific aims.