Proposed study focuses on Youth With HIV (YWH) recruited from the University of North Carolina using a cross sectional assessment of blood samples, clinical, demographic, behavioral, [including substance use and frequency], and neurocognitive data will be evaluated from YWH treated before CD4 T cell decline.

The long-term goal for the proposed research is to apply a systems biology approach to discover evidence that provides the basis for understanding the complex and at times conflicting roles for marijuana in chronic inflammation in HIV-infected youth. To achieve the goal, a systems biology approach with two aims is designed:

Aim 1. To identify inflammatory immune pathways perturbed by recreational marijuana with or without concomitant use of tobacco products by applying a deep sequencing approach to define global transcriptome of peripheral blood cells from HIV-infected virally suppressed youth.

Aim 2. To develop biomarker profiles associated with pro- or anti-inflammatory pathways perturbed by marijuana and to discover biomarker profiles linked to neurocognitive impairment that are impacted by marijuana and tobacco use by YWH

Inclusion Criteria:

• Age 21 years 0 days - less than28 years 364 days
• Currently treated with stable ART and no ART changes for >6months.
• Willingness to participate in CASI questionnaire of self-reported substance use
• Documented behavioral transmission of HIV infection based on CLIA approved HIV antibody/antigen based testing method in medical record -HIV diagnosis greater than or equal to years. Viral load LESS THAN 50 COPIES/ML for the past 6 months. --

Patients may have had single blips in viral load to greater than 50 but less than 1000 copies/ml within the year prior to screening.

• Current Substance profile by chart review or phone screening:
• Marijuana use defined as marijuana use by any route at least 3 times per week in the absence of tobacco. N= 20.
• Tobacco use only based on report of regular (at least 3 times per week smoking). N=24
• Tobacco plus marijuana use defined as regular smoking and marijuana (at least 3 times per week) N =7
• No substance use of any type (alcohol, tobacco, marijuana or other recreational drugs in the past 90 days). N = 10
• Able to provide written informed consent in English and to adhere to protocol schedule

Exclusion Criteria:

• History of AIDS defining illness
• Pregnancy at any time during the study
• Use of substances that would interfere with the ability to complete the study
• History of significant cognitive or motor impairment or other chronic condition that would interfere with the ability to complete the study and impact neurocognitive testing
• Acute psychiatric symptoms (e.g. suicidality, mania, psychosis or severe depression)
• Other neurological disorder (e.g. multiple sclerosis, seizure disorder, etc.) requiring ongoing treatment or active outpatient evaluation
• Severe mental illness (requiring antipsychotic or mood stabilizing medications and/or inpatient hospitalization in past year)
• History of CNS infection (AIDS opportunistic (e.g. toxoplasmosis) or non-opportunistic (bacterial meningitis) with lasting or permanent neurological sequelae)
• Underlying and/or uncontrolled medical illnesses that may result in chronic inflammation , (e.g. SLE or autoimmune disease) as determined by the PI
• Nursing mothers
• Unable to read and write in English

Enrollment will consist of approximately 61 HIV-infected youth meeting the below entry criteria who are receiving antiretroviral therapy with undetectable viral levels at the time of entry (based on viral load assay within 1 year of enrollment) Recruitment will include Youth Age 21-28

• Youth who use marijuana only [targeted number 20 participants]
• Youth who use tobacco products only [targeted number 24 participants]
• Youth who use marijuana and tobacco [targeted number 7 participants]
• Youth who do not use substances [targeted number 10 participants]