HIV-1 and Brain Interaction on Smoking Comorbidity

Study Overview
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Brief Summary
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People living with HIV-1 have high rates of cigarette smoking, which may be related to nicotinic interaction with HIV-1 infection and brain function levels. The proposed project aims to understand these pathways using translational brain imaging and HIV-1 reactivation studies. The study proposes a targeted nicotine-brain investigation of the nicotinic effects in HIV-1 infection from cellular to brain circuitry levels.

Detailed Description
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Smoking remains the leading cause of preventable morbidity and mortality in the United States. The alarmingly high smoking rates and unsatisfactory performance of standard smoking cessation efforts in people living with HIV/AIDS (PLWH) interfere with the overall progress in the treatment of HIV-1 infection. Our understanding of nicotine addiction mechanisms in PLWH, and how they are related to and interact with HIV-1 neuropathology, is limited and thus hindering the development of more effective, targeted treatments. The study will directly address neurological complication of this HIV-associated comorbidity at the brain circuitry level using state-of-the-art imaging tools and methods.

Official Title
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HIV-1 and Brain Interaction on Smoking Comorbidity

Conditions
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Smoking

Intervention / Treatment
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* Other: Tobacco smoking and nicotine patch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects between ages 18-60 in good health Ability to give written informed consent For people living with HIV: should be diagnosed with HIV two years or more and on ART two years or more For people living with HIV: should have achieved virologic suppression (defined as viral loads of ≤ 200 copies/ml), and without current signs of reactivation Exclusion Criteria: Inability to sign informed consent Unable to undergo MRI scanning due to metallic devices or objects (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts) or claustrophobic to the scanner Any major medical illnesses to include, but not limited to, uncontrolled high blood pressure or high blood sugar, cardiovascular disease, asthma, peripheral vascular diseases, coagulopathies, history of superficial or deep vein thrombosis as per medical history Current substance-induced psychiatric disorders Significant alcohol or other drug use, other than nicotine dependence or marijuana use Gross structural abnormalities and/or have a history of syncope Positive urine pregnancy tests Any neurological illnesses to include, but not limited to, seizure disorders, multiple sclerosis, movement disorders, or history of head trauma, CVA, CNS tumor, For people living with HIV: having AIDS or non-AIDS-defining cancer or active CNS and other opportunistic disease For people living with HIV: on active treatment of hepatitis C virus (HCV)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIV-1 smokers<br> | Other: Tobacco smoking and nicotine patch<br>* Tobacco smoking at each participant's regular cigarette. Over-the-counter nicotine patch use<br>|
| No Intervention: HIV-1 nonsmokers<br> | |
| Active Comparator: Healthy control smokers<br> | Other: Tobacco smoking and nicotine patch<br>* Tobacco smoking at each participant's regular cigarette. Over-the-counter nicotine patch use<br>|
| No Intervention: Healthy control nonsmokers<br> | |
| Active Comparator: HIV-1 nonsmokers using nicotine patch<br> | Other: Tobacco smoking and nicotine patch<br>* Tobacco smoking at each participant's regular cigarette. Over-the-counter nicotine patch use<br>|
| No Intervention: HIV-1 nonsmokers using placebo patch<br> | |
| Active Comparator: Healthy control nonsmokers using nicotine patch<br> | Other: Tobacco smoking and nicotine patch<br>* Tobacco smoking at each participant's regular cigarette. Over-the-counter nicotine patch use<br>|
| No Intervention: Healthy control nonsmokers using placebo patch<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional and structural connectivity using magnetic resonance imaging (MRI) | Resting functional MRI and diffusion imaging MRI | one day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV-1 reactivation | HIV-1 viral protein p24 expression | one day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, nicotine, brain, smoking