HIV Infections
Conditions
Keywords
HIV infection, Positron Emission Tomography, F-AraG, Magnetic Resonance Imaging
Brief summary
This is a single center exploratory imaging study involving one intravenous microdose of \[18F\]F-AraG followed by whole-body positron emission tomography-magnetic resonance (PET-MR) imaging in HIV infected individuals to determine the anatomical distribution of the PET tracer. Participants will be enrolled if they were treated during early or late HIV infection. In addition, individuals not on antiretroviral therapy (ART) or with HIV-1 plasma RNA levels \>5,000 copies/mL will be enrolled. Up to 30 participants will be enrolled with HIV.
Detailed description
The PET radiofluorinated imaging agent, \[18F\]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine; trade name VisAcT) localizes to sites of immune activation and is predominantly accumulated in proliferative T cells. As a result, there is interest in imaging residual immune activation in the setting of both treated and untreated HIV-1 infection, a disease in which chronic immune activation and inflammation may lead to significant morbidity, despite the use of otherwise suppressive ART. The primary endpoint is to determine the anatomical distribution of \[18F\]F-AraG in HIV-infected individuals taking or not taking antiretroviral therapy. Secondary objectives are to determine if \[18F\]F-AraG PET-MRI is able to detect differences in T cell activation between patients with early versus late treated HIV infection and to determine if \[18F\]F-AraG uptake correlates with direct blood and tissue measures of HIV reservoir size and activity in the above cohorts/studies.
Interventions
\[18F\]F-AraG is a radiolabeled high affinity substrate for deoxyguanosine kinase (dGK) and a low affinity substrate for deoxycytidine kinase (dCK), which are over-expressed in activated T cells.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
University of California, San Francisco
CellSight Technologies, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Adults with HIV Infection taking or not taking antiretroviral therapy
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>18 years 2. Ability to read and understand written informed consent document 3. HIV infection, and Initiated a combination ART regimen, or, has never received ART, or, has received ART in the past, but has not been taking for a least 1 week prior to study imaging. (Of note, per Department of Health and Human Services (DHHS) guidelines, the protocol team will strongly recommend that all HIV+ participants initiate ART who not done so already, both for their own health and to prevent the transmission of HIV infection.) 4. Laboratory evaluations obtained within 60 days prior to entry. i. Platelet count ≥100,000/mm3 ii. ANC \>1500/mm3 iii. Aspartate aminotransferase (AST) \<2 x ULN iv. Alanine aminotransferase (ALT) \<2 x ULN v. CD4+ T cell count \>100 cells/mm3 for HIV infected individuals vi. Calculated creatinine clearance (CrCl) ≥60 mL/min as estimated by the Cockcroft-Gault equation: For men, (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dL x 72) = CrCl (mL/min)\* * For women, multiply the result by 0.85 = CrCl (mL/min)
Exclusion criteria
1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anatomical distribution of [18F]F-AraG | 1-4 hours | Anatomical distribution of \[18F\]F-AraG in HIV-infected individuals taking or not taking antiretroviral therapy as determined by PET-MR imaging. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| [18F]F-AraG uptake in early and later-treated HIV infection | 1-4 hours | Determine if \[18F\]F-AraG PET-MRI is able to detect differences in T cell activation in early versus late treated HIV infection, and between HIV infected and historical HIV-uninfected controls |
| Correlate [18F]F-AraG uptake with measures of HIV persistence | 1-2 weeks | Determine if \[18F\]F-AraG uptake correlates with direct blood and tissue measures of HIV reservoir size and activity in the above cohorts/studies. |
Countries
United States
Contacts
Primary ContactTimothy J Henrich, MD
Outcome results
None listed