HIV-1-infection
Conditions
Keywords
HIV-1-infection, PET scan, MRI, Viremia, Antiretroviral therapy
Brief summary
This is a single center exploratory imaging study involving one intravenous microdose of 89Zr-DFO-VRC01 followed by whole-body PET-MR imaging in HIV infected individuals and healthy volunteers. Imaging data will be obtained from up to four static PE-MR images in order to determine dosimetry and temporal tissue uptake/tissue distribution of 89Zr-DFO-VRC01. This is not a treatment study of the biological activity of 89Zr-DFO-VRC01 to impact HIV persistence.
Detailed description
This will be a single-center pilot study to determine dosimetry and tissue uptake/distribution and pharmacokinetics of 89Zr-VRC01. Up to 18 uninfected and HIV-infected subjects who are either taking or not taking ART will receive a small IV dose of 89Zr-VRC01. After administration of IV 89Zr-VRC01, subjects will undergo up to 4 whole body PET/MR imaging at 2, 6, 24 and 72-120h to determine the pharmacokinetics and radiation dose exposure. The study involves two phases with the second phase only to be performed only if a difference between PET activity in one or more region of interest can be determined between participant groups Phase I (HIV infected, viremic participants and healthy volunteers). Initially, up to 6 individuals with plasma HIV RNA levels \>1,000 copies/ml and up to 6 HIV-uninfected individuals will be administered 89Zr radiolabeled VRC01 followed by PET-MR imaging as above (Phase 1). If differences in PET activity in one or more imaging region of interest can be identified between infected and uninfected individuals, up to 6 individuals on suppressive ART will be administered 89Zr radiolabeled VRC01 followed by PET-MRI (Phase 2). Timing of the PET-MR scans will be determined based on the data from Phase 1.
Interventions
DRUG[89]Zr-DFO-VRC-HIVMAB060-00-AB
Radiolabeled monoclonal antibody that targets the envelope protein of HIV-1.
Sponsors
amfAR, The Foundation for AIDS Research
University of California, San Francisco
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Study Phase 1 1. Age ≥18 years, and 2. HIV uninfected, or 3. HIV infection, and 4. has an HIV viral load measurement within 12 months of study entry of \>40 copies/mL, and 5. HIV-1 envelope RNA or DNA consensus sequence from peripheral blood suggestive of VRC01 binding activity (HIV infected participants only) Study Phase 2 1. Age ≥18 years, and 2. HIV infection, and 3. Initiated a combination ART regimen and has HIV viral load measurements below the detection limit of a clinically approved PCR-based assay (e.g. \<40 HIV-1 RNA copies/mL of blood), or 4. HIV infection, and 5. has an HIV viral load measurement within 12 months of study entry of \>40 copies/mL, and 6. HIV-1 envelope RNA or DNA consensus sequence from peripheral blood suggestive of VRC01 binding activity, or 7. HIV uninfected
Exclusion criteria
Study Phase 1 1. For patients planning to be imaged on PET-MR scanner,
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dosimetry of 89Zr-DFO-VRC01 in healthy volunteers and HIV-infected participants. | 120 hours | To determine the dosimetry and whole body distribution of 89Zr-DFO-VRC01 in healthy volunteers and HIV-infected participants. Study Phase 1. |
| 89Zr-DFO-VRC01 temporal uptake in healthy controls and HIV-infected participants with viral load >1000 c/mL. | 120 hours | To determine the differences in 89Zr-DFO-VRC01 temporal uptake in tissues in healthy volunteers versus HIV-infected, viremic participants. Study Phase 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 89Zr-DFO-VRC01 uptake in aviremic HIV-infected individuals. | 72 hours | To evaluate the uptake and tissue distribution of 89Zr-DFO-VRC01 in HIV-infected participants on suppressive antiretroviral therapy (ART) compared with HIV-infected, viremic individuals and healthy volunteers. Study Phase 2. |
Countries
United States
Contacts
Primary ContactTimothy Henrich, MD
Outcome results
None listed