First-in-human immunoPET imaging of HIV-1 infection using 89Zr-labeled VRC01 broadly neutralizing antibody

Denis R. Beckford-Vera, Robert R. Flavell, Youngho Seo, Enrique Martinez-Ortiz, Maya Aslam, Cassandra Thanh, Emily Fehrman, Marion Pardons, Shreya Kumar, Amelia N. Deitchman, Vahid Ravanfar, Brailee Schulte, I-Wei Katherine Wu, Tony Pan, Jacqueline D. Reeves, Christopher C. Nixon, Nikita S. Iyer, Leonel Torres, Sadie E. Munter, Tony Hyunh, Christos J. Petropoulos, Rebecca Hoh, Benjamin L. Franc, Lucio Gama, Richard A. Koup, John R. Mascola, Nicolas Chomont, Steven G. Deeks, Henry F. VanBrocklin () and Timothy J. Henrich ()
Additional contact information
Denis R. Beckford-Vera: University of California San Francisco
Robert R. Flavell: University of California San Francisco
Youngho Seo: University of California San Francisco
Enrique Martinez-Ortiz: University of California San Francisco
Maya Aslam: University of California San Francisco
Cassandra Thanh: University of California San Francisco
Emily Fehrman: University of California San Francisco
Marion Pardons: Université de Montréal
Shreya Kumar: University of California San Francisco
Amelia N. Deitchman: University of California
Vahid Ravanfar: University of California San Francisco
Brailee Schulte: University of California San Francisco
I-Wei Katherine Wu: University of California San Francisco
Tony Pan: University of California San Francisco
Jacqueline D. Reeves: University of California San Francisco
Christopher C. Nixon: University of California San Francisco
Nikita S. Iyer: University of California San Francisco
Leonel Torres: University of California San Francisco
Sadie E. Munter: University of California San Francisco
Tony Hyunh: University of California San Francisco
Christos J. Petropoulos: Laboratory Corporation of America, South San Francisco
Rebecca Hoh: University of California San Francisco
Benjamin L. Franc: Stanford University
Lucio Gama: National Institutes of Health
Richard A. Koup: National Institutes of Health
John R. Mascola: National Institutes of Health
Nicolas Chomont: Université de Montréal
Steven G. Deeks: University of California San Francisco
Henry F. VanBrocklin: University of California San Francisco
Timothy J. Henrich: University of California San Francisco

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract A major obstacle to achieving long-term antiretroviral (ART) free remission or functional cure of HIV infection is the presence of persistently infected cells that establish a long-lived viral reservoir. HIV largely resides in anatomical regions that are inaccessible to routine sampling, however, and non-invasive methods to understand the longitudinal tissue-wide burden of HIV persistence are urgently needed. Positron emission tomography (PET) imaging is a promising strategy to identify and characterize the tissue-wide burden of HIV. Here, we assess the efficacy of using immunoPET imaging to characterize HIV reservoirs and identify anatomical foci of persistent viral transcriptional activity using a radiolabeled HIV Env-specific broadly neutralizing antibody, 89Zr-VRC01, in HIV-infected individuals with detectable viremia and on suppressive ART compared to uninfected controls (NCT03729752). We also assess the relationship between PET tracer uptake in tissues and timing of ART initiation and direct HIV protein expression in CD4 T cells obtained from lymph node biopsies. We observe significant increases in 89Zr-VRC01 uptake in various tissues (including lymph nodes and gut) in HIV-infected individuals with detectable viremia (N = 5) and on suppressive ART (N = 5) compared to uninfected controls (N = 5). Importantly, PET tracer uptake in inguinal lymph nodes in viremic and ART-suppressed participants significantly and positively correlates with HIV protein expression measured directly in tissue. Our strategy may allow non-invasive longitudinal characterization of residual HIV infection and lays the framework for the development of immunoPET imaging in a variety of other infectious diseases.

Date: 2022
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DOI: 10.1038/s41467-022-28727-5

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