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

• Published in: Nature communications Vol. 13; no. 1; pp. 1219 - 15
• Main Authors: Beckford-Vera, Denis R., Flavell, Robert R., Seo, Youngho, Martinez-Ortiz, Enrique, Aslam, Maya, Thanh, Cassandra, Fehrman, Emily, Pardons, Marion, Kumar, Shreya, Deitchman, Amelia N., Ravanfar, Vahid, Schulte, Brailee, Wu, I-Wei Katherine, Pan, Tony, Reeves, Jacqueline D., Nixon, Christopher C., Iyer, Nikita S., Torres, Leonel, Munter, Sadie E., Hyunh, Tony, Petropoulos, Christos J., Hoh, Rebecca, Franc, Benjamin L., Gama, Lucio, Koup, Richard A., Mascola, John R., Chomont, Nicolas, Deeks, Steven G., VanBrocklin, Henry F., Henrich, Timothy J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.03.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/31; 45/22; 45/23; 45/90; 45/91; 59/57; 59/78; 631/250/255/1901; 692/308/575; 692/699/255/1901; Antibodies; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Biopsy; CD4 antigen; HIV; Human immunodeficiency virus; Humanities and Social Sciences; Infections; Infectious diseases; Lymph nodes; Lymphatic system; Lymphocytes; Lymphocytes T; Medical imaging; multidisciplinary; Neutralizing; Positron emission; Positron emission tomography; Protein expression; Proteins; Remission; Science; Science (multidisciplinary); Therapeutic applications; Tissues; Tomography; Transcription; Viremia; Zirconium isotopes
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-28727-5

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, 89 Zr-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 89 Zr-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. Here, the authors apply positron emission tomography (PET) imaging to visualize HIV tissue-wide burden in infected individuals using a radiolabeled broadly neutralizing antibody, 89 Zr-VRC01, and show that PET tracer lymph node uptake positively correlates with HIV protein levels measured directly from cells obtained from these tissues. This strategy may allow non-invasive characterization of residual HIV infection in the setting of therapeutic interventions.