Antibody-mediated depletion of viral reservoirs is limited in SIV-infected macaques treated early with antiretroviral therapy

Adrienne E. Swanstrom, Taina T. Immonen, Kelli Oswald, Cathi Pyle, James A. Thomas, William J. Bosche, Lorna Silipino, Michael Hull, Laura Newman, Vicky Coalter, Adam Wiles, Rodney Wiles, Jacob Kiser, David R. Morcock, Rebecca Shoemaker, Randy Fast, Matthew W. Breed, Joshua Kramer, Duncan Donohue, Tyler MalysChristine M. Fennessey, Charles M. Trubey, Claire Deleage, Jacob D. Estes, Jeffrey D. Lifson, Brandon F. Keele, Gregory Q. Del Prete

Research output: Contribution to journalArticlepeer-review

Abstract

The effectiveness of virus-specific strategies, including administered HIV-specific mAbs, to target cells that persistently harbor latent, rebound-competent HIV genomes during combination antiretroviral therapy (cART) has been limited by inefficient induction of viral protein expression. To examine antibody-mediated viral reservoir targeting without a need for viral induction, we used an anti-CD4 mAb to deplete both infected and uninfected CD4+ T cells. Ten rhesus macaques infected with barcoded SIVmac239M received cART for 93 weeks starting 4 days after infection. During cART, 5 animals received 5 to 6 anti-CD4 antibody administrations and CD4+ T cell populations were then allowed 1 year on cART to recover. Despite profound CD4+ T cell depletion in blood and lymph nodes, time to viral rebound following cART cessation was not significantly delayed in anti-CD4-treated animals compared with controls. Viral reactivation rates, determined based on rebounding SIVmac239M clonotype proportions, also were not significantly different in CD4-depleted animals. Notably, antibody-mediated depletion was limited in rectal tissue and negligible in lymphoid follicles. These results suggest that, even if robust viral reactivation can be achieved, antibody-mediated viral reservoir depletion may be limited in key tissue sites.

Original languageEnglish (US)
Article numbere142421
JournalJournal of Clinical Investigation
Volume131
Issue number6
DOIs
StatePublished - Mar 15 2021
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint

Dive into the research topics of 'Antibody-mediated depletion of viral reservoirs is limited in SIV-infected macaques treated early with antiretroviral therapy'. Together they form a unique fingerprint.

Cite this