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

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...

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Bibliographic Details
Published in:The Journal of clinical investigation 2021-03, Vol.131 (6), p.1-13
Main Authors: Swanstrom, Adrienne E, Immonen, Taina T, Oswald, Kelli, Pyle, Cathi, Thomas, James A, Bosche, William J, Silipino, Lorna, Hull, Michael, Newman, Laura, Coalter, Vicky, Wiles, Adam, Wiles, Rodney, Kiser, Jacob, Morcock, David R, Shoemaker, Rebecca, Fast, Randy, Breed, Matthew W, Kramer, Joshua, Donohue, Duncan, Malys, Tyler, Fennessey, Christine M, Trubey, Charles M, Deleage, Claire, Estes, Jacob D, Lifson, Jeffrey D, Keele, Brandon F, Del Prete, Gregory Q
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antigens
Antiretroviral drugs
Antiretroviral therapy
Biomedical research
CD4 antigen
Drug dosages
Drug resistance
Drug therapy
Follicles
Genomes
Health aspects
Highly active antiretroviral therapy
HIV
Human immunodeficiency virus
Infections
Lymph nodes
Lymphocytes
Lymphocytes T
Monoclonal antibodies
Physiological aspects
Proteins
Rectum
Simian immunodeficiency virus
Viral infections
Virus diseases
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Summary: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.
ISSN:0021-9738
1558-8238
1558-8238
DOI:10.1172/JCI142421