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

  1. Author:
    Swanstrom,Adrienne
    Immonen,Taina
    Oswald,Kelli
    Pyle,Cathi
    Thomas,James
    Bosche,Bj
    Silipino,Lorna
    Hull,Mike
    Newman,Laura
    Coalter, Vicky
    Wiles,Adam
    Wiles,Rodney
    Kiser,Jacob
    Morcock,David
    Shoemaker,Rebecca
    Fast,Randy
    Breed,Matthew
    Kramer,Josh
    Donohue,Duncan
    Malys,Tyler
    Fennessey,Christine
    Trubey,Charles
    Deleage,Claire
    Estes, Jacob D.
    Lifson,Jeffrey
    Keele,Brandon
    Del Prete,Greg

  2. Author Address

    Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA.Frederick Natl Lab Canc Res, Lab Anim Sci Program, Frederick, MD USA.Frederick Natl Lab Canc Res, DMS Appl Informat & Management Sci, Frederick, MD USA.Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
    1. Year: 2021
    2. Date: Mar 15
  2. Journal: The Journal of Clinical Investigation
  3. AMER SOC CLINICAL INVESTIGATION INC,
    1. 131
    2. 6
  5. Type of Article: Article
  6. Article Number: e142421
  7. ISSN: 0021-9738
  1. 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.

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External Sources

  1. View Full Text
  2. DOI: 10.1172/JCI142421
  3. PMID: 33465055
  4. View record in Web of Science®
  5. WOS: 000667559900004

Library Notes

  1. Fiscal Year: FY2020-2021
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