Skip NavigationSkip to Content
Return Return to Search Results

TLR7 agonist administration to SIV-infected macaques receiving early initiated cART does not induce plasma viremia

  1. Author:
    Del Prete,Greg
    Alvord, W Gregory
    Li,Yuan
    Deleage,Claire
    Nag,Mukta
    Oswald,Kelli
    Thomas,James
    Pyle,Cathi
    Bosche,Bj
    Coalter,Vicky
    Wiles,Adam
    Wiles,Rodney
    Berkemeier,Brian
    Hull,Mike
    Chipriano, Elizabeth
    Silipino,Lorna
    Fast,Randy
    Kiser,Jacob
    Kiser,Rebecca
    Malys,Tyler
    Kramer,Josh
    Breed,Matthew
    Trubey,Charles
    Estes,Jake
    Barnes, Tiffany L
    Hesselgesser, Joseph
    Geleziunas, Romas
    Lifson,Jeffrey

  2. Author Address

    AIDS and Cancer Virus Program., DMS Applied Information & Management Sciences, and., Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA., Gilead Sciences, Foster City, California, USA.,
    1. Year: 2019
    2. Date: Jun 06
    3. Epub Date: 2019 06 06
  2. Journal: JCI insight
    1. 4
    2. 11
    3. Pages: pii: 127717
  4. Type of Article: Article
  5. Article Number: e127717
  6. ISSN: 2379-3708
  1. Abstract:

    Reduction/elimination of HIV-1 reservoirs that persist despite combination antiretroviral therapy (cART) will likely require induction of viral expression by residual infected cells and enhanced clearance of these cells. TLR7 agonists have potential to mediate these activities. We evaluated immunologic and virologic effects of repeated doses of the TLR7 agonist GS-9620 in SIV-infected rhesus macaques receiving cART, which was initiated at 13 days after infection and was continued for 75 weeks prior to GS-9620 administration. During cART, GS-9620 induced transient upregulation of IFN-stimulated genes in blood and tissues, increases in plasma cytokines, and changes in immune cell population activation and phenotypes but did not result in measurable increases in plasma viremia or viral RNA-to-viral DNA ratio in PBMCs or tissues nor decreases in viral DNA in PBMC or tissues. SIV-specific CD8+ T cell responses, negligible prior to GS-9620 treatment, were not measurably boosted by treatment; a second course of GS-9620 administration overlapping with later cART discontinuation was associated with increased CD8+ T cell responses during viral recrudescence. These results confirm and extend evidence for GS-9620-mediated enhancement of antiviral immune responses in SIV-infected macaques but suggest that GS-9620-mediated viral induction may depend critically on the timing of initiation and duration of cART and resulting characteristics of viral reservoirs.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1172/jci.insight.127717
  3. PMID: 31167974
  4. View record in Web of Science®
  5. WOS: 000470657800017
  6. PII : 127717

Library Notes

  1. Fiscal Year: FY2018-2019
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel