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Author Topic: Gilead TLR7 agonist  (Read 568 times)

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Offline freewillie99

  • Member
  • Posts: 317
Gilead TLR7 agonist
« on: February 27, 2015, 09:00:46 AM »
This is from the current CROI conference in Seattle.  Hoping someone can explain exactly what it is.  Thanks.

http://www.pharmabiz.com/NewsDetails.aspx?aid=86934&sid=2


Gilead reports positive results from preclinical study of investigational TLR7 agonist in SIV-infected, virally suppressed monkeys
 
 Seattle
 Friday, February 27, 2015, 13:00 Hrs  [IST] 
 

Gilead Sciences announced results from a preclinical study conducted in collaboration with researchers at Beth Israel Deaconess Medical Center evaluating a proprietary investigational oral toll-like receptor 7 (TLR7) agonist and analogue of GS-9620 as part of an HIV eradication strategy. Data demonstrate that treatment with the TLR7 agonist induced transient plasma Simian Immunodeficiency Virus (SIV) RNA, as well as reduced SIV DNA in virally suppressed rhesus macaques given antiretroviral therapy (ART). In addition, the study found that after discontinuation of ART, SIV viral loads were lower among macaques that received the proprietary TLR7 agonist compared to the placebo group. These data were presented in an oral session (Session O-9) at the 22nd Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

"One reason current therapies can't cure HIV is that latent reservoirs of the virus persist even among individuals who are virally suppressed on ART," said James Whitney, Assistant Professor of Medicine, Harvard Medical School, and study Principal Investigator in the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston. Dr. Whitney is also an Associate Member of The Ragon Institute of MGH, MIT and Harvard, which was founded in 2009 to contribute to the accelerated discovery of an HIV/AIDS vaccine and to establish itself as a world leader in the collaborative study of immunology. "These data demonstrate that, given alongside ART, the TLR7 agonist may have the potential to both stimulate virus production and eliminate latently infected cells an eradication strategy being explored today."

In this placebo-controlled study, 10 SIV-infected rhesus macaques received ART for 38 weeks, at which point they were virally suppressed (plasma RNA less than 50 copies/mL). At week 38, six macaques were given placebo and four macaques were given seven bi-weekly doses of the TLR7 agonist, while maintaining ART. Total viral DNA levels were measured at baseline and two weeks after completion of the TLR7 agonist dosing in peripheral blood mononuclear cells (PBMC), colon and inguinal lymph nodes where latent SIV reservoirs are common. ART was discontinued two weeks after the final dose of the TLR7 agonist to assess plasma viral rebound.

The four macaques receiving bi-weekly doses of the TLR7 agonist were given 0.1 mg/kg for the first dose, 0.2 mg/kg for the second dose and 0.3 mg/kg for each of the last five doses. Doses 1-3 had no effect on plasma viremia, whereas doses 4-7 led to transient and consistent increases in plasma virus (500-1,000 SIV RNA copies/mL) in all four macaques with a return to less than 50 copies/mL within four to seven days after receiving the TLR7 agonist. In addition, SIV DNA levels of the four treated macaques were reduced by 30 to 90 percent compared to the placebo group, which remained unchanged. Following discontinuation of ART in the macaques that received the TLR7 agonist, plasma SIV RNA was ~0.5 log10 lower compared to the placebo group.

"These preliminary results suggest that TLR7 agonists may have a role to play in HIV eradication strategies," says Norbert W. Bischofberger, PhD, Gilead's executive vice president, research and development and chief scientific officer. "GS-9620 is a potent TLR7 agonist currently being evaluated in a phase 2 study in patients with chronic hepatitis B for its potential to reduce HbSAg. Based on today's results, we are now also looking forward to moving GS-9620 into proof-of-concept studies in HIV-infected individuals taking ART."

The proprietary TLR7 agonist compound and GS-9620 are investigational agents and their safety and efficacy have not been established.
 
Beware Romanians bearing strange gifts

Offline Jmarksto

  • Member
  • Posts: 547
Re: Gilead TLR7 agonist
« Reply #1 on: February 27, 2015, 05:09:04 PM »
My lay person understanding here is that TLR7 was tested to see if it could stimulate the latent HIV reservoirs so they could be eradicated.  It looks like it did stimulate the latent cells, and reduced the amount of latent HIV, but did not eradicate the virus.  In other words, it kind of worked but not completely.
03/15/12 Negative
06/15/12 Positive
07/11/12 CD4 790          VL 4,000
08/06/12 CD4 816/38%   VL 49,300
08/20/12 Started Complera
11/06/12 CD4   819/41% VL 38
02/11/13 CD4   935/41% VL UD
06/06/13 CD4   816/41% VL UD
10/28/13 CD4 1131/45% VL 25
02/25/14 CD4   792/37% VL UD
07/09/14 CD4 1004/39% VL UD
11/03/14 CD4   711/34% VL UD
03/13/15 CD4   833/36% VL UD

 


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