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Author Topic: Antibody to HIV sends virus into sustained remission in rhesus monkeys  (Read 5680 times)

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Offline Cosmicdancer

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"A clinical trial in monkeys found that by augmenting the standard HIV treatment with an antibody developed in the lab, the animals were able to enter a state of sustained remission, according to a report in Friday’s edition of the journal Science. All eight monkeys that tested the regimen were able to keep the virus at low or undetectable levels for at least nine months after the treatment ended. Some have been in sustained remission for nearly 2 years."

"An early clinical trial to test the safety of the therapy in 15 humans is just now getting started at NIAID, Fauci said. Results won’t be known for more than a year."

http://www.latimes.com/science/sciencenow/la-sci-sn-hiv-art-antibody-20161013-snap-story.html

Here's the original publication in the journal Science but I don't have a subscription to open the file.
http://science.sciencemag.org/content/354/6309/157.full



Summer, 2007 - &$#@?
November, 2007 - Tested poz, 300,000 vl, 560 cd4
Feb, 2008 - 57,000 vl, 520 cd4, started Atripla
2/2008 - 5/2015 - undetectable on Atripla
May, 2015 - UD, switched to Complera
September, 2015 - UD, 980 cd4, switched to Stribild (Complera interacted with acid reflux medication)
January, 2016 - Stribild, UD, 950 cd4
June, 2016 - UD, 929 cd4

Offline Ptrk3

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #1 on: October 14, 2016, 10:57:35 am »
Here's a different write-up on the same research development, this one from the October 13, 2016, edition of the HIV/AIDS section of Science Daily:

https://www.sciencedaily.com/releases/2016/10/161013141053.htm

Progress is always good, though, of course, clinical applications are years away.  It's great to know things are moving forward to make the lives of HIV-positive better!
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Offline Skydrake

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #2 on: October 14, 2016, 11:48:09 am »
though, of course, clinical applications are years away

Maybe just a few years: the Vedolizumab has been approved two years ago for Crohn's disease and ulcerative colitis.

In any case, it's a very promising study.


Offline terrymoore

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #3 on: October 16, 2016, 12:46:55 am »
This article (and i guess the recent one from the UK) triggered a dream for me the other night. In it, i was found out that a cure was found, and that it was available in certain Western countries, but not available yet where i lived and it would take a few years until it got here (i guess the logic if my dream followed the status of meds in this country not being available because of bureaucracy - like Genvoya not being available - even though i m sure things would be different for a cure..). My
 dilemma in the dream was whether i should move to a Western country to get the cure and therefore revealing my status on record or wait here a few more years..
Weird dream, but left me very hopeful. I woke up certain that i will be facing this dilemma within 5 years...i wonder :-)

Offline em

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #4 on: October 24, 2016, 11:32:20 am »
I read the article and went over to the trial information. then I called for more info on the trial. I may be shooting myself in the foot for saying this but telling the truth and sharing info to help this study can help everyone here. So here is some info They told me.

I do not qualify for the first 15 for the study because my tcell cd4 went below 200 around 1996 just before protease inhibitors were available.

So if you have never had a tcell cd4 below 200 and a sustained undetectable viral load for while.  they are looking for you.

So by writing this here if they do not find 15 people who qualify they might open it up for people like me who had gotten sick way back when treatment was not available. so like I wrote I might be shooting myself in the foot for sharing this info. if it helps others so be it.

Offline Ichbins

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #5 on: December 27, 2017, 12:16:37 am »
I'm in this study now.  Currently in the phase of stopping ARV.
I have no real expectation that this will work. 
SIV is different from HIV and humans are different from monkeys.

For reference I knew my status after two years of becoming infected. At that time my VL was around 5,000 and my CD4 was around 325 (I was never sick thankfully)

I've been on ARV for 4 years never had any other complications with CD4 or VL.

The staff at NIH are really great.  I actually look forward to going there each time.  I hope all the blood and plasma they have taken from me sheds some information. But wouldn't it be wonderful if it just took 9 infusions over 32 weeks to create a functional cure?  vedolizumab costs between 5-6K  so a cost of around $50K as opposed $30K per year for ARV.

Offline dico

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #6 on: December 27, 2017, 02:39:40 am »
Hello Ichbins

  You are no allowed to see your VL ? Or you are forbidden to disclose it to others ?
Coz if I were you I would like to go to a lab and follow my VL :)
 And since when have you stopped your treatment ?

I am following cure research intensively and your trial is currently the only one that may produce a cure. All others are part of a greater scheme to a future functional cure. What do the scientists tell you when you go see them monthly?

Thanks 0

Offline Ichbins

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #7 on: January 17, 2018, 12:12:24 am »
Dico,
I can tell you my VL is still undetectable. But...I haven't been off my meds for very long. Preceding this study was another study that looked at VL rebound after stopping treatment. They have discovered that people who have been on the current treatments are going many months 1-9, before VL rebound as before it was 7-14 days. So...all I can say is be patient. Each person is different. I won't post much else about my results because it really wouldn't be appropriate. But I will be very happy to answer questions about the procedures, tests, and whatever else you want to ask about taking part in a study at NIH. I can tell you I am very anxious about being off my meds for a variety of reasons. But the recent studies show there is no lasting damage...and the parameters of this study to go back on meds are sound and appropriate so I do trust my doctor's.

Offline Ichbins

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #8 on: January 17, 2018, 12:26:29 am »
What do the scientists tell you when you go see them monthly?

Dico,
To directly answer your question about what they tell me.  Well they tell me everything. Infact all my blood tests and results are uploaded to my medical records and I have access to them 24x7. It's fascinating to see my CD4 counts in a long term monthly chart. Now I'm having blood tests every two weeks.
They take about 15 viles of blood each visit. I've also had three apheresis sessions.

They do full mineral panels, CD4/8 glucose, VL etc... They also forward all tests and results to my normal doctor.

Online gorka

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #9 on: January 17, 2018, 10:10:36 am »
ichbins do you know if the study will be expanded to other sites?  I asked before but never got the answer.  thanks

Offline Ichbins

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #10 on: January 18, 2018, 09:44:51 pm »
Gorka,
I believe it will be expanded in Ottowa from online news stories I have read. But elsewhere in the USA I cannot comment on. I do know they are still enrolling people. I know they desperately want people who were diagnosed soon after infection and started treatment early on.

I know some of the other study participants travel from far away.
« Last Edit: January 18, 2018, 09:52:36 pm by Ichbins »

Offline freewillie99

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #11 on: January 24, 2018, 07:30:57 pm »
Related news:

https://www.nih.gov/news-events/news-releases/study-links-gut-homing-protein-levels-hiv-infection-risk-disease-progression

Wednesday, January 24, 2018

Study links gut-homing protein levels with HIV infection risk, disease progression
NIH clinical trial is testing antibody against the protein in people with HIV.

For the first time, scientists have shown a relationship between the proportion of key immune cells that display high levels of a gut-homing protein called alpha-4 beta-7 at the time of HIV infection and health outcomes. Previous research illustrated this relationship in monkeys infected with a simian form of HIV.

The new study found that women who had more CD4+ T cells displaying high levels of alpha-4 beta-7 on their surface were more likely to become infected with HIV, and the virus damaged their immune systems more rapidly, than women with fewer such cells. The National Institutes of Health co-funded the study with the South African Medical Research Council as part of the U.S.–South Africa Program for Collaborative Biomedical Research. In addition, NIH scientists collaborated on the study. The report appears online today in the journal Science Translational Medicine.

“Our findings suggest that having a high frequency of alpha-4 beta-7-expressing CD4+ T cells, which HIV preferentially infects, leads to more HIV-infected CD4+ T cells moving to the gut, which in turn leads to extensive damage to gut-based immune cells,” said Anthony S. Fauci, M.D. Dr. Fauci co-authored the paper as chief of the Laboratory of Immunoregulation at the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. He also is director of NIAID.

The study was led by Lyle McKinnon, Ph.D., and Aida Sivro, Ph.D., both researchers at the Centre for the AIDS Programme of Research in South Africa (CAPRISA) in Durban, South Africa. Dr. McKinnon is also an assistant professor in the Rady Faculty of Health Sciences at the University of Manitoba in Winnipeg, Canada, and an honorary lecturer at the University of Nairobi in Kenya.

The research team compared the percentage of CD4+ T cells displaying high levels of alpha-4 beta-7 in blood samples drawn from 59 women shortly before they acquired HIV to the percentage of such cells in 106 women who remained HIV negative. Aged 18 to 40 years, the women were selected from participants in the CAPRISA 004 study (link is external), which evaluated the safety and efficacy of tenofovir gel for HIV prevention in KwaZulu-Natal, South Africa, from 2007 to 2010. Understanding HIV acquisition and disease progression among African women is especially important because women accounted for nearly 60 percent of new HIV infections among adults in sub-Saharan Africa in 2016.

The proportion of CD4+ T cells with high levels of alpha-4 beta-7 had an effect, albeit modest, on the risk of acquiring HIV among both the women in the CAPRISA 004 study and a separate cohort of 41 female sex workers in Kenya. The risk of HIV acquisition rose by 18 percent for each one percent increase in alpha-4 beta-7 protein. The authors show a similar association in monkeys that were vaginally exposed to a simian form of HIV.

The proportion of CD4+ T cells with high levels of alpha-4 beta-7 strongly affected how quickly HIV damaged the immune system. CD4+ T cell levels declined twice as fast among women with higher pre-infection levels of alpha-4 beta-7 as among women with lower pre-infection levels. In addition, the amount of HIV in the blood within a few months of infection was greater in women with higher pre-infection levels of alpha-4 beta-7 than in women with lower pre-infection levels. The mechanism for the immune system damage likely was HIV-related damage to the gut, the scientists report, as higher pre-infection levels of alpha-4 beta-7 were associated with higher levels of a biological marker of gut damage.

The scientists found that HIV targets CD4+ T cells displaying alpha-4 beta-7 very early in infection, particularly in the gut. In this regard, the researchers looked at data from the U.S. Military HIV Research Program-led RV254 clinical trial at the Thai Red Cross in Bangkok, Thailand, and found that starting antiretroviral therapy (ART) right after HIV diagnosis did not prevent the depletion of CD4+ T cells from the gut or facilitate reconstitution of the depleted cells.

“These findings suggest that interventions in addition to ART may be needed to restore CD4+ T cells in the GI tracts of people living with HIV,” said Dr. McKinnon. “One such intervention could be an anti-alpha-4 beta-7 antibody called vedolizumab, which is FDA-approved for the treatment of ulcerative colitis and Crohn’s disease.”

In previous studies led by Dr. Fauci and Aftab A. Ansari, Ph.D., of Emory University in Atlanta, a monkey-adapted form of vedolizumab contributed to the near-replenishment in monkeys of CD4+ T cells that had been destroyed by a simian form of HIV. Based on this and related findings, NIAID initiated an early-phase clinical trial in 2017 to determine whether short-term treatment with vedolizumab in combination with ART could generate sustained HIV remission in people living with HIV. The study is taking place at the NIH Clinical Research Center in Bethesda, Maryland. Preliminary results are expected later this year. More information about the study is available at ClinicalTrials.gov under study identifier NCT02788175.

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health®

Reference
A Sivro et al. Integrin α4β7 expression on peripheral blood CD4+ T cells predicts HIV acquisition and disease progression outcomes

« Last Edit: January 24, 2018, 07:33:45 pm by freewillie99 »
Beware Romanians bearing strange gifts

Offline Ichbins

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #12 on: January 29, 2018, 08:30:28 pm »
Thanks for sharing that. The article really took me by surprise last week. The idea of broadly neutralizing antibodies like vedolizumab and others used in recent vaccine attempts show real promise.

Offline Ichbins

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #13 on: February 21, 2018, 01:48:45 pm »
I asked about enrolling more people. But they actually are not. They had enough volunteers. I was only allowed to enroll because someone couldn't follow through.  We'll know more on the success of this study later this year.

Online gorka

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #14 on: February 23, 2018, 10:30:42 am »
I asked as well and they told me they are taking more people but that I would have to fly for all the test to east coast to NIH.  There are no sites on west coast.  This was 2 months or so back

Offline Ichbins

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #15 on: March 26, 2018, 11:43:56 am »
They pay for flights and a hotel. Some visits can be done at a quest lab as well. I was doing some blood draws at home myself.

Offline dico

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #16 on: April 13, 2018, 03:24:56 am »
Hi Ichbins

What are the latest result of your viral load ? If the drug works in humans as they work in monkeys you should have remained below detection since ATI.

Thanks
Adrien

Offline dico

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #17 on: April 19, 2018, 03:40:26 pm »
And apart Ichbins if there are other people participating in this vedolizumab trial I would be more than happy to learn if after all these months without ART their viral load are still undetectable (such as the monkeys in the pre clinical trial).

Btw I have been enrolled in a European trial which will begin in September : I will receive 7 vedolizumab doses + a therapeutic vaccine (DNA + MVA boost). I will keep you updated later this year.

Thanks

Offline dico

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Re: Antibody to HIV sends virus into sustained remission in rhesus monkeys
« Reply #18 on: April 29, 2018, 05:34:32 am »
Up...
Neither Ichbins nor anyone else answered...

Offline Ichbins

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Dico,

Sorry for not keeping a closer eye on this. I've had to deal with some family issues.

Because the trial is still on-going I'm not going to discuss my exact results publicly.  Some are still receiving their infusions but that should be all wrapped up now. I'll be monitored until about August then the trial will be over for me. Take that for what it means.

The other study in Canada that I mentioned before is testing various doses with a much more compressed interval. At NIH we received the same dosage and intervals as someone being treated for crohns disease.

It should also be noted that the monkeys received a much higher dose.  I'm theorizing that a higher dose may be necessary for some people. I've also had discussions with NIH about the human body producing antibodies or resistance to vedolizumab. As part of this study they were not monitoring that as the tests to look for resistance are only available through the drug manufacturer.  I also suspect this is going to have to be monitored in future studies. I believe they have the intention to go back and look for resistance.

The goal of NIH with this study was only to test for the tolerability of people infected with HIV. They didn't have high hopes that it would actually result in a sustained remission. They did hope that at least a few individuals respond.

Anyway, the monkey model isn't always reliable when we move into humans.

Congratulations on your participation  in the European trial.  It is important to do this as now we move into the phase of finding out all the variables and what does and does not work.  (this is why new drugs take so long to get to market and FDA approval) Just think I'm now 12 months into the trial and it wont end for another three for me.

And apart Ichbins if there are other people participating in this vedolizumab trial I would be more than happy to learn if after all these months without ART their viral load are still undetectable (such as the monkeys in the pre clinical trial).

Btw I have been enrolled in a European trial which will begin in September : I will receive 7 vedolizumab doses + a therapeutic vaccine (DNA + MVA boost). I will keep you updated later this year.

Thanks

Offline dico

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Thanks Ichbins for you answer.
I perfectly read between the lines of your answer and sorry to learn that.

In Paris the vedolizumab dose will be 300 mg, with 7 infusions. What about the NIH one ?

Btw we will indeed have a test of resistance delivered by Takeda company.

Hope you will share your results in August at least showing the movements of the viral load during your treatment interruptions.

Thanks

Offline Ichbins

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https://www.nih.gov/news-events/news-releases/fauci-hiv-remission-free-antiretroviral-therapy-feasible-goal

As y'all probably guessed things didn't work out well for me. My friend who was stable for over a year is now up and down as his last tests. I still think there is promise in this treatment. But lots more work and study to be done.

Offline geobee

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From the article linked above:

Finally, Dr. Fauci will report preliminary results of a small, early-phase clinical trial in which people living with HIV that was well controlled with ART received infusions of vedolizumab, an anti-alpha-4-beta-7 antibody that is FDA-approved for ulcerative colitis and Crohn’s disease. These volunteers received both ART and vedolizumab at the beginning of the study, paused ART while continuing to receive the antibody, and finally stopped all treatment. He will describe how the regimen was safe and well tolerated but did not generate lasting control of the virus. He also will posit potential explanations for the differences between the alpha-4 beta-7 studies in monkeys and people.

 


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