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Author Topic: HIV cure at the 2014 Institute of Human Virology Meeting  (Read 7068 times)

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Offline dico

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HIV cure at the 2014 Institute of Human Virology Meeting
« on: September 20, 2014, 01:38:22 am »
HIV Cure at 2014 IHV Meeting         
Written by Alain Lafeuillade
http://www.hiv-reservoir.net/index.php/the-news/447-hiv-cure-at-2014-ihv-meeting.html      
Wednesday, 17 September 2014 12:32
HIV cure at the 2014 Institute of Human Virology Meeting

The annual meeting of the IHV took place this year in Baltimore, Maryland, 14-17 September 2014.

An entire session on Monday morning was dedicated to HIV cure, HIV reservoirs and HIV latency.

All the renowned researchers of the field were present to give not only a State-of-the-Art of HIV cure issues, but also present new, unpublished data, from their laboratories.

Below you will find a short summary of what was presented.

 
The issue of HIV cure is now in the frontline. 

That is why an entire morning was devoted to this topic.  

The first presentation was given by John Mellors. He discussed how the Berlin Patient has been cured. According to recent data published in CID this year (Symonds et al), he had no X4 virus at baseline. However, Mellors confessed that allogenic BMT is not scalable and brings a 7-30% mortality. It was justified in the Berlin patient because he had leukemia.
Mellors also presented data from Kordelas and al. (New England Journal of Medicine 2014) showing that failure of a CCR5- transplant can be due to a shift to X4.
According to Mellors, anti-PD1 and anti-PD1L that were recently approved for cancer immunotherapy (Merck) have a bright future for HIV cure.

Louis Picker presented his model using a CMV vector for a vaccine against SIV. In his hands, the virus was controlled and even disappeared in 50% of the monkeys.

Daniel Kuritzkes recapped the difficulties to see light at the end of the tunnel. In an elegant present presentation he suggested that there is however light in the tunnel but we do not know how long the tunnel is. He emphasized the fact that long-lived tissue reservoirs inaccessible to clinical sampling may contribute to viral rebound at the end.

Robert Siliciano did a review of the huge work done by his lab. In particular he showed that CTL escape mutants are rare at the time of acute HIV infection but represent 100% of viruses later on. He also presented data showing that 12% of proviruses are non mutated and among them 92% are replication competent. To demonstrate that, he used a very time consuming PCR method. Shifting to modelization, Siliciano demonstrated that at least a 3 log reduction of the reservoir would be necessary to get 1 year free from therapy.

Edward Berger presented already published data on immunotoxins and new data on the potential use of chimeric antigen receptors.

In a nice military suit, Jerome Kim presented results during acute HIV infection. The RV254 cohort conducted in Asia by Jintana enrolled 160 patients at acute infection who were given 3 or 5 cART. The RV217 cohort is still ongoing and has included 93 patients not only in Asia but also in Africa.

Mario Stevenson showed new data on cellular antiviral mechanisms. He isolated RN18, a molecule able to stabilize APOBEC3G from Vif. This product has no off-target effect. We have to congratulate Mario for this work and for being the father of Victoria who his just 2 months old!

Dan Barouch emphasized the fact that pre-ART viremia is correlated to the size of the reservoir. He presented data on neutralizing antibodies and a trial using PGT121 to start in humans within 3 years.

Richard Koup was also on the line of using neutralizing antibodies. He also showed that CCR7 low CXCR5 high follicular CD8 T cells are abondant in germinal centers.

Franck Maldarelli presented data confirming the fact that plasma contains clonal HIV sequences.

Alain lafeuillade discussed the different approaches toward an HIV cure. He showed the failures already obtained, in particular by using HDAC inhibitors. He proposed that unless trying to activate the latent rervoirs, we could try to make them formant for ever. This functional cure would correspond to an integrated, silent HIV, without cART. This can be obtained by initiating cART at acute infection, but we do not know the percentage of patients that would be post-treatment controllers. He presented data from his clinic on a case who is post-treatment controller for 14 years. Functional cure could also be obtained by using antiretroviral drugs able to decrease the viral fitness. Lamivudine is able to do that, as well as Dolutegravir (if the 263 mutation is selected in the integrase, viral fitness decreases of 80%). According to Lafeuillade, these 2 drugs could be used in combo to get a crippled HIV. He announced the launch of a pilot trial within the end of this year to verify this hypothesis. Lamivudine and Dolutegravir will be administered for 6 months in 30 naive patients, then stopped. The trial will include acute patients and early patients with more than 500 CD4 and 4 log viral load (if 3TC can decrease viral load by 0.5 log and Dolutegravir by 2.5 log, this will allow to get low level persistent viremia in order to select the 2 mutations). John Mellors made the point that at stopping therapy the wild type virus might take over. Lafeuillade answered that this will probably be the case but they will compare baseline viral load to viral load 6 months after stopping therapy. They also will use ultra-deep sequencing in order to quantify regularly the 2 mutants. John Mellors and Mark Wainberg have already made a bet on this strategy at the last HIV Persistence Workshop in Miami in December 2013….this bet concerned a very expansive bottle of whisky!

The panel discussion was conducted by Robert Gallo. He started by asking the panel what approach should be preferred: 'reactivating' or 'smoothing and snoozing' latent HIV? No consensus was made but participants agreed that HIV cure research has to be continued in each possible way. The attended focused on the price of this research and the fact that most patients in the world will not be able to afford an HIV cure. It looked like HDAC inhibitors alone have to be abandoned because they are ineffective and gene therapy too because it will be too expansive. HIV cure research must be pursued even if long-acting antiretroviral drugs will soon come to trials. These drugs will be able to keep HIV replication at bay with only 1 intra muscular injection every 6 month….
 
NB: Both speakers and organizers have been asked permission before publishing this article.

Offline geobee

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Re: HIV cure at the 2014 Institute of Human Virology Meeting
« Reply #1 on: September 20, 2014, 01:46:25 am »
Great stuff.  Thanks for posting.  That viral fitness stuff seems really interesting!

Offline dico

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Re: HIV cure at the 2014 Institute of Human Virology Meeting
« Reply #2 on: September 20, 2014, 03:33:21 am »
You are welcome.

For me picker vaccine is my best hope.

Offline OneTampa

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Re: HIV cure at the 2014 Institute of Human Virology Meeting
« Reply #3 on: September 20, 2014, 09:17:42 am »
Very interesting.

Thanks for posting Dico.

 :)
"He is my oldest child. The shy and retiring one over there with the Haitian headdress serving pescaíto frito."

Offline tryingtostay

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Re: HIV cure at the 2014 Institute of Human Virology Meeting
« Reply #4 on: September 20, 2014, 09:41:24 am »
I hope they are not referring to the Gene Surgery being done at Temple.  While my numbers seem great to others I am definitely having issues related to HIV so while being able to keep whatever strain I have at bay having a healthy immune system is not going to be the answer.

Offline Jeff G

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Re: HIV cure at the 2014 Institute of Human Virology Meeting
« Reply #5 on: September 20, 2014, 10:41:33 am »
I hope they are not referring to the Gene Surgery being done at Temple.  While my numbers seem great to others I am definitely having issues related to HIV so while being able to keep whatever strain I have at bay having a healthy immune system is not going to be the answer.

You are not having HIV related issues .
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Offline leatherman

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Re: HIV cure at the 2014 Institute of Human Virology Meeting
« Reply #6 on: September 20, 2014, 11:13:39 am »
I am definitely having issues related to HIV so while being able to keep whatever strain
there are only 2 basic strains. unless you're living in West Africa, you more than likely have HIV-1. Of course the HIV you were infected with could possibly have developed some resistance subtype; but that just has to do with which meds might or might not work with that resistance mutation.

Your numbers (cd4 1655, VL <100) are better than "great", they are incredible. With an immune system that robust, with so little virus in your system, recently dx'ed and not on meds yet, you should probably be searching another reason than HIV as to the cause of your problems. (Neuropathy is more often than not due to long term HIV or earlier medications, and is usually an issue with hands and/or feet ie peripheral neuropathy)
leatherman (aka Michael)

We were standing all alone
You were leaning in to speak to me
Acting like a mover shaker
Dancing to Madonna then you kissed me
And I think about it all the time
- Darren Hayes, "Chained to You"

Offline Almost2late

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Re: HIV cure at the 2014 Institute of Human Virology Meeting
« Reply #7 on: September 20, 2014, 11:29:41 am »
It's great to know there's so much research going on, I'm so grateful for it :D

Offline tryingtostay

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Re: HIV cure at the 2014 Institute of Human Virology Meeting
« Reply #8 on: September 21, 2014, 02:32:42 pm »
"Franck Maldarelli presented data confirming the fact that plasma contains clonal HIV sequences."

Plasma?  Our blood plasma?  ???


EDIT:  I'd also like to know what bottle of whiskey was bet on in 2013 by John Mellors and Mark Wainberg - lol
« Last Edit: September 21, 2014, 02:46:05 pm by tryingtostay »

Offline mecch

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Re: HIV cure at the 2014 Institute of Human Virology Meeting
« Reply #9 on: September 21, 2014, 03:40:09 pm »
"Franck Maldarelli presented data confirming the fact that plasma contains clonal HIV sequences."

Plasma?  Our blood plasma?  ???


EDIT:  I'd also like to know what bottle of whiskey was bet on in 2013 by John Mellors and Mark Wainberg - lol

OK but what about the frequent ripostes when members suggest that your symptoms are not HIV related. You seem to gloss over this or ignore it.  Its going in one ear and out the other?  Or you have pursued this with specialists and there is something to your theory about it being HIV-caused?
“From each, according to his ability; to each, according to his need” 1875 K Marx

Offline Reggie

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Re: HIV cure at the 2014 Institute of Human Virology Meeting
« Reply #10 on: September 21, 2014, 03:42:07 pm »
Great to see the time and dedication people are putting into research for hiv and other diseases effecting millions. Brings us together for a real cause which is what is needed as treatment has come so far for treating hiv and gives hope to future advancements.

Offline tryingtostay

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Re: HIV cure at the 2014 Institute of Human Virology Meeting
« Reply #11 on: September 21, 2014, 04:12:21 pm »
OK but what about the frequent ripostes when members suggest that your symptoms are not HIV related. You seem to gloss over this or ignore it.  Its going in one ear and out the other?  Or you have pursued this with specialists and there is something to your theory about it being HIV-caused?

Oh mecch.  No.  I would rather keep a thread on topic.  That's why I didn't discuss it any further.  I don't think they should give up on research on gene 'surgery' like the research going on at Temple. 

I'm waiting till enrollment for insurance begins in mid Oct. There has been 1 too many "yeah you are covered there" and I'm paying with no coverage when I was told differently. 

Offline mecch

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Re: HIV cure at the 2014 Institute of Human Virology Meeting
« Reply #12 on: September 21, 2014, 04:44:02 pm »
I hope they are not referring to the Gene Surgery being done at Temple.  While my numbers seem great to others I am definitely having issues related to HIV so while being able to keep whatever strain I have at bay having a healthy immune system is not going to be the answer.

And yet you introduced the theory precisely because you feel like a cure is the answer and hope, for your symptoms, when they probably aren't about HIV at all. 
“From each, according to his ability; to each, according to his need” 1875 K Marx

Offline tryingtostay

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Re: HIV cure at the 2014 Institute of Human Virology Meeting
« Reply #13 on: September 21, 2014, 04:55:26 pm »
And yet you introduced the theory precisely because you feel like a cure is the answer and hope, for your symptoms, when they probably aren't about HIV at all.

And yet you are the one carrying it on

Offline Jeff G

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Re: HIV cure at the 2014 Institute of Human Virology Meeting
« Reply #14 on: September 21, 2014, 06:26:44 pm »
And yet you are the one carrying it on

It may help if you only post in one thread about your irrational fears that HIV is making you sick ... you started two threads last week that I merged and then you came into this thread with the same so either you are being passive aggressive or you are continuing to worry despite Ann and I's best efforts via PM's to educate you about how HIV works  . I agree this may not be the bast place to discuss this but don't act shocked you are being called out on it .
HIV 101 - Basics
HIV 101
You can read more about Transmission and Risks here:
HIV Transmission and Risks
You can read more about Testing here:
HIV Testing
You can read more about Treatment-as-Prevention (TasP) here:
HIV TasP
You can read more about HIV prevention here:
HIV prevention
You can read more about PEP and PrEP here
PEP and PrEP

Offline mecch

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Re: HIV cure at the 2014 Institute of Human Virology Meeting
« Reply #15 on: September 21, 2014, 06:30:50 pm »
Yeah, I confronted you after 2 other members suggested you not experiencing HIV related symptoms.  Which you ignored.

When you carry on this theory without any support, you are encouraging irrational fears for anyone who reads these threads. 

Now that I made this point in this thread, my apologies to the OP and my "hijack" is over. Even though I don't think its a hijack to point out free-floating anxieties and theories about HIV, in a thread where anxious people are saying its the cure that will be key to living well with HIV.  NOT.
“From each, according to his ability; to each, according to his need” 1875 K Marx

Offline dico

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Re: HIV cure at the 2014 Institute of Human Virology Meeting
« Reply #16 on: September 22, 2014, 01:39:30 am »
Regarding louis picker's vaccine the pre clinical trial began one year ago when researchers infected monkeys with shiv and gave them haart. Now the "good news" is that the shiv infected monkeys have just been vaccinated. They will stop their haart treatment within one month and see if the viral load rebounds.

We will know if the vaccine may work at the end of the year given that for monkeys,  viral load rebounds faster than for humans. In general the viral load rebounds within one week.

So if the monkeys control their viral load at the end of the year (for one quarter) it might succeed and we have to wait to see if the viral load rebounds later but if the monkeys do not control their hiv load, the vaccine research will not be pursued and only the prophylactic vaccine will be studied.

Bill and Melinda gates foundation have their focus on the prophylactic version and it is both tomegavax and Gilead that are interested in the therapeutic version of the vaccine. Louis picker's said it might take 20 years before the reservoirs in humans can be depleted with the vaccine for people treated well into their chronic plateauand less for those treated at the acute phase.

They want to begin a clinical trial in December 2016 for poz people either 1)at acute phase or 2)who have UD viral load after one year of treatment and with cd4 600+ and with low reservoirs.

If others have other information please share it.
« Last Edit: September 22, 2014, 02:00:31 am by dico »

 


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