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Author Topic: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach  (Read 143945 times)

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Offline mdh26

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #150 on: September 18, 2011, 01:09:30 PM »
http://www.prnewswire.com/news-releases/sangamo-biosciences-announces-presentation-of-groundbreaking-clinical-data-from-zfn-therapeutic-for-hivaids-at-icaac-2011-130068278.html

In an oral presentation made on Saturday, September 17th at ICAAC, data were presented from all dosing cohorts of Sangamo's Phase 1 dose escalation study (SB-728-902) in subjects on highly active antiretroviral therapy (HAART) who entered the study with CD4+ T-cells counts of <500 cells/mm3 after several years of therapy ("immunologic non-responders").  A presentation made today described data from the second cohort of a Phase 1 clinical study of the same drug, conducted at the University of Pennsylvania and Albert Einstein College of Medicine, in subjects who entered the study with CD4+ T-cell counts of  >450 cells/mm3 and underwent a treatment interruption (TI) of HAART following treatment with SB-728-T.
Data from these presentations demonstrate:

- A statistically significant relationship (p<0.05) between suppression of HIV viral load (VL) and calculated levels of circulating CD4+ T-cells that have undergone biallelic modification (i.e. modification of both copies) of the CCR5 gene in SB-728-T-treated individuals who underwent a TI. CCR5 is the major co-receptor used by HIV to infect cells of the immune system.

- The VL of one SB-728-T treated-subject decreased to undetectable levels during a TI. This subject was found to be heterozygous for the CCR5 delta-32 gene mutation, i.e. half that subject's CCR5 genes were naturally disrupted. 

- Confirmation and extension of previous observations of unprecedented improvements in overall CD4+ T-cell counts and CD4+ : CD8+ T-cell ratios, as well as engraftment, expansion, trafficking and persistence of the ZFN modified cells.

- SB-728-T treatment continues to be safe and well tolerated.

"We are very encouraged by both this early demonstration of an antiviral effect of SB-728-T as well as the marked improvement in the overall CD4+ T-cell counts in treated subjects in the SB-728-902 trial," said Ronald Mitsuyasu, M.D., Professor of Medicine, David Geffen School of Medicine at UCLA and a principal investigator of Sangamo's SB-728-902 study.  "While their viral loads are well controlled on HAART, these subjects experienced incomplete restoration of their T-cell counts.  Improvement and preservation of the immune system is of paramount importance in HIV and those seen in this study show an improvement over that seen after several years of HAART."

"There is no other drug that has been shown to have the same dramatic effect on the immune system in this setting," stated Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer. "SB-728 treatment results in unprecedented improvement in immune system health as measured by increased CD4+ T-cell levels and improved CD4+: CD8+ T-cell ratios, even in subjects that entered the trial with poor CD4+ counts. Moreover, the interesting kinetics in viral load that we observed in the first few subjects that underwent a treatment interruption has been borne out and has allowed us to correlate a statistically significant effect of the rate of biallelic ZFN-modification of the CCR5 gene on viral load during treatment interruption."

"Data presented this weekend at ICAAC suggest that, with sufficiently high levels of circulating biallelically  modified cells and good engraftment, SB-728-T can provide a 'functional cure' for HIV," said Geoff Nichol, M.B., Ch.B., Sangamo's executive vice president of research and development.  "We continue to collect valuable data about the parameters essential for optimization of this novel drug candidate. Based on these data, Sangamo plans to continue to expand our clinical trials and carry out confirmatory studies in subjects who are natural heterozygotes for the CCR5 delta-32 mutation.  We will also explore other mechanisms to enhance engraftment and maximize the impact of the HIV resistant cells on viral load and the overall immune system of HIV patients. The ground-breaking clinical data that we and our collaborators are generating continue to validate our highly specific ZFN technology as a platform for development of novel therapeutic products."

Clinical Trial Data Summary
Abst.# H2-794a: "HAART Treatment Interruption following Adoptive Transfer of Zinc Finger Nuclease (ZFN) Modified Autologous CD4+ T-cells (SB-728-T) to HIV-infected Subjects Demonstrates Durable Engraftment and Suppression of Viral Load" Presenters: Dale Ando, M.D., Vice President, Therapeutic Development and CMO and Geoffrey Nichol, M.B., Ch.B., Executive Vice President, Research and Development, Sangamo BioSciences, Inc.

In a late-breaker session on Sunday, September 18, 2011 data were presented from the six subjects enrolled in cohort 2 of the Phase 1 clinical trial of SB-728-T conducted at the University Pennsylvania and Albert Einstein College of Medicine.  These subjects entered the clinical trial with CD4+ T-cell counts of >450 cells/mm3 and underwent a twelve week HAART TI four weeks after treatment with a single dose of SB-728-T.

The data demonstrate that: 

- A statistically significant relationship between VL and the calculated percentage of circulating CD4+ T-cells that have  undergone ZFN-mediated modification of both copies (biallelic) of the CCR5 gene within a cell (P= 0.0001 for VL at the end of TI, and 0.037 for area under the curve of VL over the TI period).

- A 0.8 to >2.0-log reduction in VL from peak during TI was observed in the 3 of 6 subjects with the highest estimated circulating levels of cells with biallelic modification. 

- One subject's VL decreased to undetectable levels such that the subject was considered to be aviremic at the end of the TI period.  This subject entered the study carrying the natural CCR5 delta-32 mutation on one copy of his CCR5 gene resulting in an estimated percentage of biallelically-disrupted CCR5 genes that was twice that of subjects entering the study with wild type CCR5 genes.

- Persistent engraftment of ZFN-modified T-cells, overall improvement in total CD4+ T-cell levels and CD4+:CD8+ T-cell ratios as well as normal trafficking of the cells and the safety and tolerability of the treatment.

Offline sfpvguy41

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"Significant Progress Toward a 'Functional Cure' for HIV/AIDS"
« Reply #151 on: September 18, 2011, 01:10:39 PM »
Here's the link to Sangamo's Press Release today:

http://finance.yahoo.com/news/Sangamo-BioSciences-Announces-prnews-1313979575.html?x=0&.v=1

I'm trying to read through it to understand as best as I can, and will post my thoughts, and I'm interested in what others make of this.  Overall it seems like great news and great progress, with the caveat that they think they are on the path to modify this procedure so it will be a functional cure....but they are not announcing that they have actually cured anyone yet.

Here's the highlight:
Quote
The data demonstrate that:


•SB-728-T is safe and well tolerated in this patient population with only mild, reversible symptoms typical of infusion reactions.
•ZFN CCR5-modified cells engrafted, expanded, and persisted for the duration of the study to date (Median of 337 days, range: 115-561).
•The modified cells trafficked to the gut mucosa, an important reservoir of active HIV infection.
•Notably, an increase in total CD4+ T-cells was observed in all subjects and a normalization of the ratio of CD4+:CD8+ T-cells, a measure of immunologic health, was observed in the majority of subjects that entered the study with a ratio below one.  These immunologic improvements were persistent over the study period. 
•These data confirmed and extended preliminary data that were previously reported from the first two dosing cohorts of the trial at the Conference on Retroviral and Opportunistic Infections (CROI) in March 2011. 
•In addition, data were presented from one subject in this trial who has undergone an extended treatment interruption one year after SB-728-T infusion and saw a VL reduction from peak during TI of >1-log, suggesting a potential antiviral effect  of the treatment.


Labs: (undetectable since 2005)
12/13: 634 cdr, 37.3%, 758 cd8, total chol 183, triglycerides 131
8/13: changed to Edurant from Reyataz
12/12: 828 cd4, 34.5%, 1078 cd8, total chol 192, tri 196
12/11: 787 cd4, 37%, 979 cd8.
9/11: 758 cd4, 38%, 944 cd8, und.
8/11 dropped norvir, incr reyataz to 400 mg
6/11: 621 CD4 CD4% 41, CD8 680! Undetectable. Creatinine and eGFR are ok now.
Switched from Truvada to Epzicom in late April 2011
AGT/AST and creatinine back to normal mid-April.
Cut Norvir from regimen.
Switched back to Reyataz/Norvir late Feb 2011
2/11: CD4 664 34%, CD8 963, diagnosed with osteoporosis, high AGT/AST and creatinine.
12/10: CD4: 676 CD4%: 34 CD8: 1012
Switched from Reyataz/norvir to Isentress 10/10
8/10: CD4: 731 CD4%: 40 CD8: 866
Diagnosed Sept. 2002 started meds May 2005.

Offline mdh26

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #152 on: September 18, 2011, 01:14:20 PM »
The fact that the one subject who was heterogeneous for the CCR5 mutation went UD should mean that as long as they can improve the grafting procedure they should be able to accomplish the same thing in normal individuals. I think.

Offline sfpvguy41

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #153 on: September 18, 2011, 01:53:45 PM »
I'm following a lot of the conversation about the implications at
http://www.investorvillage.com/smbd.asp?mb=1933&pt=m

One person suggested something interesting: apparently about 10% of the population are Heterozygotes for the CCR5 mutation, meaning some of their cells are naturally mutated.  Sangamo reports that in one subject like this the VL became undetectable.  So if they could sort for this in studies they might prove the concept in this population first, while figuring out how many cells need to be manipulated (and how often) to make it work in the other 90%.

My question here is in the "Berlin patient" they transplanted marrow. Here they modify cells only but say they are "engrafting and durable"...so i wonder what that means to longevity of any treatment: would it last til these cd4s naturally die off and how long is that?

Something very exciting is they say they are restoring the ratio of cd8 to cd4 to less than 1 or a normal balance, which indicates less ongoing inflammation and activation of the immune system as I understand it, somehting that is a new and very exciting development.

Sangamo has a meeting sponsored by UBS Weds morning before the stock market opens to discuss "business strategies"...I wonder what's coming next!

Labs: (undetectable since 2005)
12/13: 634 cdr, 37.3%, 758 cd8, total chol 183, triglycerides 131
8/13: changed to Edurant from Reyataz
12/12: 828 cd4, 34.5%, 1078 cd8, total chol 192, tri 196
12/11: 787 cd4, 37%, 979 cd8.
9/11: 758 cd4, 38%, 944 cd8, und.
8/11 dropped norvir, incr reyataz to 400 mg
6/11: 621 CD4 CD4% 41, CD8 680! Undetectable. Creatinine and eGFR are ok now.
Switched from Truvada to Epzicom in late April 2011
AGT/AST and creatinine back to normal mid-April.
Cut Norvir from regimen.
Switched back to Reyataz/Norvir late Feb 2011
2/11: CD4 664 34%, CD8 963, diagnosed with osteoporosis, high AGT/AST and creatinine.
12/10: CD4: 676 CD4%: 34 CD8: 1012
Switched from Reyataz/norvir to Isentress 10/10
8/10: CD4: 731 CD4%: 40 CD8: 866
Diagnosed Sept. 2002 started meds May 2005.

Offline boi2kwik4u

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #154 on: September 18, 2011, 03:59:53 PM »
What does this mean for those virus attack CCR5 and CXCR4 ?

Offline Cosmicdancer

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #155 on: September 18, 2011, 04:43:56 PM »
Boi2, the Berlin patient actually had dual tropic HIV, and his stem cell transplant was successful nonetheless.   
http://ycopub.wordpress.com/lukesscienceblog/more-on-curing-hiv-cutting-edge-approaches-that-could-stop-the-virus-2/

I think the Sangamo news is really exciting.  Since the procedure has been found to be safe, I'm sure that in the next phase they will aim to infuse more modified t-cells, and include a cohort of people carrying the natural CCR5 delta-32 mutation on one copy of the CCR5 gene to see if they can achieve a functional cure in that subset of people first.  It will be interesting to see if they do more open ended treatment interruptions, and monitor t-cell counts and viral loads over a 1-2 year period. 

I notice they don't plan to partner with any companies on a Phase 2 trial, since they have a lot of cash on hand right now.  I hope they can enroll a substantial number of people in the Phase 2 trials. 

Over time, I imagine the treatment could be done in combination with a promising therapeutic vaccine that could train the modified t-cells to more effectively target HIV. 
Summer, 2007 - &$#@?
November, 2007 - Tested poz, 300,000 vl, 560 cd4
Feb, 2008 - 57,000 vl, 520 cd4, started Atripla
June, 2008 - undetectable, 612 cd4
January, 2009 - undetectable, 670 cd4
May, 2009 - undetectable, 593 cd4
Sept, 2009 - 83 vl, 763 cd4, 34%
Dec, 2009 - undetectable, 889 cd4, 32%
April, 2010 - undetectable, 860 cd4, 31%
October, 2010 - undetectable, 800 cd4, 38%
April, 2011 - undetectable, t-cell test not done
October, 2011 - undetectable
April, 2012 - undetectable, 850 cd4, 39%
November, 2012 - undetectable, 901 cd4, 41%
April, 2013 - undetectable, 846 cd4, 36%
October, 2013 - undetectable
May, 2014 - undetectable, 784 cd4, 48%

Offline boi2kwik4u

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #156 on: September 18, 2011, 08:28:41 PM »
This is very exciting stuff.  Thanks for the info!   One more question, I had a tropism done, would they be able to tell if I have the natural CCR5 delta-32 mutation?  Also are these folks healthier overall with HIV aka elite controllers or is that something totally different?  Thanks!

Offline sam66

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  • Keep The Faith ; Fight The Fight
Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #157 on: September 18, 2011, 11:46:31 PM »

 Exciting news, thanks for the posts spvguy , mdh26

  Any indication of what the cost of treatment might be ?
december 2007 diagnosed +ve ,

Offline buginme2

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #158 on: September 19, 2011, 12:21:39 AM »


  Any indication of what the cost of treatment might be ?

Wayyyy to early for that.  This isn't anywhere near ready for prime time and still has quite a few skeptics.  However I am sure cost would be similar to Dendrion's new prostate cancer drug which is similar to this theray in that they take your own cells tinker with them and then infuse them back into you.  Cost of that treatment is $93,000 for each treatment.   

Offline d-boy86

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #159 on: September 19, 2011, 07:13:48 AM »
Can someone break the findings down in layman terms for me please?

Offline Hellraiser

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #160 on: September 19, 2011, 03:15:48 PM »
Can someone break the findings down in layman terms for me please?

"Data presented suggest that, with sufficiently high levels of circulating biallelically  modified cells and good engraftment, SB-728-T can provide a 'functional cure' for HIV,"

That's probably the statement that stuck out at me the most.  I believe at this point they were just going for a baseline efficacy and tolerance through the trial.  The next phase would be ramping up the amount and the number of patients.  Also patients with some sort of CCR5 mutation already seem to get better results.  They represent about 10% of the total population (I believe these are mostly caucasians of German descent).

Offline sfpvguy41

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #161 on: September 19, 2011, 06:56:21 PM »
Can someone break the findings down in layman terms for me please?

Can someone break the findings down in layman terms for me please?
An interesting challenge, one I will try since I've been thinking a lot about this one (but don't have a medical background, so consider this fodder for others here to improve).

Sangamo's approach is to take a certain number of CD4 cells out of your body, and genetically manipulate their genes so that the CCR5 receptor, which HIV uses to enter and destroy such cells, is blocked. Since this manipulation (which is what Sangamo's "drug" SB-728 does) is not 100% perfect in making this manipulation, it stands to reason that it is more effective in people who have 50% of their genetic code (from one parent) already locking out the CCR5.  So with them, there's less genetic code that needs to be successfully manipulated to have more cells successfully made resistant.

Then they place these CD4s back in your body.  What they've demonstrated is that at least for one year, such cells not only survive, but they also get to the gut mucosa, which is one of the places HIV is thought to hide even when you're on treatment.  So you’d want them to be there.  And there have been no major side effects.

The thought is, if you stop treatment, the newly circulating HIV will kill off the unmodified CD4 cells, leaving only the "new" "locked-out" cells, which then provide you with a reconstituted immune system which is itself immune from HIV-1 infection.  This is what happened with the "Berlin Patient" who was functionally cured by transplanting bone marrow which generated such modified cells from a naturally CCR5-resistant donor.  A functional cure means you may still have some HIV virus in your system, but it doesn’t do damage, since it cannot enter and kill HIV cells.  It is hoped it will die off since those target cells are not accessible, but I don’t know if this can be proven.  I believe the Berlin patient has stayed undetectable, so they can’t find circulating HIV.

In the trials so far, CD4 cells went up by an average of 200 (and this is for people who were on treatment), and interestingly, the ratio of CD4 to CD8s normalized to above 1, which is not true for most of us on treatment.  It’s now thought that this chronic activation of CD8s may  correlate with inflammation which is being blamed for all sorts of long-term HIV-related issues that mimic aging, but come early for us (stroke, “brain fog”, cardiovascular problems, heart attack).

Since the first round of testing showed a statistically significant correlation between the amount of modified CD4 cells circulating, and viral load, one may assume that by modifying more cells, or doing the treatment more frequently, that one can achieve a “functional cure” if the correlation holds.  I don’t know if anyone knows what this could mean for treatment:  once a year, once a decade, once a life with more cells modified??  It will take years of testing to learn this…but sooner it could present an option for people who are treatment experienced and resistant…as noted above in reply #135 by buginme2 there’s a link to a story about an HIV activist who had great results on this trial http://www.aidsmap.com/HIV-gene-therapy/page/1793127/.

To my knowledge no one has shown such successful correlation with a treatment or therapeutic vaccine that does not require daily meds, nor that has had such a great effect on the CD4:CD8 ratio.

And to put a positive editorial spin on it, they may have just “functionally cured” HIV patient #2, the fellow they call a “Heterozygote”, but no one can say that unless he stayed undetectable for years without meds…and that remains to be seen.  No bone transplants, just a treatment, that can be eventually commercialized.  It gives us some hope, which is always a good thing.
Labs: (undetectable since 2005)
12/13: 634 cdr, 37.3%, 758 cd8, total chol 183, triglycerides 131
8/13: changed to Edurant from Reyataz
12/12: 828 cd4, 34.5%, 1078 cd8, total chol 192, tri 196
12/11: 787 cd4, 37%, 979 cd8.
9/11: 758 cd4, 38%, 944 cd8, und.
8/11 dropped norvir, incr reyataz to 400 mg
6/11: 621 CD4 CD4% 41, CD8 680! Undetectable. Creatinine and eGFR are ok now.
Switched from Truvada to Epzicom in late April 2011
AGT/AST and creatinine back to normal mid-April.
Cut Norvir from regimen.
Switched back to Reyataz/Norvir late Feb 2011
2/11: CD4 664 34%, CD8 963, diagnosed with osteoporosis, high AGT/AST and creatinine.
12/10: CD4: 676 CD4%: 34 CD8: 1012
Switched from Reyataz/norvir to Isentress 10/10
8/10: CD4: 731 CD4%: 40 CD8: 866
Diagnosed Sept. 2002 started meds May 2005.

Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #162 on: September 19, 2011, 07:41:11 PM »

And to put a positive editorial spin on it, they may have just “functionally cured” HIV patient #2, the fellow they call a “Heterozygote”, but no one can say that unless he stayed undetectable for years without meds…and that remains to be seen. 

That's an excellent rundown.

re: CCR5 mutation:

There are some people who have a genetic mutation called delta 32 which results in the deletion of the CCR5 gene. If  a person is a homozygous carrier that means they get the mutation from both parents (i.e. two copies) and they are essentially resistant to HIV-1 infection. Those who are heterozygous have one copy of the mutation and have a partial resistance.

According to wikipedia:

At least one copy of CCR5-Δ32 is found in about 10% of people of Northern Europe and in those of Northern European descent. It has been hypothesized that this allele was favored by natural selection during the Black Death. This coalescence date is contradicted by purported evidence of CCR5-Δ32 in Bronze Age samples, at levels comparable to the modern European population.[8] Smallpox may be another candidate for the high level of the mutation in the European population.

http://en.wikipedia.org/wiki/CCR5

Offline LM

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #163 on: September 19, 2011, 09:34:49 PM »
This is very, very promising. I was skeptical about its effect on viral load, but they did manage to bring one guy's VL to undetectable levels. We don't know for how long, but hey, they did it. Surely this can be much improved so it works well on everyone and it may be well on track to a functional cure. I'm more optimistic regarding this than before.

Offline boi2kwik4u

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #164 on: September 19, 2011, 10:15:17 PM »
How much did the VL drop in the other patients?
« Last Edit: September 19, 2011, 10:30:02 PM by boi2kwik4u »

Offline sam66

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #165 on: September 20, 2011, 07:41:33 AM »

 Surely this should be fast tracked somehow.

 
An interesting challenge, one I will try since I've been thinking a lot about this one (but don't have a medical background, so consider this fodder for others here to improve).



   A brilliant summery sfpvguy by the way
december 2007 diagnosed +ve ,

Online geobee

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #166 on: September 20, 2011, 01:22:17 PM »
Some questions I've been mulling over since reading this excellent news:

The press releases say something like "if you get more of these cells, you'll have more of an effect on viral load."  That seems reasonable.  But can you make people undetectable if you get enough of the modified cells in them?  If so, is it permanent?  Or will we need retreatment?  If so, how often?

Of the 6 patients that did the STI, 3 had reductions in VL.  Why not all 6?

It's good to be hetero(zygous).  That patient went undetectable.  [WOW] Does this mean that all heterozygous people can become UD?  

If I'm one of those heterozygous people, would I put these things in my body even though I'm UD and healthy on an easy meds regimen?  

It's assumed that the heterozygous patient became UD because more of his cells were modified.  That seems like a big "if" to me.  Was there something else unique about this particular patient that allowed him to go undetectable?

Just some musings... and great summary spvguy41!  (Also, I read somewhere that Timothy Ray Brown has no virus in his blood or body.  He's had biopsies all over his body and no virus was detected.)
« Last Edit: September 20, 2011, 01:24:42 PM by geobee »

Offline leatherman

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #167 on: September 20, 2011, 01:31:00 PM »
(Also, I read somewhere that Timothy Ray Brown has no virus in his blood or body.  He's had biopsies all over his body and no virus was detected.)
that's because his immune system was basically killed off by radiation and another immune system (with the CCR5 mutation) was put into him via several stem cell transplants; thus his HIV was not "cured" but rather "eradicated" as it was unable to continue replicating after the procedures were completed.
leatherman (aka mIkIE)


chart from 1992-2013; updated 2/09/13  Reyataz/Norvir/Truvada

Offline Cosmicdancer

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #168 on: September 20, 2011, 02:10:53 PM »
Geobee, I think that all 6 subjects had a drop in viral load, but I think there's been some bad reporting about the results from non-scientific publications.  One of the findings was this: "A 0.8 to >2.0-log reduction in VL from peak during TI was observed in the 3 of 6 subjects with the highest estimated circulating levels of cells with biallelic modification."  This does not mean the other 3 did not have a significant drop in viral load.  I think it just means they had a smaller decline in viral load.  The 3 subjects with the most modified t-cells had substantial drops in viral load. 
Summer, 2007 - &$#@?
November, 2007 - Tested poz, 300,000 vl, 560 cd4
Feb, 2008 - 57,000 vl, 520 cd4, started Atripla
June, 2008 - undetectable, 612 cd4
January, 2009 - undetectable, 670 cd4
May, 2009 - undetectable, 593 cd4
Sept, 2009 - 83 vl, 763 cd4, 34%
Dec, 2009 - undetectable, 889 cd4, 32%
April, 2010 - undetectable, 860 cd4, 31%
October, 2010 - undetectable, 800 cd4, 38%
April, 2011 - undetectable, t-cell test not done
October, 2011 - undetectable
April, 2012 - undetectable, 850 cd4, 39%
November, 2012 - undetectable, 901 cd4, 41%
April, 2013 - undetectable, 846 cd4, 36%
October, 2013 - undetectable
May, 2014 - undetectable, 784 cd4, 48%

Offline LM

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #169 on: September 20, 2011, 02:38:03 PM »
And the best results were on people whose modified cells expanded more. I mean, I don't know much, but the concept makes sense. HIV kills the normal cells, while the modified cells remain and expand. How long they would remain is the question.

that's because his immune system was basically killed off by radiation and another immune system (with the CCR5 mutation) was put into him via several stem cell transplants; thus his HIV was not "cured" but rather "eradicated" as it was unable to continue replicating after the procedures were completed.

leatherman, out of curiosity, what's your take on all this?

It would be interesting if newt could comment as well, since he knows a LOT.

Offline leatherman

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #170 on: September 20, 2011, 05:47:03 PM »
leatherman, out of curiosity, what's your take on all this?
same take I have about all of these items here in the research thread - some day something will pan out.  ;)

Way back in the early early 90s, they told us the cure was "just around the corner". Somedays it looked that way too, what with all the info they were learning about HIV and all the advances in HAART that were beginning. It was an amazing and life-saving event to just move off AZT monotherapy and onto a cocktail of HIV meds - much less finally being assured it was working by having that new-fangled viral load test actually show that things were getting better instead of guessing by what your tcell count was doing. ::)

Yet here we are 20 yrs later, and the cure is still "just around the corner". LOL However, now they've learned a lot about HIV - and about how tricky HIV is. They've made HUGE strides in treatment and HUGE steps towards several things that might lead to the cure; but it all takes time. Of course, I've been taking my meds for two decades, always waiting for the next better med, and waiting for a cure to show up one day. I have to keep taking those meds, even if I am hoping for a cure, because right now those meds are the only thing that keep this nasty little bug from being the death of me. I'm afraid however that I'll still be waiting a while longer yet because nearly anything that is approaching even being a "cure" is still years away with plenty more testing, studying, and refinement to be done.

I love reading all the stuff here in the research thread, but I don't make any judgement call on which ones will pan out. Although I try to stay educated about these things, I'm no scientist and can't make any calls like that. LOL However, if I could guess which venture would turn out to be the cure, I could make a fortune buying up the right stock. :D So instead, I read, I follow the links, I study, I look for the "flaws" in the trials, I research who has backing, I try to understand the science of each possibility. And I enjoy each day I'm alive as much as I can because I know too many people who aren't here to enjoy any days because of this stupid virus/disease.

However, what I do know for sure is this - as long as someone somewhere is still looking for a cure, then I have hope that a cure really is "just around the corner". ;) With a little luck (and a lot of HAART LOL), I hope one day to be utterly amazed to have outlived my friends and my partners and to have lived long enough to be cured.
leatherman (aka mIkIE)


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Offline Hellraiser

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #171 on: September 20, 2011, 05:51:51 PM »
I'm a natural born pessimist and unlike most newly diagnosed I was sure 2 years ago that there was no cure in sight.  It does seem like they keep stacking up the lego pieces of discovery each week now though.  I figure it won't be long before there's something.  However, I remain cautiously optimistic.

Offline skeebo1969

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #172 on: September 20, 2011, 05:53:10 PM »

    I hate to minimize the discussion, but am I the only one who thinks of Lady Fingers when this thread heads the list of topic ?
I despise the song Love is in the Air, you should too.

Offline leatherman

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #173 on: September 20, 2011, 05:56:48 PM »
   I hate to minimize the discussion, but am I the only one who thinks of Lady Fingers when this thread heads the list of topic ?
nope. :D I actually bought some in the store earlier today because this thread has been (subliminally) making me think of them.
leatherman (aka mIkIE)


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Offline d-boy86

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #174 on: September 20, 2011, 06:41:59 PM »
I'm a natural born pessimist and unlike most newly diagnosed I was sure 2 years ago that there was no cure in sight.  It does seem like they keep stacking up the lego pieces of discovery each week now though.  I figure it won't be long before there's something.  However, I remain cautiously optimistic.
Same here. But at the rate their moving, I no longer worry about the "few" years that are subtracted from my previous life expectancy.

Offline spacebarsux

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #175 on: September 21, 2011, 12:29:11 AM »
Especially in the context of advancements in medicine it's been said more than once and I still believe it's a wise way to think:

"I am not opposed to optimism but I am fearful of the kind that comes from self-delusion."
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Offline sam66

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #176 on: September 21, 2011, 07:07:12 AM »

 Yep, I feel so sorry for all those deluded researchers working tirelessly towards a cure
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Offline spacebarsux

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #177 on: September 22, 2011, 06:21:11 AM »
<sigh> Not deluded researchers. Just saying that I prefer to be cautiously optimistic about the research so that when (please note I didn't say "if") a cure comes along, I am pleasantly surprised rather than delude myself into thinking it's gonna be available for all of us in 2015 which is a sure way to set yourself up for disappointment.

But I digress, I came here to say that I just read this:

A person with HIV who didn't take antiretroviral drugs for three months remained free of the virus, thanks to a groundbreaking gene therapy. The success raises the prospect of keeping HIV in check permanently without antiretrovirals.

The gene therapy works by locking the virus out of the CD4 white blood cells it normally infects. Of six people with HIV given the treatment, one cleared the virus completely and another two saw 10-fold drops in circulating virus.

"We're over the moon to have seen that in this small phase I study," says Jeff Nichol, executive vice president for research at Sangamo BioSciences, the company in Richmond, California, that is developing the treatment. "Having one virus-free patient and 10-fold reductions in another two is amazing."

Most importantly, analysis of data from the six patients, and from four others in a separate trial, revealed the secret of the more successful outcomes, paving the way for the therapy to work better in future.


http://www.newscientist.com/article/dn20948-double-whammy-gene-therapy-clears-hiv-from-body.html
Infected-  2005 or early 2006; Diagnosed- Jan 28th, 2011; Feb '11- CD4 754 @34%, VL- 39K; July '11- CD4 907@26%,  VL-81K; Feb '12- CD4 713 @31%, VL- 41K, Nov '12- CD4- 827@31%

Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #178 on: September 22, 2011, 08:47:03 AM »
I wouldn't be surprised if the heads of the large pharmaceutical companies that make HIV meds (Gilead, Bristol Myers, etc) are seriously considering buying Sangamo.

This treatment could possibly be a game changer and it would eat up their profits unless they get in on it.

Offline buginme2

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #179 on: September 22, 2011, 10:48:17 AM »
I wouldn't be surprised if the heads of the large pharmaceutical companies that make HIV meds (Gilead, Bristol Myers, etc) are seriously considering buying Sangamo.

This treatment could possibly be a game changer and it would eat up their profits unless they get in on it.

Maybe, however I read an article about this treatment in MIT's tech magazine and the author was Arguing how this treatment would NOT be a game changer on a global scale due to its expected cost.  Gene therapy isnt cheap (it could run close to $100,000) which would make it Impractical in the majority of the world.  They also said that Sangamo has enough money on hand to continue its clinical trials on their own without seeking money from any of the major pharmaceuticals.  Sounds like they are investing quite a bit hoping for a big payout.

Offline LM

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #180 on: September 22, 2011, 11:10:15 AM »
A person with HIV who didn't take antiretroviral drugs for three months remained free of the virus, thanks to a groundbreaking gene therapy. The success raises the prospect of keeping HIV in check permanently without antiretrovirals.

This is great, let's hope this guy continues virus-free.

But I also think that, even if this comes as a cure, ARVs will continue to profit, as most people won't be able to pay for such treatment.

Offline Tim Horn

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #181 on: September 22, 2011, 01:53:26 PM »
A person with HIV who didn't take antiretroviral drugs for three months remained free of the virus, thanks to a groundbreaking gene therapy. The success raises the prospect of keeping HIV in check permanently without antiretrovirals.

The gene therapy works by locking the virus out of the CD4 white blood cells it normally infects. Of six people with HIV given the treatment, one cleared the virus completely and another two saw 10-fold drops in circulating virus.

And here we have journalism that is either lazy or irresponsible, depending on your point of view.

The "one patient" being referenced here never became "HIV free." His viral load basically remained undetectable when his antiretroviral therapy was stopped. But he was no more "HIV free" than the rest of us with undetectable viral loads. What's more, this patient wasn't your usual HIV case -- he had a natural variation in the CCR5 gene (he inherited one delta-32 mutated form of the gene from a parent) that resulted in lower CCR5 coreceptor expression on his CD4 cells and, with that, a much slower course of HIV disease progression (inheriting a mutated gene from both parents essentially blocks all production of CCR5 on CD4 cells; but this is a rare situation). So basically, the infusion of gene-modified stem cells made a good thing even better for this one particular patient.

So this guy head a head start that more than 90 percent of the rest of us shouldn't expect. But there's something to be learned here. Along with data from the study showing that those who had maintained the highest percentage of CCR5-deficient CD4 cells following infusion -- both in the blood an in the gut -- had the lowest viral loads while off treatment, these data suggest that if Sangamo can find a way to safely and economically increase the number of gene-modified CD4 cells infused back into the patient, the results may be even better in a majority of study subjects.  The Phase I study looked at infusions of 10 to 30 billion cells (approximately 1/4 of which were successfully modified); future studies may want to look at infusing an even higher number of cells and/or developing a method of increasing the percentage of CCR5-deficient cells before infusion.

Tim  
« Last Edit: September 22, 2011, 01:59:07 PM by Tim Horn »

Offline Jake2011

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #182 on: September 22, 2011, 04:26:37 PM »
I wouldn't be surprised if the heads of the large pharmaceutical companies that make HIV meds (Gilead, Bristol Myers, etc) are seriously considering buying Sangamo.

The thing that worries me about this Inch is that it could actually happen, if sangamo got bought out by the big pharmies all they would then have to do is bury it, stick it in a safe and throw away the key, research stopped at phase I or II trials, no credible reason given, it's happened before! It's all about the greenback and if that’s what they have to do to protect their billion dollar industry, then surly they'll do it!?
« Last Edit: September 22, 2011, 04:38:24 PM by Jake2011 »

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #183 on: September 22, 2011, 08:58:47 PM »
I agree that it's a leap to say that the undetectable patient is virus free.  But, well, do we know conclusively that he isn't? 


Offline VariGam

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #184 on: September 22, 2011, 09:29:51 PM »
The thing that worries me about this Inch is that it could actually happen, if sangamo got bought out by the big pharmies all they would then have to do is bury it, stick it in a safe and throw away the key, research stopped at phase I or II trials, no credible reason given, it's happened before! It's all about the greenback and if that’s what they have to do to protect their billion dollar industry, then surly they'll do it!?

The Sangamo CEO has specifically said that they will not be partnering for a Phase II trial.  According to their financials they do have sufficient cash available to pay for a Phase II.  If this can make it to Phase III it will be a different story.  Those are much more expensive, so I assume they would have to take on a partner.  (which would be good for the stock price! yay)

As for your point about big pharma shutting this down, simply put thats not going to happen imo.  There would be a ton of money to be made from this type of treatment.  It would be very expensive and its not like you would just go to a clinic, get one shot, then be cured.  There would likely be many many treatments throughout the course of your life.  This could be a gold mine for them as well.  Also, as someone else mentioned, many would not be able to afford this treatment so ARVs would still be profiting handsomely.

edit: I also wanted to add that this type of treatment is likely a looooong way away.  Someone in this thread mentioned 5-6 years, but reality is closer to 10-15.  They are just beginning the initial research and lots of tweaking/testing has to be done before its ready for the clinic.  However, it is very exciting research!
« Last Edit: September 22, 2011, 09:33:22 PM by VariGam »
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Offline mdh26

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #185 on: September 22, 2011, 09:30:43 PM »
It makes absolutely no sense to consider the UD guy to be cured / virus free. Like none, nobody is making that claim.

And it will not last forever. It will be interesting to see how long he'll remain UD without another treatment, but until they can modify his stem cells that produce the cd4 cells, it's just a temporary treatment, even if it lasts for a year or two.

Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #186 on: September 22, 2011, 10:04:54 PM »
And here we have journalism that is either lazy or irresponsible, depending on your point of view.


Yea, when I read that part about the patient having "cleared the virus" it was a definite red flag indicating the statement was obviously wrong. People who are not as in tune with HIV research as are those of us with HIV wouldn't bat an eye when reading such a claim.

 
The thing that worries me about this Inch is that it could actually happen, if sangamo got bought out by the big pharmies all they would then have to do is bury it, stick it in a safe and throw away the key, research stopped at phase I or II trials, no credible reason given, it's happened before! It's all about the greenback and if that’s what they have to do to protect their billion dollar industry, then surly they'll do it!?

Apart from the fact that, as others have said, Sangamo isn't planning on selling the rights to this, the fact is that even if they did partner with someone, the contracts for such rights I'm sure include protections to the effect of "if the product isn't developed and 'exploited' the rights would revert, etc."


Offline John2038

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #187 on: September 22, 2011, 10:26:19 PM »
On the paper, this can lead to a functional cure:

1) To replicate, HIV needs the co-receptors CXCR4 and CCR5.
2) Without them, it can't replicate.
3) ZFN is able to disrupt these R5 and the X4 co-receptors in T cells
4) ZFN proof of concept has shown that there was a good uptake (grafting) of the modified CD4

I'm not trying to say that in the reality, ZFN IS a functional cure. But rather, being given the fact above, it is definitely a very interesting study that will have most probably positive outcomes.  My two cents are that ZFN will be part of our treatments options tomorrow. It would be interesting to see if ZFN can be the answer to resistances. I would be interested seeing another study blocking both co-receptors (we will then become even closer to the conditions that has lead the Berlin patient to be cured).
If only we could make the chemio much safer and find a way to transplant our own bone marrow that has been, gentically manipulated in a way that 100% of the T cells it produce are R5 free (or R5/X4 free). That would be something I guess.

Offline LM

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #188 on: September 23, 2011, 12:27:26 AM »
I ended up saying "virus-free" from following the article, but I meant undetectable. Of course it doesn't mean he has cleared his body from HIV.

Besides, I remember I read somewhere that if this worked, it wouldn't take 10-15 years, but less. They are on human trials already. Anyway, let's hope this works.

Offline sam66

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #189 on: September 23, 2011, 12:30:54 AM »

The "one patient" being referenced here never became "HIV free." His viral load basically remained undetectable when his antiretroviral therapy was stopped. But he was no more "HIV free" than the rest of us with undetectable viral loads.

 Yes, this is someting that always puzzled me, how can we ever know if someone is free of the virus or cured,  even in the case of Berlin patient until we know where all the viral reservoirs are, or until you test every organ in the body for the virus.

  Is this what is meant by a functional cure ? some one can remain UD without treatment
december 2007 diagnosed +ve ,

Offline sfpvguy41

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #190 on: September 23, 2011, 01:10:07 AM »
Yes, this is someting that always puzzled me, how can we ever know if someone is free of the virus or cured,  even in the case of Berlin patient until we know where all the viral reservoirs are, or until you test every organ in the body for the virus.

  Is this what is meant by a functional cure ? some one can remain UD without treatment

As i understand it yes, that would qualify. But if there was some small amount of virus in the body, and it was controlled and didn't do damage, that would still be a functional cure. The reason we have immune systems is there are always viruses around the cd4s and other cells attack and destroy them.  We are never virus-free, just some attack in ways way more dangerous than others.
Labs: (undetectable since 2005)
12/13: 634 cdr, 37.3%, 758 cd8, total chol 183, triglycerides 131
8/13: changed to Edurant from Reyataz
12/12: 828 cd4, 34.5%, 1078 cd8, total chol 192, tri 196
12/11: 787 cd4, 37%, 979 cd8.
9/11: 758 cd4, 38%, 944 cd8, und.
8/11 dropped norvir, incr reyataz to 400 mg
6/11: 621 CD4 CD4% 41, CD8 680! Undetectable. Creatinine and eGFR are ok now.
Switched from Truvada to Epzicom in late April 2011
AGT/AST and creatinine back to normal mid-April.
Cut Norvir from regimen.
Switched back to Reyataz/Norvir late Feb 2011
2/11: CD4 664 34%, CD8 963, diagnosed with osteoporosis, high AGT/AST and creatinine.
12/10: CD4: 676 CD4%: 34 CD8: 1012
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8/10: CD4: 731 CD4%: 40 CD8: 866
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Offline sfpvguy41

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #191 on: September 23, 2011, 01:16:59 AM »
I agree that it's a leap to say that the undetectable patient is virus free.  But, well, do we know conclusively that he isn't? 



As I understand it, there were two cohorts in the recent Phase 1 studies.  In the first cohort, they never stopped ARV treatment. In the second, it was part of the protocol that they stop treatment for 12 weeks only, and the undetectable patient was in this group. Presumably for safety reasons, he went back on treatment so we will never know for how long he would have stayed undetectable.

We need to focus on the fact that anyone became undetectable at all was amazing, and that all had viral load drops correlated with the amount of modified CD4 cells when they went off treatment was also good news. One would expect anyone going off meds to have viral load increase, so it clearly shows proof of concept.  Onward to new trials!
Labs: (undetectable since 2005)
12/13: 634 cdr, 37.3%, 758 cd8, total chol 183, triglycerides 131
8/13: changed to Edurant from Reyataz
12/12: 828 cd4, 34.5%, 1078 cd8, total chol 192, tri 196
12/11: 787 cd4, 37%, 979 cd8.
9/11: 758 cd4, 38%, 944 cd8, und.
8/11 dropped norvir, incr reyataz to 400 mg
6/11: 621 CD4 CD4% 41, CD8 680! Undetectable. Creatinine and eGFR are ok now.
Switched from Truvada to Epzicom in late April 2011
AGT/AST and creatinine back to normal mid-April.
Cut Norvir from regimen.
Switched back to Reyataz/Norvir late Feb 2011
2/11: CD4 664 34%, CD8 963, diagnosed with osteoporosis, high AGT/AST and creatinine.
12/10: CD4: 676 CD4%: 34 CD8: 1012
Switched from Reyataz/norvir to Isentress 10/10
8/10: CD4: 731 CD4%: 40 CD8: 866
Diagnosed Sept. 2002 started meds May 2005.

Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #192 on: September 23, 2011, 08:38:53 AM »
Yes, this is someting that always puzzled me, how can we ever know if someone is free of the virus or cured,  even in the case of Berlin patient until we know where all the viral reservoirs are, or until you test every organ in the body for the virus.

  Is this what is meant by a functional cure ? some one can remain UD without treatment

Well, in the case of the Berlin patient they are doing very sophisticated tests that check virus in every nook and cranny. They might still be missing some areas but they have also found that, as time goes by, he has fewer and fewer levels of HIV-antibodies in his system so it's predicted that at some point he will actually test HIV-negative, if those antibodies disappear.

Offline sam66

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #193 on: September 23, 2011, 09:49:17 AM »

 they have also found that, as time goes by, he has fewer and fewer levels of HIV-antibodies in his system so it's predicted that at some point he will actually test HIV-negative, if those antibodies disappear.

 I guess that would be the litmus test, if he does eventually test hiv -ve, then we can say at least one person
has been cured,.. Amazing I hope that day comes soon for him, I will celebrate that date for him.

 Just to digress a little , I read in the news today, " The absolute truth, The universal constant " nothing
 travels faster than light may not be true.
    Scientist at CERN may have discovered a Neutrinos which can travel faster than light, if this turn out
 to be true, that would be amazing, the impossible has happened.

     http://www.bbc.co.uk/news/science-environment-15017484

  may be oneday we may have a cure for everybody........ impossible ?

december 2007 diagnosed +ve ,

Online geobee

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #194 on: September 28, 2011, 04:19:28 PM »
Just listened to one of Sangamo's investor webcasts.  There are going to be two new trials in the first half of next year:

1.  Using SB 728 with a heterozygous population.  This is to try to replicate the one patient going undetectable after the 12-week STI.  (Interesting, after going back on meds, this patient blipped up to 100).

2.  Using enhanced engraftment techniques with SB 728.  Ed Lanphier (Sangamo's CEO) said that techniques can increase engraftment up to 1000 times.  (My guess here is that they will somehow suppress one's own T-Cells to give "space" for the modified T-Cells to expand.  Like I said, this is a guess here.)

The trials this year gave a clear result -- the more cells you modify, the greater the anti-viral effect.  These next two trials should result in a lot of modified cells -- and even greater control of the virus.  Cool stuff!

Here's the link.  I think you have to log-in to see it.  The slides and Q&A at the end are worth looking at.

http://wsw.com/webcast/jmp14/sgmo/

Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #195 on: September 28, 2011, 08:36:20 PM »
Thanks for that, geobee . . . it's a good overview of what's to come.

Offline VariGam

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #196 on: October 03, 2011, 03:02:43 PM »
Shouldn't more results for treatment naive patients be coming out later this year?

Also, this isn't relevant to the topic but the stock is down 26% today on news of the failure of their diabetic neuropathy therapy. 
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Online geobee

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #197 on: October 04, 2011, 09:27:48 PM »
Results for the treatment-naive cohort are coming out near the end of the year.

Also, they are actively screening for the heterozygote/STI trial at Quest in San Francisco (www.questclinical.com).  They took some blood to see if I qualify -- a 10% chance.  They are looking for a) undetectable on meds b) good T-Cells and c) of northern European descent (most likely to be a heterozygote).   If you're interested, their contact info is on their website.  This trial isn't yet listed on the website, but they told me today they are actively looking for more people.
« Last Edit: October 04, 2011, 09:29:48 PM by geobee »

Offline mbpoz6

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #198 on: October 08, 2011, 12:52:39 PM »
http://www.insidebayarea.com/news/ci_19064977

Small HIV studies show promising signs

A novel chemical editing of a gene strengthened immune systems in HIV-positive men, and one participant even cleared the virus without drugs, scientists recently announced.

"We were stunned," said Elizabeth Wolffe, a scientist with Sangamo BioSciences in Richmond, which developed the gene therapy. "It isn't usual that someone would clear their virus without having medication."

The gene therapy altered a critical class of immune cells -- T cells -- the front line in battling the virus. HIV defeats this defense by latching to T cells and destroying them.

The therapy snipped out a gene that enables the virus to attach to T cells, so they could deflect the deadly virus, study results indicate. On its own, the virus exists for less than a day, and it needs the immune cells to survive and multiply. An army of genetically altered T cells deflecting HIV would deplete the virus' ranks, one researcher said.

The altered immune cells were also replicating, buoying hopes of long-term protection.

Given the small size of the trials -- nine men in one and six in the other -- researchers tempered their responses to the early results. But scientists say they point to a promising way to clear the virus without the difficult side effects and high cost of a lifetime of antiretroviral medications, which run $15,000 to $20,000 a month. Patients in the trials had only minor and transitory side effects, Sangamo BioSciences reported.

"Do I think we have a cure?" said Dr. Pablo Tebas, a University of Pennsylvania researcher running one of the trials. "No, but I think it's a very exciting result that points in the direction we need to go. And then maybe we will one day reach that holy grail, not needing antiretroviral therapy.

Medical advances rely on repeated successful tests of a treatment with large groups of study subjects, and many questions also remain unanswered with the Sangamo trials, including how long the genetically modified cells will last.

The genetically altered T cells retain their typical behavior, racing to attack bodily invaders. During the study, the modified cells traveled where "HIV reservoirs" are known to hide out, such as in the gut, Wolffe said.

It's these hidden reservoirs that keep T cell counts low for some HIV carriers even when blood levels of the virus are undetectable, as the virus can still destroy T cells from its redoubt.

The findings were presented Sept. 17 and Sept. 18 at a Chicago medical conference.

A Brisbane man in one of the trials said his low T cell count almost doubled two weeks into it and has remained there.

For the first time in years, Matt Sharp, 55, said he hasn't picked up an upper respiratory infection, such as a cold, the flu or pneumonia. "It's phenomenal," he said.

Sharp knows he can't prove it, but he attributes his rise in T cell levels to his illness-free year.

The scientists used a type of genome manipulation that employs "zinc fingers," which are two protein strands bound by a zinc atom that resemble a finger. They precise "edit" genetic material.

For both of the studies, researchers collected T cells from the blood of each participant and with zinc fingers deleted the gene for the HIV attachment site. The patient's own genetically modified cells were then reinfused into his blood.

In the Sangamo-run trial in California, Sharp and eight others had been taking medications that had driven HIV to an undetectable level in their blood. But they still had low T cell counts -- the sign of a weakened immune system vulnerable to disease. HIV infections can lead to AIDS, the syndrome in which the weakened immune system is unable to fight off a range of serious infections.

The California study is expected to end in 2012. Sangamo BioSciences said results so far show the altered T cell infusions led to "unprecedented improvements" in all the men's T cell counts compared with prescription drugs, including antiretroviral therapy.

The six men in the University of Pennsylvania trial also were taking HIV medications that had cleared the virus from their blood but had high T cell counts -- so their immune systems were relatively strong.

They were given a 12-week "drug holiday" to test the effect of the altered cells alone.

As expected, Tebas said, their HIV blood levels spiked.

But then with infusions of their modified T cells, the HIV levels declined. One participant who carries a gene that naturally creates T cells lacking the HIV receptor even cleared the virus without help of drugs.

Tebas said the man simply had more of the modified T cells in his blood, given his natural supply and the infused T cells.

"So it clearly suggests it's a dose issue," Tebas said.

Sangamo BioSciences next plans to begin studying the effect of the modified T cells on those who are HIV-positive and also carry one of the genes for HIV resistance.

"It's promising," said Dr. Jay Levy, a UC San Francisco AIDS researcher who codiscovered HIV. "You can't say anything less than that or any more than that. But the results put forward are very encouraging."






From reading this article a few things are not that clear to me. What I don't understand is when they say one participant "cleared the virus"....does that mean its gone from his/her body due to the treatment? OR was it just not detected during the STI then returned? Or is it something else?

Online geobee

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #199 on: October 25, 2011, 06:38:42 PM »
Just a quick update -- Sangamo is dropping the current trial SB-728-1002, the treatment-naive cohort, in an effort to focus on their two new cohorts.  However, from what I can tell, there will be an update on SB-728-1002 next Tuesday. It will be discontinued in favor of the other two trials (heterozygotes and enhanced engraftment) to be begin enrolling in the first half of next year.   -- George
« Last Edit: October 25, 2011, 06:41:00 PM by geobee »

 


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