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Author Topic: Calimmune: Safety Study of a Dual Anti-HIV Gene Transfer Construct to Treat HIV-  (Read 36859 times)

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Offline Tadeys

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This is an early phase research study looking at whether an experimental gene transfer, LVsh5/C46 (also known as Cal-1), is safe and if it can protect the immune system from the effects of HIV without the use of antiretroviral drugs.

Cal-1 is an experimental gene transfer agent designed to inhibit HIV infection through 2 active parts:

Removing a protein named CCR5 from bone marrow and white blood cells
Producing a protein named C46 on bone marrow and white blood cells
Detailed Description   
It is estimated that 33 million individuals are currently infected with HIV. HIV/AIDS is a disease that impairs immune function, primarily by decreasing CD4+ T lymphocytes. The progression can be contained by daily dosing with antiretroviral therapy (ART) but there are side effects that can be treatment limiting, and the development of HIV drug resistance can force the physician to modify the ART regimen. There are no effective vaccines currently available for HIV.

LVsh5/C46 (also known as Cal-1) is a dual therapeutic, self-inactivating lentiviral vector that encodes for both a short hairpin RNA against the HIV-1 co-receptor CCR5 (sh5) and a HIV-1 fusion inhibitor, C46 and inhibits two processes required for HIV-1 infection:

Binding of the virus to the cellular CCR5 co-receptor and
Fusion of the virus with the host cell
The rationale is that Cal-1 introduced into hematopoietic progenitor/stem cells (HSPC) and mature CD4+ T lymphocytes will protect these cells and their progeny cells from HIV-1 infection and its pathogenic sequelae. This may provide a continuous means of controlling HIV-1 after a single or infrequent dose(s), thereby decreasing or delaying (partially or completely) the need for antiretroviral drug therapy.

http://clinicaltrials.gov/ct2/show/record/NCT01734850

Offline Matts

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It seems they want to repeat the success of the "Berlin Patient" but without a transplantation.

http://www.calimmune.com/therapy.php
triumeq

Offline geobee

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I've been on the list at Quest Research in SF for this trial.  I've been following the Sangamo trials (also at Quest) and am going to wait and see what becomes of them first.

Offline geobee

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Just got an email from Quest -- they are now recruiting for the CalImmune trial.

Offline Matts

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Maybe You are "cured" soon. I would be scared if somebody botches on my lovely genes. But CalImmune works with Benitec, and they really have the money and experience with the small hairpin ddRNAi, I think it will be a succes. :)
triumeq

Offline JazJon

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I'm on the Calimmune list as well, I'll post what I can if I make it.  I'm excited to help move research forward.

Offline geobee

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Well I didn't qualify again for the Sangamo T-Cell trial.  My adenovirus titre went from 500 something to 100 something but it needs to be below 40.  So... nixed again for that trial.

But Quest called back today and I did qualify for the CalImmune trial and am considering it.  I'm pretty comfortable replacing some of my T-Cells -- but more apprehensive re: stem cells.

Offline JazJon

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Well I didn't qualify again for the Sangamo T-Cell trial.  My adenovirus titre went from 500 something to 100 something but it needs to be below 40.  So... nixed again for that trial.

But Quest called back today and I did qualify for the CalImmune trial and am considering it.  I'm pretty comfortable replacing some of my T-Cells -- but more apprehensive re: stem cells.

If we both get on board, we'll have to share and compare our experiences.   I was told you can either do Stem cell without chemotherapy, with "light" chemotherapy. or with "medium" chemotherapy.    I think the logic of doing chemo to reset your immune system is very logical, so I'm going for the chemo if I get to pick.   Our hair won't fall out or anything, it's not the intense long dosage they give cancer patients.   It won't happen until later that year probably from what I understood. 

Offline POZnLA

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If we both get on board, we'll have to share and compare our experiences.   I was told you can either do Stem cell without chemotherapy, with "light" chemotherapy. or with "medium" chemotherapy.    I think the logic of doing chemo to reset your immune system is very logical, so I'm going for the chemo if I get to pick.   Our hair won't fall out or anything, it's not the intense long dosage they give cancer patients.   It won't happen until later that year probably from what I understood.

I have an appointment for a consult, not screen yet, this coming Wed in LA at UCLA Center for Aids research. Wish me luck. I have been off meds since 3/15, due to drug reactions. They said that they expect to start screening this week, or the next.

Offline geobee

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After mulling it over, I'm leaning towards doing this trial.  I sent an email to my doc and will let you know what her opinion is.   If she's neutral or better I'm going to talk to Quest and schedule a short informational session with Dr. Jay.

Offline Matts

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I wish the 3 brave guinea pigs the best of luck. It has to be a difficult decision; getting Busulfan and an unapproved Gene product.
I think that we will know the results in a decade or so.

http://en.wikipedia.org/wiki/Busulfan
http://clinicaltrials.gov/ct2/show/NCT01734850
triumeq

Offline Hoyland

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While not using the same targets as the Calimmune trial the City of Hope has run and is running a ddRNAi trial for HIV. One of the lead investigators is Dr Rossi. Here is a video of him speaking about the use of ddRNAi in the treatment of HIV. This may help some who are considering the Calimmune trial. Good luck.

http://www.youtube.com/watch?v=9XqJyYrYgwU


Offline freewillie99

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I wish the 3 brave guinea pigs the best of luck. It has to be a difficult decision; getting Busulfan and an unapproved Gene product.
I think that we will know the results in a decade or so.

http://en.wikipedia.org/wiki/Busulfan
http://clinicaltrials.gov/ct2/show/NCT01734850

A decade?  More like inside a year.  Seriously, dude...where'd you pull that one out from  :o

Best of luck to all.
Beware Romanians bearing strange gifts

Offline jaace24

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Do you know when the study is supposed to start?  And how long it will be?

Offline POZnLA

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Do you know when the study is supposed to start?  And how long it will be?
The Study has selected 4 persons for the 1st of 3 Arms, and participants for the second Arm are being selected now. There is a talk given by Dr. Ronald Mitsuyasu at Plummer Park in West Hollywood this coming Thursday at 6:00 pm, rsvp required, contact UCLA HIV care and research center. Dr. Mitsuyasu is the principle investigator for this study, and an associate director at UCLA AIDS Institute.
Quest labs in San Francisco as well as UCLA are the 2 investigation sites.

Offline POZnLA

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Do you know when the study is supposed to start?  And how long it will be?
Oops, I forgot something. The study is for a period of 48 weeks, and though not a full year, for researchers, it is my understanding, that it is 12, 4 week periods, and they refer to it as a year long study.
The Study officially was listed as "recruiting" as of 4/15/13.

Offline Matts

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Ok, then we will know in 1 year if it works or not?
Am I right in thinking, that You get only one shot of  LVsh5/C46 (with or without Busulfan) and the CCCR5 receptor in the bone marrow is destroyed forever?
The body produces only CCR5 free cells from then on (theoretically)?
I know the  LVsh5/C46 destroys also 2 other HIV genes; Is this also forever or only for the time of treatment?
triumeq

Offline Hoyland

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The theory is that the full treatment will be a single session (or very few sessions) and that the gene therapy component of the drug will turn off the gene that produces the CCR5 receptor. This will not happen for every white blood cell in the body immediately but the new, modified cells will reproduce and eventually replace all the ones with the receptor.

Once made, this modification is intended to last forever and not just for the period of the treatment.

This is only a Pl/ll safety study and so dosing will likely be low or lower than that anticipated for a full recovery from HIV. However, as mentioned in the video which I posted previously, a patient who was treated with the same gene silencing technology (different target) continues to see an increase in modified cells after a very low initial transfection of new cells years after the initial treatment. Participants in this Calimmune trial could, therefore, expect to see similar continued improvement.

Offline POZnLA

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Ok, then we will know in 1 year if it works or not?
Am I right in thinking, that You get only one shot of  LVsh5/C46 (with or without Busulfan) and the CCCR5 receptor in the bone marrow is destroyed forever?
The body produces only CCR5 free cells from then on (theoretically)?
I know the  LVsh5/C46 destroys also 2 other HIV genes; Is this also forever or only for the time of treatment?
I am no expert, but as a candidate and potential participant in the study, this is my understanding. CD4 cells and CD34 cells (bone marrow cells) are removed, genetically modified to be CCR5 free, as well as to produce CR46(a 2nd barrier to HIV). The modified cells are grown (allowed to multiply) so that there are many of them (billions, as opposed to millions used in other studies), then reintroduced. After reintroduction the modified cells will reside along side the unmodified cells. It is hoped that the genetically modified cells will become predominant as HIV eliminates the cells that are not modified. In the 1st Arm of the study no chemotherapy is used, in the 2nd Arm one does is used (Busulfan), and in the 3rd and last arm, 2 doses of chemotherapy are used. The purpose of the Chemotherapy is to "make room" for the newly introduced modified cells. In some of the previous gene therapy studies the newly introduced cells resisted the HIV virus, but were eventually thinned out and unable to control HIV in those study participants.
If some one else knows more or I am in error, please add your response.

Offline Hoyland

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POZnLA, your understanding is correct.

The other study that you refer to is probably the first trial conducted at CoH. This was done a few years ago when the transfection process was not very efficient. That study did prove that there was no toxicity associated with the treatment and since then levels of transfection have improved.

Dr Anderson at UC Davis is working on a similar treatment but I believe that he is yet to source funding for a trial.  Prof Berkhout in the Netherlands is also working with ddRNAi but has taken a somewhat different approach. His team my be in the clinic next year. There is also a team in Russia using ddRNAi technology to find a treatment for HIV but I am not sure of their progress.

Offline Matts

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Ok thank You. I think its for sure, if there will be a cure it will be a "CCCR 5 thing". I wrote a mail to Dr.Hütter, and I hope he will answer.
Today another vaccine trial has totally failed (HVTN 505). So long everything  has failed within the last decades. It's about time for a success after 30 years. :)
Anyway, I think the CalImmune trial is not dangerous for the guinea pigs, its already tested in humans.
So long I take my Selzentry that blocks the CCR5 receptor; but it would be better to disrupt CCR5 definetely in the bone marrow, than taking pills everyday :).
If there will be no cure, then there will be even better drugs. GSK1265744 is very promising; a nano drug that will be administered once a month.

The future is bright. :)
« Last Edit: April 25, 2013, 05:12:29 PM by Matts »
triumeq

Offline buginme2

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". I wrote a mail to Dr.Hütter, and I hope he will answer.


What did you say in our letter? Was it like fan mail or was their a specific request?
Don't be fancy, just get dancey

Offline Hoyland

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Does anyone know when the first patients will dosed?

Offline JazJon

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Does anyone know when the first patients will dosed?

I originally was interested in volunteering for gene therapy when I was first diagnosed early 2012.  Since nothing was available I went ahead with a trial med that blocks ccr5
http://www.aidsmeds.com/archive/cenicriviroc_2656.shtml

I just ended the 12 month trial and switched over to complara for now. 
(It worked great, no sides, undetectable)

I have a follow up appointment later this week to make sure I'm still undetectable on Complara (should be fine)

Since I was told they want me for the Calimmune study at my last appointment I should know more this month on timelines. 

I'm actually doing a short study in a few weeks (one time thing) where they Harvest a ton of my white blood cells.  This is for research that involves finding/waking the hidden reservoirs.  (Not related to Calimmune)

But yeah I'm confident enough to go for the double Busulfan immune system format c: so the custom Firmware update of my new immune system takes root.   Best case scenario I can then give people hope by reporting I'm still undetectable month after month while completely off meds. (And do the happy dance)

I think I'm a great Canadiate.  When I discovered I was poz in march 2012 I was still testing neg for antibodies.   I dove into the cenicriviroc trial meds study and became undetecable in weeks.   I should have very little reserves in my body from what I understand. 

Offline Dr.Strangelove

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I remember reading an article about Dr. Gero Hütter recently. He is not working on HIV any more. Also, he never really was a HIV researcher but a hematologist. It was more of a happenstance that one of this leukemia patients was HIV positive. So, I doubt that he is still in the 'cure business'.

The approach for the Calimmune trial sound pretty promising. But it's still early on.

Offline Matts

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Yes he is only a simple hematologist in Heidelberg. I think he gave only his good name for CalImmune for a decent amount of money. :) Don't know what to think about the trial, there is not much information.  Let's see what will happen.
triumeq

Offline Hoyland

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Quote
there is not much information

This is the abstract of a paper that Calimmune will be presenting in two weeks time at the ASGCT conference. I hope this helps.

[48] Engineering Resistance to HIV-1 Infection with a Dual Therapeutic Lentiviral Vector

Bryan P. Burke, Maureen P. Boyd, Michelle L. Millington, Helen Impey, Jane Zhang, Maria V. Carroll, Joanna Camba-Colon, Naomi Keech, Frederic Delebecque, Orit Wolstein, Annett Howe, Rachel Koldej, Tamara Nicolson, Bernard R. Levin, Valerie Rezek, Dimitrios N. Vatakis, Scott G. Kitchen, Louis R. Breton, Jeffrey S. Bartlett, Geoff P. Symonds. Calimmune, Inc., Los Angeles, CA; Division of Hematology-Oncology and UCLA CFAR, The David Geffen School of Medicine, University of California, Los Angeles, CA

We have developed a dual therapeutic anti-HIV lentiviral vector (LVsh5/C46) capable of generating cellular resistance to multiple strains of both R5- and X4-tropic HIV-1. LVsh5/C46 (Cal-1) has two separate mechanisms of action for inhibiting HIV-1 infection: (1) down-regulation of CCR5 expression via RNAi; and (2) inhibition of HIV-1 fusion via cell surface expression of the gp41-derived peptide, C46. This combinatorial approach allowed for two points of inhibition for R5-tropic HIV-1 reducing the potential of escape mutations, and was also active against X4-tropic HIV-1. Cal-1 is being clinically developed for use in cell-mediated gene therapeutic applications for treatment of HIV-1 infected patients, for engineering HIV-resistant CD34+ hematopoietic stem/progenitor cells (HSPC) and CD4+ T-cells. Here we report Cal-1 pre-clinical safety and efficacy data for inhibition of HIV-1 infection in vitro and in vivo. Peripheral blood mononuclear cells (PBMCS) and CD4+ T-cell lines treated with Cal-1 were resistant to both clinical isolates and laboratory strains of HIV-1 that were R5-tropic, X4-tropic, or dual-tropic. In addition, Cal-1 modified PBMCs displayed greater protection from HIV-1 infection compared to PBMCs modified with either transgene alone. The ability of Cal-1 modified CD34+ HSPC to confer protection from HIV-1 infection in vivo was determined using the humanized Bone Marrow, Liver, Thymus (BLT) mouse model. Following intravenous challenge with R5-tropic HIV-1, Cal-1 transduced human CD34+ HSPC treated animals demonstrated recovery and maintenance of CD4+ T-cells and significantly reduced viral load compared to control animals that received non-modified human CD34+ HSPC. Four of six animals treated with Cal-1 modified cells had undetectable viremia at terminal analysis, whereas HIV was readily detected in all control animals. Cal-1 modification supported normal hematopoietic development and function without evidence of toxicity. Cal-1 treatment of PBMCs did not induce apoptosis, proliferation, or inflammatory responses; and CD34+ HSPCs treated with Cal-1 displayed normal differentiation, low potential for immortalization in vitro, and oligo-/polyclonal hematopoietic repopulation in vivo. As such, the preliminary safety profile and current efficacy data for Cal-1 strongly support the use of this vector and therapeutic paradigm for clinical treatment of HIV-1 infection.

Offline JazJon

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We have developed a dual therapeutic anti-HIV lentiviral vector (LVsh5/C46) capable of generating cellular resistance to multiple strains of both R5- and X4-tropic HIV-1.

Peripheral blood mononuclear cells (PBMCS) and CD4+ T-cell lines treated with Cal-1 were resistant to both clinical isolates and laboratory strains of HIV-1 that were R5-tropic, X4-tropic, or dual-tropic.

Four of six animals treated with Cal-1 modified cells had undetectable viremia at terminal analysis, whereas HIV was readily detected in all control animals. Cal-1 modification supported normal hematopoietic development and function without evidence of toxicity.

Very interesting, especially the humanized animal reactions to it so far.   I'm really excited to volunteer the more I learn about Callimune.  I'm more than ready to help move medical science forward.  As with anything new, the first run has the potential for yet another failure.  Having said that,  I'm still feeling more confident 2013 could be a true breakthrough year with cure or "functional" cure news.  I think we are all growing restless with the "cure" news popping up each year that soon fades into the what happened to it category. 

I didn't realize this was hitting both R5-tropic & X4-tropic HIV. (I thought it was a dual approach to R5 only)   Any friends I talk to about CCR5 cures usually remind me about the XCR4 re-exposure threat out there.   I'm really impressed that they are able to move forward with the dual approach. 
« Last Edit: April 30, 2013, 10:42:09 PM by JazJon »

Offline JazJon

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Here's an update.   I assumed groups 1, 2 & 3 were happening at the same time but I was mistaken.

-Group 1 (no-chemo) is screening right now, and treatment is then weeks away.
-Group 2 (low-chemo) is screening at the end of 2013, and treatment early  2014
-Group 3 (medium-chemo) is screening mid/end 2014 and treatment 2015

I'm on the list.   Based on the results of Group 1, I'll have to decide if I want to do Group 2 sooner, or wait an extra year for Group 3.  I'm looking forward to seeing how the Group 1 responds, and happy at least a few people are trying out the actual treatment process before I will. (assuming I qualify etc)

It's too early to tell if low vs med chemo pre-conditioning will be all that important.   If Group 1 has outstanding results, I'd drive into Group 2 no questions.  If Group 1 only has ok'ish results, then I might wait the extra year for Group 3.    I'm happy to be in ANY Group to be honest, & just typing up my thoughts.   

I'm glad I formed a good relationship with Quest early on to at least be on the list.
(and looking forward to that call in a few months)  I'm apparently their healthiest patient :)

Here's the other interesting thing.  Calimmune only have 12 slots total SHARED between LA and SF.   Apparently it's almost a first come first serve thing based on screening etc.  That's 4 slots per group, and it's hard to say who will get more LA or SF.   So again having said that, I'd be happy to be in ANY group with such a small number of spots potentially available.

P.S. Group 1 is full obviously, so if you haven't already signed up, it will be a long shot at this point.    Let's hope this actually works and turns into a Phase I/II/III trial by 2016!
« Last Edit: May 01, 2013, 06:25:23 PM by JazJon »

Offline POZnLA

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Here's an update.   I assumed groups 1, 2 & 3 were happening at the same time but I was mistaken.

-Group 1 (no-chemo) is screening right now, and treatment is then weeks away.
-Group 2 (low-chemo) is screening at the end of 2013, and treatment early  2014
-Group 3 (medium-chemo) is screening mid/end 2014 and treatment 2015

Thanks for update JazJon, I received similar info here in LA, from UCLA, They said that the 3 groups were consecutive, not concurrent with a review for safety after each group gets into the study, at what point that review occurs I am unsure. The study recruiting opened 4/15/13 and the study has a estimated primary completion date of June 2015, that's according to the listing on clinicaltrials.gov. Based on that and some dates I was given for screening and the apheresis. I was assuming that it was going faster then that. Maybe not.

Offline JazJon

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Well things are always changing it seems, so maybe what I wrote is just the conservative estimated schedule.   I wouldn't be surprised if Group 2 ends up happening sooner rather than later if Group 1 goes better/smoother than expected.  The wait begins.  I hope the Group 1 data is shared right away, or a Group 1 person chimes in on here. (or if anyone else hears an update they can share)

Offline Dr.Strangelove

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There was a poster by the Calimmune people presented at CROI this year.
I think it hasn't been posted yet in this thread. Here is the abstract:

http://www.retroconference.org/2013b/Abstracts/47457.htm

Looking good
« Last Edit: May 03, 2013, 12:20:13 AM by Dr.Strangelove »

Offline JazJon

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There was a poster by the Calimmune people presented at CROI this year.
I think it hasn't been posted yet in this thread. Here is the abstract:

http://www.retroconference.org/2013b/Abstracts/47457.htm

Looking good


Interesting, I only wish I had the medical training to understand every nuance of that page.   I get the gist of it though.

They said:
"Conclusions: These data provide proof of principle that shRNA targeting HIV-1 promoter is able to suppress HIV-1 replication"

I know they have to  be careful which words they pick, but I'm hoping "suppress" is to the point of the virus being eliminated over time.    Do we know if these humanized mice will be monitored long term? (assuming the humanized mice live very long to begin with)    I wonder what length of time a mouse would need to remain undetectable to be considered a functional cure and finally a cure cure.  (again assuming they live for very long to begin with)      Google said a wild mouse only lives less than a year!

Interesting stuff,  I'm looking forward to finding out how real humans respond long term. 
(assuming the short term goes as well, one step at a time)

Offline JazJon

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I just had an interesting discovery.    Anyone that volunteers for a clinical trial that has you STOP your ART (such as Calimmune) might actually be doing TWO experiments.  Check this out.

Topic: Early HIV drugs 'functionally cure about one in 10'
http://forums.poz.com/index.php?topic=47816.0

Here's where I possibly come in:

Here's a copy and paste:
_______________________________________________

http://forums.poz.com/index.php?topic=47816.msg587206#msg587206

Post-treatment controllers tended to have very high viral loads soon after infection, while elite controllers are more likely to keep virus levels down, even at the start, the researchers said. The immune systems of the post-treatment controllers also tended to differ in certain ways from those of elite controllers.

Maybe I'll end up as a post controller?   I actually have a potential situation where I'll be able to find out in several months.  (I'll post my results if/when it happens)

Details.........
I was diagnosed early 2012.   I had a pretty bad flu for 3 weeks so I got tested.  They told me I had a VL of 2 million, but still tested negative for antibodies.  (they have a dual HIV test at the clinic I went to)  So that means I caught it about as early as it gets.

I did research and I jumped into a clinical trial of a new CC5 blocking med:
http://www.aidsmeds.com/archive/cenicriviroc_2656.shtml  (with Truvada)
(when I started, I felt normal, and VL was pretty low naturally)
I became undetectable in several weeks. (and zero side effects)

I just completed the cenicriviroc trial and switched to complera a month ago. (again zero side effects)

The next trial I'm on the top of the list to participate in Arm 2 or 3 of the Calimmune Gene transfer trial.
http://forums.poz.com/index.php?topic=46455.0

Here's the interesting part.........

I need to STOP taking my meds several weeks before I get treated via Calimmune.    I never imagined that I might remain undetectable after I stop ART.  I'll have been on ART nearly 2 years by the time they would want me.   The fact I was on the CCR5 blocking cenicriviroc for so long and started so early gives me a decent chance at least.   I was told I was the healthiest patient in every program they have across the board too.   So pending my qualification for Calimmune, and they call me,  I'll consider it a double experiment!

I'm pretty sure I was told the Calimmune trial requires you to actually have a detectable VL before they'll treat you.    What if I remain UD month after month?  I would imagine they want test groups to be detectable so they can rule out the potential Post-treatment controller anomalies

________________________________________________
« Last Edit: May 03, 2013, 03:37:41 AM by JazJon »

Offline JazJon

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There was another "cure" post today that got me thinking.    Here's the one I'm referring to.

http://www.africareview.com/Special-Reports/After-Berlin-Man--two-reported-cured-of-HIV-in-Kenya/-/979182/1843388/-/3saq6o/-/index.html

Topic: Two reported cured of HIV in Kenya?
http://forums.poz.com/index.php?topic=48486.0

First off, it's hard to say if this is even legit, but what the article talks about still generated questions.

Quote
“I have demonstrated the HIV cure in two people by stopping rapid multiplication of CD4 progenitor cells in the bone marrow, where the HIV virus hides (to avoid) elimination by the immune system and thus achieved the first complete cure without bone marrow transplantation,” Dr Barasa said.

His treatment, he says, is based on the world’s first known cure of HIV, that of Timothy Ray Brown, 47, who was diagnosed with HIV in 1995 and put on ARVs, but in 2006 developed leukaemia (blood cancer) and, for this reason, was given a bone marrow transplant with a rare gene mutation that provides natural resistance to HIV.

His doctor, Gero Hutter, said this resistance seemed to have been transferred to Brown, but Dr Barasa says this was not the case, arguing that the removal of Brown’s bone marrow did it

“Removing the bone marrow, where the CD4 cells replicate, denied the virus the capacity to replicate and consequently the patient was free of HIV,” says Dr Barasa. Since the new bone marrow was resistant to the virus, the already existing bugs in circulation and from the secondary reservoirs — which include the brain, glands, intestines, and skin — could not create new hideouts, hence the ultimate eradication of the virus.

So again, assuming this story is even legit, I wonder if what his Theory on what REALLY happened with Timothy Brown (Berlin Patient) is true?  If you read about the new claimed cure worked, He's basically saying you only need to use Methotrexate to reset someones immune system deep enough to flush out the HIV reserves.   A full Stem Cell transplant isn't' required.

Quote
Medical doctors using antiretrovirals are able to bring down a patient’s viral load to undetectable levels, but once the patient stops the medication, the viral load goes up again.

“This means there is a reservoir in the body where the virus is hiding and where the ARVs are not able to reach. The hideout is in some parts of the bone marrow. Get rid of this reservoir and, theoretically, you are home and dry,” Dr Barasa says, adding that he has achieved this using a method that comprises the use of a cancer drug (methotraxate) in combination with other agents. Two patients who have undergone the therapy, Dr Barasa adds, have shown no signs of the virus for the past six months.

Methotrexate is used to treat cancer but is indicated to have very serious side effects and should not be used without advice from a competent physician.

“Although the drug is available in local pharmacies on prescription, it must never be used without clear instruction from your doctors,” says Dr Barasa.

How does Methotrexate compare to Busulfan for pre-conditioning?

So again if the Methotrexate did somehow work, I'm assuming you wouldn't be immune from getting re-infected with HIV again.   At least with Calimmune you hopefully permanently block CCR5 and CSCR4 entries and gain partial/full immunity after the potential "cure"

2013 is very interesting so far.

Offline buginme2

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I just had an interesting discovery.    Anyone that volunteers for a clinical trial that has you STOP your ART (such as Calimmune) might actually be doing TWO experiments.  Check this out.

Topic: Early HIV drugs 'functionally cure about one in 10'
http://forums.poz.com/index.php?topic=47816.0

Here's where I possibly come in:

Here's a copy and paste:
_______________________________________________

http://forums.poz.com/index.php?topic=47816.msg587206#msg587206

Maybe I'll end up as a post controller?   I actually have a potential situation where I'll be able to find out in several months.  (I'll post my results if/when it happens)

Details.........
I was diagnosed early 2012.   I had a pretty bad flu for 3 weeks so I got tested.  They told me I had a VL of 2 million, but still tested negative for antibodies.  (they have a dual HIV test at the clinic I went to)  So that means I caught it about as early as it gets.

I did research and I jumped into a clinical trial of a new CC5 blocking med:
http://www.aidsmeds.com/archive/cenicriviroc_2656.shtml  (with Truvada)
(when I started, I felt normal, and VL was pretty low naturally)
I became undetectable in several weeks. (and zero side effects)

I just completed the cenicriviroc trial and switched to complera a month ago. (again zero side effects)

The next trial I'm on the top of the list to participate in Arm 2 or 3 of the Calimmune Gene transfer trial.
http://forums.poz.com/index.php?topic=46455.0

Here's the interesting part.........

I need to STOP taking my meds several weeks before I get treated via Calimmune.    I never imagined that I might remain undetectable after I stop ART.  I'll have been on ART nearly 2 years by the time they would want me.   The fact I was on the CCR5 blocking cenicriviroc for so long and started so early gives me a decent chance at least.   I was told I was the healthiest patient in every program they have across the board too.   So pending my qualification for Calimmune, and they call me,  I'll consider it a double experiment!

I'm pretty sure I was told the Calimmune trial requires you to actually have a detectable VL before they'll treat you.    What if I remain UD month after month?  I would imagine they want test groups to be detectable so they can rule out the potential Post-treatment controller anomalies

________________________________________________

Regarding methotrexate, the NIH states methotrexate may cause serious side effects including death.  You should only take methotrexate to treat life threatening cancer or certain other conditions that cannot be treated with other medications.

Bulsulfan, while not as dire as methotrexate can cause a severe decrease in blood cells in your bone marrow and has been shown to increase the risk that you will develop other cancers.  It is considered a class 1 carcinogen.
Don't be fancy, just get dancey

Offline buginme2

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It's highly doubtful the fda would allow a study to use methotrexate to treat hiv.  Kenya must not have as strict a regulatory system to protect patients.
Don't be fancy, just get dancey

Offline POZnLA

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I just had an interesting discovery.    Anyone that volunteers for a clinical trial that has you STOP your ART (such as Calimmune) might actually be doing TWO experiments.  .......  .................  ..............  .................................................  .................  ........................
I need to STOP taking my meds several weeks before I get treated via Calimmune.    I never imagined that I might remain undetectable after I stop ART.  I'll have been on ART nearly 2 years by the time they would want me.   The fact I was on the CCR5 blocking cenicriviroc for so long and started so early gives me a decent chance at least.   I was told I was the healthiest patient in every program they have across the board too.   So pending my qualification for Calimmune, and they call me,  I'll consider it a double experiment!

I'm pretty sure I was told the Calimmune trial requires you to actually have a detectable VL before they'll treat you.    What if I remain UD month after month?  I would imagine they want test groups to be detectable so they can rule out the potential Post-treatment controller anomalies


The Calimmune study does not have you stop your ART, what they do is look for persons that have already stopped at least 6 weeks prior to thier 1st screening.

copy and paste from the study posting of inclusion requirements
__________________________________________________________

* Not taking antiretroviral therapy for ≥ 6 weeks prior to Screening 1, for one or more of the following reasons:

i) Concerns over short-term or long-term toxicities associated with antiretroviral agents, or ii) Treatment fatigue from the daily regimen of life-long therapy
____________________________________________________________

Now if you wanted to be in the study, you may first stop because you have these concerns. I stopped my ART meds at the recommendation of my Dr. because of severe allergic reactions to my meds,  I am scheduled for screening and study procedures this summer.

Offline JazJon

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I almost forgot about that important part.  It's true, they can't ethically ask you to stop taking your meds.    It's assumed you will and want to stop taking meds for "other" reasons before hand.    (such as the one you listed)

"i) Concerns over short-term or long-term toxicities associated with antiretroviral agents, or ii) Treatment fatigue from the daily regimen of life-long therapy"
((works for me))

Offline SFGMOMO

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I hope the Group 1 data is shared right away, or a Group 1 person chimes in on here. (or if anyone else hears an update they can share)

I very much appreciate the info being shared here -- the folks at Quest tell me I'm the first participant in Group 1 in San Francisco, so hopefully I'll have something worthwhile to contribute soon.  So far I've completed all the screenings, and the first apheresis was this week.  I agree it's an exciting study, and am looking forward to learning about the results.

Offline JazJon

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I very much appreciate the info being shared here -- the folks at Quest tell me I'm the first participant in Group 1 in San Francisco, so hopefully I'll have something worthwhile to contribute soon.  So far I've completed all the screenings, and the first apheresis was this week.  I agree it's an exciting study, and am looking forward to learning about the results.

Excellent!
Welcome to the forums.
We're looking forward to hearing how it goes.
Did the medicine you took pre-apheresis to release stem cells cause much discomfort?
I heard it might make your bones ache a bit. 
How long was apheresis? 1,2,3 hours?
« Last Edit: May 10, 2013, 03:02:24 PM by JazJon »

Offline SFGMOMO

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Excellent!
Welcome to the forums.
We're looking forward to hearing how it goes.
Did the medicine you took pre-apheresis to release stem cells cause much discomfort?
I heard it might make your bones ache a bit. 
How long was apheresis? 1,2,3 hours?
The first apheresis (about 3 hours, and other than a couple of painful initial jabs, not all that bad) was just for T-cells, rather than stem cells, so no prep med (Neupogen) necessary -- that's for apheresis #2 (end of next week).    That one's supposed to be longer (5-6 hours), but having been through it once, I'm not as apprehensive as I was about this week's (okay, so I admit I almost fainted, but that lidocaine needle hurt like hell!).

Thanks for the welcome -- looking forward to staying in touch!

Offline Hoyland

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Quote
Thanks for the welcome -- looking forward to staying in touch!

I wish you well SFGMOMO. You could be chronicling a history making event in the annals of HIV treatment. Good luck.

Offline freewillie99

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The first apheresis (about 3 hours, and other than a couple of painful initial jabs, not all that bad) was just for T-cells, rather than stem cells, so no prep med (Neupogen) necessary -- that's for apheresis #2 (end of next week).    That one's supposed to be longer (5-6 hours), but having been through it once, I'm not as apprehensive as I was about this week's (okay, so I admit I almost fainted, but that lidocaine needle hurt like hell!).

Thanks for the welcome -- looking forward to staying in touch!

Best of luck to you as well, SFGMOMO.  Hopefully since Calimmune isn't a publicly traded company you'll be able to get away with posting updates as you move through the process.

Signed,

A Charter Member of the Club for Junior Scientists
Beware Romanians bearing strange gifts

Offline Tadeys

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Can anybody tell me the diference between Calimmune and Benitec? Are they both working on HIV?  Benitec licences their RNAi technology to Calimune? Thank you.

Offline Hoyland

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Quote
Can anybody tell me the diference between Calimmune and Benitec? Are they both working on HIV?  Benitec licences their RNAi technology to Calimune?

Benitec is an Australian company that has exclusive rights to a technology call DNA Directed RNA Interference or ddRNAi which was developed by the Commonwealth Government Scientific Research Organisation, CSIRO. This technology is a way of turning off genes which make unwanted proteins and because it works at the DNA level in the cell the effect can be passed on through cell division thus providing a lasting "turning off" effect. This technique can be used to treat many types of diseases including HIV, HCV. HBV and various cancers.

3/4 years ago Benitec did a Pl trial in conjunction with the City of Hope for the application of the technology against HIV. This proved that the treatment was safe, however, the level of engraftment (the number of modified patient cells affected by the treatment and re-introduced to the patients) was low and so more work was required to increase the efficiency of the treatment. CoH is still conducting this work and there is a Pll program that they are working on for patients with HIV and Non-Hodgkin Lymphoma.

That said, one of the five patients treated in the Pl trial continues to have increased numbers of modified cells in their body and in theory eventually could be permanently free of the disease without any further intervention.

Benitec is no longer funding this research but one of its scientific advisors, Dr John Rossi, is still very much involved.

Calimmume has connections to Australia. They have a lab at the Uni New South Wales which is also used by Johnson and Johnson. Benitec are also using the labs at the UNSW to develop their Non-Small Cell Lung Cancer treatment. As Calimmune were working with ddRNAi as a possible treatment for HIV, albeit that their genetic constructs are different to that used by Benitec/CoH, they decided to licence ddRNAi from Benitec for the treatment of HIV.

So HIV is no longer Benitec's primary focus for the application of ddRNAi; it has left that to Calimmune, its licencee, which does have a cure for HIV as its primary goal.

UC Davis also has a ddRNAi HIV program that has been recommended for a clinical trail. This program is being run by Dr Joseph Anderson but the last I heard they have yet to secure funding. This program is very similar in its approach and targets as the CoH research.

Next year a team in Europe will start a clinical trial using ddRNAi to treat HIV. They will apply the technology in a different way to Calimmune but still with the hope of providing a single (or very limited) treatment for a complete cure from HIV.

I hope this answers your question Tadeys.

Offline POZnLA

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Benitec is an Australian company that has exclusive rights to a technology call DNA Directed RNA Interference or ddRNAi which was developed by the Commonwealth Government Scientific Research Organisation, CSIRO. ............................................... . . .         ................ ................   .......  .............. .  . . . .  .  ...................

Next year a team in Europe will start a clinical trial using ddRNAi to treat HIV. They will apply the technology in a different way to Calimmune but still with the hope of providing a single (or very limited) treatment for a complete cure from HIV.

I hope this answers your question Tadeys.

Thank you very much, a great explanation, and It is appreciated that you took the time to explain.

Offline POZnLA

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I very much appreciate the info being shared here -- the folks at Quest tell me I'm the first participant in Group 1 in San Francisco, so hopefully I'll have something worthwhile to contribute soon.  So far I've completed all the screenings, and the first apheresis was this week.  I agree it's an exciting study, and am looking forward to learning about the results.

SFGMOMO, Thanks for joining and posting. And most of all thanks for being the lead on this study.

If I understand correctly, I am the 4th, or last subject of the 1st Cohort. I was originally to be the 1st of the 2nd Cohort, I think some one dropped out and I was moved forward.

I am scheduled for my first of 2 screenings here in LA at UCLA Center for Clinical AIDS Research this coming June 10th, 2nd Screening June 26th. Assuming all goes well with the screenings 1st apheresis is July 5th, and then 5 days of Neupogen before the 2nd apheresis on July 19th.

Each study subject is done one at a time because the lab can only modify and grow one subject at a time. After the 1st cohort is finished there is a safety review before the 2nd cohort begins, again as I understand it.

Offline Tadeys

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Thank you Hoyland  ;)

It's good to know that there are other gene therapy trials under way.  Dr John Rossi says in an interview--on Youtube--, that a breakthrough using this technology will be just explosive. I agree. But not just for HIV, but for many, many, diseases.

Cheers

Offline Hoyland

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Sangamo has just released its data on the use of Zinc Fingered Nuclease against HIV. This was presented to the ASGCT and while some positives can be taken from the results, reading between the lines, I suspect that they are disappointed with the degree of engraftment. This was the same problem that CoH/Benitec encountered and one that CoH is still working on.

This makes the Calimmune trial even more important because CoH have spent the last three years on improving engraftment for their version of ddRNAi and if Sangamo are forced to do the same for ZFN that will be a major setback.

Hopefully, Calimmune has cracked that problem and Cal-1 will prove to not only be safe but efficacious too.

 


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