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Author Topic: Gene may be key to neutralizing HIV, researchers say  (Read 5661 times)

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Offline jportland

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« Last Edit: September 04, 2008, 04:47:05 PM by jportland »
2001 tested neg
8/2002  seroconvert
9/2002 Tested Poz
No Meds
2/2003 302/25% 76K
9/2004 463/23% 14K
8/2005 342/22% 19K
7/2006 381/29% 24K
3/2007 386/34% 34K
3/2008 230/21% 269K
3/2008  Started Meds
7/2008 485/23% VL 140
9/2008 465/24% VL Undetectable
1/2010 581/29% VL Undectectable

Offline bimazek

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #1 on: September 04, 2008, 05:33:26 PM »
http://www.medpagetoday.com/HIVAIDS/HIVAIDS/tb/10788

30-year-old mystery in retrovirus biology and in the process made a discovery that might impact future development of HIV vaccines

this is definately a huge discovery, because even fauci said
""This research delineates a potential genetic mechanism behind the production of neutralizing antibodies to HIV, which are critical to preventing HIV infection," he said in a statement.
"Further research on the function of human Apobec3 could yield promising insights that inform the discovery of HIV drugs and vaccines," Dr. Fauci said.
An inactive gene may be the reason why most people infected with HIV don't produce effective neutralizing antibodies to the virus, researchers here said.
Action Points 

    * Explain to interested patients that neutralizing antibodies are the body's first line of defense against infection, but that most people do not produce them in response to HIV.
    * Note that this study -- in mice -- suggests that a gene called Apobec3 plays a role in producing antibodies to retroviruses, which may allow new approaches to an HIV vaccine.
Their studies -- conducted in mice -- suggest that a gene called Apobec3 plays a central role in producing antibodies to retroviruses, according to Warner Greene, M.D., Ph.D., of the Gladstone Institute of Virology and Immunology at the University of California San Francisco, and colleagues.

But the finding also opens the door to new approaches to an HIV vaccine, a process that has been fraught with difficulty.
"We set out to solve a 30-year-old mystery in retrovirus biology and in the process made a discovery that might impact future development of HIV vaccines," Dr. Green said in a statement. "Science really is full of unexpected twists and turns."
Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, also pointed to the potential for blunting the HIV pandemic.
"This research delineates a potential genetic mechanism behind the production of neutralizing antibodies to HIV, which are critical to preventing HIV infection," he said in a statement.
"Further research on the function of human Apobec3 could yield promising insights that inform the discovery of HIV drugs and vaccines," Dr. Fauci said.

The authors pointed out that "the human Apobec3 family has been implicated in the control of HIV-1 infection, but HIV-1 encodes Vif, which thwarts the actions of Apobec3G (A3G) and Apobec3F (A3F)."

"Compromised A3G/A3F antiviral activity may therefore contribute to the generally poor neutralizing antibody response observed in HIV-1 infection," they continued. "Vif antagonists, if and when they are available, may enhance the generation of effective humoral immune responses against HIV-1."

http://www.reuters.com/article/scienceNews/idUSN0443071820080904

DEtailed science here...................................................................

http://www.jem.org/cgi/content/abstract/203/1/41

http://www.retrovirology.com/content/5/1/75

http://www.genengnews.com/news/bnitem.aspx?name=41307805

"These findings add a new and quite unexpected dimension to our understanding of Apobec3 biology that might help us attack the HIV neutralizing antibody problem, an area where scientific progress has been slow," says Warner C. Greene M.D., Ph.D., director of the Gladstone Institute of Virology and Immunology and the study's principal investigator.  The idea that Apobec3 can influence not only the ability of HIV to cause infection but also antibody responses to the virus is supported by a previous study demonstrating that the human chromosomal region containing several Apobec3 genes is linked to anti-HIV antibody responses in a group of Italian subjects who were repeatedly exposed to the virus by their HIV-infected partners but remained uninfected.  the new research by the Gladstone Institute and NIAID is also intriguing in light of an earlier study demonstrating that HIV uses one of its own proteins, Vif, to destroy two human Apobec3 proteins. Given that Apobec3 seems to help the immune system make neutralizing antibodies against retroviruses, the destruction of Apobec3 proteins by Vif might help explain why most people do not make neutralizing antibodies against HIV. "Our mouse studies suggest that neutralization of Vif could provide the unexpected benefit of better antibody responses to HIV and therefore better control of HIV infection," says Dr. Kim Hasenkrug, chief of the retroviral immunology section at NIAID's Rocky Mountain Laboratories and the study's lead NIAID investigator. "We knew that Apobec3 had very interesting antiviral properties, but this new discovery that it affects antibody responses will generate even greater interest in both Apobec3 and Vif."


http://www.google.com/search?q=Apobec3

http://www.ncbi.nlm.nih.gov/pubmed/18448535
2008 Jul;82(13):6566-75. Epub 2008 Apr 30.Click here to read Links
    Interactions of murine APOBEC3 and human APOBEC3G with murine leukemia viruses.
    Rulli SJ Jr, Mirro J, Hill SA, Lloyd P, Gorelick RJ, Coffin JM, Derse D, Rein A.
 HIV Drug Resistance Program, National Cancer Institute-Frederick, Frederick, MD 12702-1201, USA.
    APOBEC3 proteins are cytidine deaminases which help defend cells against retroviral infections. One antiviral mechanism involves deaminating dC residues in minus-strand DNA during reverse transcription, resulting in G-to-A mutations in the coding strand. We investigated the effects of mouse APOBEC3 (mA3) and human APOBEC3G (hA3G) upon Moloney murine leukemia virus (MLV).

http://www.jem.org/cgi/content/abstract/203/1/41
lethal activity against human immunodeficiency virus (HIV). Packaged into progeny virions, APOBEC3G enzymatic activity leads to HIV DNA degradation. As a counterattack, HIV virion infectivity factor (Vif) targets APOBEC3G for proteasomal proteolysis to exclude it from budding virions. Based on the ability of APOBEC3G to antagonize HIV infection, considerable interest hinges on elucidating its mechanism(s) of regulation. In this study, we provide the first evidence that an innate, endogenous host defense factor has the potential to promote APOBEC3G and rebuke the virus-mediated attempt to control its cellular host. We identify interferon (IFN)-{alpha} as a potent inducer of APOBEC3G to override HIV Vif neutralization of APOBEC3 proteins that pose a threat to efficient macrophage HIV replication. Our data provide a new dimension by which IFN-{alpha} mediates its antiviral activity and suggest a means to render the host nonpermissive for viral replication.

http://www.informatics.jax.org/searches/accession_report.cgi?id=MGI:1933111
Apobec3 Gene Detail
 Symbol NameID    
Apobec3=
apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3

http://jvi.asm.org/cgi/content/abstract/79/13/8201
While members of the APOBEC3 family of human intrinsic resistance factors are able to restrict the replication of Vif-deficient forms of human immunodeficiency virus type 1 (HIV-1), they are unable to block replication of wild-type HIV-1 due to the action of Vif, which induces their degradation. In contrast, HIV-1 Vif is unable to block inhibition mediated by APOBEC3 proteins expressed by several heterologous species, including mice. Here, we have asked whether the simple retrovirus murine leukemia virus (MLV) is sensitive to restriction by the cognate murine or heterologous, human APOBEC3 proteins.

http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0002315
The APOBEC family members in the mouse that have RNA or DNA deaminase activity, or both are: APOBEC1, APOBEC2, APOBEC3 and AICD (activation-induced cytidine deaminase; also known as AID). The function of APOBEC2 is not known. It is expressed mainly in muscle cells [18] and has lower, but still detectable cytidine deaminase activity compared to APOBEC1. APOBEC3, is expressed in the testes, adult germ cells [19] and a wide variety of tissues. Human APOBEC3 is able to hypermutate the cDNA derived during replication of exogenous and endogenous retroviruses in cells. Thus APOBEC3 inhibits viral replication [20] and functions to maintain innate immunity of cells. AICD is found mainly in B-cells and is involved in class-switch recombination and somatic hypermutation of antibody genes [21]. Deamination within the immunoglobulin loci by AICD initiates antibody gene diversification. A new Apobec gene family member, Apobec4 was recently identified by genomic analysis but its protein and enzyme function has not been determined [22]. Mice and humans encode one gene each for APOBEC1, APOBEC2, APOBEC4 and AICD. The mouse genome also encodes one Apobec3 gene on chromosome 15. However, in humans there has been an expansion of the APOBEC3 gene family such that eight APOBEC3 genes are tandemly encoded on human chromosome 22q13.1 [17], [19]. These genes are designated APOBEC3A to APOBEC3H. Of these, APOBEC3G and APOBEC3F have been extensively studied because of their ability to restrict human immunodeficiency virus (HIV)

« Last Edit: September 04, 2008, 05:49:33 PM by bimazek »

Offline newt

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  • the one and original newt
Re: Gene may be key to neutralizing HIV, researchers say
« Reply #2 on: September 04, 2008, 07:32:52 PM »
I am not a mouse

While mouse models have value, in the final analysis, I am not a mouse. I have seen enough interesting, even stunning, bits of science that works for mouses but not for humans, to, er, reach for the deckchair and whisky at this point.

I am not above hope* but I am not below realism either. Especially when there are no phase II or phase III studies of a therapeutic approach translating this basic science into effective therapy in humans.

- matt


* indeed, I have a great deal of hope as it happens
"The object is to be a well patient, not a good patient"

Offline bimazek

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #3 on: September 05, 2008, 01:44:52 AM »
personally i think that since 20 or 30 people are dying every day in USA from hiv they should be able to try things on a much much more accelerated basis, but somehow that is not allowed, medical ethics do not allow random trail and error, everything has to be approved by a committee, even though if you look at history in 1776 the presidents wife allowed her on children to be experimented on for a primitive vaccine, did you see the movie john adams, i think that if a Doctor tells someone, things are very bad, there is nothing more we can do with approved medicines and it is only a matter or weeks, or months before death,  that the INDIVIDUAL should have the right to try anything they want --
i mean the reality is so so many people are killing themselves in a kind of suicide with heavy chemical hard street drugs, and smoking, and heavy heavy drinking -- seems it would make sense to me that someone
should have the option to at least try something experimental

but that is not way it works, it takes hundreds of millions of dollars and many many years and so
15,000 per year will die in USA alone from hiv every year

that would be 15,000 tests of 15,000 different experiments, and you are right they can only be really tested in a human, a mouse or a simian is not a perfect model and very expensive

i guess the issue is that the Dr. that gives the person access to the experiment has a real true responsibility and ethical giant hurdle and the Dr. does not want to damage his reputation, but can there not be some special category of

compassionate use for hiv- people who are dying - who all the meds have stopped working
http://www.google.com/search?hl=en&q=compassionate+use&start=10&sa=N

single-patient compassionate use medicine
 Physicians can receive permission to use an unapproved drug for a single patient. This consent, called emergency use and sometimes referred to as single-patient compassionate use, is granted if the situation is desperate and no other treatment is available. The FDA also sometimes grants approval to acquire drugs from other countries that are...

I believe any person should be allowed to put any drug or medicine in thier body if it does not hurt another person

it would accelerate research

it is kind of like a sacrifice like Jesus sacrifice on the cross for many other people

why has this concept of sacrifice become taken out of our rights as usa citizens?

many big big issues

but the truth is many are still dying, and we are not as different from a small animal as many would think

for example

did you know that all vertebrates start out in the womb as females -  all men were females in the dev. process in the womb --  then the clitoris elongates and the urethra rises up and the clitoris gets bigger and surrounds the urethra and forms the penis, also all females at the start in the womb are designed as sexually attracted outwardly toward and to the other - then there is a shock in the 5th month of pregnancy that turns the attraction of the newly created male back toward a female, for gay and bi - the change does not take place

info from

http://www.amazon.com/Evolutions-Rainbow-Diversity-Gender-Sexuality/dp/0520246799/ref=sr_1_1?ie=UTF8&s=books&qid=1220594015&sr=8-1

From Publishers Weekly
This brilliant and accessible work of biological criticism has the potential to revolutionize the way readers conceive of gender and sexuality in the natural world. Roughgarden, a professor of biology at Stanford University and a member of the Academy of Arts and Sciences, argues that the diversity of gender and sexuality one finds in many species suggests that evolutionary biologists of a strictly Darwinian bent are often misguided, since, according to Roughgarden, they erroneously assume a universally applicable gender binary in all species. The first half of the book brings that sexual diversity to light through innumerable examples among birds, reptiles, fish and mammals provided in highly readable anecdotes. The significance of this first section lies not only in this startlingly original portrait of nature, but also in how it suggests that contemporary Darwinian sexual selection theory is in part a result of cultural bias, since it "predicts that the baseline outcome of social evolution is horny, handsome, healthy warriors paired with discreetly discerning damsels." Roughgarden critiques this theory through an expansive study of biological scholarship, highlighting the frequent contradictions between such claims and the data used (and, she argues, manipulated) to prove them. The second and undoubtedly more controversial section discusses sexual diversity in humans. Taking as a given the presence in our own species of gay, lesbian, bisexual, transgendered, transsexual and intersex persons, she reads current scientific writing-on a supposed "gay gene," on gender reassignment and other issues-through a perspective that sees diversity as an advantage, not a handicap. Readers more accustomed to traditional categories of gender and sexuality in humans will undoubtedly be surprised at how different a portrait emerges from Roughgarden's deeply personal and insistently ethical point of view.
« Last Edit: September 05, 2008, 01:58:33 AM by bimazek »

Offline leit

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #4 on: September 05, 2008, 07:29:25 AM »
All things considered, I agree with you, "bimazek": Many accurately selected, both scientifically and ethically, small and quick "proof-of-concept" trials.
A trial gives some *clear* result? Ok, let's go on! It doesn't? Throw everything away and that's it.

They cannot spend tons of money and years to carry other MRKAd5-like trials to a phase IIb complete failure that one could probably have sensed before.

« Last Edit: September 05, 2008, 08:17:35 AM by leit »

Offline bimazek

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #5 on: September 05, 2008, 11:45:37 PM »
very very very very very very very very very very very very good point and i didnt even think of that, the huge amount of money and trying that clinical trial all over the world at the same time,
what a waste, could have tried on a small group, i agree with your point

small human trials for all the many new things in development

and people who are hiv and failing all meds should get the compassionate use option of trying something new

what activism is needed

Offline bocker3

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  • You gotta enjoy life......
Re: Gene may be key to neutralizing HIV, researchers say
« Reply #6 on: September 06, 2008, 10:54:16 AM »

what activism is needed

Here's an idea -- why don't you and Leit stop scouring the net for all that is wrong in the world and go be an activist!  or better yet -- go and volunteer to be a guinea pig for every "major, major, major breakthrough" that you litter this site with.  You can bitch all you want on AidMeds, but you really are no better than everyone you keep railing against if this is ALL YOU DO.   ::)

Why do scientists insist on large, random human trials??  Ethics and.............  LAWSUITS -- big fat $100,000,000+ lawsuits that would be filed by those hurt in a "bad experiment" or by their surviving heirs.  These suits make the papers all the time -- pull your head out of the internet and you'll see them.

Bim -- you keep bringing up the people dying in the US -- many (maybe most, I don't know) die because they either did not take their meds (substance abuse, mental health issues interfere) or got diagnosed way too late to be saved.  Yes, some have no real options for meds, some can't access them -- I suspect they are a small part of your numbers though.  Compassionate use of experimental therapies for these folks can and do happen.
Who the hell is going to roll the dice on an unproven, potentially lethal, experiment when there are proven ways to live with this virus.

Mike
Atripla - Started 12/05
Reyataz/Norvir - Added 6/06
Labs - Pre-Meds
Sep05 T=350/25% VL98,559
Nov05 288/18%  47,564
Current Labs
May2013 691/31% <20

Offline sunzidog

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #7 on: September 06, 2008, 11:40:17 AM »
Great points, Bocker.
« Last Edit: September 06, 2008, 11:42:09 AM by sunzidog »
Infected 01/02/07
03/07: VL<3800 CD4s 506 (Started Atripla)
04/07: VL<500 CD4s 585
05/07: VL<500 CD4s 606
07/07: VL<50 CD4s 1000

Offline leit

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #8 on: September 06, 2008, 12:12:57 PM »
Great points, Bocker.

Oh yes, really GREAT!!! ;D

« Last Edit: September 06, 2008, 12:22:27 PM by leit »

Offline leit

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #9 on: September 06, 2008, 12:23:11 PM »

why don't you and Leit stop scouring the net for all that is wrong in the world and go be an activist!

Because the USA are the center of the world and "Leit" doesn't live there.
Moreover, criticism and discussion are always far from useless.

Quote
or better yet -- go and volunteer to be a guinea pig for every "major, major, major breakthrough"

Why not? For instance, I wouldn't have had any problem to do like Dr. Hütter transplanted patient.
Present "activists", on the contrary, seem not to care whether the virus was eradicated from this patient or he had a clinical remission, or what else, even if it would be THE FIRST TIME that an HIV+ person has been CURED (or "funtionally cured" - the latest Fauci's gimmick).

Quote
Why do scientists insist on large, random human trials??  Ethics and.............  LAWSUITS -- big fat $100,000,000+ lawsuits that would be filed by those hurt in a "bad experiment" or by their surviving heirs.

I see: "big fat $100,000,000" to thousands of people each are LESS than to dozens!  :D
And, anyway, I spoke of "accurately selected, both scientifically and ethically, small and quick 'proof-of-concept' trials", not of "every 'major, major, major breakthrough'".

Quote
Who the hell is going to roll the dice on an unproven, potentially lethal, experiment when there are proven ways to live with this virus.

Some recent headlines from "AIDSmeds Treatment News":
- PAD [peripheral arterial disease] Common in HIV-Positive Patients Over 50
- Norvir and Heart Conduction Disturbances
- Worsening Depression in Four Patients on Isentress
- SMART Study Findings on Abacavir and Cardiovascular Risk
- PML Still a Risk and Often Progressive
- Rapid Hep C Disease Progression in HIV-Positive Men
- Suicidal Thoughts Common in People With HIV


Former activists left us a much better future. Now, people that don't give a damn and flatter themselves thinking that HAART is the solution risk to prepare a disaster for those to come.

« Last Edit: September 06, 2008, 01:44:14 PM by leit »

Offline Miss Philicia

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #10 on: September 06, 2008, 12:28:13 PM »
Because the USA are the center the world and "Leit" doesn't live there.

So where do you live leit?  We'll all chip in and find an a organization in your home country that you can get involved with.

Thanks
"I’ve slept with enough men to know that I’m not gay"

Offline newt

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  • the one and original newt
Re: Gene may be key to neutralizing HIV, researchers say
« Reply #11 on: September 06, 2008, 02:34:26 PM »
Leit has highlighted perhaps the most important piece of science of the year (Treatment of HIV-1 Infection by Allogeneic CCR5-D32/D32 Stem Cell Transplantation: A Promising Approach- http://www.retroconference.org/2008/Abstracts/31704.htm) and I agree, the silence from most people who speak about these things was very loud, if these folk noticed the paper in the first place.

The frustration about laurel cushions I get too.

But on shorter trials etc, I disagree. Activists have helped set important precedents on balancing safety with shorter drug approval period. A big credit here.  The methods of already cut-down, drug development trials for HIV, need to be rigorous. Poisoning people, immediately or in 10 years ain;t a good result (even if good for some companies' share prices).

Combo, as an approach, can be improved. It is a good approach, and a significant advance, but not good enough.

If it is to be combo, we need people saying things like "Sustiva - would you prescribe this if it was an antibiotic with general indication for a broad range of infections?" To which the answer is no, it's side effect profile is lousy. Ahem >cough< it's 1st line standard of care. Yes, we need some energy directed at questions like this.

And if it is to be genes/vaccines etc, they need to (1) work (2) be safe (3) be practical. Which means proper (lengthy even) phase I, II, III and IV testing.

- matt 
"The object is to be a well patient, not a good patient"

Offline MYSTERY

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #12 on: September 06, 2008, 02:42:03 PM »
With all this arguing you guys are not going to die from hiv but a stroke. :o
Atheist don't believe in GOD, but GOD believes in them and loves them. Never let the failure of man conflict with your love of GOD.

Offline bocker3

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  • You gotta enjoy life......
Re: Gene may be key to neutralizing HIV, researchers say
« Reply #13 on: September 06, 2008, 02:48:35 PM »
Because the USA are the center of the world and "Leit" doesn't live there.
Moreover, criticism and discussion are always far from useless.

I agree -- but you aren't looking for discussion -- unless they agree with you.  All you do is criticize and restate your positions.

Quote
I spoke of "accurately selected, both scientifically and ethically, small and quick 'proof-of-concept' trials", not of "every 'major, major, major breakthrough'".
Go and learn the proper way to select the size of a study population to gain MEANINGFUL data.  A proof of concept is a very different animal from a phase 2 or 3 trial.  I do agree that compassionate access to those people out of options should be (and often is) available.  Moving forward with too small of a study is DANGEROUS.

Quote
Some recent headlines from "AIDSmeds Treatment News":
- PAD [peripheral arterial disease] Common in HIV-Positive Patients Over 50
- Norvir and Heart Conduction Disturbances
- Worsening Depression in Four Patients on Isentress
- SMART Study Findings on Abacavir and Cardiovascular Risk
- PML Still a Risk and Often Progressive
- Rapid Hep C Disease Progression in HIV-Positive Men
- Suicidal Thoughts Common in People With HIV

Yep -- HAART ain't easy on the body -- but if it kills me in 10, 20, 30 yrs -- I've still had a far better outcome than if it wasn't here. 

Quote
Former activists left us a much better future. Now, people that don't give a damn and flatter themselves thinking that HAART is the solution risk to prepare a disaster for those to come.
I agree and am VERY thankful for the activists who helped lead the way to the development of <gasp, could it be true> HAART.  I am alive because of them.  I, also, do not think that HAART is the final answer, nor do I think we shouldn't be looking for a better way to treat and, someday, cure this virus.  However, I will also not overlook the tremendous benefits that exist from HAART -- Nor will I subscribe to the grand conspiracy theories being thrown around that BIG PHARMA is or would supress any advance that might lead to the end of a need for HAART.  It is pure fantasy and would be a bad business move -- imagine the prestige and MONEY that the company who finds a cure would make from it -- you see finding a cure won't necessarity eradicate the disease formt he face of the earth.  Perhaps eventually, but not for a while and in the meantime, their "cure" will be in demand.

Mike


[/quote]
Atripla - Started 12/05
Reyataz/Norvir - Added 6/06
Labs - Pre-Meds
Sep05 T=350/25% VL98,559
Nov05 288/18%  47,564
Current Labs
May2013 691/31% <20

Offline leit

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #14 on: September 06, 2008, 05:54:35 PM »

With all this arguing you guys are not going to die from hiv but a stroke. :o

I fear you will be right, seriously.


Offline leit

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #15 on: September 06, 2008, 06:07:58 PM »

the silence from most people who speak about these things was very loud

Right, but silence was however much better than disgraceful comments like Tae-Wook Chun's (a Fauci's associate - as if their approach was realistic!!!): "It's interesting, but the bigger picture is that doing stem cell transplants is not a realistic approach for curing AIDS." Period.

Quote
if these folk noticed the paper in the first place.

As you know, the paper was "discovered" (or "co-discovered") by Martin Delaney, a long time AIDS activist. I'd like to believe he has informed "these folks".
Nevertheless, no following peer review nor updates, to my knowledge (nor some German activist visting doctor Hütter and reporting). And I cannot accept that research slows down even just a bit because of vanity, envy, laziness, ineptitude or dishonesty of anybody.

Quote
But on shorter trials etc, I disagree. Activists have helped set important precedents on balancing safety with shorter drug approval period.

I'd like to be crystal clear about that. I spoke of "proof-of-concept" trials, meaning the opposite of making DESIGNEDLY SLOW AND BADLY/VAGUELY DESIGNED myriads of phases and subphases (phase I of Bionor Immuno's Vacc-4x was a masterpiece, but unfortunately it has been deleted from http://www.clinicaltrials.gov/), so that the results are kept messy and/or partial and/or impossible to evaluate AS LONG AS POSSIBLE.
IMHO, this has nothing to do with safety, but is only a dirty trick to increase one's number of publications or issue the usual hyped press releases.

Quote
Combo, as an approach, can be improved.

I totally agree with you. And, more than anything else, combo is a STEP, not a goal, as Siliciano stated loud and clear at the last IAC.

Quote
If it is to be combo, we need people saying things like "Sustiva - would you prescribe this if it was an antibiotic with general indication for a broad range of infections?" To which the answer is no, it's side effect profile is lousy. Ahem >cough< it's 1st line standard of care. Yes, we need some energy directed at questions like this.

Yes, I also think that, except NRTI like 3TC, FTC and maybe some others, none of the drugs we take would have been approved if it wasn't an anti-HIV drug.
And what about the trick to boost drugs having a poor pharmacokinetics by inhibiting cytochrome P450 with ritonavir? Quite poisoning, uh?!

Anyway, these steps forward are Pharma's business. I think that the main task of public research is making a jump.



P.S. "bocker3", your last message is very stimulating. I'm going to reply you as soon as I can.

« Last Edit: September 06, 2008, 06:10:43 PM by leit »

Offline leit

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« Reply #16 on: September 06, 2008, 06:09:23 PM »
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Offline MYSTERY

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #17 on: September 06, 2008, 06:11:44 PM »
I will say however that you guys do a wonderful job in providing information and I appreciate it.
Atheist don't believe in GOD, but GOD believes in them and loves them. Never let the failure of man conflict with your love of GOD.

Offline newt

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #18 on: September 06, 2008, 06:35:24 PM »
Quote
stem cell transplants is not a realistic approach for curing AIDS.

This is true

But as a proof of concept paper this is dammit some of the most interesting science I have ever seen

I agree with all the rest of your comments btw

- matt
"The object is to be a well patient, not a good patient"

Offline leit

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #19 on: September 06, 2008, 07:25:59 PM »

> stem cell transplants is not a realistic approach for curing AIDS.

This is true

IMHO, it isn't so important whether it's true or not: Perhaps not such radical intervention as those done on Dr. Hütter patient - who had a relapse of acute myeloid leukemia, too! - is needed for a "simple" HIV infection. And this is one of the many things that only a peer-review can ascertain.

Quote
But as a proof of concept paper this is dammit some of the most interesting science I have ever seen

I believe it: It would be THE FIRST TIME that an HIV+ patient has been CURED ON THE BASIS OF A RATIONALE (not miraculously saved by the still indefinite genetic makeup that makes a person an elite controller or so)!!!

« Last Edit: September 06, 2008, 07:29:25 PM by leit »

Offline leit

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #20 on: September 08, 2008, 02:31:03 AM »

I will also not overlook the tremendous benefits that exist from HAART

Wait a moment, please! IMHO, we are only beginning to realize what the "new disease HIV+HAART" is (and sometimes, I only hope I'll not have to look back with nostalgia to when one could die from a sharp and quick AIDS PCP).

Quote
Nor will I subscribe to the grand conspiracy theories being thrown around that BIG PHARMA is or would supress any advance that might lead to the end of a need for HAART.

Please believe me if I say that conspiracy theories have always been completely out of my cast of mind.
BUT... it's undeniable that there are some inexplicable facts. I'll tell a recent couple of them:

- Koronis' KP-1461. Well, after thinking and rethinking, it seemed to me that the least implausible explanation of what happened is that someone told to Koronis: "I give you X dollars if you state that EVERYTHING was wrong and give all up". I'll be glad if you suggest a more realistic alternative.

- No funds for "a major discovery on a unique group of patients who control HIV without medication, [...] even though the potential savings is more than $14,000 annually per patient". Well, I don't know how much "major" this discovery really was, how much it was suitable for a quick clinical application, nor how much those funds would be amounted to, but I DO know that the US Parliament devolved 10 million dollars to a foreigner stillborn "HIV vaccine" (Ensoli's anti-TAT).

I hope you agree there is something inexplicable in facts like these...


Offline bocker3

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #21 on: September 08, 2008, 07:59:30 AM »
Please believe me if I say that conspiracy theories have always been completely out of my cast of mind.
BUT... it's undeniable that there are some inexplicable facts. I'll tell a recent couple of them:

- Koronis' KP-1461. Well, after thinking and rethinking, it seemed to me that the least implausible explanation of what happened is that someone told to Koronis: "I give you X dollars if you state that EVERYTHING was wrong and give all up". I'll be glad if you suggest a more realistic alternative.

- No funds for "a major discovery on a unique group of patients who control HIV without medication, [...] even though the potential savings is more than $14,000 annually per patient". Well, I don't know how much "major" this discovery really was, how much it was suitable for a quick clinical application, nor how much those funds would be amounted to, but I DO know that the US Parliament devolved 10 million dollars to a foreigner stillborn "HIV vaccine" (Ensoli's anti-TAT).

I hope you agree there is something inexplicable in facts like these...
I do agree that someting strange is going on here...  However, I am not prepared to make a leap that because something is inexplicable it means there is something nefarious going on.
Why did Koronis change so drastically -- I haven't a clue.  However, I find it tough to believe that someone paid off a scientist to invalidate what could be a huge finding.  It IS unfortunate and it IS perplexing -- but a "pay-off" scenario??  I don't think so -- but I certainly can't say it did NOT happen that way -- it simply doesn't make sense that it happened like that IMO.

Now, I think your intent may be very good, but really -- you need to start looking for some good in things and not focus on the negatives all the time.  I have never heard anyone refer to the "new disease HIV+HAART" or worry about potentially wishing "one could die from a sharp and quick AIDS PCP". 
If not for HAART, I may not have been here when my granddaughter was born 10 days ago.  If not for HAART I would certainly have missed out on the coming years of seeing all 4 of my grandchildren continue to grow older -- I would not have this continued time of GOOD HEALTH to be spending with my partner -- or be able to take my coming Transatlantic cruise from Lisbon to RIO, or lots of other experiences that I will have because I did not "die from a sharp and quick AIDS PCP".  If I end up dying from something that was HAART induced, so be it -- HAART has already stopped me from dying.  And.............  is allowing me to, perhaps, be here when the next big thing comes along to help people with this virus.  This is the sort of thinking that I am not seeing in your posts -- it is all so negative and sinister -- stress and a lack of hope may indeed kill you faster than any HAART induced complication.
Atripla - Started 12/05
Reyataz/Norvir - Added 6/06
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Offline leit

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #22 on: September 08, 2008, 12:28:25 PM »

you need to start looking for some good in things and not focus on the negatives all the time.

Not "all the time", "bocker3"! I was recently accused of being too optimistic and therefore damaging people (see threads concerning Siliciano/IAC).

Quote
I have never heard anyone refer to the "new disease HIV+HAART"

:) It was a tentative definition of mine, and I wasn't simply referring to HAART adverse effects. Perhaps I'd better have called it "the new host+HIV+HAART disease", whereas the "old HIV disease" is simply AIDS.

Anyway, what I meant is that it appears increasingly evident that the damage is done very early after the infection (consider gut-associated lymphoid tissue (GALT) depletion -> leaky gut -> elevated lipopolysaccharide in the bloodstream -> constant immune activation + contribution to brain damage, for instance) and that neither HAART nor the body then repair it.
The matter is not yet completely focused and they haven't yet come to a clear definition as for the classic AIDS, but I fear it will resemble that of an early, progressively accelerated ageing.

Quote
or worry about potentially wishing "one could die from a sharp and quick AIDS PCP".

Nobody can hear thoughts... :)

Quote
HAART [...] is allowing me to, perhaps, be here when the next big thing comes along to help people with this virus.

Let's hope it comes soon!!!


Finally, I'm truly glad there are many beautiful things in your life and you are able to enjoy them in despite of HIV. Keep going like that, please; I think is the wisest way (though not always within everybody's reach).


Offline bimazek

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #23 on: September 08, 2008, 05:55:35 PM »
If i was betting and on a gambling table, with the information i have read in last two years I would put most or all my bets on this new discovery for yielding a new great great treatment someday soon.
It even made it to the front page of aidsmeds website so it must be good, lol.
Actually reading what was on front of aidsmeds website today about Apobec3 gene and antibodies shows to me that the major breakthru it is ----- i mean guys they just found an antibody, that is naturally produced by human genes that stops hiv, but that gene in humans probably because of evolution is not very active and kind of dormant and if they can get it to produce antibodies, natural hiv fighters, then it is a great done deal, a good step forward
i would bet on this today
that is fun of science is new things are constantly coming out
antibodies are a bodies natural killers of infection
so this is a big thing -

"30-year-old mystery in retrovirus biology and in the process made a discovery that might impact future development of HIV vaccines
this is definately a huge discovery, because even fauci said
""This research delineates a potential genetic mechanism behind the production of neutralizing antibodies to HIV, which are critical to preventing HIV infection," he said in a statement.
"Further research on the function of human Apobec3 could yield promising insights that inform the discovery of HIV drugs and vaccines," Dr. Fauci said.
An inactive gene may be the reason why most people infected with HIV don't produce effective neutralizing antibodies to the virus, researchers here said.
Action Points
    * Explain to interested patients that neutralizing antibodies are the body's first line of defense against infection, but that most people do not produce them in response to HIV.
    * Note that this study -- in mice -- suggests that a gene called Apobec3 plays a role in producing antibodies to retroviruses, which may allow new approaches to an HIV vaccine.
Their studies -- conducted in mice -- suggest that a gene called Apobec3 plays a central role in producing antibodies to retroviruses, according to Warner Greene, M.D., Ph.D., of the Gladstone Institute of Virology and Immunology at the University of California San Francisco, and colleagues."




regarding me being an activist instead of reading science -- i prefer to read science, i did march in 80s and 90s in SF many times also in NYC, and not in gay parades, but in protests

also i am not into walking i like to swim

maybe i could swim across some body of water as a protest

really politics and protests are completely beyond my grasp having to deal with all those human egos

i like pure science and finding out the science

i initially started reading all the hiv science to see how far science was along and how bad the side effects of the meds that i would have to take would be and how long my true life expectancy would be
and if it made any sense for me to go to school and do research and add my small small tinu part to hiv research (it took hundreds of hours of reading but i quickly decided that science was very very close to huge breakthrus because of the human genome and because of robotic testing and gene testing and all the breakthrus that have been revealed in last 2 years and last 5 years)

science seems frightening to many on this site because it is not revealed yet, and it is new and changing every day and it deals with creativity and the mind

anyway if i was betting i would put all my chips on the new

APOBEC discovery

but that could change tomarrow

another thing is that the human immune system is NOT a linear system, it is not the sum of its parts, it is not a+b+C+D+E=x  it is so so complex like trying to tune a radio station or tv station with those old rabbit ear tuner on top of the tv, that is a complex system, you can move the antenna around and get a clear picture (lower VL) but when you step away or when the weather conditions change with time or many factors the picture goes bad again, that is why the gene therapy trials can give confusing results

but once they get it dialed in and get the right antenna and the right tuning and the right combo then it works

the immune system has trillions of moving parts, and they interact in trillions of ways
and you change one thing and it messes up another, but many approaches are getting very very close to a final solution

regarding living 10, 20 30 years longer of course we are all happy that haart exists and everyone should take haart but the side effects that my friends in a big city have had

and i have wanted to post about this in living with... but i dont want to scare anyone
but just look at the aids meds website head lines -- they are not sure if it is haart or damage from the virus

hip replacement
heart attack
artery plaque and stroke
leukemia
ks

so a natural antibody like the apobec could be a revolution
suppression of virus by the natural gene that the human body has for that purpose

exciting stuff




Offline leit

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #24 on: September 08, 2008, 07:46:12 PM »

i like pure science and finding out the science
[...]
anyway if i was betting i would put all my chips on the new
APOBEC discovery
but that could change tomarrow

Sorry, "bimazek", but, IMHO, in your situation you don't "like pure science and finding out the science", but you cling to the latest piece of news, hoping it's the one that will spare you the HAART.
This is not a correct, let alone critical, way of thinking.

P.S. You seem more terrified by the HAART than by the virus and the damage it has already done - that's absurd, believe me.


Offline Assurbanipal

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #25 on: September 08, 2008, 08:46:04 PM »
Wait a moment, please! IMHO, we are only beginning to realize what the "new disease HIV+HAART" is (and sometimes, I only hope I'll not have to look back with nostalgia to when one could die from a sharp and quick AIDS PCP).

Leit

I'm really puzzled by your post.  It appears to romanticize the ease of dying of AIDS and underestimates the improvements in both life and potentially even in death from HAART.  I started down the road of dying from PCP a couple of years ago and it was protracted and painful until it was eventually diagnosed -- and the path back was not particularly easy.  Frankly, I find it a little offensive for you to casually and inaccurately dismiss that experience in a forum where a lot of others had similar or worse experiences.

Having been there, I'd much rather be alive for the extra 10, 20 or 40 years I can get from HAART even with some side effects.  But someday we all die, and if my HAART-induced high cholesterol takes me off in a quick heart attack I suspect that may be easier on me and on those left behind than a classic AIDS death.

A
5/06 VL 1M+, CD4 22, 5% , pneumonia, thrush -- O2 support 2 months, 6/06 +Kaletra/Truvada
9/06 VL 3959 CD4 297 13.5% 12/06 VL <400 CD4 350 15.2% +Pravachol
2007 VL<400, 70, 50 CD4 408-729 16.0% -19.7%
2008 VL UD CD4 468 - 538 16.7% - 24.6% Osteoporosis 11/08 doubled Pravachol, +Calcium/D
02/09 VL 100 CD4 616 23.7% 03/09 VL 130 5/09 VL 100 CD4 540 28.4% +Actonel (osteoporosis) 7/09 VL 130
8/09  new regimen Isentress/Epzicom 9/09 VL UD CD4 621 32.7% 11/09 VL UD CD4 607 26.4% swap Isentress for Prezista/Norvir 12/09 (liver and muscle issues) VL 50
2010 VL UD CD4 573-680 26.1% - 30.9% 12/10 VL 20
2011 VL UD-20 CD4 568-673 24.7%-30.6%
2012 VL UD swap Prezista/Norvir for Reyataz drop statin CD4 768-828 26.7%-30.7%

Offline leit

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #26 on: September 08, 2008, 10:13:20 PM »

I started down the road of dying from PCP a couple of years ago and it was protracted and painful until it was eventually diagnosed -- and the path back was not particularly easy.  Frankly, I find it a little offensive for you to casually and inaccurately dismiss that experience in a forum where a lot of others had similar or worse experiences.

Dear "Assurbanipal",
- I was speaking ONLY for myself: "sometimes, I only hope I'll not have to look back with nostalgia to when one could die from a sharp and quick AIDS PCP"
- I only tried to express a sort of paradox (hoping it will always remain a paradox).

Anyway, please forgive me if I didn't manage to convey correctly what I meant and I offended you or other people.


P.S. I don't ever "romanticize" ANYTHING concerning HIV.


Offline bimazek

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #27 on: September 09, 2008, 04:02:20 AM »
regarding Ethics and..  LAWSUITS and trials --- the post above about big lawsuits if small clinical trials were allowed is completely false, because there are tons of clinical trials now that are giving 3 months, 7 months, 1,3,5 years of extra life to people with aids who are on salvage therapy (or have been on them in last few years when they were not approved yet) in major research univ. all over usa, and the docs , legal docs, they sign are like 35 pages long minimum so the lawsuits do not happen,

when lawsuits happen is after fda approves something

anyway -- the ethics is the same as the ethics of giving the two new classes of meds which were just approved but they have been testing them on people for years before approval,

so the huge amount of paperwork and the issues are the same -- it is a matter of trying things
and there are too many things to try and not enough money to bring them all to clinical trials
which costs tens of millions which

brings me back to the point of    compassionate use, single use, pre clinical trials

remember it was aids activists that revolutionized the entire fda clinical trials system in 80s and 90s
and what did we get for the billions of revenue we put into the pharmas pockets--- lots of political donations to republicans is what we got from most pharma execs

anyway, regarding my looking into things, that is my interest, and HAART is not fearful
HAART is the best cool thing that every existed in history of a terminal illness
not something to fear
the side effects are something to  lessen

and i read about an amazing company that has learned how to fuse a bad med to a med with no side effects actually fusing the molecule and one of the first they will put into cliical trials is an hiv med which will not hurt the liver or kidneys so that is fantastic
they are just now getting VC funding

HAART is fantastic and is not something to fear it is something to embrace
After UCLA lecture 18 months ago i felt haart should start below 350 now i think it should be 500 from all that i read, and never never stopped unless big good reasons

anyway

improvement in science is scary thing for those who cling to orthodoxy and unchanging ways

that is not my interest

i am all for haart and think it is best thing in world
and the day
a vaccine or gene therapy or apobec3 antibody comes out i will be all for progress
and advancement of science

ten other areas of science i read about include, nano, light and wave particle duality, evolutionary biology, many areas of economics, esp. international currency economics, and such, also interests in human sexuality, dev bio, so many areas

there is a giant revolution in science going on right under our feet in the area of hiv and genes and viruses, and genetics, and vaccines and gene therapies, very interesting stuff

I have dealt with the CFO of Genetech Corp and been in their offices.

Chief Financial Officer of Genetech Corp (largest and first gene biotech company)
i was in i think thier conference room discussing a business deal and it was just the two of us
in 80s

check out there amazing DNA approved therapies here..........................................................
http://en.wikipedia.org/wiki/Genentech

Offline Andy Velez

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Re: Gene may be key to neutralizing HIV, researchers say
« Reply #28 on: September 09, 2008, 07:51:36 AM »
Dear All,

The line between expressing opinions and becoming acerbically critical can get blurry sometimes. Please be mindful of what you write, keep it from the "I" or "my experience" point of view and avoid throwing darts at anyone else. You're just expressing your thoughts here and no one has to "win" anything.

Thanks for your cooperation. 
Andy Velez

 


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