Quantcast

Subscribe to:
POZ magazine
E-newsletters
Join POZ: Facebook MySpace Twitter Pinterest
Tumblr Google+ Flickr MySpace
POZ Personals
Sign In / Join
Username:
Password:
Welcome, Guest. Please login or register.
October 20, 2014, 07:37:36 AM

Login with username, password and session length


Members
  • Total Members: 23730
  • Latest: lume
Stats
  • Total Posts: 642742
  • Total Topics: 48891
  • Online Today: 183
  • Online Ever: 585
  • (January 07, 2014, 02:31:47 PM)
Users Online
Users: 5
Guests: 137
Total: 142

Welcome


Welcome to the POZ/AIDSmeds Community Forums, a round-the-clock discussion area for people with HIV/AIDS, their friends/family/caregivers, and others concerned about HIV/AIDS.  Click on the links below to browse our various forums; scroll down for a glance at the most recent posts; or join in the conversation yourself by registering on the left side of this page.

Privacy Warning:  Please realize that these forums are open to all, and are fully searchable via Google and other search engines. If you are HIV positive and disclose this in our forums, then it is almost the same thing as telling the whole world (or at least the World Wide Web). If this concerns you, then do not use a username or avatar that are self-identifying in any way. We do not allow the deletion of anything you post in these forums, so think before you post.

  • The information shared in these forums, by moderators and members, is designed to complement, not replace, the relationship between an individual and his/her own physician.

  • All members of these forums are, by default, not considered to be licensed medical providers. If otherwise, users must clearly define themselves as such.

  • Forums members must behave at all times with respect and honesty. Posting guidelines, including time-out and banning policies, have been established by the moderators of these forums. Click here for “Am I Infected?” posting guidelines. Click here for posting guidelines pertaining to all other POZ/AIDSmeds community forums.

  • We ask all forums members to provide references for health/medical/scientific information they provide, when it is not a personal experience being discussed. Please provide hyperlinks with full URLs or full citations of published works not available via the Internet. Additionally, all forums members must post information which are true and correct to their knowledge.

  • Product advertisement—including links; banners; editorial content; and clinical trial, study or survey participation—is strictly prohibited by forums members unless permission has been secured from POZ.

To change forums navigation language settings, click here (members only), Register now

Para cambiar sus preferencias de los foros en español, haz clic aquí (sólo miembros), Regístrate ahora

Finished Reading This? You can collapse this or any other box on this page by clicking the symbol in each box.

Author Topic: Waking up dormant HIV  (Read 12479 times)

0 Members and 1 Guest are viewing this topic.

Offline freewillie99

  • Member
  • Posts: 311
Waking up dormant HIV
« on: March 16, 2009, 03:45:04 PM »
huh........anyone heard of this before?  as follows:


HAART (highly active anti-retroviral therapy) has emerged as an extremely effective HIV treatment that keeps virus levels almost undetectable; however, HAART can never truly eradicate the virus as some HIV always remains dormant in cells. But, a chemical called suberoylanilide hydroxamic acid (SAHA), recently approved as a leukemia drug, has now been shown to 'turn on' latent HIV, making it an attractive candidate to weed out the hidden virus that HAART misses.

Matija Peterlin at UCSF and colleagues had previously identified another chemical called HMBA that could activate latent HIV, but the risk of several toxic side effects made HMBA clinically non-viable. However, the chemically similar SAHA had received FDA approval, making it a potentially safer alternate.

So, the researchers examined whether SAHA had any effect on HIV latency. They found that SAHA could indeed stimulate latent HIV to begin replicating, which exposes the infected cell to HAART drugs. SAHA could activate HIV in both laboratory cells as well as from blood samples taken from HIV patients on antiretroviral therapy. Importantly, this successful activation was achieved using clinical doses of SAHA, suggesting toxicity will not be a problem.

This study appeared in the March 13 issue of Journal of Biological Chemistry

and...

Suberoylanilide Hydroxamic Acid Reactivates HIV from Latently Infected Cells*

Human immunodeficiency virus (HIV) persists in a latent form in infected individuals treated effectively with highly active antiretroviral therapy (HAART). In part, these latent proviruses account for the rebound in viral replication observed after treatment interruption. A major therapeutic challenge is to purge this reservoir. In this study, we demonstrate that suberoylanilide hydroxamic acid (SAHA) reactivates HIV from latency in chronically infected cell lines and primary cells. Indeed, P-TEFb, a critical transcription cofactor for HIV, is released and then recruited to the viral promoter upon stimulation with SAHA. The phosphatidylinositol 3-kinase/Akt pathway is involved in the initiation of these events. Using flow cytometry-based single cell analysis of protein phosphorylation, we demonstrate that SAHA activates this pathway in several subpopulations of T cells, including memory T cells that are the major viral reservoir in peripheral blood. Importantly, SAHA activates HIV replication in peripheral blood mononuclear cells from individuals treated effectively with HAART. Thus SAHA, which is a Food and Drug Administration-approved drug, might be considered to accelerate the decay of the latent reservoir in HAART-treated infected humans.

* This work was supported, in whole or in part, by National Institutes of Health Grants AI49104 and AI058708 (to B. M. P.) and R01 AI40312 and AI47062 (to J. M. M.). This work was also supported by the University of California, San Francisco, Center for AIDS Research Grants P30 AI027763, P30 MH59037, and CC99-SF-001 and the University of California, San Francisco, Clinical and Translational Research Institute Grant UL1 RR024131, a component of the National Institutes of Health Roadmap for Medical Research. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Supported by a grant from the California Foundation for AIDS Research.

2 Supported by the University-wide AIDS Research Program Grant F05-GI-219.

3 Recipient of National Institutes of Health Grant DPI OD00329 (Director's Pioneer Award Program, part of the National Institutes of Health Roadmap for Medical Research) and the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research.

4 To whom correspondence should be addressed: University of California, San Francisco, 533 Parnassus Ave., Rm. U432, Box 0703, San Francisco, CA 94143. Fax: 415-502-1901; E-mail: matija.peterlin@ucsf.edu.
Beware Romanians bearing strange gifts

Offline carpediem98

  • Member
  • Posts: 66
Re: Waking up dormant HIV
« Reply #1 on: March 16, 2009, 05:42:15 PM »
I rushed over here to try to be the first to post this, lol.

Looks very, very exciting.  Could be another possible breakthrough. 

http://www.sciencedaily.com/releases/2009/03/090316120848.htm

Offline Inchlingblue

  • Member
  • Posts: 3,119
  • Chad Ochocinco PETA Ad
Re: Waking up dormant HIV
« Reply #2 on: March 16, 2009, 06:25:05 PM »
This sounds very promising. The brand name of the drug is Zolinza (generic: Vorinostat). This link discusses it's use in treating CTCL or cancer of the T-cells that affects the skin (ouch):

http://www.medicalnewstoday.com/articles/77532.php

I wonder what the mechanism is with this drug for waking up dormant HIV since it seems to be harbored in different types of cells, not just T-cells. Oh well, bring on the clinical trials....NOW ;)

The link below discusses US Gov't and Gates Foundation committing money to eradicate HIV from the body once and for all and it mentions Zolinza as a drug that seems promising in doing just that. It says they are looking for people in the earliest stage of HIV infection in order to test the drug:

http://organizedwisdom.com/helpbar/index.html?return=http://organizedwisdom.com/Zolinza&url=www.busrep.co.za/index.php?fArticleId=4834299&fSectionId=561&fSetId=662

US government and Gates Foundation offer scientists bounties to destroy HIV
February 10, 2009

By John Lauerman

The US government and the richest charity are offering bounties to scientists to wipe out HIV, the virus that causes Aids and is one of the world's biggest killers.

Frustrated by failures, the US is asking scientists to outline a major programme to find a cure for HIV, while the Bill & Melinda Gates Foundation is offering grants of $100 000 (R960 000) for researchers working on ways to drive the virus from patients' bodies for good.

Scientists are responding with new methods to stamp HIV from human cells and tissue, where traces of it can hide for years, evading treatment.

Experimental vaccines and sexual gels called microbicides have failed to prevent the spread of the disease, which strikes 2.7 million new patients a year. The challenge is all the more urgent since Merck's Ad5 vaccine, the most promising effort to date, flopped in 2007.

"Getting so close to an effective vaccine and then having to start from scratch again has made people wisely step back and re-evaluate the whole playing field of options," said David Margolis, a doctor at the University of North Carolina who has been working for years to cure HIV.

The National Institutes of Health asked scientists last year to describe how they would eliminate HIV from body cells. The effort, which may involve scientists at Harvard University, the University of California at San Diego and other institutions, will be a major topic at the annual Conference on Retroviruses and Opportunistic Infections in Montreal this week.

Margolis, along with researchers at Merck, Johnson & Johnson, Harvard, Johns Hopkins University and other institutions, proposed a state-funded effort to discover how HIV persists in the body. The Gates Foundation, the biggest private charity, is asking for proposals aimed at the same goal.

To cure HIV, scientists must devise a way to expunge the virus from the human body. The most effective HIV drugs so far aren't powerful enough to accomplish that goal.

For about 12 years, doctors have known that HIV can lie dormant in cells, where it evades detection by the body and is safe from drugs. HIV hijacks genetic machinery to make copies of itself that are released as an infected cell dies.


"It's very easy to get the number of viruses circulating in the system down to an undetectable level," said Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases. "To knock it out, we'll either have to get true eradication or get the reservoir of virus that's inside cells so low that it can't come back."

Decreasing the amount of virus hiding inside cells might allow the body's immune system to handle the infection on its own, without drugs. That would be equivalent to a "functional cure", similar to a remission cancer patients achieved when they did not have to take drugs, Fauci said.

Latent HIV acts like a smoldering fire that can burst into flame at any time. What that meant, said Myron Cohen, the director of the University of North Carolina's Center for Global Health and Infectious Diseases, was that without a cure, once a patient was diagnosed with HIV and began taking drugs, the need for taking medicine never ended.

Pressure to find a cure has increased in the two years since Merck's Ad5 vaccine flopped. Gels to prevent HIV transmission during sexual intercourse also proved futile.

For now, that leaves only the option of giving lifelong drugs to sustain people who are infected. The lifetime cost of treatment for US HIV patients is more than $600 000.

The US had committed $50 billion over the next five years to combat HIV in Africa, where cheap generic drugs were staples of treatment, Cohen said. "Can we sustain this spending for 50 years?" he asked last month.

Margolis would like to start testing a drug, Merck's Zolinza, that shows potential to flush out latent HIV. He is hoping the medicine will turn on the growth of HIV in cells where it is latent, so that the virus will kill them and its hiding place will be gone.

To test such drugs, scientists are searching for patients in the earliest stages of HIV infection - possibly the first candidates for curative treatment.

"The cancer field is always talking about cure," said Cohen. "It's a good thing, it's inspirational, and now it's time for us in the HIV field to do the same." - Bloomberg
« Last Edit: March 16, 2009, 07:28:56 PM by Inchlingblue »

Offline freaky_dream

  • Member
  • Posts: 132
  • mmm
Re: Waking up dormant HIV
« Reply #3 on: March 17, 2009, 02:38:52 AM »
Interesting read. I wonder how early in infection they are looking for. I would take it that they are looking for someone recently infected as early as a month. Is Zolinza basically a chemo therapy drug? Seems to be awfully potent but then anything that's going to be curative is probably going to have to give us a good kick in the guts to help rid us of the virus.

Offline veritas

  • Member
  • Posts: 1,410
Re: Waking up dormant HIV
« Reply #4 on: March 17, 2009, 09:22:26 AM »
Freakydream,

It looks like its pretty safe:


" the researchers examined whether SAHA had any effect on HIV latency. They found that SAHA could indeed stimulate latent HIV to begin replicating, which exposes the infected cell to HAART drugs. SAHA could activate HIV in both laboratory cells as well as from blood samples taken from HIV patients on antiretroviral therapy. Importantly, this successful activation was achieved using clinical doses of SAHA, suggesting toxicity will not be a problem."

The above quote from carpediem's link.
Carpediem,

Should we combine it with resveratrol?  (lol )

Good find Free!

Offline sensual1973

  • Member
  • Posts: 195
Re: Waking up dormant HIV
« Reply #5 on: March 17, 2009, 12:56:23 PM »
this sounds interesting,but the question is : are there any official trials going to take place soon to find out the efficacy of this cancer drug on latent hiv ?,and if so,whats expectied ? to eradicate or adding to HAART to achieve higher CD count ?
God grant me the serenity to accept the things i can not change.

Offline carpediem98

  • Member
  • Posts: 66
Re: Waking up dormant HIV
« Reply #6 on: March 17, 2009, 04:17:29 PM »
Veritas,
Yes, I think we should.

The new drug shall then be called:  baviresverzolivir, brand named "Hivexitrol."  LOL

Offline veritas

  • Member
  • Posts: 1,410
Re: Waking up dormant HIV
« Reply #7 on: March 17, 2009, 05:13:39 PM »


Carpe,

"Hivexitrol"  ----  I'll take it by IV in both arms. (lol )

Offline John2038

  • Member
  • Posts: 1,529
  • Happiness is a journey, not a destination.
    • HIV Research News (Twitter)
Re: Waking up dormant HIV
« Reply #8 on: March 17, 2009, 07:13:04 PM »

:)    :)  :) :)     :)     :)  :)     :):):)      :) :)  :)    :)  :) :) :)   :)   :)
:) :) :)  :)  :)   :)      :)  :)     :):):)      :)     :)    :)  :)         :) :)   
:)    :)  :)   :) :)       :)  :)     :)  :)      :) :)  :)    :)  :)         :)  :) 
:)    :)  :)    :)         :):):)     :)    :)    :)     :) :) :)  :) :) :)   :)    :)




well I hopes at least it's a good start :)


About the study, the accepted submitted manuscript is available here
http://www.jbc.org/cgi/reprint/M807898200v1

Offline Inchlingblue

  • Member
  • Posts: 3,119
  • Chad Ochocinco PETA Ad
Re: Waking up dormant HIV
« Reply #9 on: March 17, 2009, 07:56:29 PM »
There are obviously many kinks to iron out with this. For example, could or should it be taken alongside ARV meds. It's one thing to try this out on newly infected individuals who have never taken meds and quite another to try it out on someone who is on a successful ARV regimen. The drug activates HIV replication, after all, so taking it alongside ARV meds would seem like they would counteract each other. Not to mention other interactions that may exist.  And hopefully it's not very toxic, the article I linked above which discusses its use with cancer patients mentions some pretty serious side effects with some people, such as pulmonary thrombosis.

I'm not trying to sound negative (no pun intended), I'm very gung ho about new discoveries and I'm optimistic that a functional cure will be found in the not-too-distant future, all I'm saying is I'm sure it's all to be approached with caution.

I'm definitely very curious to know when clinical trials will start on this, sooner the better.
« Last Edit: March 17, 2009, 10:59:32 PM by Inchlingblue »

Offline J220

  • Member
  • Posts: 587
Re: Waking up dormant HIV
« Reply #10 on: March 17, 2009, 10:41:30 PM »
Wow this came out of left field...I hope it doesn't fizzle out like Valproic Acid...at least since this drug has already been approved for other uses it's possible trials would not take as long as a completely untested drug. What I find most intriguing/ promising is that this was able to reactivate hiv-infected cells directly in blood, not just in a culture in petri dish. Well, fingers crossed!
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline georgep77

  • Member
  • Posts: 148
Re: Waking up dormant HIV
« Reply #11 on: March 17, 2009, 11:03:36 PM »
Maybe this is Holy grail # 2, Verita's Holy grail is the number # 1...

             Thanks for the info & the links guys       :D
Come on Sangamo,  Geovax,  Bionor immuno, ...Make us happy !!!
+ 2008

Offline dearestgrandson

  • Member
  • Posts: 45
Re: Waking up dormant HIV
« Reply #12 on: March 17, 2009, 11:04:25 PM »
I often wonder if I were HIV+ what lengths would I be willing to go to in order to be cured. My grandson killed himself because he could not take being HIV+ anymore. I would venture to say that many people would put themselves at great risk in order to not be infected any longer.

It irks me to no end when people say that HIV is like diabetes or something, because it is not. In the letter my grandson left after he killed himself he talked about people not wanting to touch him after they found out he was HIV+, he talked about not being able to find a date. When have you ever not wanted to touch someone after finding out they had diabetes? Or not wanting to date a diabetic?

And, like I have said before HAART has HUGE limitations. There are many problems that are not cured or amoreliated by an undetectable viral load and an increased CD4 cell count.
« Last Edit: March 17, 2009, 11:30:32 PM by dearestgrandson »

Offline a2z

  • Member
  • Posts: 193
Re: Waking up dormant HIV
« Reply #13 on: March 18, 2009, 04:32:06 AM »
this sounds interesting,but the question is : are there any official trials going to take place soon to find out the efficacy of this cancer drug on latent hiv ?,and if so,whats expectied ? to eradicate or adding to HAART to achieve higher CD count ?

While my virus seems to be under control, this kind of study (providing I got more information and was comfortable with the risks) would be the kind I'd like to sign up for.
Dates are blood draw dates:
9/4/14: CD4 948, 37.9%, VL 150
5/23/14: CD4 895 --.-% VL UD - Truvada/Isentress
09/21/09: CD4 898 27.0% VL 120 - back on track, same meds.High level enzymes, but less so
06/15/09: CD4 478 21.8% VL 1150 - high liver enzymes... looks like I may not be resistant
05/22/09: Fixed insurance, resumed medicine
04/17/09: Ran out of medicine, could not resolve insurance problems
04/01/09: CD4 773 28% VL 120 - high liver enzymes
12/01/08: CD4 514 23% VL 630
10/17/08 started Reyataz, Norvir and Truvada. -- possibly minor neuropathy, but otherwise okay.
9/10/08: CD4 345 17%, VL > 78K
8/18/08: CD4 312 18%, VL > 60K (considering meds)
12/19/07: CD4 550 28% VL > 100K (no meds yet)
Diagnosed 10/23/07

Offline rocky48

  • Member
  • Posts: 37
Re: Waking up dormant HIV
« Reply #14 on: March 18, 2009, 06:23:43 PM »
Zolinza can wake up hiv in CD4 cells but will it wake up the dormant cells in other tissues like the brain or other organs?

I hope this is the answer we are all looking for.  I know I have only been positive for seven months but I want a cure for everyone.

Started Atripla on 4/23/11
5/27/11   CD4 - 572 VL - 130
9/30/11   CD4 - 566 VL - UD
3/23/12   CD4 - 640 VL - UD
9/21/12   CD4 - 699 VL - UD

Offline Sky

  • Member
  • Posts: 225
    • Myspace
Re: Waking up dormant HIV
« Reply #15 on: March 18, 2009, 08:58:25 PM »
If it does indeed work it would be a multiple step process to eliminate the virus.  We'd have to take Zolinza in segmented treatments to ensure complete eradication.  Activate the latent, hit it with HAART, repeat.
Here's the side effects associated with Zolinza...none of them are really that bad!  I say bring it on!

The following Zolinza side effects are common (occurring in greater than 30%) for patients taking Zolinza:

    * Fatigue
    * Diarrhea
    * Nausea
    * Taste changes
    * Increased blood glucose level (hyperglycemia)
    * Increased creatinine level (transient)
    * Increased level of protein in the urine
    * Low platelet count (thrombocytopenia)

These are less common side effects (occurring in about 10-29%) of patients receiving Zolinza:

    * Loss of appetite (anorexia)
    * Weight loss
    * Muscle spasms
    * Hair loss (alopecia)
    * Dry mouth
    * Chills
    * Fever
    * Vomiting
    * Dizziness
    * Constipation
    * Low red blood cell count (anemia)
    * Headache
    * Itching
    * Swelling in hands or feet
    * Cough
    * Upper respiratory infection
    * Dehydration
    * Shortness of breath
Poz since 2003.

Offline dearestgrandson

  • Member
  • Posts: 45
Re: Waking up dormant HIV
« Reply #16 on: March 18, 2009, 11:25:59 PM »
"Doesn't seem that bad".... this is all relative. Could these same side effects be expected when used in conjunction with HAART? Look at what happens when DDI is combined with hydroxyurea. They have a synergistic effect, but the side effects are also synergistic. I have read on this board that some people experience their worst lipoatrophy on HU. People also develop peripheral neuropathy on HU, which is also a side effect of DDI.

Increased blood glucose levels are side effects of protease inhibitors, and this may just add to that and make it worse. It could be raised to life threatening levels. Diabetic Coma?

Remember it is a cancer chemotherapy. Cancer chemotherapies are not known or their benign side effect profiles. This is not an aspirin. This is heavy duty stuff.

Offline Inchlingblue

  • Member
  • Posts: 3,119
  • Chad Ochocinco PETA Ad
Re: Waking up dormant HIV
« Reply #17 on: March 19, 2009, 12:20:51 AM »
Remember it is a cancer chemotherapy. Cancer chemotherapies are not known or their benign side effect profiles. This is not an aspirin. This is heavy duty stuff.

For treatment of HIV it's not expected to be needed in the same doses as those used for cancer patients; as Sky mentions in his post, this would be used intermittently. The article that John linked (above) goes into detail about the studies done so far in HIV and mentions, regarding the levels of the drug they used: "these levels may only need to be achieved intermittently, thus suggesting the possibility of lower or pulsed administration and hence a better safety profile than that observed with SAHA in cancer patients."

 

Offline dearestgrandson

  • Member
  • Posts: 45
Re: Waking up dormant HIV
« Reply #18 on: March 19, 2009, 12:41:14 AM »
We don't know what the case will be yet, though, these are assumptions that need to be verified by clinical trials and scientific evidence. Remember many theories or projections do not end up being what they had hoped to be. They may, theoretically, find that HAART works against the drug and that higher dosages need to be used to obtain the exact goal they are trying to obtain. Eradication may require much higher dosages then are required for cancer treatment. We just don't know right now. Suppose that they were antagonistic of each other when it comes to the effect they are desiring.

What if it actually can cure HIV infection and it needs much higher doses? I mean there are so many possibilities that need to be verified by scientific studies, not projections.

Is "sky" a scientist directly involved in the study? I don't see anything in the sciencedaily account that suggests it would only need to be used intermittenly.

I would think that most people who are interested HIV science know that theory and projections mean next to nothing. Remember that they originally projected that HAART would cure an HIV infection based on flawed models and theories of HIV infection? However, scientific evidence proved this to be incorrect. Think about how many vaccines looked promising in simian animals, but later failed to show the same results in humans.

Projection and theory means next to nothing in HIV science. Facts are what count. Nobody knows until we know.
« Last Edit: March 19, 2009, 12:54:48 AM by dearestgrandson »

Offline freewillie99

  • Member
  • Posts: 311
Re: Waking up dormant HIV
« Reply #19 on: March 19, 2009, 09:55:13 AM »
They may, theoretically, find that HAART works against the drug and that higher dosages need to be used to obtain the exact goal they are trying to obtain. Eradication may require much higher dosages then are required for cancer treatment.

What if it actually can cure HIV infection and it needs much higher doses?

I don't see anything in the sciencedaily account that suggests it would only need to be used intermittenly.

On the contrary, from the report that John linked to: "Suberoylanilide Hydroxamic acid reactivates HIV from latently infected cells":

"Moreover, these levels may only need to be applied intermittently, thus suggesting the possibility of lower or pulsed administration and hence a better safety profile than that observed with SAHA in cancer patients"

Your other point of "Nobody knows until we know" is well taken.  Obviously this study is quite encouraging, but we don't and won't know more until there are further in vivo trials.  I look forward to hearing more in the not so distant future.


Beware Romanians bearing strange gifts

Offline dearestgrandson

  • Member
  • Posts: 45
Re: Waking up dormant HIV
« Reply #20 on: March 19, 2009, 11:00:48 AM »
I said the sciencedaily.com article didn't mention anything about possible dosing. I didn't get a chance to read the other one, because I assumed they all said the same things or there about.

What I was saying about antagonism was that the HAART and Zolinza may antagonise each other when it comes to the desired effect. They may find that those with HIV who are not on HAART have a greater degree of "woken" HIV versus those on HAART. If their desired effect is to eradicate HIV or possibly bring it to a level so low that the human immune system can control it it will probably be difficult to do. Eradication may require doses that are too toxic to the body or it may not. No one knows yet.
I just hope for the sake of the HIV+ community that this doesn't fizzle out like Valproic Acid did.

I guess I would say this is my projection, just based off of the research I have done and what I know about the immune system and HIV.
I believe that maybe it may have to be intermittent, but intermittent may not be such a short period. It could be between 6 months to a year, and then off for a while. I also believe that Integrase Inhibitors will be key to eradicating the virus. I would venture to say that if one hopes to be cured by this they should get on an INH as soon as they can until it gets approved for the purpose. I am also projecting that 3 drugs will not be enough to keep virus levels at bay when this drug gets approved for the purpose. I believe that an entry inhibitor, two NRTI's or an NNRTI, plus an Integrase Inhibitor will each have to be in someone's cocktail. Protease Inhibitors and Maturation Inhibitors would be pretty worthless for this purpose because they step they prevent in HIV replication is too late to prevent genetic material from being integrated into the host cell's DNA.

Just my projections based on what I know. No actual clinical or scientific evidence to back it up.
« Last Edit: March 19, 2009, 11:13:18 AM by dearestgrandson »

Offline Inchlingblue

  • Member
  • Posts: 3,119
  • Chad Ochocinco PETA Ad
Re: Waking up dormant HIV
« Reply #21 on: March 19, 2009, 03:03:42 PM »


Is "sky" a scientist directly involved in the study? I don't see anything in the sciencedaily account that suggests it would only need to be used intermittenly.

 

Dearestgrandson: Please do me the courtesy of actually reading what I've written, as I do to you, before responding. What you're saying makes no sense as a response to my post. I gave Sky credit for mentioning intermittent use since that's what the scientists have said. I then backed it up with a quote from the scientists. The quote is taken not from Science Daily, which is intended for a general audience but from John's link, which is an abstract written by the actual scientists who conducted the research on HIV and SAHA.

If you get a chance, you should read it. It has the information about intermittent use that you didn't find in the Science Daily piece, along with much more information, including the fact that they expect integrase inhibitors will be an important part of this eradication approach (something you mentioned in one of your posts).

Here's the link again (thanks John@!):

http://www.jbc.org/cgi/reprint/M807898200v1

In an earlier post, I brought up some of the same concerns you have regarding the use of SAHA/Zolinza and its possible interaction/contraindication with HAART.  We are in agreement that there's a lot still to be figured out.
« Last Edit: March 19, 2009, 07:37:42 PM by Inchlingblue »

Offline Sky

  • Member
  • Posts: 225
    • Myspace
Re: Waking up dormant HIV
« Reply #22 on: March 19, 2009, 08:16:50 PM »
Thank you Inch.

Dearestgrandson, I'm a RN and am familiar with this medication because of my career.  Like Inchlingblue stated it has already been stated that it would be used intermittently, simply to activate latent infection.
Poz since 2003.

Offline dearestgrandson

  • Member
  • Posts: 45
Re: Waking up dormant HIV
« Reply #23 on: March 20, 2009, 12:18:30 AM »
It has been projected, not verified by clinical trials. If they hope to cure an HIV infection with this medication it may take a lot more then that it may take less. Haven't you learned that theory and projection in HIV science mean next to nothing and that clinical trials and scientific fact are what win out?
I can't imagine what it must have been like to start ARV's believing it would cure you, due to a faulty projection, and then find out that you were going to be on these drugs for a lifetime. That must have really been a drag.
« Last Edit: March 20, 2009, 12:20:46 AM by dearestgrandson »

Offline freaky_dream

  • Member
  • Posts: 132
  • mmm
Re: Waking up dormant HIV
« Reply #24 on: March 20, 2009, 09:26:34 PM »
Dearest I think you are belittling the fact that ARVs saved countless lives. So what if it didn't cure HIV it allowed those infected to carry on with semi normal lives. I will take that over not having anything any day. Skepticism is healthy but being fatalistic is not.

Offline dearestgrandson

  • Member
  • Posts: 45
Re: Waking up dormant HIV
« Reply #25 on: March 21, 2009, 12:37:50 AM »
I am not belitting the benefits of ARVs and I don't know why you think that. I am discouraging knee jerk optimism, because there have been many predictions in HIV science that have not panned out. It was once believed that ARVs would cure an HIV infection, but they don't. Many people got their hopes up, and dared to dream of a life without HIV only to have it crushed. One only needs to do a quick search on Pubmed for HIV articles from the 1980's, 1990's, and early 2000's to see how many things looked great in the beginning and then didn't pan out. When 1 out of every 1000 ideas actually makes it to the market I believe we should remain very skeptical.
I believe the benefits of ARVs are often overstated or that their negatives are often understated. Scientists and HIV researchers seem very complacent with the way things are now. So what if a potential treatment is toxic if it may cure an HIV infection? Cautioning against further research because what is available right now stupid. The situation can not be maintained the way it is currently. There are too many side effects of ARVs that can not be reversed or treated, there are too many effects of HIV that can not be reversed or treated with ARVs, and there are too many people out there who are infected who can not gain access to these medications. The situation just can not be maintained the way it is.
My mother recently died from complications of Alzheimer's disease. She was one of a fortunate few who got into a clinical trial involving a vaccine against plaques in the brain. It ended up not working, and we didn't get our hopes up. We knew however that there was no way she would get any better without the treatment, so we figured that it couldn't hurt her. As I have talked about before my grandson committed suicide and he was HIV infected. He would have been more then happy to put his life at risk if he thought it would have cured his infection. He took Reyataz and Truvada and had what his doctor classified as grade 3 lipoatrophy after less then a year on therapy. These medications are supposedly less toxic and had less side effects then others, but he ended up with the side effects. He was told there was nothing that could be done to prevent it from progressing or to reverse it. He was also developing neurological problems and his ID doc told him there was nothing that could be done to prevent further decline or improve his symptoms, he even lied to him and told him he wasn't developing HIV dementia in order to help him not to worry. So he killed himself. According to his letter he did not want to end up demented and looking like a dying AIDS patient. He wanted to die with some dignity. ARVs may have given him more quantity of life, but they did not improve his quality. He just got more and more depressed because he didn't recoginise himself in the mirror and because nothing could be done to help his neurological problems.
This research actually does look promising, but I would rather believe it is not going to work and have it work in the end and be pleasantly suprised. Expect the worst, hope for the best.
« Last Edit: March 21, 2009, 12:41:42 AM by dearestgrandson »

Offline J220

  • Member
  • Posts: 587
Re: Waking up dormant HIV
« Reply #26 on: March 21, 2009, 11:36:14 AM »
am discouraging knee jerk optimism...

Thank you for sharing your opinions but, please, don't presume to patronize by telling us how we should view things, especially by trying to validate your arguments by constantly throwing in the tragedy you have lived through- you are not the only one who has suffered.

If we wish to be (over) optimistic that is our prerogative, and if we want to use any little good news, even if they may turn out to be unfounded, to help us get through the day, then that's our decision. I am sure you have the best of intentions, but you don't have to worry about us and warn us of the impending doom of possible disappointment- we can handle it. Best regards.
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline dearestgrandson

  • Member
  • Posts: 45
Re: Waking up dormant HIV
« Reply #27 on: March 21, 2009, 12:40:12 PM »
I am definitely not throwing around a tragedy. The situation with HIV makes me very angry. There are a lot of really good people putting their time and money towards this cause, yet for some reason I believe that religious fundamentalism is preventing further cure efforts. It makes me very angry that people with HIV are kind of falling by the wayside. Research for a cure has really fallen by the wayside, and has really been focused on a vaccine. I have read articles where scientists have admitted that we are no closer today to finding a vaccine then we were 25 years ago. It really makes me angry that people act like ARVs are some panacea and that research towards a cure could be put on hold.

Some of these articles on HIV research read like a tabloid magazine, which also makes me angry because it provokes an optimism that may or may not be displaced. Constantly getting excited about research on a disease you have to only be let down later on has to be very frustrating. I know it was to my grandson.

Offline freaky_dream

  • Member
  • Posts: 132
  • mmm
Re: Waking up dormant HIV
« Reply #28 on: March 21, 2009, 01:21:02 PM »
Your grandson has passed away and you don't have HIV so what is your stake in participating in this forum other then projecting your feelings of despair and negativity onto the discussions? It's obvious from your posts that you have some issues not dealt with yet regarding your grandson but this isn't the place to resolve them. We come to this forum to discuss new research and treatments, not to grovel about how destitute we must all be. The mental health forum is that way --->

Offline sensual1973

  • Member
  • Posts: 195
Re: Waking up dormant HIV
« Reply #29 on: March 21, 2009, 03:00:28 PM »
ok guys lets not divert from the main topic of this thread which is SAHA and waking up dormant hiv infected cells.
God grant me the serenity to accept the things i can not change.

Offline Inchlingblue

  • Member
  • Posts: 3,119
  • Chad Ochocinco PETA Ad
Re: Waking up dormant HIV
« Reply #30 on: March 21, 2009, 03:46:25 PM »
ok guys lets not divert from the main topic of this thread which is SAHA and waking up dormant hiv infected cells.

Tell that to Dearestgrandson who keeps repeating the same thing post after post. We get it@!

He's a very nice man and I know he means well so I'm not trying to knock him, it's just that his point about the possible dangers and uncertainty about SAHA was made more than once and after a while it just gets repetitive.

Since he does not have HIV himself, maybe he doesn't realize the effect of what he keeps saying over and over could have on those of us who do have HIV.
« Last Edit: March 21, 2009, 04:01:00 PM by Inchlingblue »

Offline freewillie99

  • Member
  • Posts: 311
Re: Waking up dormant HIV
« Reply #31 on: March 21, 2009, 05:55:54 PM »
research towards a cure could be put on hold.

All due respect, but who said research towards a cure has been "put on hold"?  As an example, I've had discussions with researchers working with gene therapy and rnai and their sense of optimism for the progress they've made is fantastic.  Now of course you could say that they're somehow deluded and because there have been letdowns in the past that they're doomed to inevitable failure.  That would be completely irrational though and it's why I don't choose to believe it.  Science moves forward at it's own pace, more often than not slower than we'd perhaps like, but forward nevertheless. 

I have all the empathy in the world for your personal situation, but frankly I find you misinformed on this particular topic.
Beware Romanians bearing strange gifts

Offline Inchlingblue

  • Member
  • Posts: 3,119
  • Chad Ochocinco PETA Ad
Re: Waking up dormant HIV
« Reply #32 on: May 23, 2009, 04:05:29 PM »
This is not about Zolinza but it is about "waking up dormant HIV."  There's an upcoming clinical trial that will use Raltegravir (Isentress) and Valproic Acid to try and activate latent HIV. The description below makes it all sound very logical and straightforward.

Detailed description: When HIV has just been made, it enters a CD4 cell's nucleus. An enzyme in the nucleus called integrase helps HIV hide in the cell's own DNA, and another enzyme called histone deacetylase (HDAC) helps it stay hidden. While HIV is hiding in the DNA, it is not active and cannot be targeted by currently available highly active antiretroviral therapy (HAART). VPA, a drug used to treat seizures, is an HDAC inhibitor, and raltegravir is a newly FDA-approved integrase inhibitor. Taking VPA and raltegravir may prevent HIV from being able to hide in CD4 cells, allowing HAART to eliminate HIV that would normally be hidden. The purpose of this study is to determine whether adding raltegravir and VPAto the participant's current HAART regimen will reduce the number of resting HIV in CD4 cells.


LINK:

http://www.druglib.com/trial/90/NCT00576290.html

This other study evaluated SAHA (Zolinza) to see how well it inhibits HDAC, which is what helps HIV stay latent, as summarized above. They concluded that

In the resting CD4(+) T cells of antiretroviral-treated, aviremic HIV-infected patients clinically achievable exposures to SAHA induced virus outgrowth ex vivo. These results suggest that potent, selective HDAC inhibitors may allow improved targeting of persistent proviral HIV infection, and define parameters for in vivo studies using SAHA.

LINK:

http://www.leaddiscovery.co.uk/articles/19239360/dailyupdate
« Last Edit: May 23, 2009, 04:26:59 PM by Inchlingblue »

Offline xman

  • Member
  • Posts: 288
Re: Waking up dormant HIV
« Reply #33 on: July 30, 2009, 05:37:20 PM »
Any news about this? Still wondering why there are no clinical tests on patients ongoing.
sign the petition launched by the aids policy project addressed to the nih aimed to increase the money needed to find the cure:

http://www.aidspolicyproject.org/petition_for_the_nih

we can make a difference and we need to fight. please support them! it doesn't cost you anything. they need it now more than ever!

Offline GNYC09

  • Member
  • Posts: 702
Re: Waking up dormant HIV
« Reply #34 on: July 30, 2009, 07:25:40 PM »
This reminds me of a quote that says (to paraphrase): To hope is to risk disappointment but this risk must be taken because the greatest hazard in life is to have no hope at all.

That said, I hope that this and/or some other research leads to a cure...may not be during my lifetime but some day...

Offline Inchlingblue

  • Member
  • Posts: 3,119
  • Chad Ochocinco PETA Ad
Re: Waking up dormant HIV
« Reply #35 on: September 02, 2010, 11:55:03 AM »
Update on Zolinza (SAHA):

AIDS Quest to Kill `Sleeping' Virus Enlists Merck Cancer Drug

By Simeon Bennett - Sep 1, 2010 9:01 PM MT

The 30-year-long search for a cure for AIDS, the world’s deadliest viral infection, may get a renewed boost from an unlikely source: a little-used Merck & Co. cancer drug.

Researchers at the University of North Carolina in Chapel Hill plan to test Merck’s drug, Zolinza, next year in about 20 people infected with HIV, the AIDS virus. The goal is to determine if Zolinza, or a medicine like it, can force HIV out of cells where it can reside, concealed from attack by potent antiviral treatments, said David Margolis, a professor of medicine who’s leading the research.

While AIDS drug cocktails can eliminate more than 99 percent of virus from an infected person, the treatment isn’t a cure because a remnant of the virus remains hidden in certain cells. For years, scientists have sought a simple way to drive the remaining virus into the bloodstream where the drugs can clear them from the body. Zolinza, approved in 2006 for use against a rare type of blood cancer, may work by blocking an enzyme that helps the virus avoid detection.

“It’s really all about trying to move the field ahead,” Margolis said in a telephone interview. “We don’t expect to cure anybody, but we expect to really show whether it can work the way we think it does in people -- or not.”

Zolinza earned Whitehouse Station, New Jersey-based Merck $15 million in 2008, the last year it disclosed sales of the drug, for treating a malignancy of white blood cells that affects the skin. In a laboratory test published last year, Margolis used the medicine to coax HIV out of hiding in cells taken from infected patients. Now he wants to replicate the result inside the body. Success would show he’s on the right track to finding a cure.

Continued . . .

LINK:

http://www.bloomberg.com/news/2010-09-02/aids-cure-quest-to-kill-sleeping-viruses-enlists-merck-cancer-medicine.html

Offline rocky48

  • Member
  • Posts: 37
Re: Waking up dormant HIV
« Reply #36 on: September 05, 2010, 11:48:59 PM »
I need all the hope I can get about a cure. At 62 my time is running out.  You guys do a wonderful job keeping everyone info.

Thanks
« Last Edit: September 05, 2010, 11:50:58 PM by rocky48 »
Started Atripla on 4/23/11
5/27/11   CD4 - 572 VL - 130
9/30/11   CD4 - 566 VL - UD
3/23/12   CD4 - 640 VL - UD
9/21/12   CD4 - 699 VL - UD

Offline tednlou2

  • Member
  • Posts: 4,968
Re: Waking up dormant HIV
« Reply #37 on: September 11, 2010, 01:57:52 AM »
Dr. Gallant thinks this would be hard to do, but talks about other things he feels are promising.

http://www.hopkins-hivguide.org//q_a/patient/recent_questions/...until_something_better_comes_along_.html?contentInstanceId=535008&siteId=7151

 


Terms of Membership for these forums
 

© 2014 Smart + Strong. All Rights Reserved.   terms of use and your privacy
Smart + Strong® is a registered trademark of CDM Publishing, LLC.