How far would you go to find a cure for AIDS?

[David Evans]

Dear Gals and Guys,

A couple of weeks ago I attended a meeting sponsored by the Treatment Action Group, Project Inform and AmFAR on cure-related research. It was a terrific conference, and certainly highlighted how far and how quickly researchers have moved in their thinking about trying to find a cure for HIV. In fact, things have progressed in some cases to the point where the first human trials are already underway or will be in the next year or two.

While this is truly exciting, the experts there warned that the road ahead is likely to be bumpy. First, most of the initial trials will be to test a concept and almost certainly won't benefit those who volunteer for the studies. Also, many, if not most, of the first treatments are likely to fail. Even more concerning is the fact that some studies could pose significant risks for the participants.

What activists, researchers and regulators are beginning to discuss is how best to protect people who volunteer for these studies without stifling the field altogether. One of the biggest questions posed by a medical ethicist at the conference was how to determine when people are capable of deciding that they want to take greater risks to their own health when the only benefits may be altruistic--to help move research forward so that a cure may be found later.

Some experts think that no one should be allowed to take such risks, while others—including many of the HIV-positive activists in the room—asserted that the most informed and motivated of their HIV-positive peers might want to take those risks and that they should be allowed to do so.

What do you think?

I'm going to write an article about this important issue for AIDSmeds. Though I'm curious to know what you all will post here, I'd be truly grateful if at least a few of you would be willing to be interviewed for this story. Generally, we ask people to be willing to give their full names when we interview them, so this means being publicly out about your status. I'm not going into this thinking that there's one right answer here. In fact, I think it is the difficult nature of the issue that makes it so compelling and I'd love to talk to people who fall on both sides of this issue.

If you're interested in being interviewed, the best way to reach me is to send me a personal message with your email address here on the forums (just hit the PM button). It's best not to include your email in a post here, as it is public to the world.

I look forward to your thinking.

Warm Regards,

David Evans
Senior Editor for AIDSmeds and POZ and Forums Moderator

[thunter34]

Some experts think that no one should be allowed to take such risks, while others—including many of the HIV-positive activists in the room—asserted that the most informed and motivated of their HIV-positive peers might want to take those risks and that they should be allowed to do so.

What do you think?

I think that I would ultimately have to side with the activists, and here's why:  

I understand how the potentially grave risks can tug at people emotionally and make agreeing to such circumstances extremely difficult - and believe me that I do not make this pronouncement lightly, but I have to ask why particular risks of this magnitude should be deemed unacceptable in this realm when life threatening risks are undertaken all the time in other areas without this same type of moral conflict.  

Perhaps I am being entirely too simplistic in my assessment, but why should anyone have ever been allowed to volunteer to be shot into space or to submerge into the depths of the sea under this same line of thinking?  How would the participants of the very meeting you attended have all made it there from various points around the globe if some people hadn't been willing to crash so that one day others could fly?  Am I completely off base in drawing these parallels?  Aren't perilous sacrifices made by some people every day for solely altruistic purposes?  Has anyone ever argued against the existance of volunteer fireman, for example?  

I guess what I am trying to say is that there some people in this world who are simply brave and fucking heroic people, ones who will dare where others will not - and who do it solely for the benefit of others.  I think a proper psychological evaluation can be made to discern precisely who these candidates may be, and then beyond that point research can proceed without further ethical unrest.

At least that is how it seems to me.

[Miss Philicia]

Perhaps I am being entirely too simplistic in my assessment, but why should anyone have ever been allowed to volunteer to be shot into space or to submerge into the depths of the sea under this same line of thinking?  How would the participants of the very meeting you attended have all made it there from various points around the globe if some people hadn't been willing to crash so that one day others could fly?  Am I completely off base in drawing these parallels?  Aren't perilous sacrifices made by some people every day for solely altruistic purposes?  Has anyone ever argued against the existance of volunteer fireman, for example? 

It's simplistic in some respects because those examples would have been evaluated as to what level of risk they were.  If something has a 10% chance of death it's entirely different than a 90% chance, so after that it's just a matter of deeming what is acceptable.  Plus the examples you gave there are training levels for participants because they're not just passive participants, where in an HIV cure-related study the participants are passive.

[newt]

If I liked the science, my doc liked the science, and Tracy Swan, Simon Collins, Polly Clayden, Richard Jefferys and Tim Horn liked the science I'd do it (otherwise I'm just gonna visit the south of the USA for recreational purposes)

- matt

[David Evans]

Matt -

Your response is very germaine to the discussion. One of the problems with any type of human research is how to ensure that people thoroughly understand the risks. Folks like you, who are extremely knowledgable and connected to others who know the science, are exactly the kind of people that the activists were holding up as examples of the kinds of people who are capable of judging the risks and deciding to participate anyway.

I'm glad to see the responses generated here so far.

-David

[newt]

This is true, but I wouldn't go on the PI monotherapy study I myself recommended for funding, so my bar is set very high.

- matt

[thunter34]

It's simplistic in some respects because those examples would have been evaluated as to what level of risk they were.  If something has a 10% chance of death it's entirely different than a 90% chance, so after that it's just a matter of deeming what is acceptable.  Plus the examples you gave there are training levels for participants because they're not just passive participants, where in an HIV cure-related study the participants are passive.

I'll buy that, but I think my general point still stands, doesn't it?  That there are some people who are both knowledgeable and courageous, and therefore the blanket assertion that "no one should ever be allowed to take such risks" is somewhat overreaching?

And although I understand the terminology, it sure is difficult for me to personally accept terming anyone willing to do this as a "passive participant".  Boy howdy.

I am way happy about the presence of this thread, btw. 

[newt]

Emotional motivations are perfectly valid, loads of people have done studies cos they wanted to live, not cos they thought the benefits outweighed the risks (which, let's face it, in many cases they did not..hello AZT monotherapy).

- matt

[newt]

On the medical ethics point, Ben Goldacre did a top article on this in relation to treatment delay

http://www.badscience.net/2011/03/when-ethics-committees-kill/

- matt

[richie]

David --

While it's a pandora's box for all of us to discuss here, this is settled law.  It's all been discussed already, and there are Federal guidelines already established which set the bar for allowing informed consent for volunteers.  In fact, the FDA can even allow non-consent trials to take place, as in the case with Polyheme (NFLD), a blood-substitute trial for extremely injured trauma patients who could not consent.  The ethicists had an anurysm over the trial, and my personal opinion is that all medical ethicists would disallow ANY medical trials whatsoever as there is no such thing as a perfect informed consent.

http://www.hhs.gov/ohrp/policy/

The Common Rule is triggered whenever a patient (or even non-patient) participates as a human subject in federally funded medical research.  The primary purpose of the Common Rule is to ensure that human subjects participate voluntarily in medical research and provide their informed consent for any treatment they receive. Federal regulations spell out the specific duties and responsibilities of both the medical professional and the entity sponsoring the research. 

My own personal opinion, regardless of all these policies, is that if people wish to volunteer, that is their right.  By volunteering, they are assuming certain responsibilities and risks, all of which should be as known as possible, and the medical professionals have a responsibility to disclose.  Once someone has had these risks and responsibilities explained, they can examine the issue for themselves and make a personal decision.   Just as Newt might have a high bar, others might be satisfied with less. 

And damn the ethicists.....

[newt]

I have a high bar cos I'm selfish. The ethics people need bigger knickers that don't ride up so much when the end user speaks.

- matt

[Jody]

Great thread here and I am not knowledgeable enough as you fellows to add very much but starting meds back in the mid 90's, just before Crixivan and the cocktail of drugs came out, and those meds having a Lazarus like effect on me- gaining 40 pounds, joining a gym and getting my life back were all results.  

So I am not sure, as I am still surviving well enough, if I would have the guts to put myself into this type of precarious sort of study if given the option.  Would one want to shake up something working well enough for the possibility of life without AIDS and any meds at all?  Or would many of us survivors hope that others who weren't doing well on failing or no regimens at all would volunteer resulting ideally in the research being perfected and benefit us all down the road with time to spare in many cases?

Jody

[richie]

"Would one want to shake up something working well enough for the possibility of life without AIDS and any meds at all?  Or would many of us survivors hope that others who weren't doing well on failing or no regimens at all would volunteer resulting ideally in the research being perfected and benefit us all down the road with time to spare in many cases?"

In my opinion, yes.  Status quo is never good enough.  It isn't as black and white (doing well or not) as you postulate.......individuals can make their own decisions based on their past, present, and future outlooks  Some currently healthy might volunteer, some unhealthy might.  And it depends on the study criteria as to whether they would qualify or not. 

[poz91]

One of the biggest questions posed by a medical ethicist at the conference was how to determine when people are capable of deciding that they want to take greater risks to their own health when the only benefits may be altruistic...

...but for it to truly be "altruistic," the end product would need to be affordable and readily available to anyone and everyone who needs it.

...and that's simply not the case when it comes to the pharmaceutical industry in general. It's big business that generates billions upon billions of dollars a year in profits for these companies:

http://money.cnn.com/magazines/fortune/fortune500/2010/industries/21/index.html

So once you take this false sense of "altruism" out of the equation, the real ethical question is how much should these companies realistically be compensating the folks who are risking their health and well-being to help them develop new avenues and sources of income?

[Hellraiser]

...but for it to truly be "altruistic," the end product would need to be affordable and readily available to anyone and everyone who needs it.

...and that's simply not the case when it comes to the pharmaceutical industry in general. It's big business that generates billions upon billions of dollars a year in profits for these companies:

http://money.cnn.com/magazines/fortune/fortune500/2010/industries/21/index.html

So once you take this false sense of "altruism" out of the equation, the real ethical question is how much should these companies realistically be compensating the folks who are risking their health and well-being to help them develop new avenues and sources of income?

Actually the altruism would be geared towards reaping no medical benefit from the treatment personally.  You would merely be testing the science and proof of concept for other members of the hiv+ community to potentially be cured.  I believe David was even saying that due to the nature of the experimentation and the mutative nature of HIV being a part of the experiment may allow the virus to potentially become resistant or immune to whatever medicine was eventually deemed successful.

If I were to take part in this experiment though and put my life and health on the line for the chance to be a part of helping a new generation of people not have to deal with this disease you can be sure that I would want to know that everyone would have reasonable access to the cure.  If it were only available to the extremely wealthy that would pose a different question entirely.

[David Evans]

Thanks to all of you for your thoughtful comments. Just to clarify, my primary purpose was to find folks to interview, but I also wanted to see what you thought about your own willingness to participate in riskier research where the only benefit might be to forward the field and hopefully, one day, lead to a cure for HIV.

Though there are explicit laws and regulations in place to guard the safety of clinical trial participants, those regulations are open to interpretation and subject to the whims of the moment and of politics. One disastrous trial can set back an entire field for years, even if the actual risks to participants in future trials is theoretically no more or less than it had been before.

The FDA and institutional review boards have grown far more conservative of late—the former for political reasons and the latter to limit liability for the institutions they represent—so it will likely be up to HIV-positive activists and others in the community to convince these more conservative regulatory bodies about about the necessity for certain trials to move forward and to vote with their feet and enroll in studies.

Thus, the question ends up becoming, "How much are you, personally, willing to put on the line in the search for a cure and under what conditions?"

I hope that helps clarify matters. I'm really thrilled that a couple of you whose opinions I sincerely respect have contacted me with a willingness to be interviewed.

My best,
David

[eric48]

Hi,

There has been a few threads recently about how far away a cure might be.

I think that the odds are that the initial condition of the Berlin patient met, namely:

- Be HIV + under HAART / UD
- need a bone marrow transplant
- find a Delta32 compatible donor

given the high number of people with HIV and access to modern care is high enough for the initial experiment can be reproduced.

one patient was cured, then will be a small group of 5-10, from whom we will learn a lot.

my hunch is that the first ones who will benefit from a functional cure will have to meet a number of criteria:

- amount of HIV in the body will have to be reduced to a very minimal to get started with (UD and even below 1 copy + depletion of reservoirs)
- intervention to lock the CCR5 door.

I think this is doable. Not for every one at first, of course, but doable from some of us.

The only intervention that is currently 'practical' for me to lock the CCR5 is maraviroc.

How far would I go ?

certainly as far as participating in a trial.

I tried to enrol in one already (NCT01033760) but did not meet one of the criteria (seroconversion had to be less than 6 months and mine was already 8 months)

I am considering this one now:

NCT00966329
Pilot Study to Assess the Safety and Efficacy of Switching the Nnrti or pi to Maraviroc in Hiv-1-infected Subjects With Persistent Viremia Suppression

and this one

NCT01190293
A Pilot Evaluation of the Pharmacokinetics, Efficacy and Safety of Switching From Efavirenz to Maraviroc Administered at 600mg Then 300mg Twice-daily in Patients Suppressed on an Efavirenz-containing Regimen as Initial Therapy

(but the problem is that I am under NVP and not EFV...)

How far would I go ?

I guess it may require a bit of travelling.

My doc was a bit against my first attempt to participate in a trial. I guess because of my age...
He did not seem to happy that I had applied without asking him first... The (kind) letter of exclusion I received also kind of implied that applications should be made by the doctor, not the patient directly.
Also, I support a family and a business, so I will have to make sure that things are covered on that end (but I have been working on this already).

But, yes, I am getting myself ready for a trial that would fit into that path. And this is on my list of items to discuss with my doc for my next visit.

Eric

[Ann]

Thus, the question ends up becoming, "How much are you, personally, willing to put on the line in the search for a cure and under what conditions?"

I'd put quite a bit on the line, of course depending on the specifics of the studies and like Matt, the opinions of those I respect in the field, including my own hiv doctor. (Saye Khoo, an hiv pharmacologist researcher and professor with The University of Liverpool and who is in part responsible for the http://www.hiv-druginteractions.org/ website.)

You can interview me. You have my email address.

[David Evans]

That's terrific Ann. I'll be in touch.

-D

[Tim Horn]

David's thoughtful piece is now live:

What Would You Do to Cure HIV?

[hope_for_a_cure]

Quick answer:

Had this question been posed to me a little over a year ago my answer would be 'I would go anywhere and do anything to find a cure'.  The possibility of a functional cure is not out of the question but now that I am actually feeling healthy again, I am not sure I would personally go to all extremes to find it.

Your subject line question did make me think though.  Would I participate in new drug trials?  Probably.  Would I make myself available for such if it required that I go off my current meds in order to achieve a more compromised state of health for the study?  No. 

[phildinftlaudy]

Great article David.

BTW, when do I begin my leg of the "book signing tour."