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HIV is a disease of the immune system and it is a chronic viral infection. It is two sides of the same coin. The virus side of the equation is not exactly solved, but we have many useful tools and a good and growing understanding of how best to use them. I wish I could say the same for the immune system side, but I can't. While myriad studies of anti-retrovirals (ARVs) continue to be enrolled and reported on, IBTs seem stuck somewhere between bench science and early human studies.
During most of my time at Project Inform, we had an IBT maven- a brilliant, prototypical activist-turned-expert Brenda Lein (who is happily retired). While never lacking for interesting and cutting edge discoveries to talk and write about, most of her activism work was on topics and interventions that were many years away at best from human application. One of our snarkiest activist once went off to me about how, in his organization, there would never be a person working on IBTs- because there was nothing to work on.
He had a point , and he was wildly wrong.
Immune based therapies (IBTs) have been held back by a combination of technical, financial and activist hurdles. While all of these challenges are real and often quite vexing, they are not intrinsically unsolvable; and solve them we must- at least in this writer's opinion.
It is helpful to remember that medicine has cured exactly one chronic viral infection- the Hepatitis C Virus (HCV). Leaving aside the real limitation and drawbacks of HCV treatment, it is nonetheless noteworthy that it has been cured. How? By immune based therapies: interferon and ribavirin. Interferons are a family of immune system proteins, with anti-viral properties. Ribavirin is a widely studied anti-viral drug, that does not exhibit anti-HCV properties in and of itself, but is thought to work by some for of immune system effect.
Both interferon and ribavirin have been studied unsuccessfully in HIV. In fact, ribavirin was one of the first drugs studied against AIDS- showing limited efficacy and significant toxicity.
Our immune systems 'cure' viral infections all the time. Somebody reading this post has a viral infection right now that is being fended off by his or her immune systems. The immune system is highly complex and not well understood. In terms of complexity, it is second only to our central nervous system (CNS). This complexity makes it fertile ground for basic scientists seeking to deepen our collective knowledge, but poses great challenges to drug development.
In HIV one of the most glaring problems is the lack of a clinically validated surrogate marker for immune dysregulation. To study an ARV, viral load and CD4 count are used as surrogate markers of disease progression. While we know HIV wreaks many kinds of havoc on our immune systems, studying this in detail in the absence of an easy to use and reliable surrogate marker is a problem.
Another problem is the success of ARVs. Prior to establishment of a more-or-less successful anti-viral treatment paradigm (HAART), IBTs were heavily studied- not just in academic centers, but by pharmaceutical companies looking to develop drugs to sell. The success of ARVs has raised the bar so high for the development of alternatives, that the logistic and economics become almost insurmountable. Getting a pharmaceutical company to invest in research and development in this environment is a tough sell.
Many similar problems have been overcome in this epidemic. Activism has been a consistent factor is this- concerted and scientifically sound community involvement from basic science through product development and study has played a part in getting us where we are.
We don't have the kind of activist presence in the field of IBTs. Richard Jefferies, of NYC's Treatment Action Group seems to be the lone wolf at this juncture. As smart and capable as Richard is, it is a tough hill to climb alone.
Many activists, including myself- have been put off by the complexity and density of this topic. When I go to ARV meetings, I know what they are talking about- more or less. At immunology meetings, not so much.
There was a time when ARVs were as mysterious to me as IBTs are now- more so in fact. But there were meeting to attend, publications to read and activists to learn from. Where does a less experienced activist interested in IBTs go to learn? What community level publication dose she read? What mentors does he look to?
I am not sure any of this is solvable. I am not sure it isn't either. I do think that truly solving the problem of HIV infection is going to involve manipulating the immune system, while also treating the virus. I fear we are falling too far behind on the immune based piece of this puzzle, and until we make real progress we will be truly unable to meet the full challenge that HIV poses to us.
HCV has been cured??? Really? Tell that to all the thousands that don't respond to the current treatment. Puh-lease.
Paul,
Yes, could n't agree more with the need to develop IBT's for HIV infection. One question; do you think if there was as much profit to be made in going down the IBT route (which should lead to eventual long term control / eradication) there would be MUCH more effort in this area.
FACT: there are BILLIONS of dollars to be made (have been made) from drug based HIV maintenance therapy and with all that lovely money coming in, there is not a real fiscal incentive to go down a route that will lead to a cure.
I would like to add that I am ever grateful for drug development and recognise the HUGE impact it has had on my life, but let's get real, there's not going to be any real development in IBT's for the reasons given.
Cheers,
Michael.
I too welcome the possibility of immune based therapies. As you may recall, a couple of researchers in Quebec discovered that the only thing preventing T-Cells from killing hiv was a missing protein. It has been over 3 years since this discovery. In addition, we have the experience of the bone marrow transplant patient in Germany who got a match from someone who had both parents with the CCR5 blocker. As a result, this patient is now reporting no evidence of viral load whatsoever.
IBT is the only way to go and I too am convinced that this is where the cure lies. But my own observations would seem to indicate that companies outside of the USA are more likely to develop it. The problem with the USA is that things are done by the lobby and big $$$. Most recently I contacted the FDA to make some suggestions on drug applications. And they routinely delete my email without even reading it. Do I need to say anything more?
i agree that IBT needs far more research. i strongly suspect that part of the IBT inertia among activists is due to vestigial paranoia about giving time to AIDS/HIV denialists. that group was always very vocal about IBT ("AIDS has more to do with poppers, illegal drugs, stress and depression than with HIV"), so i really suspect that some of the very-justified vigilance against HIV-denialists has spilled over into a general distrust of IBT.
of course, the complexity and skimpy HIV/IBT track record contribute as well...i think MOST activists really started learning about ARV after The Cocktail developed, meaning that most activists only want to know about something that they think/know will WORK.
unfortunately, that fact and the past association of IBT with denialists suggests that IBT activism will remain a lonely business for some time to come.
i think that's a shame, because i also suspect that the key to a CURE for HIV lies with IBT.
Hi Paul,
It was good to see you recently in San Francisco - sorry we didn't have the chance to chat for very long. I've been wanting to read your POZ blog for a while now, and tonight was the night. I'm glad I found this IBT piece of yours - it's quite well written, by the way, as all of your entries are.
As you know, I've been fascinated by IBT for many years, since my induction into clinical research studies for HIV Controllers. I may have started on a clean slate back then, but that's not true anymore. I continue to learn by reading about the human immune system every chance I get (not easy with a full time job plus establishing a new non-profit organization), and gleaning information directly from the many brilliant immunologists who conduct the many studies I am enrolled in.
I agree with you that the manipulation of the immune system holds an important part in the solution of HIV infection. I live with the hope that one day, this robust immune response within my body will get defined, and then shared, with the entire PLWHA community through the wonders of science. And, who knows, with a couple more years of study under my belt, I can team up with Richard Jeffries to keep him company on that climb up the hill!!
Peace,
Loreen