May 2009 Archives

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. 

As expected the California Supreme Court has upheld the institutionalized bigotry of Proposition 8- the anti-Gay Marriage law. In somewhat of a split decision, one which defies my ability to reason, the court is allowing marriages which happened in the period when Gay marriage was legal in California to stand.

It looks like the ruling was made on fairly narrow legal grounds, with the justices attempting to side-step the larger ideological question. The fact remains that these jurists, in a 6-1 vote, upheld the right of the voters of California to legally discriminate against a segment of the population.

One certain result from this is a lot of work for lawyers. The mixed nature of the ruling opens up many possibilities for suits, on both sides of the issue. Full employment for lawyers!

A pro gay marriage website reads, 'No Civil Rights Struggle Has Ever Lost,' which while heartening, doesn't ring true to me. Inequality in basic civil rights still runs riot throughout the world, despite universal struggle for equality.

Rights are not granted, they are won. Those who wield power over others cling to it with unrivaled jealousy. It must be wrested from their clutches by concerted struggle.

All in all the struggle is winning. I have little doubt that if my 16 year old daughter wants to marry a woman someday, she will be able to- here in California, in my home State of New York- and possibly in every State in the US.

The tide of public opinion is strong and clear: equality will win out in the end- but we should not rely on the courts or the next Governor to ensure basic equality- we must force their hands- through sustained, concerted, grass-roots organizing. 

The drug KP-1461 has long fascinated me (1, 2). It's novel mechanism- called Viral Decay Acceleration attempts to treat HIV infection by coaxing the virus into mutating itself to death. Years ago, I met with Koronis, the company developing the drug, as the were ramping up their development program. Fascinated by the sheer audacity of this mechanism, I have followed this drug a bit more closely than other drugs at similar stages of development.

As I wrote about in the earliest days of my blog, KP-1461 hit a major road block a while back. While still at Project Inform, I received a panicky sounding phone call from Stephen Becker- then the medical director for Koronis- and I knew something was up. Without rehashing details here, conflicting study results led to a full stop hold on development.

Last week Koronis issued a press release- copied below- claiming that their scientific advisory board had reviewed all of the clinical trials and laboratory data on KP-1461 and confirmed that it has measurable anti-viral activity and development of this compound will move forward.

As is typical, the press release is short on details. It states that 'recently completed passaging experiment' confirmed results from earlier, similar work. It was those passaging studies that were in question- the first set showed activity, a second set did not, and now apparently this third set confirms the first set of results.

I am not satisfied. I am awaiting a formal presentation of these results, with a thorough explanation of what went wrong with round 2. I have high hopes for  this drug, but the discordant passaging results plus the hasty, quiet departure of Dr. Becker have cast a bit of a pall over things. I haven't lost hope in the drug, or the Koronis- but they need to do more to convince me that all is well in KP-1461 world.

Koronis Pharmaceuticals' Scientific Advisory Board Confirms KP-1461 Clinical Drug Activity, HIV Ablation
 
Seattle, WA (May 19, 2009) - Koronis Pharmaceuticals, Inc., a biotechnology company focused on the development of antiviral therapeutics, today announced that its Scientific Advisory Board (SAB) completed a comprehensive review of the current in vitro and in vivo data for its lead HIV drug, KP-1461. The SAB concluded that recently completed in vitro serial passage studies corroborated the original published data, demonstrating that KP-1212, the active form of the oral prodrug KP-1461, ablated HIV in equivalent laboratory experiments. Additional studies are underway to assess ablation with greater sensitivity.
 
The SAB also reviewed statistical analyses of in vivo data from clinical trials of KP-1461. They concluded that KP-1461 demonstrated a statistically significant decrease in HIV RNA at the highest dose level as compared to placebo in the Phase 1b study. Decreases in HIV RNA were seen in some patients in Koronis' Phase 2a study, though the results were not statistically significant. Each clinical study met its primary endpoint of demonstrating that KP-1461 was generally safe and well tolerated.
 
"The current data confirms that the drug results in a substantial loss of HIV in tissue culture, demonstrates antiviral activity in HIV-positive patients and supports the continued development of KP-1461 and Viral Decay Acceleration™," stated James Mullins, Ph.D., Professor of Microbiology and Medicine at University of Washington and Koronis SAB Chair.
 
According to Dr. Mullins, "Koronis has shown that in a repeat of previous work KP-1461 reduces HIV titer to below detectable levels without noting the drug resistance that is seen with currently approved HIV drugs. This demonstration of the VDA mechanism, if confirmed by further clinical studies, will dramatically alter the treatment paradigm for HIV patients."
 
Koronis is in the process of completing formulation refinement and designing the next clinical studies of KP-1461.  

I am a revolutionary leftist. I hate listening to my people- other leftists- talk about science. So much left discourse on science is rooted in a fundamental lack of understanding of the scientific method and a confusion between what science is and what scientists do.

Science is not a thing- it is not an institution, it is not an ideology, it is not a group of people. Science does not have a point of view, nor an agenda. It is a structural framework for expanding what we know. It is much like language- a tool or method fully capable of being used for good or bad, but rather neutral on its own.

Assigning motive to a method is silly. If someone bakes a rotten cake, is the baking method to blame? Is the German language to blame for Mein Kampf?  Is music to blame for the Pussycat Dolls?

Science is sort of like technology- misunderstood and maligned in some quarters, misunderstood and lionized in others. The term technology simply means the collection of knowledge. Sure super fast computers are technology, but so are rotary dialed telephones and farming.

Science is just a method for learning and testing truths. Sure science is used to make atomic weapons, but so it metallurgy. Yet, so often science is treated like an entity- a coherent, self aware thing, with interests, agendas and so on. 

Take the song 'Science' by System of a Down (a band I love, but this song (which rocks) makes me cringe):

Science fails to recognize the single most

Potent element of human existence

letting the reigns go to the unfolding

Is faith, faith, faith, faith.

Science has failed our world

Science has failed our Mother Earth.

First, no science does not 'fail to recognize' faith. Scientists are keenly aware of faith, and the scientific method can be used to test aspects of it, just like it can to test most anything. Tons of scientific work has been done on faith- attempting to understand what roles it plays in the world, where it comes from, how it affects disease outcomes and so on. Perhaps what Serge meant to say is that 'science fails to defer to faith' that it doesn't assign a privileged place for faith. 

And how exactly has 'science failed our mother earth?' I am guessing this refers to pollution, overpopulation, deforestation, islands of plastic choking the oceans- that kind of thing. Science is not to blame, any more than George Eastman is to blame for all of those awkward teenage pictures of me.

It isn't science that causes pollution- people do. The process of polymerization- which underlies the production of plastics (and the formation of DNA) is not to blame for the ever growing blob of garbage floating in the pacific.

To take it one step further- this song seems to imply that faith- being the opposite of science (fair enough in a sense)- is the solution to the devastation wrought by big-bad science. 

Really? I mean, really, are you serious? 

While it would be a gross oversimplification to assign blame for the world's wars on different systems of faith- it is beyond argument they have played a big role. Have warheads ever been fired over a difference in scientific orthodoxy? I have seen some heated arguments between the lab coat set, but wholesale bloodshed has never been the result. Can 'faith' say the same?

On an unrelated note: Celia Farber, the yellow journalistic hack is suing Richard Jefferies of the Treatment Action Group for exposing her shoddy work to a group called the Sammelweis Society. Richard is one of the true quite giants of AIDS activism- one of the sharpest knives in our drawer. Farber is denialist posing as a journalist.

Hopefully the courts will quickly see this for what it is and dismiss the case with prejudice. I will follow the case closely and give updates as they come.

In case you read this Celia- yes you are a hack, and embarrassment to the idea of journalism. The only award you deserve is the igNobel or perhaps a Pee-Ew-litezer prize for rotten writing. Worse than simply being an incompetent journalist, you actively spread the lie of HIV denialism, perpetuating a falsehood that has literally killed millions.

How do you live with yourself. Really, how? 

I never thought I would something in common with Manny Ramirez. I am a life long Yankees fan, and he hasn't exactly been good to us. He is one of 

It isn't news anymore that Manny has been suspended for 50 games for violation of Major League Baseball's doping rules. The policy in question does not share what drugs people are being suspended for, but it always comes out. The story right now is that he was busted for using testosterone and human chorionic gonadatropid (HCG).

A statement issued by Manny claimed that he was being treated by a doctor for a 'personal medical condition' and the doctor gave him something that turned out to be banned.

Reports say that MLB decided to suspend him for the HCG, reportedly because he was going to challenge the testosterone finding, and the penalty is the same for one or two drugs.

The minute I heard HCG, I stopped thinking about this in baseball terms, and started thinking drugs. I have taken both drugs. A guy with HIV taking testosterone isn't exactly unusual, but HCG I imagine isn't that common.

I took HCG experimentally years ago when I had KS. My immune system was shot and nothing was really working. I had read somewhere that some people thought HCG might be a useful as a KS treatment, based on a couple of cases where women with KS went into remission when they got pregnant.

My doctor was willing to give it a try, with little to no guidance. We injected the stuff right in to my lesions. It didn't really seem to work. Luckily Doxil and HAART did the trick.

Only Manny and his doc know for sure why he was using it- as is should be. Ockham's Razor says Manny was using it to restart his body's own production of testosterone, which can shut down when you take exogenous (not produced by the body) testosterone. HCG can kick start your body's own production of testosterone.

It makes me wonder what MLB's drug testing exception policy looks like. I know that exceptions are made for prescription amphetamines for treatment of ADHD.

In any case, I just never thought I would have something in common with Manny .

According to several reports (1,2,3)

The media however just can't seem to get a handle on how to report these kinds of stories. One story never mentions the name of the drug- leaving the reader with the impression that any HIV drug could be ground up and smoked to get high. The most recent story- from ABS News,  story claims the drug is highly addictive- which is certainly not true when one takes it as an ARV, but in any case, this claim is made with no evidence to back it up. Of course, a bit of hysteria and demonization gets thrown in to the mix- with one headline calling the users 'thugs' and making claims that the problem is sweeping through communities across South Africa- with very little actual reporting to back it up.

It is also funny how this story keeps cropping up. The first of these stories was published almost 2 years ago, another in 2008 and the ABC story just last month. Each article treats this as a new story, with no context whatsoever. 

The wisdom du jour is that the H1N1 influenza, or 'Swine Flu', story has been over hyped by the media. I actually don't think that is the case on the whole, but that is not what I want to write about today.

No, what I want to talk about is a real example of hysteria in the media: a UPI article raising the specter of HIV combining with H1N1 to form the WORST VIRUS EVER!

Pure hysteria- and very poor journalism.

Most of the story is about whether or not the reaction to the emergence of H1N1 by world governments was proper. Buried in the story however is this outrageous sentence: "Health authorities are particularly worried that the capability to mutate already exhibited by the virus could eventually let it combine with the human immunodeficiency virus, which causes AIDS."

Oh, please.

The story does not say who these health authorities are or on what basis they are concerned that these two very dissimilar viruses are going to somehow combine. The writer, or these 'health authorities' seem to betray a real lack of understanding of the basics of virology.

The article cites the influenza viruses ability to mutate as the basis for this fear. How do influenza viruses mutate? In two important ways: First through random mutation- where genetic changes happen literally by mistake. The second is through recombination- that is the mixing of genes from different strains of the virus.

The same can be said for HIV. HIV is able to mutate quite well. It mutates through the same two pathways as influenza- so isn't that scary? Not really. Both viruses recombine with variants of themselves- not with entirely different, not closely related viruses.

I am not what you would call an expert in molecular biology, but a quick look at the structure and viral life of cycle of influenza suggest to me that these two viruses are far too dissimilar to ever combine.

This is an old story recycled. I remember back in the 1980s, when 'health experts' warned of the possibility of HIV combining with common cold viruses and wiping out humanity.

So those of living with HIV don't need to lose any sleep that our bodies are the microbial mixing vessels giving rise to the super virus to end all super viruses.  

The UPI should be ashamed of themselves. 

Today's post will be short- much to do. I saw a quote from the following on Facebook- and it spoke to me. The perspective is quite similar to a group of revolutionary students in France and elsewhere in the late 60s called the Situationists International. While I have never enjoyed reading Situ tracts- the most important of which are 'The Revolution of Everyday Life' by Raoul Vaneigem and 'The Society of the Spectacle' by Guy Debord- there is something to be said for their analysis: Modern life (in industrialized countries) is characterized by 'the spectacle'- an ongoing set of performances or real life theater. If you accept this to be true, you have a choice to be an actor (participant), an author (creator) or the audience (passive viewer). Simply put- the world is a stage- it is up to us to decide if we are players.

When I wrote this I didn't realize that the author had just died. RIP. 

World Theater Day Message 3/27/09

by Augusto Boal

All human societies are "spectacular" in their daily life and produce

"spectacles" at special moments. They are "spectacular" as a form of

social organization and produce "spectacles" like the one you have come to

see.

Even if one is unaware of it, human relationships are structured in a

theatrical way. The use of space, body language, choice of words and voice

modulation, the confrontation of ideas and passions, everything that we

demonstrate on the stage, we live in our lives. We are theater!

Weddings and funerals are "spectacles", but so, also, are daily rituals so

familiar that we are not conscious of this. Occasions of pomp and

circumstance, but also the morning coffee, the exchanged good-mornings,

timid love and storms of passion, a senate session or a diplomatic meeting

--all is theater.

One of the main functions of our art is to make people sensitive to the

"spectacles" of daily life in which the actors are their own spectators,

performances in which the stage and the stalls coincide. We are all

artists. By doing theater, we learn to see what is obvious but what we

usually can't see because we are only used to looking at it. What is

familiar to us becomes unseen: doing theater throws light on the stage of

daily life.

Last September, we were surprised by a theatrical revelation: we, who

thought that we were living in a safe world, despite wars, genocide,

slaughter and torture which certainly exist, but far from us in remote and

wild places. We, who were living in security with our money invested in

some respectable bank or in some honest trader's hands in the stock

exchange were told that this money did not exist, that it was virtual, a

fictitious invention by some economists who were not fictitious at all and

neither reliable nor respectable. Everything was just bad theater, a dark

plot in which a few people won a lot and many people lost all. Some

politicians from rich countries held secret meetings in which they found

some magic solutions. And we, the victims of their decisions, have

remained spectators in the last row of the balcony.

Twenty years ago, I staged Racine's Phèdre in Rio de Janeiro. The stage

setting was poor: cow skins on the ground, bamboos around. Before each

presentation, I used to say to my actors: "The fiction we created day by

day is over. When you cross those bamboos, none of you will have the right

to lie. Theater is the Hidden Truth".

When we look beyond appearances, we see oppressors and oppressed people,

in all societies, ethnic groups, genders, social classes and casts; we see

an unfair and cruel world. We have to create another world because we know

it is possible. But it is up to us to build this other world with our

hands and by acting on the stage and in our own life.

Participate in the "spectacle" which is about to begin and once you are

back home, with your friends act your own plays and look at what you were

never able to see: that which is obvious. Theater is not just an event; it

is a way of life!

We are all actors: being a citizen is not living in society, it is

changing it.