Paul's POZ Blog

The logo below appears fairly small in the scoring box during TBS television's coverage of the American League Division Series. When I see it out of the corner of my eye, I see AIDS not ALDS. Maybe it's just me. 

For the next few days at least- and hopefully longer- I will be in a New York groove. No, I won't be in the City, but following the Yankees playoff drive.  Game 1: CC is a horse, Jeter is a stud, A Rod has chased away his ghosts, and the Yankees lead the series 1-0. 

In HIV land, you might have seen this story from the fine folks across the hall in the aidsmeds.com cubicles about the early closure of a phase III trial of apricitabine (ATC). Apricitabine is an NRTI, like AZT or tenofovir- that was being tested in people whose HIV had developed resistance to 3TC or FTC. 

Avexa, the company developing apriciabine, released a cryptic (a-vexing?) press release saying that the study, meant to be 48 weeks, was being closed early in order to 'offer key insight into ATC's role in the overall HIV treatment landscape, and discussions with regulatory authorities may clarify the ATC approval path. Secondly, this will allow for a mature enough data point to enable potential partners the ability to make a definitive decision on licensing of ATC'

I have no insider scuttlebutt on this story, but it doesn't sound good. The development of this drug has been slow and meandering. The studies done to date have shown some efficacy, but nothing really special. 

The Avexa press release, while not really telling us anything, suggests to me that this drug is dead in the water. Typically when companies have positive news they share it. This is even more true of smaller companies, who are dependent on investors.

The need for such a drug is questionable as well. On one hand, many (most?) people's HIV will develop resistance to FTC or 3TC. These drugs are part of most HIV regimens and a single point mutation- called M184V- is enough to greatly reduce the virus' susceptibility to the drugs. However, some research- including a study presented at the recent ICAAC conference, shows that people seem to do just fine clinically if they keep taking these drugs after that resistance mutation emerges. 

The bigger picture question for me is the need for NRTIs. NRTIs- the first class of HIV drugs developed and still the 'backbone' of the vast majority of HAART regimens- don't match up favorably when compared to the rest of the anti-HIV armementarium. They are relatively weak and toxic and their place in the 'HIV treatment landscape' is largely an accident of history- that is it has more to do with when the drugs were developed than any strong research. 

This should not be read as 'stop taking your NRTIs.' While I have doubts about this entire class of drugs, there simply aren't enough data yet to adequately understand the role they play, or more accurately should play in HIV treatment. 

As we wait for more data- Go Yankees!

After I hit save word came down the proverbial wire that the FDA has voted to approve Selzentry (maraviroc) for people taking HIV drugs for the first time. Stay tuned for more info. 

I admit it it. My first reaction to this story was, 'told ya so!' My second reaction wasn't much more evolved- something along the lines of 'duh!' Eventually I was able to access a deeper part of my humanity and feel genuine disappointment that the vaccine breakthrough is even less than it appeared on first blush. 

To review: Almost 2 weeks ago, the mainstream press ran stories trumpeting the first ever successful HIV vaccine test results. The basic story was that researchers combined two failed vaccines, using a two step prime-boost method, and tested them in Thailand. It was a large, expensive, randomized, controlled trial- enrolling 16,000 people and following them for five years. 

The press release touted an approximately 1/3 reduction in the number of new infections among people in the vaccine arm, compared to those who received a dummy or placebo vaccine. If validated a vaccine with even this modest level of protection would indeed be a breakthrough.

I was initially skeptical for two reasons. First, the vaccines used in the study had failed in previous studies, and combining two ineffective vaccines seemed highly unlikely to result in a successful vaccine. The second reason is some of the people involved in this study, were with Vaxgen when they engaged in unethical data spinning, in a desperate attempt to secure more funding. 

So, I was not surprised when I read that another analysis of these data showed that the results failed to meet statistical significance, and that analysis was suppressed. This second analysis removed anyone from the calculations who did not strictly follow the study protocol. Analyzing the results this way amounts to a strength test for the original analysis- a vaccine that is truly protective, even modestly so should test out so in either way. 

The fact that it didn't and that the researchers chose not to share that analysis deepens my skepticism. 

And while I felt a bit of schadenfreude, I do feel an honest sense of disappointment. The HIV

 vaccine effort could really use some good news- a proverbial shot in the arm if you will forgive me. But this kind of data cooking is exactly not what is needed. Science relies on honesty, failed studies are often just as valuable as successful ones, when they deepen our understanding. A full, unbiased understanding of this, or any study might serve as something to build on. Nothing of meaning can be built on scientific dishonesty. 

I have a bit of a bee in my bonnet this morning. The New York Times had the following sentence in an article on the Pope's European tour: ''The Pope came to this decidedly skeptical nation (The Czech Republic) as part of a Continentwide mission to urge the nonbelieving out of their collective apathy".

To be a non-believer or skeptic in a world dominated by faith is not to be apathetic. It takes a courage of convictions to embrace reason in the face of world where to question a person's faith is akin to calling their Mother a bad name.

A recent poll, widely reported in the media, found that atheists and non-believers are considered amoral and wicked. The study asked the question, "This group does not at all agree with my vision of American society," about every major religious group and ethnic group, as well as recent immigrants and of course of atheists.

Atheists won the most reviled award.

Why is it that it is verboten to question virtually any aspect of someone's faith, but is fine to criticize the lack of faith? I am used to being out of the mainstream and I don't need the warm embrace afforded to the in-groups of the world.  You can have your stories, I'll take mine. But if you are a so-called 'person of faith' ask yourself why so many of your compatriots think I am wicked and amoral for opting out of your hegemony.

The good works of churches and other faith-based institutions in combating the AIDS epidemic is commonly reported, and rightly so. What about the great works of the non-believers? Every survey of scientists finds the vast majority are atheists. That means the pills that keep us alive, the lab tests that monitor our health, the studies that detail the dizzying complexities of our pandemic, not to mention the vaccines and cures that are being worked on- those are all the works of the reason-based community, of the non-believers.

We are a mostly-quiet and growing minority. We are far from apathetic. Every non-believer faces a moment, or more likely moments when we actively choose to reject what we have been told, and embrace what we have learned. To do so takes bravery- we know our lack of faith is fair fodder for dismissiveness and hostility.

We swim against a mighty tide, and do so at our own peril. We are not apathetic. We are, each of us in some way activists.

 

What in the world to write about today? The 'Vaccine Breakthrough'? Abbott? The Fires of Montana? The Yankees? The Pope and Science? 

The world has provided me an embarrassment of riches to e-scrawl my thought on. Being more of a 'both/and' than 'either/or' person, my thought is to embrace the deluge and hold forth on it all.

Topic 1: The "Vaccine Breakthrough"

The Story: This past week the mainstream media was filled with almost breathless stories on reports of a major breakthrough in the struggle to develop a vaccine against HIV. Researchers had announced results from a trail of a prime-boost combination of two failed vaccine candidates, and found an approximately  one-third reduction in infections.

My Take: Be skeptical. Be very, very skeptical. The minute I read this story with my first cup of coffee on Thursday, a gnawing sense of déjà vu crept in. The 2 vaccines in question- ALVAC and AIDSVAX, have been tested before with quite poor results. Moreover, in the AIDSVAX case, the developers engaged in some highly unethical shenanigans- attempting to spin their full-bore failure, into a unsupportable partial success.

The vaccines in question had been fairly extensively studied previously and showed no protective effect whatsoever. While it is conceivable that combining two ineffective vaccines could be combined to make a marginally successful one, it is unlikely. As veteran AIDS activist Gregg Gonsalvez  was quoted as saying in the New York Times, 'two duds don't make a firecracker'.

The data, such as we have seen aren't exactly spectacular. The study followed over 16,000 Thais: half getting a 2-stage vaccine (called a prime-boost) and half a placebo. Everyone was given condoms and counseled about safe sex. At the end of the trail there were 51 new HIV infections among people in the vaccine arm, compared to 74 in the placebo group- or a 31% reduction in infections.

While on the surface this modestly positive result looks good- like something researchers could build on to create a more broadly protective vaccine, a close look at the limited data available to us gives me much less hope.

I am skeptical for two reasons. First these results are barely- and I do mean barely statistically significant. Second, as mentioned previously there is a history with one of the 2 vaccines used in the study of unethical data spinning.

What do I mean by 'barely statistically significant'? In research, it is understood that a single study can only provide a best estimate. There is always an element of chance involved. To account for this, statisticians use something called a 'confidence interval'- which basically provides an upper and lower range (or bound) where we have a 95% degree of confidence the real results lie within. If the lower part of that interval is at or below 1, the results are not significant- that is there is enough possibility they are from chance, they cannot be counted on. In this study the lower bound of the confidence interval is 1.1%, meaning that just a handful more infections in the vaccine group, or fewer in the placebo group would have rendered the results non-significant.

Moreover, the people developing one of these two vaccines- the AIDSVAX- have a sketchy history. In an earlier study of their vaccine, they attempted to spin the overall negative results from their study, by engaging in a bit of data mining. Data mining is when you crunch the numbers from a study over and over, looking for something positive. In this case, they claimed that while their vaccine failed to protect the overall study group, it seemed to work quite well in people of African and Asian ancestry.

The problem was there simply were close to enough people of African or Asian ancestry to make such a claim. This led to wider than wide confidence intervals, not even close to statistically significant. Looking more closely at the results among African Americans, they hinged on just a handful of fewer infections at one study site (Chicago if I remember correctly). While I can wrap my head around the notion of a vaccine working differently in people of different ethnic groups, I cannot imagine a vaccine working differently in African Americans from Chicago compared to those in Los Angeles.

I hope this result is real- we need something positive to build on. Let's just stay I am not confident.

Story 2: Abbott buys Solvay.

My Take: Abbott, the makers of Kaletra and Norvir- along with a bevy of other drugs- are buying Solvay Pharmaceuticals- the makers of Marinol among others. This is bad news on two levels. First, Abbott are the worst or the worst in the rouge's gallery of big Pharma. Their behavior towards people with HIV and the activist community is abhorrent. Anything that makes Abbott bigger, and increases their reach in HIV is bad news.

Bore broadly though, this is another step in the consolidation of the industry. Fewer and fewer players in the pharmaceutical industry is bad news for people with HIV- for people in general.

Boo to Abbott. Boo to corporate consolidation.

Story 3: The Fires of Montana.

My Take: I just got back from my latest trip to Montana. I have written before about my love for my adopted third home Montana. This latest trip was, well a trip- as we spent the whole weekend under an evacuation warning due to a near by wild fire. As we approached the bucolic beauty of the Feather Pipe Ranch outside of Helena, a tower of dark smoke rose from a near-by mountaintop. As we drove closer, we could see flames and ash began falling from the sky.

The fire stayed far enough away that we didn't need to skedaddle.  The people of the FDH and Associates, and the Montana Gay Men's Task Force deserve so much praise for the great work they do on behalf of people living with HIV in Montana. The weekend was filled with workshops, community building and fun. I am always impressed by the quality of the presentations and the sense of togetherness I experience when I fly in those little puddle jumper airplanes to the great state of Montana.

Story 4: The Yankees.

My Take: I am a huge New York Yankees fan. Yesterday, as I soared through the clouds somewhere between Salt Lake City and Oakland, the Yankees won their division, and secured home field advantage throughout the playoffs. The proverbial icing on this delicious cake was they did it by sweeping the hated Red Sox in the Bronx. I come from a family evenly divided between Yankees and Red Sox fans. I am resisting the urge to call my Red Sox loving father and gloat today. I am evil. I know.

This season has had a special feel to it. After struggling a bit in the first few weeks of the year, the 26 time world champs have player remarkably consistently great baseball since May. After dropping the first 8 games of the season versus the Sox, the Yanks won 9 of the last 10 to split the season series. Back in June I told my roommate- a life long baseball fan and Yankees hater- that whatever happened this year, I liked this year's Yankees. They had the feel of a good team. While the last few years have seen early playoff exits (or last year no playoffs at all), I like our chances this year.

Story 5: Last but not least the Pope and Science

My Take:

Pope Ratzinger- or Benedict- gave a speech in the Czech Republic warning of the dangers of secularism and calling for a repair of the rift between science and religion. I am a cultural Catholic and a committed atheist. Being scolded by the former Hitler Youth Pope about the dangers of non-belief, is, well beyond belief. The science thing is especially galling. The rift between science and religion is 1) largely beyond repair and 2) mostly the product of the repression of science by religion. Religion is at war with Science. From Copernicus and Galileo to attempts to force the anti-science of 'intelligent design' into science classes the forces of faith have long worked to silence free scientific inquiry. Where has science sought to suppress faith? Where? Unbelievable. 

Today's New York Times has an interesting article about Dr. Richard Pazdur, the FDA's cancer guy. If you get a chance to check it out. It brings up a few interesting issues that drug companies, advocates, regulators and patients face when dealing with drug development for serious illnesses.

What struck me most from this story is how good we have it in HIV. Through many types of dogged activism, we ended up with a system where, for the most part, the right drugs get approved in a timely fashion. We have validated surrogate markers, bright and dedicated community activists and a track record of success.

How different it could have been. What would the world be like had the FDA remained unmoved, unchanged by the early AIDS activists? Without parallel track, expanded access, accelerated approval, CABs- where would we be.

The business of drug approval is fraught with competing interests. Drug companies want their drug approved. Patients and advocates struggle with the desire for new drugs against the realities of toxicities and side effects. Regulators have to shepherd the process, balancing the desire for new treatments against the many vagaries of biomedical research.

AZT was approved based on its ability to extend lives by a matter of weeks. The first combination therapies- dual nucleosides (d4T plus 3TC for example), were used because the could be shown to slow the rate of immune decline. Three drug therapy- or HAART as it has become known- showed the potential to reverse HIV disease progression.

In the early days, it was a given that the drugs would make you sick. The main question was would they give you more life. Now, it is pretty much a given that new HIV drugs will 'work'- they will reduce HIV levels, improve or stabilize CD4 counts- and mostly we argue over tolerability and durability.

I am not familiar enough with the state of cancer research to have opinions on their drug development process. This article makes it clear there is still a lack of agreement on how these drugs should be studied and evaluated.

Cancer is the second leading killer in the US- behind only heart disease. Most research shows that people with HIV are at a higher risk of cancer overall, in addition to being at specific risk for HIV associated cancers like KS, and lymphomas. In short we have a dog in this fight.

Speaking of dogs and cancer- it is the 40^th anniversary of the declaration of the war on cancer, and the 40^th anniversary of Scooby Doo. How little both have changed over this time.

The FDA has issued a new safety warning for the NNRTI Intelence (etravirine). The text reads:

 

August 2009
Dear Healthcare Professional:
 
Tibotec Therapeutics, in cooperation with the U.S. Food and Drug Administration, would like to inform you of an important safety update to the Severe Skin Reactions WARNINGS AND PRECAUTIONS section (5.1) of the INTELENCE (etravirine) tablets prescribing information.
 
Specifically, the existing Warning and Precaution regarding Severe Skin Reactions has been strengthened to reflect that there have been postmarketing reports of:
• fatality due to toxic epidermal necrolysis
• hypersensitivity reactions, sometimes accompanied by hepatic failure
Additionally, Guidance has been added that INTELENCE should be immediately discontinued when signs and symptoms of severe skin or hypersensitivity reactions develop. Given the clinical relevance of these adverse reactions, the following information regarding severe skin and hypersensitivity reactions has been included in the INTELENCE Prescribing Information

 

These kinds of reactions have been seen with other drugs in this class. 

 

Intelence (aka worst HIV drug name ever) is a second line NNRTI for use in people whose HIV has developed resistance to other NNRTIs, like Sustiva (efavirenz) and Viramune (niravapine). 

The New York Times has an article today on the possibility the CDC might recommend routine male circumcision in the US to prevent HIV infection. Both sides in this argument fail to make their case.

Male circumcision is an effective prevention method- in areas with high seropravelence (lots of people with HIV) and high rates of heterosexual sex transmission. Data of this began emerging around a decade ago, and eventually randomized trials showed it to be effective.

So, if it has been show to work, why not do it here? Because there is little reason to think it would work.

To begin with, the US is not a high seroprevalence country. Nor do we have high rate of heterosexual sex transmission. And around 70% of boys already are circumcised.

The studies on male circumcision have looked exclusively at its effect on heterosexual transmission in areas of high seroprevalence. Extrapolating their findings to the US doesn't make much sense.

The opponents of circumcision don't manage to make much of a case themselves. They have rented mobile billboards to cruise around Atlanta during the ongoing HIV Prevention conference, simply saying- Circumcising Babies Doesn't Stop H.I.V." A spokes-person is quoted as saying that the studies done in Africa only found that circumcision reduced HIV infection risk, and that 'Men still need to use condoms.'

Sigh.

No prevention method is perfect- none works all the time. That is, simply put, irrelevant.

I honestly don't know where this debate will go. The prevention world is riddled with flimsy science and even flimsier extrapolation from that science. I am in favor of increased exploration of novel HIV prevention modalities, particularly biomedical ones. I think we have long since hit a wall on our behavioral interventions (not that they should be abandoned, but we are past the point of diminishing returns). As with questions of treatment, these examinaitons should be driven by good, solid science.If this is any indication- I am not hopeful.  

In addition to being an AIDS activist, I am an anarchist. I have been mixed up in radical and revolutionary activism since I was a teenager, attending anti-nuclear demonstrations at the Seneca Army Depot in upstate New York.

The worlds of AIDS activism and anarchist activism don't overlap much (Liz, this is me winking at you, if you read this), but they do act a lot alike.

Recently there was a dust up between two groups of anarchists in Pittsburgh. It happened at this meeting called by a group called Crimethinc- who I really have no love for. The short version of the story is a small group of anarchist people of color disrupted the larger gathering and used intimidation and petty thuggery to force the attendees to leave the space.

I wasn't at the meeting, so I can't speak in any real detail about what went down. I have read pages upon pages of accounts from people on both sides of the controversy- and I think it is fair to say the whole thing is an embarrassment.

It is also highly evocative of the AIDS activist movement. Specifically it speaks to a tendency to attack each other while simultaneously wondering why there aren't more of us.

Every activist strain I have been involved in has struggled with the impact that racial, sexual and other forms of inequality have on the internal dynamics of the movement. AIDS activism in the US is disproportionately white, educated and male- something we are aware of, we talk all the time about, we seriously grapple with how to change, and ultimately fail to overcome.

Social conditioning is tough to overcome. What doesn't help matters I think is our tendency to attack those who we feel are not as right as us. In the anarchist world this often translates to people being called out for not behaving in ways entirely consistent with their politics (e.g. feminist men dominating meetings). In AIDS it takes on a more personal aspect, possibly because there are so few of us.

 

In both cases the net affect is a movement that can't grow. AIDS activists struggle to find ways of nurturing and helping to develop young, or just new cadre. It is complicated stuff. Years ago at the now-defunct NATAF (North American Treatment Action Forum), I overheard a woman say, "Treatment activist eat their young," What she meant was we are viscous and harsh with each other. At the same conference I heard and participated in many conversations lamenting the lack of new activists in our mix.

Activists are often playing from a sever deficit. We are usually outmanned, outgunned, outflanked and out-funded. This is as true of AIDS activism as it is for anarchists. Our adversaries hold most of the cards. We would do well to better recognize the value of imperfect bodies on our side.

This story from CNN.com announces the discovery of a new strain of HIV. Briefly, scientists have identified a 4^th major type of HIV-1, this one originating from gorillas, unlike the previously identified strains that came from chimpanzees.

What does this mean? Likely not much, but it warrants keeping an eye on.

This discovery will likely be mostly of interest to few. It isn't likely to change the epidemic in any meaningful way- and if it does, it would take years and years before that became true.

It interests me because it deepens our understanding of the origin of HIV. Where HIV came from, how and when it jumped to humans and how it grew to a world wide pandemic are fascinating questions.

Many people favor conspiratorial approaches to understanding complex questions, I favor natural explanations. In the HIV world, we are beset by a group of flat-earthers who believe that HIV was cooked up in a lab by evil government or pharmaceutical or illuminati agents. This world view is not restricted to HIV- apparently as the Swine Flu epidemic is hitting Argentina quite hard, various forms of denialism are rearing their cretinous heads- saying either the virus was engineered by big Pharma, or by the vaccine makers, or as a social control mechanism- or all of the above.

To me this is anthropocentric hubris- the fatally flawed belief that humans are the center of the world. We are certainly special creatures- capable of much. But our influence is much more limited than we tend to think. The microbial world is more complex, varied and impactful than any of us can likely imagine. I like to point out to people that our bodies have 10 times as many microbial cells than human cells. Our planet is not really ours- we are just bit players in a much bigger, more interesting story.

I don't choose to see 'nature' or 'the earth' in human-centric terms (mother earth, gia, father sun...). We are of nature, it is not of us. I am certain that humans are capable of the kind of evil that would brew up a deadly virus and seek to use it to harm whole populations. I am also certain that viruses have been morphing long before human avarice was a sly glint in a troglodyte's eye. Again with Occam's Razor- the simplest explanation is most often the correct one.

So, we have another strain of HIV to study. And study it we will.