In yet another setback for the star-crossed CCR5 drug class, Merck has announced it will not seek approval for the drug vicriviroc in treatment experienced patients. Merck acquired Vicriviroc, once known as Schering D, when they merged with Schering-Plough in late 2009. While the company's press release promises continued development of the drug for use in people taking HIV drugs for the first time, it remains to be seen whether this drug, long stalled in development, can gain the sort of traction needed to be approved.
Vicriviroc is an HIV drug that works by attaching to the CCR5 receptor that HIV can use to gain entry in to CD4 and other immune system cells. Not long ago, this drug class was considered to be the 'next big thing' in anti-HIV drugs, holding the potential for strong activity and few side effects. This promise has largely failed to materialize due to a combination of unexpected toxicities, poor performance and company missteps.
A few short years ago, there were three promising CCR5 drugs bunched closely together in the development pipeline. The first to fall was apliviroc, being developed by GlaxoSmithKline. GSK halted development of apliviroc when rare, but catastrophic liver toxicity occurred. Maraviroc- sold in the US as Selzentry- did gain approval a couple years back, but it has been beset by poor sales and the need for an expensive and slow blood test required for its use.
This announcement was based on vicriviroc's failure in two, phase III trials. While disappointing, this is hardly surprising. It had shown marginal benefit at best, and its development was plagued by delays and the lack of a clear development plan by Schering. When Merck and Schering merged, there was a glimmer of hope that Merck's better track record of drug development would finally move vicriviroc forward. This faint glimmer may prove to be a mirage.
The future of HIV drug development is uncertain and troubling. Pharmaceutical companies are looking elsewhere, to markets that are larger (like heart disease), more profitable (like aging) or less crowded (like HCV). While the need for new HIV drugs is undeniable, the simple truth is that more and more companies do not see HIV as an attractive, or even viable option. The failure of another HIV drug is likely to add to this worrying trend.
The HIV drug development pipeline isn't exactly empty. New drugs are being studied. Good drugs, handled correctly by the company developing them can make their mark on the epidemic. HIV is a very data driven market, one where good drugs win out, at least eventually. Whether or not activists and interested scientists can convince the corporate bean counters to invest the necessary capital and other resources to developing these vital new drugs remains to be seen.
In and of itself the latest setback for vicriviroc isn't huge. While Reuters' coverage claimed that 'some industry analysts' considered vicriviroc to be, 'potentially the best' drug of its type, I certainly don't. This drug has languished in development, making halting progress at best. It is more important for the psychology of the HIV drug development field, than for the drug's merits.
The New York Times today ran an article detailing the ongoing hurdles that researchers face when trying to study marijuana for medical uses. It got me thinking about both the power of anecdote and the influence of politics on the scientific process.
I have been living with HIV now for 17 years. I went on treatment in the mid '90st. I started with dual nucleosides (d4T and 3TC), and moved on to protease inhibitors as soon as they were available. I had a rough go of it with the early PIs- particularly Crixivan and full dose Norvir.
When I started treatment one of my issues was being underweight. I was also prone to GI side effects, like nausea in fact my family doctor curses what he calls the 'Dalton Stomach'). My doc prescribed Marinol for me, and said that most of her patients preferred the 'herbal form,' meaning of course marijuana. At the time, it had been years since I smoked any pot, but the medical marijuana movement was starting up and the first such club had opened in San Francisco.
One weekend I went camping with some close friends. On our way home, I was really nauseated. My then-young daughter was on the trip with me, and I tried to avoid using marijuana when I was with her. We stopped along the way to eat lunch, and I was doing all I could not to vomit. Finally, I walked down the road a bit, took out my pipe and smoked a little bit of pot.
Almost instantly I felt better. The people I was with were quite struck with the difference it made- more so than I was. They said my color and affect and energy changed dramatically. They instantly believed in medical marijuana.
Anecdotes like this are powerful and important. Many, perhaps most, medical advances are sparked by anecdotes, or simpe observation. I learned recently that lithium's use to treat bipolar disorder came when researchers studying it for seizures noticed that people's moods seemed to be impacted. Viagra was being studied as a heart medicine when its affects on erectile dysfunction were noticed. These stories are very common.
I used medical marijuana based entirely on anecdotal evidence. Word was it helped with things like nausea and weight gain. I tried it and it worked well for me. I had to make the choice to try it based entirely on what I was hearing from others living with HIV.
Anecdotes must be followed up by careful research if they are to become part of evidence based medicine. There is a lot of interest among researchers at looking at various medical uses for marijuana, but the roadblocks in their way are enormous. It is a classic catch-22: the government claims that there is not enough evidence of marijuana's medical benefits for it to be used in this way, while at the same time blocking the research that would show whether or not it works.
While I have been fortunate to live in California, where voters semi-legalized medical marijuana, I am reminded of what can happen under other circumstances. I learned a while back that one of my favorite teachers had to buy marijuana for his mother who was being treated for cancer. This was back in the 80s. If he had been arrested buying this medicine for his mom, he would have lost his job- plain and simple.
The government needs to get out of science's way. Take down the barriers to scientific study of marijuana. If it doesn't offer any benefit over currently available options, so be it- the point is to allow the research. There is no compelling public health reason not to allow such research to go forward- it is simply politics and institutional inertia.
The earthquake in Haiti is one of those events so vast in scope as to be impossible to really comprehend from afar. While no place deserves this kind of devastation, Haiti is perhaps the worst place for such a disaster. If, as it has been said, Afghanistan is where empires go to die, Haiti might be where misery goes to live.
Haiti and AIDS are indelibly linked. Haitians were perhaps the most feared and reviled of the original 'Four H Club' of Haitians, Homosexuals, Heroin users and Hemophiliacs. Extreme poverty, language and cultural barriers served to isolate and demonize people from Haiti- especially those seeking refuge from the western hemisphere's poorest country.
If any place on earth deserves a break it is Haiti. Haiti was the first independent nation built by freed slaves. While Pat Robertson might like to entertain the racist fantasy that Haiti's long suffering is due to a 'deal with the devil' they supposedly struck to win independence, the truth is they shrugged off the all to human evil of slavery and have been suffering its lingering effects along with those colonialism, ineffective governance, a lack of natural resources, an inadequate infrastructure and international neglect ever since.
'Mother Nature,' can be exceptionally cruel, as can be seen by the bodies currently rotting in the streets of Port au Prince. The pictures of collapsed buildings, roads and hillsides tell of both the power of nature and the consequence of a country that just doesn't have what it needs. The lack of building codes has led to untold death and misery- and a bit of condescending recrimination all too reminiscent of the immediate aftermath of Katrina.
It doesn't have to be this way. Yesterday I read somewhere that every day cruise ships throw away more food than the average family in Haiti uses in a year. I don't know if that is accurate, but it at least serves as a good metaphor for the very real consequences of massive economic inequality. There is much that is out of our control in this world, and certainly earthquakes are one of those things. How we allocate and use the world's resources however is very much in our control.
While the 'Teabag Movement' gets its collective panties in a wad over entirely imagined 'creeping socialism'- the greatest threat to the world is on display today in Haiti, just as it was in New Orleans, as it was in Biafra, as it was with the Tsunami of 2004. While we have some influence on what we call 'natural disasters', they will always be a part of life on earth. As long as we tolerate a world where bankers get multi-million dollar bonuses for running their businesses in to the ground, while just a few hundred miles south of the richest country on Earth most people live on less than a dollar a day- those natural disasters will have very unnatural consequences.
I am part way through the book, 'Denialism: How Irrational Thinking Hinders Scientific Progress, Harms the Planet, and Threatens Our Lives,' by Michael Specter. I will review the book properly when I am done reading it. Right now though, I want to talk about one of the important concepts he talks about- one that is of vital importance to people living with HIV/AIDS. The concept is how harm and risk are understood and misunderstood in our society.
It is my experience that people with HIV/AIDS, and those who work with us think about risk and harm quite a bit. We think of it in terms of our meds, of our sex lives and increasingly of things like heat disease, cognitive decline and other consequences of aging. It is also my experience that we often talk about risk and harm in ways that are both inaccurate and unhelpful. While some of this can be chalked up to inadequate math and science education, the important concepts involved are neither highly technical nor particularly complicated.
Most importantly: all risk is relative. In other words if you want to understand how risky something is, you have to compare it to something else. So to say something is 'safer' means nothing if you don't say what it is safer than. For example if you want to understand how risky it is to fly on an airplane you can't just look the likelihood of perishing in a plane crash (the number of plane crash fatalities divided by the number of people taking flights during a defined time), you need to compare it to something appropriate- like driving a car, taking the train, or not traveling at all.
Relative risk is what we need to understand to make good healthcare decisions. As a person living with HIV I have to weigh the risk of taking an HIV drug. I can do this in a few ways. I can look up the list of possible side effects and leave it at that. This will give me important, but incomplete information. It will tell me what to look for, and that is all. A better way to look at the same thing would be to look at how likely any possible side effect is- what percentage of people got the side effect- is it 5% or 25%? This way gives me a better, but still incomplete basis to make a decision. I now know how likely a side effect is, but I need to know one more thing- what is my risk of not taking the drug? This should be though of in two ways- both by comparing that risk to other drugs I might take, and to the risk of not taking any drugs at all?
The foundation of medicine is the concept of 'do no harm.' Sometimes the most harmful thing to do is nothing at all. An easy example would be whether or not to take something like Septra or Bactrim to prevent PCP (pneumocystis jerovici pneumonia) if your CD4 count is below 200. There are known risks to taking these drugs, including the risk of death. If the question is posed as 'is taking Septra more risky than not taking it?' the answer may be different if you only look the risk of a fatal drug reaction than if you compare that risk to the risk of getting PCP if you don't take it. While there is a small risk of a fatal drug reaction from taking Septra, there is a bigger risk of getting PCP if you don't take it.
This is made more difficult because of the power of the anecdote. To most anyone who isn't a statistician or scientist, anecdotal evidence (otherwise known as our real life experience) is much more powerful and compelling than an incidence calculation or risk ratio. Back to flying as an example- as Specter says in the book- we are bound to remember dramatic and compelling events like a plane crash, and just as likely to forget all of the planes that didn't crash. But the risk of flying is demonstrably lower than the risk of driving. Plane crashes are more dramatic and much less common that car accidents- this leads many of us us to be more fearful of flying than driving, even though our chance of dying in a plane crash is a tiny fraction of our risk of dying in a car crash.
I had a discussion about this with a friend recently as I was starting a non-HIV related meds. She was telling me of some online forums she had used when taking the same drug, and warning me of the horror stories people posted. I thanked her for the resource and told her that because of my work in HIV treatment activism, I had a pretty good lens to view those kinds of things.
Whenever I talk about HIV drugs and side effects, I start off by stating that I think that almost everyone with HIV or any close connection to people with HIV is highly likely to have an exaggerated sense of both the frequency (how often) and the severity (how bad) of side effects from any HIV drug. The reason for this is simple- we notice when people have side effects, especially the more severe ones. We don't notice when people don't have them, just like we don't really notice when planes don't crash.
This is not to discount the reality of side effects- they happen and should be paid attention to. It is simply to remember that most every medical decision we make entails risk and the only way to really understand that risk to compare the risk of the alternatives, including the risk of doing nothing at all.
I am not a math person. Numbers make me cranky. I take comfort however in the realization that I make relative risk calculations for myself every day, the same way anyone reading this does. If I get in a car, I know there is some risk in doing that. I try to minimize the risk by wearing seat belts, and not texting while I drive. The risk is never going to be zero, but neither is the risk of not getting in a car. So, if you need to drive to your job every day you accept the risks of driving because they are more tolerable than the risks of not driving (losing your job for example).
AIDS activism grew out of this understanding- people were willing to fight for the right to take very real risks with their lives by taking drugs that were not well understood or even known to work, because the risk of not trying them was understood to mean almost certain death. A drug like Hivid (ddc) would never stand a chance of being approved (or probably even getting in to human studied) today, because it caused too many side effects and there are safer alternatives. When the drug was approved the risk of side effects was pretty much (but incompletely) understood- but there weren't really safer alternatives. Therefore it made sense for the drug to be approved at that time. It equally makes sense for the drug not to be used now- the relative risk has changed.
Today's New York Times Science Section has a ridiculous
article titled, 'Sorry Vegans, Brussels Sprouts Like to Live.' While I am not
vegan, and I dislike brussels sprouts, this article deserves some of my scorn.
Today's New York Times Science Section has a ridiculous article titled, 'Sorry Vegans, Brussels Sprouts Like to Live.' While I am not vegan, and I dislike brussels sprouts, this article deserves some of my scorn.
The gist of this thought piece is that plants do what they can to survive, that they in some sense 'want' to live and therefore there really isn't a substantive difference between eating a head of cabbage or a head of a pig.
One of the most basic features of all life- from the simplest single celled amoeba to the most complex mammal- is the instinct to survive. So it shouldn't exactly be news to anyone, be they herbivore or carcass chewer, that plants- no less than any member of the tree of life, do whatever they can to survive when threatened.
The article gives some fairly neat-o examples of this: almost instant chemical reactions by plants in response to insects chewing or the production of tumor like cells to rid themselves of larvae. Cool. And irrelevant to the questions arisen by dietary choices.
The subset of vegetarians and vegans who base our food choices on ethical principles are, I feel safe in saying, universally aware that plants are alive, and hence attempt to stay alive. Given that photosynthesis isn't an option for us, we draw the line at the Kingdom level (remember high school biology? Kingdom Phylum Class Order Genus Species- the basic hierarchy of taxonomy King Phillip Came Over From Greece Stoned?)
We are well aware that plants are alive and that they want to stay alive. We also know that chemical changes are not the same thing as thought or feeling. Responding to stimuli isn't equal to sentience. Simply, we aren't vegetarians because we can't stomach any form of killing, just the killing (and torture, warehousing, and other forms of mistreatment involved in the meat industry) of animals.
Hell, if the standard is not to kill any living thing, well we couldn't wash our hands lest the millions of staphylococcus aureus critters be destroyed. We couldn't take antibiotics. We couldn't brush our teeth, sterilize surgical instruments or pretty much do anything.
All life seeks to live- to persist and usually to reproduce. It is our prime directive, our most basic of instincts. Vegetarians and vegans do not labor under the illusion the food we eat wasn't once alive. In short, we are not as delusional, misinformed or just downright silly as this article is.
Happy Holidaze everyone. Time to make the Tofukey.
First there is the death of Dennis deLeon. Dennis was the president of the Latino Commission on AIDS, a lawyer in the Koch administration and the Civil Rights Commissioner when David Dinkins was the Mayor of New York City. Under his leadership, the LCOA grew from an organization with 2 employees, to a nationally prominent force, working with groups across the US and employing 45. I will leave it to people who knew him better to eulogize Dennis. I will say that the fights against AIDS and for civil rights lost a lion.
The next story is a candidate for the worst headline ever: 'Koalas in Australia Dying of AIDS...'. Koalas get AIDS? As the kids say these days, WTF? Reading the story you find out that Koalas are suffering from the twin threats of habitat decline and a viral infection that destroys their immune system. The viral infection is called KoRV, or Koala associated Retrovirus. KoRV is not related to HIV, but has some similar properties. It does not cause AIDS, but a similar disease called KIDS, or Koala Immune Deficiency Syndrome. KoRV acts like a typical retrovirus. It is an endogenous retrovirus, meaning it has successfully incorporated itself into the Koala genome and is passed from mother to infant. It is thought that virtually all Koalas carry the virus, but it only sickens some. When it does sicken an animal, it is much more aggressive than HIV.
I don't know much about marsupial retroviruses. What I can say is the headline of this article is misleading (they get KIDS not AIDS). All headlines seek to draw a reader's attention, but when they do so by misleading it is simply bad journalism. As Eric Cartman once said, 'I am not just sure, I am HIV positive.'
Next up: yet another setback in the search for an effective vaginal microbicide. Researchers studying PRO 20000 reported results from a large trial which showed the gel failed to protect women from acquiring HIV. The study followed over 9,000 women in South Africa, Uganda, Zambia and Tanzania. The study started with 3 arms- two different doses, or concentrations of PRO 20000 and a placebo arm. One of the PRO 20000 arms was closed early by the study's Data Safety and Monitoring Board- an independent group of scientists who review unblended results from an ongoing trial to protect the safety of the participants.
The development of an effective and safe microbicide is among the most important fronts in the fight against HIV, particularly- though not by any means exclusively- for women. These results are the latest setback in this much-fraught search. Several once-promising candidates have proved either ineffective or even harmful. The focus of microbicide research will now be firmly on gels or rings that contain anti-HIV drugs. PRO 20000 was designed to attach to HIV before it could invade cells. One of the lead investigators described it as, 'a large sugary molecule with a charge on it.' Several anti-retroviral (ARV) microbicides are under investigation, including one containing maraviroc (the compound in Selzentry), one with tenofovir (Viread) and another with an NNRTI called daprivirine or TMC120.
To end on some good news, a report out of Switzerland found that the widespread availability of ARVs led to a dramatic drop in suicide among HIV positive Swiss. This is not terribly surprising, but does lead to a couple of interesting questions. The two I wonder about is the impact of HIV on the brain and the role of hope in living successfully with HIV.
On the brain: We know full well that HIV replicates in the brain. We know that cognitive function might be affected by HIV, and we have some limited data on the affect of HIV drugs on the brain. Teasing out whether or not HIV replication itself leads to emotional changes would be quite tricky I imagine. Nonetheless it is an interesting question, especially as it might relate to risk of suicide.
On hope: I have long thought, and often said that one of the most important factors in long term survival with HIV is a belief that one can live a long, healthy life with HIV. This idea can and is overplayed and warped by people who take it to mean that our health outcomes are mostly or entirely determined by how happy we are (Louise Hay are you listening?!) Not so. But hope- the emotional sense of optimism and wellbeing- can influence our health in obvious and subtle ways. Making the daily decision to take our meds, having an active and fulfilling social life, being involved in the world around you- these are things that make us healthier and are often only possible when one has hope. Depression, social anxiety, isolation, self-harm- these are things that often spring from a sense of hopelessness- and lead to poor health.
So mourn the loss of Dennis, save the Koalas from KIDS, onward in the fight for a microbicide and keep hope alive.
Warning: No HIV Content Below:
A dear, dear friend of mine Carol posted this to me on Facebook recently: 'One day, Paul Dalton, we will have to have a conversation about how you reconcile your anti-capitalist tendencies with your love for Major League Baseball. I am curious about this dichotomy.' This is a common, and totally understandable question for the people I run with, who don't exactly embrace the world of sports, particularly the big money, professional ones.
I was actually thinking about this last night while trying to get to sleep. While baseball is far and away my sport of choice, I follow football, hockey and college basketball as well. Part of the answer is I simply enjoy the organic drama of sport and the physicality and athleticism.
I generally fight against disparity- economic, social, political, gender- you name it- my politics are all about leveling the playing field, sharing the wealth if you will. So, how is it I root for the Yankees, the greatest symbol of disparity in sports? The Yankees are the richest, most successful franchise in major US sports. They have the most money, they spend the most money and they win the most. They had a payroll last year topping $200 million dollars, and christened their $1.5 billion stadium with their 27th World Series title. The Saint Louis Cardinals are second with 10.
Sports for me are a way of connecting with myself as a child. The Yankees of the 1970s were among the first things outside of my immediate life (family, school) that I really cared about as a kid. As a 10 year old, the 1977 Yankees became the center of my life for the summer. Whenever possible, I would listen to games on the radio, and I never missed the rare opportunity to see them on TV.
As I grew older, I came to care about many thing outside of myself, many of them much more important than sports. The nuclear arms race, war, gender equality, homelessness, Apartheid- these things began to animate me, to drive me. Music and politics became the focus of my life. I found Punk- a milieu where music and activism sat well, if not always comfortably together. Sports and I drifted apart.
The mid 90s Yankees brought be back to sports. Following their rise from over a decade of futility to dominance was beyond compelling. These Yankees of Derek Jeter, Andy Pettitte, Jorge Posada and Joe Torre were an easy team to love- talented, successful and home grown.
Watching a Yankees game- or a Syracuse Orange basketball game, an Alabama Crimson Tide football game or a Buffalo Sabres hockey game, helps me connect with my most child-like self, to tap in to that part of me that never grew up. I know that is pretty pop-psychology/self-help-ish, but so bit it.
The original question though was how do I reconcile my antipathy to capitalism with my love for Major League Baseball and, I would add the Yankees. Mostly it boils down to 1) I don't really care about economic inequality in sports and 2) I think baseball is economically the fairest major sport. Major League Baseball has a very strong players union- the strongest in sports. Efforts in other sports to 'level the playing field' have resulted in less competitive balance, more money for the owners and less security for the players.
I abhor inequality. I just can't bring myself to care about it in the context of professional sports. I am much more concerned that the top 10% of American families own about 70% of the wealth, than I am that the Yankees payroll was over 5 times higher than the lowest. Sure I think Alex Rodriguez is way over paid, but nothing compared to Warren Buffett or any of the folks who ran Lehman Brothers into the ground. The inequality I care about is the kind that leads to people with HIV not having access to life saving drugs, not the kind that leads the Minnesota Twins to trade or lose their best players.
I won't go in to the economics of baseball and how they do, or do not directly affect the fairness of the game. It is complex and frankly a bit beyond me. Also this post is already way too long.
So, in short how do I reconcile my love of Major League Baseball with my anti-capitalist politics? I don't try to. Baseball is my refuge from important things, the space in which I let myself simply enjoy the action- not worrying about the problems of the world. Is there a contradiction here? Probably, yes- but it is one I am comfortable with.
Interesting juxtaposition in today's New York Times about the perils of politicizing science. While I believe that virtually nothing can be exempted from political meaning and influence, these two quite different cases illustrate the peril of allowing political agendas to drive scientific endeavors.
The first article is about South African President Jacob Zuma announcing new measures to combat HIV in its epicenter. The actions themselves would be less noteworthy (but still laudable), if not for the deadly dance with denialism of South Africa's previous President Thabo Mbeki.
Mbeki embraced the thinking of the disparate and desperate group we call AIDS denialists. This club-led by folks like Nobel Laureate gone soft in the head Peter Duesberg, snake oil salesman Matthias Rath and criminally negligent child-killer Christina Maggiorre- don't really believe anything per se- at least not anything they can all agree on. Instead they are bound by an unshakable disbelief that HIV causes AIDS.
I have written about AIDS denialism before and don't have time to go in to detail here about the mental gymnastics necessary to hold such a belief today. Mbeki is a special case though, because he led the country most impacted by HIV/AIDS for almost a decade and his dithering, obstructionism and denial caused over 300,000 deaths, including some 35,000 babies. Some in South Africa are calling for him to be charged with murder or even genocide.
On the same page is an article about climatologist Phil Jones resigning from his position at a UK university, in the wake of scandal over the suppression of minority opinion on the question of climate change. Hacked emails apparently show Jones and others conspiring, or thinking about conspiring to keep the work of scientists who question the majority opinions about global warming out of journals, to skew and hide data when it didn't agree with their position and to 'overstate' the data in support of their position.
On the surface these two stories seem at odds. The climate scientists are accused of suppressing minority opinion, while Mbeki embraced it. But really they are about the same thing- allowing political or really any pre-determined agenda to drive science. In the case of Mbeki, he embraced a position that was attractive to him- maybe because it harmonized with aspects of his political world view, maybe because he realized how daunting the reality of HIV in South Africa was and couldn't wrap his head around dealing with it. In the case of Jones, it sounds likely that he and others allowed their sense of urgency over the threat of climate change to justify their efforts to marginalize their opponents and overstate the data in support of their position.
The strength of science is that it should have no agenda. Scientists of course are human and do have agendas- political, professional, personal- and the process of peer review and publication seeks to account for that. Science is not a set of beliefs or stories- it is a methodology, a way of uncovering what is hidden. Put another way- science is not so much about discovering what is, as showing what isn't. The greatest accomplishment of modern medicine is not germ theory, but the discrediting of once widely held beliefs like miasmas and humors.
One needs to go where the truth is- where the data tells it is. In the case of Mbeki and his cohorts, they had to reject out of hand the crushing weight of the accumulated data showing HIV to be the cause of AIDS- and instead embrace a hodgepodge of crackpot ideas, paranoia and gaps in understanding to make their case. For Jones it appears there is a lack of trust in the process, a fear that an honest hearing of the facts wouldn't support their idea, or might fuel their opponent's efforts to sew doubt.
Let the truth win out. Let the data be your guide.
Happy World AIDS Day just doesn't sound right does it?
Haven't blogged in a while. Why? No real reason- just a bit of ennui plus inertia. But today is our day, so here is what I am thinking today.
The new Guidelines were released this morning. I am a community member on the panel that writes the recommendations, and this update includes some important changes. Just so we are clear- I do not speak for the Guidelines panel- these are just my thoughts.
One major change is the 'when to start' language. Specifically starting treatment with a CD4 count between 350 and 500 in now recommended. There was significant difference of opinion on how to characterize the strength of evidence for this- most saying the evidence is strong, but a significant minority seeing the evidence as more moderate. Treatment with a CD4 count above 500 is talked about- basically stating that the panel was evenly split between those basically supporting treating virtually everyone with HIV and those who feel that the evidence is just not strong enough and that treatment could be initiated, but should not be recommended.
My thinking? I have come to believe that, in most cases treatment is better than no treatment. The panel bases it's guidelines on the available evidence- which is where these questions become sticky. There simply isn't a large, prospective, randomized, controlled clinical trail answering the 'when to start' question. Lacking this gold standard means we have to look at other forms of research- non-randomized trials, retrospective analyses, cohorts and so on- to build the recommendations.
To me the data, while not straight forward, are convincing. Most of the studies done in the past 5 years or so show strong benefit of treatment, in most cases. While there is no debate that HIV drugs can cause harm, it is increasingly clear that the untreated virus wreaks much havoc, beyond CD4 counts. Looking at heart disease, liver disease, kidney disease, cognitive function, aging- whatever measure you look at, people on meds seem to do better than those not on treatment.
The other major changes are in the 'what to start' section where Kaletra was 'demoted' to alternative (while still preferred for pregnant women), and Isentress was added to the 'preferred' list. This boils down to side effects- most widely used HIV drugs work well now in terms of reducing viral load- the real differences (for the most part) are around toxicity. Simply put, Kaletra's effect on lipids (fats) and some data suggesting it might increase the risk of heart attack, dragged it down to alternative.
Adding Isentress to the 'preferred' first line group made sense to me. The STARTMRK data show it works quite well as part of initial therapy. The real question for me is more philosophical- given how well this drug works in later treatment and with no back up integrase drug in the foreseeable future, is it wise to use this drug as a first option. In my opinion- probably not. But that is just my opinion- the data support its use this way, and so I supported adding it to the list.