April 2009 Archives

This is Trip Gulick, a rock star HIV doc and researcher talking about swine flu on Countdown. In general I think he hits the right tone. It does seem important to me to remember that 1) the numbers just aren't in yet. Such as the numbers are, they are improving (most cases manageable- everywhere). The lack of community (called herd) immunity increases the chances of it being more problematic 3) the seasonality of flu outbreaks might affect its dynamics- the first phase of this story focused on the higher than normal number of flu deaths for this time of the year. 3) part of the story of some of the big flu outbreaks is a wave phenomena, with an early milder phase followed in some time by a more widespread and severe illness. It is 

While the swine flu is the story of the moment- maybe for good reason, maybe not- HIV was in the news today as well. The New York Times reports more data supporting earlier treatment for HIV.

This is an interesting study. It looked at a large number of people- over 17,000- living in the US or Canada, between the late 1990s and 2005. Two questions were asked. 1) is there a difference when people start taking HIV drugs with CD4 counts between 350 and 500 compared to below 350? and 2) is there a difference when people start with CD4 counts over 500 compared to under 500.

The answer to both questions was yes. In the first analysis, people who started treatment with CD4s less than 350 had an almost 70% increased risk of death compared to those who started with CD4 counts over 350. The difference was even larger in the second analysis, where people who started treatment with CD4 counts below 500 had virtually double the risk of death compared to those who started with CD4s above 500.

There are some important limitations to this study. Most importantly it is a retrospective cohort study- which is much more prone to bias and confounding factors than a prospective randomized trial. In each analysis, many more people delayed treatment than started it- at a ration of around 3:1. This can skew the data- although in what direction is unclear.

What does this study mean for people with HIV? Alone, not too much. Simply put, it is a good study, which adds evidence to the idea that earlier treatment leads to better outcomes.

Along side other similar studies- it might mean much more. Treatment activist, doctors, researchers and guideline writers struggle with questions of evidence all the time. Rarely does the evidence line up in clear, unambiguous ways. In the case of the 'when to start' question, the major hang up is the lack of prospective randomized controlled clinical trial data. Such a trial would go a long way to answering the question- but such trials are difficult and take a long time- and for many the answers just can't wait.

So, we look at lesser data types- things like cohort studies. While they are more prone to biases, they can be very useful. This is especially true when multiple studies point in generally the same direction. This study suggest earlier treatment is better. Other recent studies have said pretty much the same- including a subgroup analysis from the SMART study.

It is tempting to see this as the latest incarnation of the swinging pendulum. A cursory view of treatment recommendations does appear to support the notion that they swing from one extreme- hit hard, hit early- to the other- delay as long as possible- and back.

The pendulum view is overly simplistic, and fundamentally incorrect. The guidelines for treating HIV evolve as the evidence evolves. When the studies of protease inhibitors showed a major jump in life expectancy the though was go on as soon as you can. When the limitations of the available drugs became clear, the equation changed, arguing for a more conservative approach. As the drugs have improved and our understanding of the myriad ways HIV harms our bodies, the calculus has changed once again.

When asked 'when should I start treatment', I usually answer 'when you are ready.' It is important to be ready, as HIV treatment is a major commitment. Left unsaid most of the time is, ' get yourself ready.' I don't say it because it isn't my place to tell people what they should or shouldn't do. I just give out information along with some opinion- but no advise.

But in my head, I am thinking that what ever problems there are with taking HIV drugs, the consequences of not taking them are worse. The data are piling up in support of earlier treatment. I don't know if these studies are enough to change the guidelines or doctors' prescribing practices. I do know they have convinced me- at least for now.

Quick note: Just to be clear- in my swine flu post, I was not saying that people with HIV are going to be less affected by this flu bug- or even that they were by SARS. The pathophysiology of this strain is not well enough understood to have any such opinions- I was just thinking outloud. 

The Swine Flu is story number one on most people's minds. Here are some titdbits.

• The terms 'swine flu' and 'bird flu' and 'avian flu' have always puzzled me. All influenza viruses circulate through both pigs and birds- some making there way to humans.\

• Read a story that some are calling for this outbreak to be renamed, 'Mexican Flu' out of respect for Muslim and Jewish sensibilities around pork. I am tempted to rant about this, but will leave it at: good luck with that.

• One of the scary aspects of this story is that young, healthy people are dying from the flu. The flu kills many people, every year- but they are most often very young (under 3 years old) or very old, often the elderly who are confined to bed.  The large pandemic flu outbreaks- 1918, 1957 and 1968- all killed a high proportion of young and otherwise healthy people.

The theory here is that these influenza strains trigger a 'cytokine storm'- an overly aggressive immune system response- which overwhelms tissues, particularly in the lungs.   This was also hypothesized as part of the SARS outbreak.

While it is typically thought that people with HIV are at higher risk of catching the flu, and of experiencing sever symptoms, could it be that in these cases the opposite could turn out to be true?

During the SARS outbreak, I read somewhere that in China, SARS ran rampant throughout this one hospital- but left the AIDS ward virtually untouched. Could it have been that the people in that AIDS ward had immune systems that were too weak to cook up a cytokine storm? Thing that make you go, hmmm?

Now, I am not suggesting that the key to surviving this flu scare is to go off your meds and make sure your immune system is weak enough to avoid the cytokine storm. Not at all. I am just thinking  outloud.

• Heard through the grapevine that a doctor who I admire and respect talked about this flu outbreak with a group of infectious disease experts and they are confident that this will blow over. Cheers to that. 

Disclosure can be a tricky topic. Living with HIV means having to decide who to tell and when. The issues involved are complicated and differ from person to person.

Usually telling family members and sexual partners poses the biggest challenge to people, and no wonder. The intimacy and gravity of those relationships adds intensity and complexity.

Disclosure discomfort has two main ingredients for me. One is the potential that the person will react badly- that they will judge me, shun me, discount me. Nobody wants to be rejected or treated as less than- but it is always a real possibility.

The second facet is the internal- what it brings up inside my own psyche to disclose. First there are the self -judgments, the self-shunning, the self-discounting. Then there is the simple issue of privacy- who has the right to know, who do I want to know, who is going to find out anyway?

The odd thing for me is that I struggle more often with telling people whose reactions shouldn't mean as much. When I learned I had HIV, I called my family immediately. I always tell my sexual partners.

Where I find it more challenging is when I meet new people- new friends, friends of friends, or when I reconnect with lost friends. The internet has made it possible for me to find and be found by a good number of people I have lost track of over the years- classmates from high school, my punk rock comrades from Syracuse, friends who moved away.

I always wonder if people know already. For example, I went to a tiny high school- there were 36 in my graduating class. I have found a few on Facebook recently, and am getting together for coffee with one of my classmates, Liz, later this week. I find myself wondering if she knows, and assuming she doesn't, will I disclose (probably) and how.

Liz and I weren't super close in school, and have not been in any contact in almost 25 years. So why does it matter a whit to me how she might react to my HIV status?  Don't know, but there you go. 

A few short items.

First: I was privileged to see Leonard Cohen in concert on Monday night. I am late to the cult (and it is very cultish) Leonard Cohen thing- turned on to his music by my friend David, who downloaded some of his music on my computer years back, which ended up on my iPod- and I ended up a fan.

Music is as close as I get to going to church. My favorite moment of the night was the song, Anthem. The chorus goes:

Ring the bells that still can ring

Forget your perfect offering

There is a crack in everything

That's how the light gets in.

Speaks volumes.

Next: there have been a couple of comments from religious folks about my post on confirmational bias. I try and maintain some sense of equipoise when dealing with religion or spirituality- and sometimes it is difficult. These post boil down to, 'God is real, you are going to hell if you don't believe what I believe. End of story.

Well I am (not really) sorry. For me,  that isn't good enough. It is never enough to simply state that something is- if you believe something, make your case, convince me, explain yourself.

That is why I like the scientific method, which is founded on the idea of questioning and testing what you believe to be true. I simply do not have time for any set of beliefs that does not test itself, does not challenge itself.

Last: There was a slightly off blurb in the New York Times science section which read:

Researchers have identified a new benchmark for starting drug treatment for AIDS, according to a report published online last week in the journal Lancet.

Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies (The Lancet)

The question of when to start therapy has been a "swinging pendulum," notes an editorial accompanying the study. The marker in question is the CD4 count, which represents how many of the cells that the AIDS virus attacks are found in a microliter of blood.

In poor countries, the World Health Organization recommends starting when counts are anywhere from 200 to 350; in rich countries, the decision is made by patients and doctors. The new analysis, which looked at 18 studies with 45,000 American and European patients, concluded that starting earlier saved more lives, so treatment should begin when the count falls to 350.

It is a tradeoff. Aggressive early treatment may forestall full-blown AIDS and death, but antiretroviral drugs can cause fat redistribution, hepatitis, kidney failure, pain and elevated heart disease risk. Newer regimens are less toxic, but they are not always available in poor countries, where fewer than half of those who need drugs get them.

The finding has complex implications for Africa, where the number of people sick enough to need the drugs is increasing by about one million a year. If the W.H.O. adopts the new benchmark, the number could grow by another million, some estimate. Global donations to pay for treatment have not kept up with even today's needs.

There are two problems with this little story. First, there is nothing new here. There has been evidence for some time that HIV treatment is more effective when started with CD4 counts above 350. That is what the DHHS guidelines recommend after all. Second, the 'tradeoff' noted here is not wholly accurate. For example, the author states that ARVs can lead to an increased risk of heart disease. Fair enough, but not necessarily true in this context- being compared to later treatment. Untreated HIV also increases the risk of heart disease, and most of the research- particularly the research done more recently suggests the risk from untreated HIV is higher than the risk from drug side effects. 

An interesting article in today's New York Times reports that esomeprazole- aka Nexium- is ineffective at treating poorly controlled asthma. Esomeprzole is a proton pump inhibitor, a widely used class of medicines used to treat gastric reflux.

Why would anyone think that a medicine which reduces stomach acid might treat asthma? The article states that doctors have noted that people with asthma are more likely to have gastric reflux than non-asthmatics. Some studies have found estimated that over 40% of people with asthma have gastric reflux, compared to 5-10% estimated for the general population. 

I experienced the connection between stomach acid and breathing difficulty quite dramatically. One night, out of nowhere I woke up unable to breath. I don't know how long it went on for, but it felt like forever. I was pretty freaked out and went to see the doctor the next day.

The first question she asked me was, 'did you have any unusual taste in your mouth?' I had, but didn't think it was related. Specifically I had a strong sour taste. She explained that stomach acid- which like all acid tastes sour- can churn up in to your mouth while you sleep. When it does, some might start to go down your trachea- or windpipe- which triggers your breathing to shut down, as a protective mechanism. She called what I experienced as paroxysmal nocturnal dysmia  or PND.

About 2 years ago, I was driving with Marty Delaney- and he shared with me that he had been having bouts of waking suddenly unable to breath. His doctors had done a typical sleep apnea work up, showing he didn't have that problem. Remembering my incident, I asked him if he had a sour taste in his mouth when this happened. Turned out he did- and he started taking acid reducers before bed and the problem went away.

While the study found no benefit to use of esomeprazole, there is reason for further study- possibly in people who have clear cut cases of reflux.

I am no expert on asthma. I do know that it can be triggered by many things, including exercise, allergies and so on. The connection between reflux and asthma is unclear- is it cause, effect or simply conincident? Some studies have shown improvement in asthma symptoms from reflux treatments- both drugs and surgery. This newest study didn't, but it looked at anyone with poorly controlled asthma. Perhaps if people with document reflux, plus poorly controlled asthma were studied the results would be different.