|When Will Early Treatment Be Taken Seriously?
Dec 17, 2007
Our federal government recently changed the recommended CD4+ T cell level at which to start treatment from 200 to 350 CD4+ T cells. At about the same time, I heard (via a webcast) Anthony Fauci, MD tell Mark Harrington, BS (Biology) of Treatment Action Group, that he remembered Mark requesting that a "When To Start" be initiated ten years earlier, but because of a lack of an acceptable study/trial proposal Anthony never supported one.
Several months earlier to the above, an socialized medicine organization in the UK reported success in refining "When To Start" via a study called CHIC, which continues to run since the mid-to-late-1990s. The authors of the CHIC study claimed that they produced EVIDENCE (as in Data, as opposed to "FAITH") that clearly indicates that starting treatment above 650 CD4+ T cells was significantly better, for survival, than starting under 650 CD4+ T cell. The authors of the study speculated that they will soon have enough data to recommend starting treatment earlier in HIV disease than at the 650 CD4+ T cell level.
As someone who started treatment within about six months of becoming infected, about twenty years ago, and who had undetectable viral loads (<50 copies/mml) on just AZT+3TC, or AZT+ABC for a ten year period between 1994 and 2004, and whose HIV specialists have few minimum treatment clinical studies to draw from, when I want to switch my treatment to a less toxic one, (here's my question) would someone care to speculate when early treatment will finally be taken seriously?
FAITH VERSES EVIDENCE --------------------- I've read that new HIV infections in America are actually running 50% higher than the present federal administration (I won't mention names, but it's the "Faith Based" organization in the Whitehouse) has made public. It should be obvious to the most casual of observers that if one wants to slow (or stop) the growth of a pandemic, that early detection AND early treatment should be taken seriously. With this soon to be made announcement, it appears that "Faith" has won-out over evidence and logic, and that we are now suffering the consequences.
One "Faith Based" argument, that I regulary read on this web site and others, is that one has to be cautious about early treatment because it could lead to drug resistance. If that were true we wouldn't have twenty years of clinical trials results showing us over-and-over that HIV+ patients with the highest CD4+ T cell nadirs (the lowest level to which CD4+ T cells ever fell is highest) consistantly do the best. And the argument contradicts the published evidence and logic of at least one of the doctors on this web site.
M. Holodniy, MD, co-authored the 2002 poster "Low Levels of Adherence Do Not Increase Risk of HIV Drug Resistance" for a major conference (Retrovirus? ICAAC?). Which concluded (quote) "1) High levels of adherence are associated with more prolonged exposure to antiretroviral therapy. 2) The rate of new Drug Resistance Mutations (DRMs) increases with increasing levels of adherence for individuals with Viral Loads greater than 50 copies/mml. 3) These findings suggest that [the] largest proportion of drug resistance mutations (42%) occurs in the highest quartile of adherence (90-100%) even when considering higher rates of viral suppression at this level of adherence."
What I take from the above is that hundreds of millions of years of evolution produced BOTH our immune systems AND HIV, and that we should be doing everything we can to preserve our immune systems from HIV with early treatment. And given the above poster on "Adherence", We may also need to regularly stop our treatments, for a few weeks or months, to allow the immune system to "retarget" the peptides of HIV - because HIV continues to mutate, even when we are suppressed to <50 copies/mml.
When looked at from the view-point of an evolutionary biologist, or just an average "Joe" (or "Joanne"), one has to question why we have let the "wolf" (HIV) guard the "chicken coop" (body) until only a few "chickens" (CD4+ T cells) are left. Wouldn't it make more sense to find a way to get rid of (or suppress) the "wolf" (HIV) ASAP? Our bodies can't repair all the damage that HIV causes. So, if we can't repair it, we must make preserving it a higher priority.
From approximately 1994 to 2004 I kept my viral load under 50 copies/mml with simply two NRTIs. During each of those ten years I took either one three month drug holiday or three one month holidays. I always found that I could restart the drug regimen and achieve <50 copies/mml of viral load after three months of treatment. Then, in 2004, I stopped all treatment, until just three months ago, because I was having problems with my hip - I was losing the ability to walk. After about six months off treatment, I was walking without hip pain. Time will tell if my immune system can recover from three years without treatment. I wonder if any clinical trials have answered the question. If not, why not?
Response from Dr. Pierone
Hello, and thanks for posting. You raise many interesting points and I agree with most of them. I will also attempt to answer some of the questions you pose.
I agree that early treatment for HIV should be taken seriously. A while back I answered a question in which I shared what I would personally do if I became infected with HIV. The short answer was that I would start treatment immediately. For the long answer which explains why I would make this choice, here is the link" target=_new>link to my previous post.
The CHIC study is an observational collaborative cohort study based in the UK. Although data sets of this nature are important, they cannot fully answer the "when to start" question because of the biases which are inherent in these descriptive studies. The National Institute of Health will be starting a randomized, controlled trial called START, which will attempt to provide a better answer to this question (but don't hold your breath since any answers will be years away).
Your specific medical situation is unusual since less than 10 percent of people with HIV will achieve viral suppression with a dual nucleoside regimen. Also, starting and stopping a dual nuke combination will typically lead to development of drug resistance over time. So your personal antiretroviral strategy is not applicable to the HIV community at large. Just because you can do 20 one arm push ups and not break a sweat does not mean others can do the same.
The adherence resistance studies offer a mixed bag and one really has to delve into the details to order to make sense of them. Very low levels of adherence tend not to produce resistance because the virus is not pressured by the occasional stray encounter with an inhibiting molecule. High levels of adherence to potent fully suppressive regimens tend not to lead to resistance because the virus is nailed to the carpet. Moderate to high levels of adherence to a marginal or less potent regimen seems to be the best ticket to resistance-land. This is an oversimplification, but these general principles are valid.
The one point you make which does not resonate is the notion of stopping therapy to retarget the immune system against HIV peptides. I am not aware of any studies which show this potential effect in any way outweighs the unbridled viral replication which develops when medications are stopped.
Although the arguments for early treatment are plentiful, the point remains that the current strategy of waiting to start therapy at a 350 CD4+ lymphocyte count threshold has worked fairly well. I say this because very few people get ill or have HIV-related complications if they wait to start treatment at this benchmark.
So in closing, chances are quite high that your immune system will bounce back quite well even though you have been off antiretroviral therapy for the past 3 years.
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