February 26, 2002
The symposium tonight about controversies in antiretroviral therapy was probably the most interesting of the meeting so far. It was surprising to see so many people skipping dinner and staying until 9 p.m. to hear these presentations. It was an extraordinarily long day.
Richard Chaisson from Johns Hopkins gave a very good talk on the question of when to start antiretroviral therapy. This issue has been discussed many times, and so many presentations about it have been made that the topic has become repetitive. There is a limit to the number of times you can hear similar arguments without thinking you should be somewhere else. In spite of that, it was a good talk worth the time invested.
Chaisson focused his talk on the chronically-infected patient. As you all know, there is some evidence to support HIV treatment during acute infection. He discussed the well-known arguments used years ago to support the use of antiretroviral therapy at relatively high levels of CD4 cells and then he proceeded to discredit them.
The first argument to support the use of antiretroviral therapy during chronic infection was the idea that maintaining antiretroviral therapy would lead to the eradication of HIV infection. We now know that this was wishful thinking. Chaisson discussed the data from Bob Silicano's studies, also from Hopkins, demonstrating that it will take several decades of complete suppression to eradicate the virus from the integrated memory T cells compartment (and that might not be the only long term reservoir in the body).
The second argument generally used was that early treatment leads to a better virologic outcome. Although this might be the case in some patients, it is not in many others. Chaisson discussed data from the Hopkins cohort showing that, although patients with very advanced disease (CD4+ cell count <50 cells/mm3) have a lower probability of response to a given antiretroviral regimen, the same assumption cannot necessarily be made for patients with moderately advanced disease (CD4+ cell count >200 cells/mm3).
The third argument was that patients treated early would have a broader and more significant immunologic recovery. However, we now know that HAART is associated with clinical and laboratory evidence of immune reconstitution capable of protecting against opportunistic pathogens, even in patients who initiate HAART in advanced disease.
Then Chaisson discussed the problems of toxicity in antiretroviral drugs and how it is very likely that the longer drug exposures in patients who begin therapy early will likely also be associated with increases in the toxicity of therapy.
He concluded that if there is no clear benefit in starting treatment early using any of the previously considered arguments, then the decision should be based on the presence of clinical benefits by starting therapy early.
Then Chaisson reviewed several studies presented during the last year which support a more conservative attitude to antiretroviral therapy. These studies include cohorts from his own group at Hopkins, the British Columbia cohort, and the European cohort.
Finally Chaisson concluded that, in his opinion, it is very clear that chronically-infected patients with CD4 cell counts below 200 cells/mm3 should always be treated, and that the time to start therapy should be somewhere around 200 to 350 CD4 cells. He did not want to be more specific than that. CD4 count, he said, should be the main factor influencing when to start therapy -- and maybe the only factor to consider. The only contributions of viral load are to determine how quickly a given individual is likely to reach the CD4+ cell count threshold at which therapy is indicated, and perhaps to determine the frequency of CD4+ cell count monitoring.
Although Chaisson's arguments were not new, and the conclusions represent the current prevailing wisdom, it was an excellent, well-organized talk.
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