July 8, 2001
Julio Montaner was the second speaker. He is Argentinean and he was playing at home. He began his talk by celebrating the victory of Argentina against Ghana in the soccer sub-20 World Cup, which set a more relaxed tone.
He tried to tackle the issue of when to start therapy. First he admitted that there is no clear answer to this issue and that we need prospective trials to evaluate it. Then he reviewed the arguments in favor of prompt initiation of therapy, and he basically made holes in every single one of them. He stated that it is unrealistic to expect that with the current antiretroviral drugs we will be able to eradicate the infection -- our initial hope when we started these very aggressive combinations a few years ago. The preservation of the CTL response against HIV can only be attained with the treatment of seroconverters very early in the course of the infection. It is obviously not an argument that can be applied to the 36 million people already infected in the world.
He presented data demonstrating that immune reconstitution can occur even in quite advanced stages of the disease, another "classic" argument to push for early therapy. Although the control of HIV replication is easier early after infection, the virologic success of currently available HAART regimens is similar when they are started in more advanced phases of the disease, so it is difficult to justify early initiation on that basis. Another classic line of reasoning in favor of starting early has been that this prevents the evolution of resistant quasi-species that could compromise the future response to antiretrovirals. However, this has not happened, and the response to HAART regimens is similar among patients who delayed the initiation of therapy.
We are left only with the argument that we should treat early in order to decrease the overall viral load of the population, and, in this way, prevent transmission to others. Unfortunately, we know that the availability of therapy changes behavior, and that people quickly resume high-risk practices. The epidemic is spreading again in places with excellent access to treatment like San Francisco.
There are several arguments favoring a delayed initiation of therapy, and he also reviewed them.
If we are not itching to start treatment, then the question becomes when should it be done? How long can we wait without compromising future response and preventing morbidity and mortality? The question is where do we put the line to start antiretroviral therapy? Julio Montaner reviewed some of the data from the British Columbia Cohort and pointed out that the responses were pretty good at multiple levels of CD4 (if the individual maintains adherence to therapy) and that he would put the line of initiation at around 200 CD4 cells.
He also stated, at the end of his talk, that this threshold obviously is not written in stone and that we should conduct more trials to try and answer this question. The decision of when to start has incredible implications in terms of the total cost of treatment, especially now that we are trying to provide access to these therapies for the whole world.
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