• Learning Basic Science from Clinical Trials (Presentation PL1)
  Speaker: David Ho
  Aaron Diamond AIDS Research Center, The Rockefeller University, New York, USA

Here I am at another meeting in a far away land. Do we need more HIV meetings? I really don't think so. There are way too many meetings, and there is no way that sufficient new information is generated between them. I can't figure out why there are so many of them during the year. Somebody with much more power than I should put an end to this craziness. For once I don't think that the pharmaceutical industry is to be blamed. I think the problem has more to do with regional egos in the scientific community than anything else. One, or at the most, two meetings a year is more than enough to discuss the new science -- both basic and clinical -- generated during the year. That would save time and money, the quality of the information presented would improve, and best of all, we would avoid the feeling (and the fact) that we are repeating ourselves.

That statement does not imply that this is the meeting to sacrifice. We need meetings in the "South"; they definitely serve an important purpose. This is my second meeting in an underdeveloped country, although nobody can say that Argentina is the "South" in the same sense that South Africa is. The International AIDS Conference in Durban was probably the most important meeting since the Vancouver one, because it really broke the silence about the global nature of this epidemic. We all knew the numbers, but until we could see the problem with our own eyes, we did not feel the pressure to act. And that is what Durban was about. Meetings like this one in Argentina will help in the same sense because it gives everybody a more global picture of the issues in antiretroviral therapy. For the same reasons, I am pleased with the fact that the 2004 International Conference will be in Thailand and not in Toronto. The most interesting stuff is happening in the third world, not in the "first world," so don't expect me to be very critical of this meeting.

David Ho opened the conference today. He talked today about how we can learn basic science from clinical studies. We are always talking about how to translate the basic science into clinical interventions that benefit our patients. His talk reverses the issue and focuses on our learning from clinical science and how it gives insight into basic problems. He reviewed, again, what we learned from the initial trials of protease inhibitors: that HIV replicates continuously, and that in order to stop that process, we need to use combination therapy.

We also have learned that viral replication continues in spite of tight virologic control, so that if we want to eradicate the infection (something that very few people think is possible nowadays) we will need even more potent regimens. He also presented data on how the kinetics of viral load decay after the initiation of therapy allows us to evaluate the "potency" of a given regimen. He talked about a regimen of Kaletra, efavirenz, 3TC and tenofovir in combination. This combination is extremely potent. The viral load of patients on this therapy became undetectable very quickly. He proposed that looking at the speed at which regimens make you loose your viral load could be a quick way to look at the potency issue.

This idea is not new (he proposed it before), but this time he presented some data about the long-term validity of it. He made a big jump when he compared the data of this cohort study to his previous studies. That was not a fair comparison because the methods were different and the patients were not randomized to the different regimens, but that is the kind of stuff that basic scientists have to learn from clinical research scientists. David Ho focused on the potency question. We do need more potent regimens that completely suppress viral replication. However, potency is not the only important issue -- nowadays, toxicity is also very important. Even if we can use the more potent regimen, if it is associated with significant toxicity we will not be able to use it for prolonged periods of time in a significant proportion of patients. The regimen that David Ho is proposing seriously limits future therapeutic options. Thus I don't think it will be used frequently in clinical practice. But, as he pointed out, we can learn a lot about the biology of the virus and this disease.

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