September 15, 2000
The second session of the day focused on vessels and endothelial dysfunction. Frank Ruschizka gave an overview of the endothelial function and the critical role that nitric oxide plays in it. It was an interesting presentation.
Then came the most stellar presentation of the day (and probably of the meeting) from Matthias Egger from Bristol, England. Egger tried to balance the benefits that patients obtain from therapy and the increased cardiovascular risk that's a consequence of this therapy. He gave an overview of the epidemiology of cardiovascular disease, with emphasis on insulin resistance, central obesity and dyslipidemia and how these factors increase the risk of cardiovascular problems in non-HIV infected individuals.
Antiretroviral treatment is always a trade-off between well-known benefits that patients obtain from therapy and the toxicity that comes with it. The benefits of treatment, in many occasions, especially in the patients with advanced disease, outweigh any risks associated with treatment. However, it is also true that sometimes it does not, especially for some patients with early disease. There are cases in which antiretroviral therapy is more harmful than good.
The problem with the current American guidelines for HIV treatment is that this trade-off is not taken into account and the focus instead is only on the virus itself. We need to realize this, and start discussing these kind of issues more openly. The gap between what the guidelines say and what clinicians and patients think is becoming wider than ever before. Until a few months ago, one could not openly say in any meeting that therapy should be delayed for many individuals. This only caused most others to criticize you for going against the "dogma" and not acknowledging that HIV is invariably bad. Fortunately, things are now changing and talks like the one from Egger will help.
He used risk data equations from large cardiovascular studies, like the Framingham or the Caerphilly cohort, to calculate the increase in the relative risk of cardiovascular complications attributable to HAART. Then, using unpublished data from the Swiss cohort, he calculated the improvements in the risk of death and infectious complications of HIV-infected individuals as a consequence of HAART treatment. With that information in hand, it's easier to start making more rational decisions about antiretroviral treatment.
He calculated that the attributable risk of cardiovascular complications, when using antiretrovirals, is approximately 1.5 to 4 times the risk if you do not take them. And this depends on how many complications of treatment you develop. For example, if an individual develops diabetes as a complication of therapy, the risk of having cardiovascular complications go up. They go up even further if you develop hypercholesterolemia and diabetes, and rise even further if the individual is a smoker.
This was the most controversial part of his talk. Some people may say that nobody has proven that the risk of cardiovascular complications go up with antiretroviral treatment. However, I think that view is very short sighted; it can take years to detect those increases. There is no biological reason to think that having a total cholesterol of 400 mg/ml or being a diabetic is not as bad in an HIV-infected individual than it is in a non-infected patient. We do not need to prove things that have been demonstrated multiple times in the last 30 years!
Then Egger discussed the concept of patients needed to treat to obtain a clinical benefit based in the CD4 cell count and the viral load. In some cases, you only need to treat two patients to benefit one. But, in some cases, the balance shifts, and you need to treat 50 patients or more to benefit one (because the risk of having problems related to HIV was very low to start with). In some cases, the balance shift is so dramatic that treating the patient (for example, somebody with very early disease) can in fact be more harmful than good.
Egger's premise is that when you make the decision to start antiretroviral therapy you have to balance the risk associated with HIV infection itself, with the increased cardiovascular risk associated with treatment. It is not the same thing to treat a 50-year-old smoker, with a family history of diabetes and whose CD4 count is 450 cells/mm3, than it is to treat a 30-year-old female who doesn't smoke and has a CD4 of 185 cells/mm3.
HIV is a chronic disease that affects real individuals that, on top of HIV infection, have what everybody else has: cardiovascular problems, tobacco addiction, diabetes, poor calcium intake, hypertension, etc! Isolating the problem of HIV, thinking that the decision should be made based mainly on viral load, as our guidelines do, and making treatment decisions outside the context of the whole individual, could potentially be dangerous. The aphorism, "It is the virus, stupid" is too simplistic!
It was really a fascinating, refreshing talk that put things in perspective and made people think about the current guidelines of antiretroviral therapy. It is obvious that they will need to do a major rewrite of the guidelines to reflect a more balanced approach. Just this talk made the trip worthy. Matthias Egger is supposed to give the same talk at ICAAC, where I am sure it will be a big hit. We need independent thinkers like him.