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Heart Attack
Jan 11, 1999

As if having HIV was not enough, last week I had a heart attack and after nine days in the hospital I am back home wearing a Coronary Stent. Since I have not taken medication yet, please provide information on the implications of this event, particularly as it relates to PI medication.

Response from Dr. Cohen

An important issue - so a long answer...

Your question refers to the concern that we have all noted increased levels of blood fats - including both triglycerides and cholesterol - in some who have taken at least some of the protease inhibitors. And these changes appear to be of the type that would only increase the risk of progressive heart disease, since unfortunately it is usually the LDL, or "bad" cholesterol, that goes up. And we assume for now that these measures will lead to an increased risk of heart disease - but this is still an assumption - since we don't know yet if the test results that we measure mean the same thing when elevated by a drug as it does when it is elevated without these drugs.

What is also clear, however, is that the risk of developing elevated blood fats is not uniform - some who take the PIs have no problem at all with blood fats. And if it going to happen at all, it appears in the first 12 weeks or so. So if you decide to go with a PI containing combination for treatment, you would know soon if these changes will be a problem for you. But not everyone has the problem. For example - our site was involved in the first study of ritonavir and saquinavir in combination - which appears to have one of the higher rates of these changes, perhaps because of both the use of ritonavir as well as the use of two PIs. But there really are some who are now into year three on this combination, with completely normal blood fat levels, that have not changed at all compared to when they started these meds. And their viral load is still below 50 copies. So PIs can be used safely and successfully.

There are some recent reports to suggest a possible difference in the rate of these blood fat elevations between the different agents - with some data suggesting less of this problem when using either nelfinavir (altho this is a bit controversial), saquinavir (as Fortovase without ritonavir), or the newest agent called amprenavir.

But - what if you wanted to avoid a PI entirely in your first combination? You have likely heard that there are combinations without PIs that create similar degrees of viral suppression, with what appears to be similar durability of response (although we've had less time with some of these combinations to be sure of this last key issue). Some of the combinations use two nucleosides and a nonnucleoside, while others are using just nucleosides.

There are examples of virtually any triple using two nucleosides and one nonnucleoside with a high rate of successful viral control. And there are two keys to success to making these work. First is that people take all three meds as prescribed (true for all combinations of course). Second, all three meds must be working fully, which is easiest to count on when this is the first combination. (For those who might have taken one or two nucleosides in the past, there is some risk that there will be cross resistance from the "nukes" previously used and the ones to be used in the new triple.) While there is some debate about which nonnuke is the 'best' to use, and ongoing debate about which dual nucleoside to use, there are increasing examples of success with almost any of them.

With all nucleoside combinations there are fewer examples of success. One has been based on the use of abacavir - the newest nucleoside so far studied with AZT and 3tc - and abacavir was just approved in the US. The other is based on using hydroxyurea to increase the potency of ddI - for example using d4T and ddI with hydroxyurea has shown evidence of high rates of success.

And there are studies now going on working on combining these two themes - for example, in the US and France is a study of d4T, ddI, and efavirenz/sustiva, either with or without hydroxyurea to see if four are better than three. Our site in Boston is one site for this study, since we hope that combining these approaches should be one way to even further increase the success rate.

And in about three weeks we expect results presented at a big antiviral meeting of yet more studies going on to further define ways of getting successful suppression.

So - lots of choices. As always, you need to review the details with your clinicians and those you trust, and decide. But there appear to be enough options to create viral suppression that does not put you at any increased risk of heart trouble.

Hope that helps. CC



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