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What now after Combivir/Sustiva (stocrin) failure?

Apr 15, 2007

my son has been using stocrin and combivir for his hiv treatment. his CD 4 started to drop and his viral load was very high it was 1190 the last time i checked. the doctor has prescribed him KALETRA, VIDEX and ZERIT or TENOFOVIR as the second line of treatment. what i want to know is whether this is the correct second line of treatment and second is it advisable to change drugs without checking which one of the three you have developed resistant to. your help will be very appreciated.

Response from Dr. Pierone

Hello, and thanks for posting.

The best approach for anyone with evidence of viral breakthrough on a regimen is to have a resistance test performed. This allows one to best determine which medications are still available if the decision is made to change therapy.

It sounds like your son's physician has recommended a change to a protease-inhibitor based regimen. Even without a resistance test, this approach is likely to be successful, based mainly on the potency of Kaletra. There is a growing body of clinical experience which indicates that Kaletra alone is sufficient to suppress viral replication in the majority of patients who have not been treated with a protease inhibitor. So it could be reasonably argued that in the case of failure of Combivir and Stocrin (Sustiva), a Kaletra-based regimen should work. That being the case, the least toxic drug(s) should be selected. Tenofovir (Viread) clearly is less toxic than Zerit. Videx (ddI) is an older HIV medication which is not one of my favorites because of the risk of pancreatitis. This complication is uncommon, but occasionally fatal (not fun having to explain this to grieving family members) so we try to avoid using this agent unless there are no better options. The good news is that there are almost always better treatment options.

For first virologic failure on Combivir and Sustiva, our team would typically use Norvir, Reyataz, and Viread as the new regimen. The reason is that Norvir and Reyataz are better tolerated than Kaletra, and just about as potent. We use Viread because it is better tolerated than the other nucleosides. We don't bother adding a second nucleoside for the simple reason that it is not needed and adding it only adds toxicity and cost. Now, you will not find this approach in any of the treatment guidelines, probably because it has never been studied.

The treatment guidelines are evidence based, and most of that evidence is generated by grants from pharmaceutical companies. These companies are not at all eager to support a trial which aims to see if a cocktail with fewer agents would work as well as a traditional multi-drug regimen. Hence, these studies are not funded, the evidence cannot be produced, and physicians continue to prescribe aggressive triple (or more) drug combinations based on the information at hand.

Sorry for the screed. Now back to your son's situation. A resistance test should be performed and based on this information a new regimen can be devised. Most often, resistance mutations M184V and K103N develop first and produce resistance to the Epivir component of Combivir and Stocrin (Sustiva). This generally means that a PI-based regimen will be needed to achieve an undetectable viral load. See above discussion for these options.

Best of luck to your son and let us know how things go for him.

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