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Ziagen/Agenerase
Sep 7, 1999

Dear Drl Holodniy: I have recently had a genotype worked and found that I am resistant to all HAART medications currently approved by the FDA. The only meds that they did not test for were Ziagen and Agenerase, the newly approved treatments for HIV/AIDS. I've been taking these new meds for about 2 months now and have had only a slight difference in viral load and CD-4 count from counts done approximately 5 months ago. My viral load (5 months ago) was 298,000 and now is 211,000 and my CD-4 count went from 18 to 29. To be honest, this slight difference does not inspire much hope as to the efficacy of these new meds. My question(s): What makes these 2 new meds, Ziagen and Agenerase, different from the other meds that I am resistant to? Can I be resistant to these new medications as well? Please, any information that you can give me will be greatly appreciated. I feel that I am living on "borrowed-time" as it is. I've been HIV+ for 13 years and have had full blown AIDS for 6.5 years....and honestly, I am scared....

Response from Dr. Holodniy

The key info you need (and me to make the call)is what mutations were present on the genotype. I can answer both of your questions together. Key mutations to AZT and 3TC, will make the virus resistant to Ziagen. In fact the more AZT mutations you have, with the critical one mutation for 3TC, the higher the resistance to Ziagen. So there is definitely cross resistance to Ziagen from previous exposure to other drugs. With Amprenavir, there is one key mutation, that confers resistance to that drug. But if other key protease mutations are present, which cause class resistance to protease inhibitors, Amprenavir will not work. The difference in the two viral loads is not significant. If you are truly resistant to everything, a drug holiday might be helpful, both in terms of your mental health (pill burden, toxicities, etc), and the possibility of reverting some of you virus back to wild type, so that older drugs might be active again. There are second generation drugs in development and early trials which are active against certain resistant viruses. MH


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