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viread/ddi
May 12, 2002

According to drug company literature and different source of imformation viread is supposedly less toxic and not as likely to cause mitochondrial toxcity as ddi.How can this be,if they are both anologues of adenine?I would think the side effects would be similiar.Does this mean if viread is less toxic, it is also less potent? Is there a disadvantage to using a nucleotide such as it affecting more than rt inhibition,like inhibiting healthy cell replication?I just don't hear about alot of people using it, so I don't know what to believe.

Response from Dr. Young

Thanks for your question.

Yest both didanosine (Videx) and tenofovir (Viread) are both adenosine analogues. Past this, the two drugs have very dissimilar structures, and dissimilar toxicity profiles. Indeed, with regard to mitochondrial toxicity, the in vitro studies presented at this years Conference on Retroviruses and Opportunistic Infections (www.retroconference.org) would suggest that tenofovir causes very little, if any toxicity (as measured by lactic acid production and alterations in mitochondrial DNA content). The use of a nucleotide versus nucleoside reflects differences in the structure of the phosphate-containing part of the two drugs, but both drugs actually are modified to nucleotides (nucleoside triphosphates) prior to becoming the active RT-inhibiting drug. Intrinsic differences in this chemical structure may actually play a role in the activity and resistance profile of tenofovir.

Furthermore, clinical data presented have not showed significant symptomatic or laboratory abnormalities associated with tenofovir.

Lastly, with regard to potency, data also presented this year at the Conference on Retroviruses examined the potency of tenofovir during short-term monotherapy and found a dramatic 1.6 log reduction in viral loads, a value comparable to protease inhibitors or potent non-nucleosides.

Overall, the drug appears to be very potent, and very well tolerated. The fact that the two drugs are adenosine analogues simply means that they will Watson-Crick basepair with thymidine positions within the reverse transcriptase. Potency and toxicity are often determined by other chemical aspects (moieties) of the drug.

Hope this helps to clarify your question. BY



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