I am looking for a more complete list of nucleoside reverse transcriptase inhibitors that select for the M184V mutation. The literature always only mentions the four FDA approved drugs ddI, ddC, abacavir, 3TC. I would appreciate if you could name a source where I could find other compounds as well. I'm sure the above four are not the only ones known.
Dr. Mark A. Wainberg responds:
Of all the reverse transcriptase inhibitors that fall into the nucleoside category, only one is able to efficiently select for the 184V mutation. This drug is 3TC, and, indeed, the levels of resistance that 184V confers against 3TC are extremely high. Other compounds, such as ddI, ddC, and abacavir, can sometimes select for the 184V mutation, but do so with a much lesser efficiency than is the case for 3TC. At the same time, the levels of resistance that are conferred by 184V against each of these latter compounds is relatively slight—approximately 3–5 fold.
There is, however, an additional drug that selects for 184V with high efficieny and against which 184V also confers extremely high resistance. This drug has not yet been approved by the FDA, but may receive approval during the next year or so. It is FTC, and is produced by Triangle Pharmaceuticals. There are, to my knowledge, no other compounds that actively select for the 184V mutation nor are there other molecules against which the 184V mutation can be responsible for resistance. However, there is evidence that the 184V mutation can marginally increase the susceptibility of HIV-1 to tenofovir (PMPA) and that this may occur to some extent as well in the case of both AZT and d4T. (2/21/2001)
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