The Body Covers: The 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy
FTC Similar in Most Ways to 3TC
September 15, 2003
FTC (Emtricitabine, Emtriva) is the most recently approved HIV medication in the U.S. The drug is chemically similar to the often prescribed 3TC (lamivudine, Epivir) and can be dosed once daily (one pill) but has a longer chemical lifespan in the body (called "half-life").
3TC is made by GlaxoSmithKline and is the centerpiece to the popular twice-daily combination pills, Combivir (with AZT) and Trizivir (with AZT [zidovudine, Retrovir] and abacavir [ABC, Ziagen]). FTC, manufactured by Gilead, is well tolerated and has stirred attention because of the possibility that the drug might be combined into a single pill with another Gilead medication, tenofovir (TDF, Viread; an extremely popular, well tolerated, once-daily drug) -- a possible one-pill, once-a-day combo.
The similarities between FTC and 3TC go past their abbreviations; when HIV becomes resistant to either drug, the very same atomic change in the viral reverse transcriptase (the viral part that the drugs inhibit) occurs. This change, called the M184V amino acid substitution (or "mutation"), causes resistance to both drugs and in many previous studies, occurred quite commonly in persons experiencing failure of 3TC-containing treatment regimens.
This study explored the frequency of M184V among people who received FTC-containing regimens in three different clinical trials. The study was sponsored by Gilead. Overall, over 700 patients received FTC regimens, with documented virologic failure in 73, or 11 percent of subjects. In contrast with the expectation that the virus obtained from these 70-odd persons might frequently harbor M184, the substitution was only seen in 35 percent of the viruses. This frequency was lowest (27 percent) among people who received FTC in combination with a non-nuke and a second nuke.
Interestingly, these numbers are similar to the frequency of the emergence of the M184V substitution in the Gilead 903 clinical trial (a study of 3TC with efavirenz [EFV, Sustiva] and either tenofovir or d4T [stavudine, Zerit]). In the 903 clinical trial, treatment failures were infrequent, but among those who experienced viral failure, M184V was seen in 38 percent and 34 percent, respectively.
This analysis doesn't really allow us to answer directly the following question: Does the half-life of the drug make the emergence of drug resistance less likely? There are too many differences among the analyses and drug regimens to compare across all of these studies. But, in contrast to my guess, so far, there is not a dramatic difference between the rates.
So does any of this matter? 3TC remains one of the most widely prescribed nukes -- it has a quite lengthy and favorable track record. FTC is very similar, though the new kid on the block. Understanding the similarities and differences among the drugs will be important to know, though in the end (at least until a large head-to-head clinical trial is done), the greatest distinction between the drugs are the companies that manufacture them.
Authored by: J. Quinn
Affiliations: Gilead Sciences, Inc., Durham, NC
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