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Emtricitabine May Lead to Less Resistance than Related Drug Lamivudine

SUMMARY: Although structurally similar, the nucleoside reverse transcriptase inhibitor emtricitabine (Emtriva, also known as FTC) is less likely to lead to emergence of the M184V resistance mutation than the older drug lamivudine (Epivir, also known as 3TC), according to a study published in the August 24, 2010 online edition of the Journal of Acquired Immune Deficiency Syndromes.

By Liz Highleyman

Emtricitabine and lamivudine are structurally related and have demonstrated similar efficacy in clinical trials, so many clinicians consider them more or less interchange.

Emtricitabine is an ingredient in the Truvada (tenofovir/emtricitabine) and Atripla (tenofovir/emtricitabine) combination pills, while lamivudine is included in the Epzicom (lamivudine/abacavir), Combivir (zidovudine/lamivudine), and Trizivir (zidovudine/lamivudine/abacavir) coformulations.

Valentina Svicher from the University of Rome and colleagues performed a study comparing genotypic resistance profiles for emtricitabine plus tenofovir and lamivudine plus tenofovir, both in vivo and in vitro.

The researchers analyzed a total of 352 HIV-1 subtype B pol gene sequences from 42 patients taking emtricitabine/tenofovir, 40 people taking lamivudine/tenofovir, and 270 patients taking lamivudine plus a NRTI other than tenofovir. All participants were taking emtricitabine, lamivudine, and tenofovir for the first time and experienced treatment failure, defined as 2 consecutive viral load measurements < 50 copies/mL.


The key NRTI resistance mutation M184V was significantly less common among patients treated with emtricitabine/tenofovir (14.3%) compared with those receiving either lamivudine/tenofovir (40.0%) or lamivudine plus another NRTI (55.6%).
In a multivariate analysis, factors significantly associated with a lower probability of M184V emergence at the time of treatment failure were:
Use of emtricitabine rather than lamivudine: odds ratio (OR) 0.32, or 68% reduction in risk;
Use of a ritonavir-boosted protease inhibitor: OR 0.20, or 80% reduction;
Use of tenofovir versus another second NRTI: OR 0.47, or 53% reduction.
Laboratory phenotypic testing showed that emtricitabine/tenofovir was significantly more likely than lamivudine/tenofovir to clear HIV in cell cultues.
Emtricitabine/tenofovir was found to have a higher "barrier to resistance" compared with lamivudine/tenofovir.
However, in vitro selection experiments and docking analysis showed that other reverse transcriptase (RT) mutations could be selected by both lamivudine/tenofovir and emtricitabine/tenofovir in the absence of M184V.

Based on these findings, the study authors concluded, "Our study shows lower rates of M184V development in emtricitabine/tenofovir regimens versus lamivudine/tenofovir and suggests a potential role of boosted protease inhibitors and tenofovir in delaying the M184V emergence."

"The lower prevalence of M184V can be explained by the higher potency" of emtricitabine compared with lamivudine, they added.

"Novel RT mutational patterns, more complex than currently known, can contribute to lamivudine, emtricitabine, and tenofovir resistance," they wrote. Understanding these patterns "is crucial to maximize the opportunity for successful and subsequent therapies after viral rebound, not only in western countries but also in resource-limited settings."

Investigator affiliations: Department of Experimental Medicine, University of Rome "Tor Vergata," Rome, Italy; Department of Pharmacobiological Sciences, University of Catanzaro "Magna Graecia," Roccelletta di Borgia, Italy; I.N.M.I. "L. Spallanzani," Rome, Italy; Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.


V Svicher, C Alteri, A Artese, and others. Different Evolution of Genotypic Resistance Profiles to Emtricitabine Versus Lamivudine in Tenofovir-Containing Regimens. Journal of Acquired Immune Deficiency Syndromes (Abstract). August 24, 2010 (Epub ahead of print).



















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