Emtricitabine
May Lead to Less Resistance than Related Drug Lamivudine
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.
Results
 |
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.
10/8/10
Reference
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).
