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Session 122
Poster Abstracts Resistance to Specific Drugs and Drug Combinations Friday, 1:30 - 3:30 pm Hall A |
Background: Emtricitabine (FTC) and
lamivudine (3TC) are structurally related nucleoside
inhibitors of HIV-1 reverse transcriptase. The phenotypic susceptibility to FTC
of viruses containing common NRTI mutations is not well characterized. A large
database was used to examine the resistance profiles of both drugs and
the potential cross-resistance conferred by nucleoside reverse transcriptase
inhibitor (NRTI)-resistance-associated mutations.
Methods: The ViroLogic
database was queried to identify samples with M184I/V only and those without
M184I/V but containing: 2-3 TAM from 41/210/215, 2-3 TAM from
67/70/219, any 3-4 TAM,
any 5-6 TAM, K65R, or T69
insertions (with TAM allowed). The median fold change in resistance and the
percentage of isolates above assay cutoff were determined for both FTC and 3TC.
Mutations/patterns which were represented by fewer than 10 samples were not
included in this analysis.
Results: Median fold change to FTC and
3TC in the presence of the M184I/V mutation only was always above the maximum
measurable level. The median
fold change and percentage samples over cutoff for the other mutations
are presented. More samples had an FTC than 3TC median fold change over the cutoff in every
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FTC |
3TC |
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mutations |
N |
Median Fold Change |
% over
cutoff |
N |
Median Fold Change |
% over
cutoff |
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65R only |
31 |
6.7 |
93.5% |
161 |
8.8 |
98.1% |
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T69ins (TAM allowed) |
10 |
14.7 |
90.0% |
96 |
9.2 |
89.6% |
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2 or 3 TAM from 41/210/215 |
61 |
2.3 |
9.8% |
450 |
1.9 |
6.2% |
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2 or 3 TAM from 67/70/219 |
27 |
2.2 |
18.5% |
227 |
1.9 |
6.2% |
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any 3-4 TAM |
89 |
3.3 |
49.4% |
645 |
3.0 |
38.8% |
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any 5-6 TAM |
22 |
6.8 |
100.0% |
183 |
4.9 |
79.2% |
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Conclusions: Differences in FTC and 3TC resistance for M184I/V containing-samples could not be assessed as both exceeded upper assay limits. Slightly more resistance was observed for FTC than 3TC in samples containing TAM or T69 insertions, and a greater percentage of isolates retained phenotypic susceptibility to 3TC than FTC in the presence of TAM for each TAM subgroup analyzed. With respect to K65R, the median fold change for FTC was lower than for 3TC. These data highlight small but statistically significant differences in the median fold change for FTC as compared to 3TC. It is unclear whether any of these differences are clinically significant.
Keywords: lamivudine; emtricitabine; resistance
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