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Fitness of 3TC Mutation
Apr 2, 2004

My doctor told me that the mutation that causes resistance to 3TC is a worthless mutation because it can't infect CD4 cells. Have you heard about that? I would like a second opinion.

Response from Dr. Sherer

You should talk again with your doctor about this, because you have misunderstood the message. A virus containing the M184V, which is the most common 3TC resistance mutation, is still infectious, i.e. it can infect CD4 cells and other cells.

There is evidence that a virus with this mutation may have reduced 'fitness', i.e. a lesser ability to replicate compared to wild type virus. One aspect of fitness can be measured as part of a phenotype test in single replication cycle assays in the laboratory, recorded as the 'replication capacity' of the virus. There is some evidence that a virus with a lesser replication capacity may have a lesser clinical impact than more fit viruses, but we are still learning about the clinical impact of fitness in general, and the specific measurement of replication capacity. I would be reluctant to put too strong an emphasis on this point in choosing a first line or later line regimen.

Regarding the M184V, there is evidence that 3TC is still active, causing a one half log decline in viral load, even with a virus containing the M184V. There is also evidence that other drugs, such as AZT and D4T, get a resistance benefit from the presence of the M184V, and viruses with the M184V may have an improved susceptibility to these drugs.

One recent trial sought to show whether leaving 3TC in a second regimen even with the M184V had a clinical benefit, compared to second regimens without 3TC. There was no different in 100+ patients who were maintained on 3TC compared to another 100+ patients who had 3TC removed from their second regimen. While this study does not completely answer the question, it suggests that in this context, there was no benefit to leaving 3TC in a second line regimen in patients with the M184V mutation.

Again, I urge you to review these data with your doctor, as your individual circumstances, including your previous treatment history, might add additional important information.


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