Oct 5, 2002
Somewhere I read that the 3tc mutation will eventually reverse itself after several years? Is there any truth behind this? I would love to be able to use this drug again in the future because it didn't give me any grief like all the others, however a resistance profile 3 years ago showed resistance.This was due to dual nukes 6 years ago.Everything else is okay, but being able to combine epivir with viread and viramune would be a dream combo for me.So is a reversal ever possible?
Response from Dr. Young
Thanks for your question.
Lamivudine (3TC, Epivir) is a commonly used medication for the treatment of HIV. Resistance to 3TC is usually caused by a mutation in the gene for reverse transcriptase that results in a valine amino acid substitution at the 184th position of the enzyme (abbreviated M184V). The mutation can occur quickly in the presence of non-suppressive combination therapy.
In most pateints, the M184V substitution (as measured by HIV genotypes) becomes less prevalent once 3TC treatment is discontinued. This does not mean that the mutation reverses itself, rather, that the viral population in such persons is mixture of the wild type (184M) and mutant (184V). Since the drug presure is gone, the wild type virus is able to replicate again; since the wild type virus is more "fit" than mutant, this becomes the predominate virus in the population.
The ability to use 3TC after the emergence of resistance is a very interesting question; on the basis of what you've asked, one could pretty safely expect that the potency of 3TC against your virus (if with the 184V variant) will be less than previously (even if the genotype obtained off therapy does not show the presence of the mutant). Recent data (see the presentation by Whitcomb at this years Conference on Retroviruses and Opportunistic Infections) shows that the M184V substitution has interesting and likely important implications for the potency of other drugs- in the presence of M184V, some drugs (AZT, d4T, tenovofir) have increased potency; while other drugs (3TC, abacavir, ddI) have diminished activity. Hence, the interaction of 3TC and other drugs (after the presence of M184V) depends on the nature of the drug regimen.
So, the combination of 3TC with tenofovir and nevirapine might be expected to have slightly increased virological potency of tenofovir (provided that there weren't other mutations in the reverse transcriptase gene). There is scant clinical data to support this claim-- this conclusion is based mainly on laboratory testing of HIV viruses. Unfortunately, once present, HIV drug resistance mutations will likely be there for ever. With the possible presence of other mutations, I would definately recommend very close clinical and lab monitoring following the initiation of any new regimen. -BY
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