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drug resistance
Apr 11, 2008

Dear Dr. S, Do the following nrtis have any anti viral effect even in the presents of resistance: 3tc,d4t,or fc. I read somewhere that 3tc still retains a .5log anti viral effect even with 184v. Thankyou

Response from Dr. Sherer

Yes. Lamivudine (3TC or epivir) and emtricitabine (FTC or Emtriva) both retain the ability to reduce the viral load by 0.5 log in the presence of their signature mutation, the M184V. This mutation also impairs viral fitness, which appears to have advantages regarding the rapidity of the fall of the CD4 cell count and the degree of viral rebound in patients with virologic failure. For this reason, these drugs are often recycled and used, even in the presence of the M184V.

D4T is a separate issue. D4T and AZT share the same resistance mutations called thymidine analogue mutations or 'TAMS'. A single TAM will not cause a reduction in susceptibility to these two drugs, but multiple mutations, in general three or more, will lead to reduced potency.

You have asked this question without providing the context for the question, and I don't want to create the impression that it is wise to continue to use one drug or a drug regimen in the face of known virologic failure, i.e. a viral load consistently above 50 copies/ml. In general, there are effective second line regimens that can be used to completely suppress the virus in the event of virologic failure and drug resistance to one or more members of the initial drug regimen. These second line regimens are available or are becoming available in most countries of the world.

Therefore, once treatment failure has been established, either by a rising viral load (proving virologic failure) or by a falling CD4 cell count (immunologic failure) or a new HIV-related opportunistic infection (clinical failure), the HAART regimen should be switched immediately to a regimen containing three new drugs (if possible and if available), including one new class of drugs. In most parts of the world where an NNRTI like nevirapine or efavirenz in part of the initial regimen, the new class of drugs in the second line therapy will be a boosted PI.

The evidence is increasing that in the developing world, in which people with HIV are monitored with CD4 cell counts and clinical follow up, but without viral loads, higher level drug resistance to the NRTIs, and particularly with TAMs that developed to AZT or D4T, there is more resistance and a lesser likelihood of any residual activity of AZT or D4T in a second or third line regimen, and reduced likelihood that other second line NRTIs such as abacavir, tenofovir (which is a nucleotide) or didanosine will be fully active.

To sum up simply, resistance is always undersirable, and a new second line regimen should always include three active drugs, including one drug in a new class. Also as noted above, it is common for 3TC or FTC to be part of a second line regimen, in spite of the presence of the M184V mutation.

I suggest that you talk to your doctor about your question and this response.


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