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new report on resistance
Jan 4, 2004

Please help!

I received this article this morning and it really scared me. I do not understand what it is saying-the terminalogy is over my head. I am on first line of meds, kaletra, viread and emtriva. I appear to be a rapid progressor. My genotype showed "senstive" to all meds with mutations of M361 and L63P to several PI's. Is this article telling me that the genotype test may not really be picking up all my virus is resistant to and that I may be resistant to more drugs? It is baffling!

NATAP - www.natap.org

Progressive reversion of HIV-1 mutations may have serious consequences

By Megan Rauscher

NEW YORK (Reuters Health) - Although multidrug-resistant HIV strains, because they are potentially less virally fit than non-drug resistant strains, were hoped to be less likely to cause disease, a report published this month suggests just the opposite.

After transmission of a resistant HIV strain, the virus is able to evolve to become more fit and cause significant disease, according to the study in the December 15th issue of Clinical Infectious Diseases.

"The frequency of HIV that is resistant to current medications seems to be growing, and this may limit global treatment strategies," Dr. Rajesh T. Gandhi from Partners AIDS Research Center in Boston, who led the study, noted in comments to Reuters Health.

Dr. Gandhi and colleagues monitored viral evolution after transmission of HIV-1 containing multiple reverse transcriptase (RT) and protease mutations (PR) in a 32-year-old previously healthy man.

In the absence of ongoing antiretroviral therapy, 5 of 12 drug resistance mutations reverted in a stepwise fashion to wild type over the course of one year. Of note, reversal of the M184V mutation alone did not produce a change in replicative capacity but it did enhance resistance to zidovudine and tenofovir.

However, "reversions of a second (RT) mutation and 3 PR mutations were associated with an increase in viral replicative capacity and this was temporally correlated with a marked decrease in CD4 cell number," the researchers report.

Dr. Gandhi and colleagues say this study "demonstrates the gradual stepwise back-mutation of certain drug resistance mutations in vivo in the absence of ongoing drug selection pressure."

While larger studies are needed to confirm these findings, Dr. Gandhi told Reuters Health, this report "emphasizes that the recent increase in HIV transmission among men who have sex with men in the United States may result in acquisition of multidrug resistant virus, with very serious consequences."

Response from Dr. Pierone

This was a very interesting and somewhat surprising report. The conventional wisdom was that people that acquired multi-drug resistant virus would have more challenges with selection of antiretroviral therapy, but this detrimental aspect would be counterbalanced by a virus with lower replication capacity which might be less harmful.

This report indicated that multi-drug resistant virus could back-mutate towards more virulent wild-type virus. The concern is that when antiretroviral therapy is started, resistance might develop quickly because of archived resistance from the transmitted virus. How commonly this phenomenon occurs is not clear, but more longitudinal follow up of people with transmitted drug resistant virus should help us better understand how often this occurs.

The report does not sound like it relates to your situation and I would not worry about it. The regimen that you are on is very potent and if your viral load is undetectable and you are adherent to therapy you should do well.



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