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11th retrovirus presentation about resistance
Feb 24, 2004

Can you give a short summary or feedback whether any new recommendations to address resistance were presented at the 11th retrovirus conference- esp. in the presentation there by Lisa Demeter? should triple nrti regimens be avoided?

Response from Dr. Sherer

While that would not be a short answer, there are a few useful issues to note:

When stopping an NNRTI such as nevirapine or efavirenz, which have long plasma half lives, one of two strategies is recommended, either stop the NNRTI one week before stopping the other drugs in the regimen, or add a PI for one week when stopping the NNRTI, in order to prevent resistance.

Some drug resistance can be overcome with higher drug levels. In a study of lopinavir/ritonavir in higher doses, e.g. 5 pills twice daily, or the usual dose with 2 ritonavir pills twice daily, high level PI resistance was overcome and good virologic control was achieved in a group of highly experienced patients in about half the patients. The results were best when the patient's virus was also susceptible to other drugs in the regimen.

HIV 'superinfection, i.e. when one HIV+ person transmits their virus to another HIV+ person, has now been well documented. The effects appear to be harmful; the new virus can disrupt a stable response to ART, for example, and the newly acquired species can rapidly become the dominant species. For years HIV physcians have counseled HIV+ persons to follow safe sex practices with HIV+ persons out of concern for this possibility, as well as other possible infections such as STIs and hepatitis. This further supports that recommendation.

The phenomenon of 'hypersusceptibility' shows that not all mutations have negative effects on treatment (though all are undesirable). Following some NRTI mutations, an increased susceptibility to NNRTIs has been observed, i.e. a more profound antiviral response. Several studies have now shown that this leads to better outcomes in patients in whom it occurs than in those in whom it does not.

There is great variability in reports of increases in the tranmission of resistant HIV. Additional evidence that it occurs and that the acquisition of transmitted virus can effect outcomes was presented. However, in three studies from Amsterdam, North Carolina, and Switzerland, there was not an increase in resistance among new HIV infections, and in some cases a decrease from past surveys. There are several possible reasons for these variations. The take home point remains that it can occur, and precautions to prevent transmitting or acquiring a resistant virus should still be taken.

Finally, more evidence that some mutations persist for a year or longer was presented, and the switch from resistant virus back to wild type (called reversion) can take < 1-2 weeks or up to 4-6 months.

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