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Avoiding resistance
Feb 5, 2004

Dr. Sherer--

Welcome to The Body! I love this site and all you guys for the work you do.

My question is what combo for first starting treatment is best for avoiding resistance down the road? If not one combo, are there at least some drugs that are safer than others for avoiding resistance?

Thanks in advance, Chuck

Response from Dr. Sherer

Hello Chuck, and thanks for the kind words for the Body site.

As you may be aware, the HHS Guidelines for the use of antiretroviral therapy lists two preferred regimens, one in the protease inhibitor class and one in the NNRTI class. They are lopinavir/ritonavir (LPV/r) when paired with lamivudine (3TC) and either zidovudine (AZT) or stavudine (D4T; or efavirenz (EFV) when paired with 3TC and either tenofovir (TDF), AZT, or D4T.

One of the considerations in this selection was the likelihood of preventing resistance, as well as potency, tolerabilty, and convenience.

The protease class appears to have an advantage in preventing resistance, particulary when the regimen contains a boosted protease such as LPV/r. In several studies, no resistance to the PI class, and lower levels of resistance to the other members of the regimen, have been seen in patients on LPV/r; this was supported recently by a trial of another PI as well, i.e. boosted fos-amprenavir.

In contrast, while the efavirenz-based regimens have several advantages, their performance at preventing resistance is not as strong. When patients fail on those regimens (an infrequent occurrence, i.e. around 10% of patients after 2 years in on study), 25-40% of patients devlop resistance to more than one class, e.g. resistance to EFV and TDF, or EFV and 3TC.

So the regimens with the best record of preventing resistance are those with boosted PIs, of which, according to the HHS guidelines, LPV/r is the best choice.

I have provided a link to the HHS guidelines so that you can review their description of the choice of initial agents.


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