Drug Resistance More Likely in NNRTI plus NRTI Regimens Compared with Ritonavir-boosted Protease Inhibitors

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By Megan Rauscher

In the long term, there is "an appreciable" level of viral load failure and emergence of drug resistance in HIV-infected patients initiating potent three or four antiretroviral drug regimens in routine clinical practice, according to UK researchers.

However, Dr. Andrew Phillips told Reuters Health that "it looks as though resistance emergence is more likely in those starting some regimens" than others, in particular, non-nucleoside reverse transcriptase inhibitors (NNRTIs) plus nucleosides compared with ritonavir-boosted protease inhibitors.

In the March 25th issue of AIDS, Dr. Phillips of Royal Free and University College Medical School, London and colleagues note that they studied 4,306 patients initiating antiretroviral therapy (ART) with two nucleosides plus either a single protease inhibitor (PI), a PI with ritonavir, abacavir, or an NNRTI.

The overall cumulative risk of viral load failure was 38% by 6 years, the risk of developing one or more major mutations was 27% by 6 years and the risk of mutations from at least two of the three main drug classes was 20% over the same period.

These findings, the researchers point out, are "lower limit estimates," because test results were not available for many patients with viral load failure.

The risk of PI mutations being detected in patients initiating a PI-containing regimen with ritonavir was significantly lower (hazard ratio, 0.31) than the risk of NNRTI mutations being detected in patients initiating a NNRTI-containing regimen.

Thus the researchers conclude patients treated in routine clinical settings experience "relatively high levels" of ART drug resistance over the first 6 years of therapy, despite receiving potent drug combinations from the outset.

In light of these findings, Dr. Phillips added that "it is important that patients maintain complete adherence to therapy in order to try to avoid resistance emerging."

04/25/05

AIDS 2005;19:487-494.