NEW YORK (Reuters Health) - Certain reverse transcriptase mutations that confer resistance to nucleoside inhibitors are associated with a hypersusceptibility to nonnucleoside reverse transcriptase inhibitors (NNRTIs), according to a recent study by Italian researchers.
In the May 1 issue of the Journal of Infectious Diseases, Dr. Valerio Tozzi and colleagues at the National Institute for Infectious Diseases Lazzaro Spallanzani in Rome describe their observational study of a cohort of HIV-infected patients for whom highly active antiretroviral therapy had failed. All the patients were therefore receiving either efavirenz or protease inhibitors, with therapy guided by genotypic resistance testing.
The researchers report that in patients treated with efavirenz-based regimens, “the baseline reverse transcriptase mutations M41L, M184V, l210W, and T215Y and the M41L/T215Y and M41L/T215Y/M184V combinations were associated with virological suppression.” In patients treated with protease inhibitor, the only mutation associated with virological suppression was M184V.
In patients taking efavirenz, the M41L/T215Y/M184V combination was also associated with higher increases in CD4 cell counts.
The authors add, however, that while patients with these mutations had “an increased probability of achieving undetectable virus loads,” such results were not correlated “with the probability of virus loads remaining undetectable without virological rebound.”
“The latter finding suggests a need for additional therapeutic strategies to maintain a stable virological response if efavirenz is used” in HIV-infected patients for whom antiretroviral therapy has failed, the authors conclude.
Source: J Infect Dis 2004;189:1688-1695 [ Google search on this article ]
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