Biochemical Mechanism of HIV-1 Resistance to Rilpivirine

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Biochemical mechanism of clinical resistance to rilpivirine

Background The introduction of HAART has significantly prolonged the life span of HIV-infected patients. However, the error-prone nature of HIV-1 reverse transcriptase (HIV-1 RT) results in the emergence of drug-resistant viruses and threatens the effectiveness of HAART. HIV-1 RT is a primary target of two classes of drugs: nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside ...

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Rilpivirine, emtricitabine and tenofovir resistance in HIV-1-infected rilpivirine-naive patients failing antiretroviral therapy.

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Resistance mechanism of human immunodeficiency virus type-1 protease to inhibitors: A molecular dynamic approach

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Role of the K101E substitution in HIV-1 reverse transcriptase in resistance to rilpivirine and other nonnucleoside reverse transcriptase inhibitors.

Resistance to the recently approved nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) commonly involves substitutions at positions E138K and K101E in HIV-1 reverse transcriptase (RT), together with an M184I substitution that is associated with resistance to coutilized emtricitabine (FTC). Previous biochemical and virological studies have shown that compensatory interaction...

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The HIV-1 reverse transcriptase M184I mutation enhances the E138K-associated resistance to rilpivirine and decreases viral fitness.

BACKGROUND The registrational phase III clinical trials of the nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) rilpivirine (RPV) in combination with two nucleoside/nucleotide RT inhibitors (NRTIs) found a unique genotypic resistance pattern involving the NNRTI mutation E138K with the NRTI mutation M184I. Eighty percent of subjects used emtricitabine (FTC) and tenofovir disoproxil fum...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 2012

ISSN: 0021-9258

DOI: 10.1074/jbc.m112.398180