Clinical and genotypic correlates of mutation K65R in HIV-infected patients failing regimens not including tenofovir
| Autor: | Sandro Bonfigli, Francesca Ceccherini-Silberstein, Patrizia Lorenzini, Mauro Zaccarelli, Andrea Antinori, Pasquale Narciso, Carlo Federico Perno, Federica Forbici, Fabio Soldani, Ubaldo Visco Comandini, Rita Bellagamba, Maria Concetta Bellocchi, Roberta D'Arrigo, Valerio Tozzi, Evangelo Boumis, Maria Paola Trotta, Patrizia Marconi |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Male
viruses Drug Resistance HIV Infections Cohort Studies chemistry.chemical_compound immune system diseases Abacavir Antiretroviral Therapy Highly Active Treatment Failure Anti-HIV Agents Humans Retrospective Studies Aged CD4 Lymphocyte Count HIV-1 Reverse Transcriptase Inhibitors Multivariate Analysis Drug Resistance Viral Anti-Retroviral Agents Adult Adenine Middle Aged HIV Reverse Transcriptase Phosphonic Acids Mutation Female Viral Sida biology virus diseases Lamivudine Resistance mutation Settore MED/07 - Microbiologia e Microbiologia Clinica Infectious Diseases Lentivirus Mutation (genetic algorithm) medicine.drug Efavirenz Organophosphonates Antiretroviral Therapy Acquired immunodeficiency syndrome (AIDS) Virology medicine Highly Active Tenofovir biochemical phenomena metabolism and nutrition biology.organism_classification medicine.disease chemistry |
| Popis: | The mutation RT-K65R confers resistance to tenofovir (TDF). Although its prevalence is increasing with the use of this drug, clinical and genotypic correlates of K65R occurrence have yet to be fully identified. Clinical, virological and immunological and genotypic data of patients naive for TDF who failed HAART regimens and underwent genotypic resistance test (GRT) during 1999-2003 were collected in a database and analyzed retrospectively. Out of 1392 GRT performed for 771 patients, 12 TDF-naive patients had the K65R mutation with an overall prevalence of 1.6%. Previous AIDS, the use of abacavir, and treatment with efavirenz at GRT were independently associated with a greater risk of expressing K65R, while patients with longer exposure to lamivudine were less likely to present the mutation. Among genotypic correlates, the presence of M184V and NAMs seems to be protective for the emergence of K65R, while a strong positive correlation was found with the Q151M complex mutation. Moreover, the L100I mutation was independently associated with a higher probability of presenting K65R. The selection of mutation K65R in patients failing without TDF is rare. However, exposure to abacavir and/or efavirenz, presence of Q151M and/or L100I, and prior AIDS may favor the selection of this mutation. Conversely, long 3TC exposure, and the presence of M184V or NAMs seem to be protective. |
| Databáze: | OpenAIRE |
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