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Clinical and genotypic correlates of mutation K65R in HIV‐infected patients failing regimens not including tenofovir
Author(s) -
Trotta Maria Paola,
Bonfigli Sandro,
CeccheriniSilberstein Francesca,
Bellagamba Rita,
D'Arrigo Roberta,
Soldani Fabio,
Zaccarelli Mauro,
Concetta Bellocchi Maria,
Lorenzini Patrizia,
Marconi Patrizia,
Boumis Evangelo,
Forbici Federica,
Comandini Ubaldo Visco,
Tozzi Valerio,
Narciso Pasquale,
Federico Perno Carlo,
Antinori Andrea
Publication year - 2006
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.20573
Subject(s) - resistance mutation , abacavir , lamivudine , virology , efavirenz , genotype , mutation , drug resistance , biology , medicine , stavudine , viral load , virus , reverse transcriptase , antiretroviral therapy , polymerase chain reaction , genetics , hepatitis b virus , gene
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 naïve 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‐naïve 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. J. Med. Virol. 78:535–541, 2006. © 2006 Wiley‐Liss, Inc.