Factors associated with the emergence of K65R in patients with HIV-1 infection treated with combination antiretroviral therapy containing tenofovir.

Détails

ID Serval
serval:BIB_40D7892CFAC9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Factors associated with the emergence of K65R in patients with HIV-1 infection treated with combination antiretroviral therapy containing tenofovir.
Périodique
Clinical Infectious Diseases
Auteur(s)
von Wyl V., Yerly S., Böni J., Bürgisser P., Klimkait T., Battegay M., Bernasconi E., Cavassini M., Furrer H., Hirschel B., Vernazza P.L., Rickenbach M., Ledergerber B., Günthard H.F.
ISSN
1537-6591
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
46
Numéro
8
Pages
1299-1309
Langue
anglais
Résumé
BACKGROUND: The human immunodeficiency virus type 1 reverse-transcriptase mutation K65R is a single-point mutation that has become more frequent after increased use of tenofovir disoproxil fumarate (TDF). We aimed to identify predictors for the emergence of K65R, using clinical data and genotypic resistance tests from the Swiss HIV Cohort Study. METHODS: A total of 222 patients with genotypic resistance tests performed while receiving treatment with TDF-containing regimens were stratified by detectability of K65R (K65R group, 42 patients; undetected K65R group, 180 patients). Patient characteristics at start of that treatment were analyzed. RESULTS: In an adjusted logistic regression, TDF treatment with nonnucleoside reverse-transcriptase inhibitors and/or didanosine was associated with the emergence of K65R, whereas the presence of any of the thymidine analogue mutations D67N, K70R, T215F, or K219E/Q was protective. The previously undescribed mutational pattern K65R/G190S/Y181C was observed in 6 of 21 patients treated with efavirenz and TDF. Salvage therapy after TDF treatment was started for 36 patients with K65R and for 118 patients from the wild-type group. Proportions of patients attaining human immunodeficiency virus type 1 loads <50 copies/mL after 24 weeks of continuous treatment were similar for the K65R group (44.1%; 95% confidence interval, 27.2%-62.1%) and the wild-type group (51.9%; 95% confidence interval, 42.0%-61.6%). CONCLUSIONS: In settings where thymidine analogue mutations are less likely to be present, such as at start of first-line therapy or after extended treatment interruptions, combinations of TDF with other K65R-inducing components or with efavirenz or nevirapine may carry an enhanced risk of the emergence of K65R. The finding of a distinct mutational pattern selected by treatment with TDF and efavirenz suggests a potential fitness interaction between K65R and nonnucleoside reverse-transcriptase inhibitor-induced mutations.
Mots-clé
Adenine, Adult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Cohort Studies, Female, Genotype, HIV Infections, HIV Reverse Transcriptase, HIV-1, Humans, Logistic Models, Male, Middle Aged, Phosphonic Acids, Point Mutation
Pubmed
Web of science
Open Access
Oui
Création de la notice
26/02/2009 11:39
Dernière modification de la notice
08/05/2019 17:38
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