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

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Serval ID
serval:BIB_40D7892CFAC9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Factors associated with the emergence of K65R in patients with HIV-1 infection treated with combination antiretroviral therapy containing tenofovir.
Journal
Clinical Infectious Diseases
Author(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
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
46
Number
8
Pages
1299-1309
Language
english
Abstract
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.
Keywords
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
Yes
Create date
26/02/2009 10:39
Last modification date
25/09/2019 6:09
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