Journal Article

Factors Associated with the Emergence of K65R in Patients with HIV-1 Infection Treated with Combination Antiretroviral Therapy Containing Tenofovir

Viktor von Wyl, Sabine Yerly, Jürg Böni, Philippe Bürgisser, Thomas Klimkait, Manuel Battegay, Enos Bernasconi, Matthias Cavassini, Hansjakob Furrer, Bernard Hirschel, Pietro L. Vernazza, Martin Rickenbach, Bruno Ledergerber and Huldrych F. Günthard

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 46, issue 8, pages 1299-1309
Published in print April 2008 | ISSN: 1058-4838
Published online April 2008 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/528863
Factors Associated with the Emergence of K65R in Patients with HIV-1 Infection Treated with Combination Antiretroviral Therapy Containing Tenofovir

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  • Infectious Diseases
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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.

Journal Article.  4912 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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