title: Prevalence of K65R in patients treated with tenofovir disoproxil fumarate: recommendations based on the Frankfurt HIV Cohort Study Resistance Database (FHCS-RD).
abstract: Mutations in the genome of HIV-1 can compromise the success of antiretroviral treatments (ARTs) in HIV-1-infected individuals. The Frankfurt HIV Cohort Study Resistance Database (FHCS-RD) has previously documented a decline in the burden of resistance-associated mutations (RAMs) following the implementation of several new antiretroviral therapy regimens in 2007. In the current study, the annual burden of RAMs documented in the FHCS-RD in 2005-2013 was set in relation to the annual number of all cohort patients, drug regimens, available resistance tests, and prevalence for each RAM on relevant codons of reverse transcriptase (RT) and protease (PR) genes. A specific focus was put on the prevalence of the tenofovir disoproxil fumarate (TDF) signature mutation K65R in HIV-1 RT in relation to the application of TDF within ART. Between 2005 and 2012, a total of 4423 HIV genotyping data sets from 4509 patients were analysed. All mutations show a consistent decline, and the most impressive decrease was observed for thymidine analogue mutations (TAMs). The frequency of non-TAMs and PR mutations also decreased, but generally to a lower extent. The prevalence of K65R decreased from 2.6 % in 2005 to 0.2 % in 2012 despite increased use of TDF-containing ART. Both the improved strategic use of TDF in ARTs and generally more effective ART regimens may have resulted in decreasing RAM prevalences in FHCS-RD since 2007. These trends challenge the cost-effectiveness of resistance testing prior to failing ART.
authors.affiliation: Institute for Medical Virology, University Hospital Frankfurt, Frankfurt am Main, Germany. claudia.reinheimer@kgu.de.|Institute for Medical Microbiology and Infection Control, University Hospital Frankfurt, Paul Ehrlich-Str. 40, 60596, Frankfurt am Main, Germany. claudia.reinheimer@kgu.de.
authors.forename: Claudia
authors.initials: C
authors.lastname: Reinheimer
authors.affiliation: Institute for Medical Virology, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Wesner
authors.affiliation: Institute for Medical Virology, University Hospital Frankfurt, Frankfurt am Main, Germany.|Max von Pettenkofer-Institute for Hygiene and Clinical Microbiology, Virology, Ludwig Maximilians-University, Munich, Germany.
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Keppler
authors.affiliation: Institute for Medical Virology, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Hans Wilhelm
authors.initials: HW
authors.lastname: Doerr
authors.affiliation: Institute of Biostatistics and Mathematical Modeling, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.affiliation: Institute for Medical Virology, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Stürmer
authors.affiliation: Department for Internal Medicine II/Infectious Diseases, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Stephan
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D020125:Mutation, Missense; D015995:Prevalence; D000068698:Tenofovir / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D000068698:Tenofovir; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
keywords: Frankfurt HIV Cohort Study; K65R; Prevalence; RAM; Tenofovir disoproxil fumarate