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.

Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil

“…However, although an increasing trend was identified in a cohort from India [ 56 ], several studies report a decrease on K65R levels over the years in other countries [ 48 , 57 , 58 , 59 , 60 ]. Reinheimer and colleagues suggest that the decline on K65R prevalence rates is linked with the increasing usage of single tablet ART regimens and the inclusion of AZT on the used treatment regimen, which has been liked with K65R development suppression [ 61 ]. Moreover, Theys et al work [ 59 ] suggests that the found decline of tenofovir K65R selection rate in Portugal, between 2002 and 2010, is mainly caused by changes on treatment guidelines over the years and by the increased usage of combination of TDF and emtricitabine (FTC) [ 59 ].…”