Prevalence of the K65R resistance reverse transcriptase mutation in different HIV‐1 subtypes in Israel

Abstract

The K65R mutation in HIV-1 reverse transcriptase (RT) can be selected by the RT inhibitors tenofovir (TDF), abacavir (ABC), and didanosine (DDI). Recently, in vitro studies have shown that K65R is selected in tissue culture more rapidly with subtype C than subtype B viruses. The prevalence of K65R in viruses sequenced at the Tel-Aviv AIDS Center was evaluated. This study analyzed retrospectively sequences from 1999 to 2007 in patients treated with TDF, ABC, and/or DDI and compared rates of mutational prevalence between subtypes. Fisher's exact test was used to determine statistical significance. Forty-four sequences from patients treated with the three above-cited drugs were analyzed. Subtypes A (n = 1), CRF01_AE (n = 4), CRF02_AG (n = 2), B (n = 21), C (n = 11), D (n = 1), F (n = 3), and G (n = 1) were represented. Seven non-B viruses had the K65R mutation, which was only found in one subtype B virus. Of these seven samples four were subtype C, one was subtype CRF01_AE, and two were subtype CRF02_AG. None of the eight viruses with K65R harbored thymidine analogue mutations. In this study, non-subtype B viruses possessed the K65R mutation at higher incidence than subtype B viruses. Subtype C viruses may be especially prone to develop this mutation. Larger studies are needed to confirm these data. Efforts should be intensified to understand better differences in drug resistance between various HIV subtypes.

Clade homogeneity and Pol gene polymorphisms in chronically HIV-1 infected antiretroviral treatment naive patients after the roll out of ART in Ethiopia

“…Low rate of K65R mutation which causes intermediate resistance to most of the NRTIs and low level resistance to d4T [24,25] was observed in one patient and could be due to the recent availability of tenofovir in Ethiopia. Although this mutation is relatively uncommon, there has been an increase in its prevalence in some countries as a result of the widespread clinical use of tenofovir [26-29]. Moreover, despite the wide use of thymidine analogs (zidovidine or stavudine) in Ethiopia, thymidine analog mutations were observed in low frequency unlike previous similar studies [4].…”

A Template-Dependent Dislocation Mechanism Potentiates K65R Reverse Transcriptase Mutation Development in Subtype C Variants of HIV-1

“…In addition, numerous clinical studies have also demonstrated higher rates of K65R development ranging between 9 and 30% in subtype C-infected individuals who failed treatment [36], [37], [38], [39], [40], [41]. These rates are in marked contrast with subtype B HIV-1.…”

Reverse Transcriptase Genotypes in Pediatric Patients Failing Initial Antiretroviral Therapy in Gaborone, Botswana

“…[14][15][16][17][18] However, some have shown considerable prevalence of TAMs and other mutations associated with nucleoside reverse transcriptase inhibitors ([NRTIs] such as K65R, L74V, and Q151M) that can compromise the NRTI backbones used in second-line therapies. [19][20][21] Generally, first-line ART for children in southern Africa has traditionally followed World Health Organization (WHO) recommendations of 2 NRTIs þ 1 NNRTI, that is ZDV or d4T þ lamivudine (3TC) þ NVP or efavirenz (EFV); and 2 NRTIs þ lopinavir/ritonavir (LPV/r) is currently recommended by WHO as first-line ART for infants and children less than 24 months who have been exposed to NNRTIs. 22 Abacavir (ABC) has been recently recommended by WHO for pediatric first-line regimens and has replaced ZDV or d4T in many regional programs, including Lesotho and South Africa [22][23][24] ; however, it has yet to be included in first-line ART in Botswana, where standard pediatric first-line ART (when there is no history of NNRTI exposure through PMTCT or maternal treatment) is ZDV/3TC/NVP or EFV and pediatric second-line ART is d4T/ABC/LPV/r.…”