Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I.
PMID: 31430369
2019
The Journal of antimicrobial chemotherapy
Result: All participants with pre-existing K65R/N or three or more TAMs had virological suppression at week 48, and none qualified for inclusion in the RAP.
Result: No participant had exclusionary substitutions such as K65R or M184V/I by historical genotypic data.
Result: Participants with documented resistance to emtricitabine or tenofovir or any evidence of prior confirmed virological failure were not eligible to switch to BIC/FTC/TAF; therefore, no participants in the BIC/FTC/TAF group had K65R, M184V/I, or three or more TAMs by historical genotype analysis (Table S1, available as Supplementary data at JAC Online).
Result: Pre-existing K65R/N substitutions were found in 1.3% (7/543) of participants in the BIC/FTC/TAF treatment group.
Table:
Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs.
Discussion: Most NRTI resistance mutations interfere with the incorporation of the NRTITP, either directly (e.g., M184V/I, which causes steric hindrance involving the oxathiolane ring of 3TCTP or FTCTP) or indirectly (e.g., K65R altering the ability of the RT to bind tenofovir relative to dATP).
Pre-treatment and acquired HIV drug resistance in Dar es Salaam, Tanzania in the era of tenofovir and routine viral load monitoring.
PMID: 31273377
2019
The Journal of antimicrobial chemotherapy
Abstract: Tenofovir-resistance mutations K65R and K70G/E or >=3 thymidine analogue resistance mutations including M41L and L210W were found in 18/36 (50%) subjects on a tenofovir-containing regimen at failure.
Drug resistance from preferred antiretroviral regimens for HIV infection in South Africa: A modeling study.
Method: Prevalence of acquired drug resistance mutations represents the number of HIV-positive individuals with virological non-suppression and majority virus harboring acquired NNRT-class, K65R and/or M184V mutations (occurring as single or multiple drug-resistant viral variants/mutants), divided by the number of HIV-positive individuals with virological non-suppression and acquired drug-resistant majority virus, at a given time.
Method: The following drug resistance mutations (associated with antiretrovirals) are modeled
Result: Irrespective of the scenario, the prevalence of the NNRTI-associated (class), M184V and K65R (signature) mutations was comparable (~80%) in individuals with acquired resistance and virological non-suppression, by 2030 (Fig 3C).
Table: K65R
In vitro evaluation of novel reverse transcriptase inhibitors TAF (tenofovir alafenamide) and OBP-601 (2,3-didehydro-3-deoxy-4-ethynylthymidine) against multi-drug resistant primary isolates of HIV-2.
Abstract: With one exception, all resistant viruses had canonical nucleoside reverse transcriptase inhibitors (NRTIs)-associated resistance mutations (K65R, N69S, V111I, Y115F, Q151M and M184V).
Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population.
Abstract: The thymidine analogue mutations, M184V/I and the tenofovir-associated DRMs K65R and K70E/Q/G/N/T accounted for 82.9%, 7.3%, and 1.4% of NRTI-associated TDR, respectively.
Result: The non-TAMs K65R, L74V/I, Y115F, and Q151M each occurred in just 1 or 2 individuals.
Discussion: The rarity of K65R, other less common TDF-associated mutations, and the primary TAMs T215Y/F indicates that transmitted TDF resistance is unusual.
Epidemiology of human immunodeficiency virus (HIV) drug resistance in HIV patients with virologic failure of first-line therapy in the country of Georgia.
Abstract: K65R mutation remains below 20%, but given the high use of Tenofovir in the country, continuing surveillance of drug resistance is needed.
Abstract: The most frequent nucleoside reverse transcriptase inhibitor mutations were M184V (65.3%), K65R (19.7%) and L74V (17.0%).
Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART.
PMID: 30380053
2019
The Journal of antimicrobial chemotherapy
Result: K65R was detected in 18/72 (25.0%) and 2/17 (11.8%) participants who were on a tenofovir- and stavudine-based regimen, respectively.
Result: Among NRTI DRMs, M184IV was the most prevalent (n = 36/104, 34.6%), followed by K65R (20/104, 19.2%) (Figure 1c).
Result: Notably, two additional K65R mutations were detected at the 5% as compared with the 20% variant threshold (Figure 1d).
Result: The K65R mutation was found in one participant (n = 1/11, 9.1%).
Result: When DRM5% were assessed, double the number of NRTI mutations were found (n = 22), mostly represented by K65R (n = 4/22, 18.2%) and the TAMs D67N and
Drug resistance mutations and viral load in human immunodeficiency virus type 2 and dual HIV-1/HIV-2 infected patients in Ghana.
Abstract: HIV-2 drug resistance mutations (M184V, K65R, Y115F) were identified in 1 patient.This study is the first to report HIV-2 viral load and drug resistance mutations in HIV-2 strains from Ghana.
Result: In the ART-experienced patient, 3 major drug resistance mutations (M184V, K65R, and Y115F) were found in both the PBMC and plasma sequences.
Discussion: Major drug resistance mutations M184V, K65R, and Y115F were detected in an ART-experienced patient.
Discussion: The K65R and Q151M substitutions are known to occur more commonly in HIV-2 than in H
HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon.
Abstract: As expected, K65R was related with TDF-exposure: 0% (0/55) in group-A, 22.72% (5/22) group-B, 4.17% (1/24) group-C (p = 0.0013).
Introduction: Of note, failure on TDF leads t
Result: TDF-mutation K65R was significantly associated with TDF-exposure: 0% in group-A, 22.7% (5/22) in group-B, 4.2% (1/24) in group-C (p = 0.0013).
Discussion: As expected, K65R was only found from the group of TDF-exposed patients (group-B).
Discussion: Of note, K65R is a mutation known to reverse the excision phenotype of AZT resistance mutations, to increase viral susceptibility to AZT, which in turns improves the clinical efficacy of AZT.
Discussion: This is due to the selection of DRMs (TAMs and/or K65R) following previous ART with a thymidine analogue- and subsequently with TDF-containing regimens.
HIV mutation literature information.
PMID: 
2019
The Journal of antimicrobial chemotherapy
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