Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda.
Abstract: As expected, discriminatory DRMs such as K65R, L74I, and Y115F were noted in Tenofovir (TDF) containing regimens while the Thymidine Analogue Mutations (TAMs) L210W and T215 mutations were in Zidovudine (AZT)-based regimens.
Abstract: The most prevalent Nucleoside Reverse Transcriptase Inhibitor (NRTI) mutations were M184V/I (67.3%), K219/Q/E (22.6%) and K65R (21.1%).
Discussion: K65R is highly selected for in TDF containing regimens.
Discussion: TAMs and K65R had a prevalence of 35.7% and 23.1% respectively, similar to a study done in Uganda where K65R mutation had a prevale
Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya.
Result: Among the 59 participants with PDR, NNRTI mutations (K103N, Y181C, G190A) were detected in all but one (98 3%) and NRTI mutations (K65R, M184V) were detected in 14 (23 7%).
Table: K65R
Discussion: An economical and easy to use point of care OLA kit that assesses NNRTI mutations K103N, Y181C, G190A and NRTI mutations M184V and K65R could be used in resource-limited settings to test patients prior to starting EFV-based ART, at virologic failure
Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017).
Result: The percentages of four mutations K65R (NRTI), M184I/V (NRTI), G190A/S (NNRTI) and M230L (NNRTI) were significantly correlated with subtypes (p < 0.05) (Table 2).
Discussion: Third, two NRTI (M184V/I and K65R), three NNRTI (K103N/S, Y181C/I and G190A/S) and one PI (M46I/L) mutations had higher prevalence than other SDRMs in China.
Pretreatment HIV drug resistance spread within transmission clusters in Mexico City.
PMID: 31819984
2020
The Journal of antimicrobial chemotherapy
Result: K65R was very rare and only observed as a low-frequency variant.
Discussion: Moreover, consistent with previous observations, DRMs with low transmission fitness due to high replicative impairment such as M184V/I and K65R were not shared within the Mexican network, and were observed mostly at low within-host frequencies in the study population.
Evaluation of the management of pretreatment HIV drug resistance by oligonucleotide ligation assay: a randomised controlled trial.
Method: Peripheral blood mononuclear cells were evaluated for NNRTI and NRTI drug resistance mutations, K103N, Y181C, G190A, and K65R, and M184V, using a quantitative OLA.
Method: We evaluated K65R in all pre-ART specimens retrospectively as tenofovir became more available concomitantly with efavirenz.
Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I.
PMID: 31774913
2020
The Journal of infectious diseases
5Result: A previous study reported that L74I can restore replication to a virus with the K65R mutation without conferring drug resistance; therefore, we sought to test the hypothesis that L74I could restore replication ""fitness"" to a M184V mutant virus, thereby explaining the higher than expected VLs."
Method: We repeated this process in subgroups of patients defined by several baseline characteristics: presence of K65R mutation, presence of major NNRTI mutations, choice of NRTI, choice of NNRTI, categories of baseline CD4 count (< and >200 cells/mm3), and categories of baseline VL (< and >100 000 copies per mL).
Result: Many of these mutations have previously been associated with drug resistance t
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.
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).
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:
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).