Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy.
PMID: 29084434
2018
AIDS research and human retroviruses
Introduction: As expected, patients failing AZT-based therapy did not develop mutations K65R, K70E, L74V, or Y115F, and only rarely were DRMs from the Q151M complex seen.
Introduction: Based on drug availability to the program, 3TC was prescribed more frequently in patients enrolling in the year 2008 and later, so a logistic regression model was used to determine whether year of ART start or time on treatment could explain the differences in the emergence of K65R.
Introduction: However, in the 31 patients with no Introduction: examined 167 Indian patients with immunological failure on TDF-based 1L regimen, all with subtype C infection, and found TAMs, some coexisting with K65R.
HIV drug resistance following a decade of the free antiretroviral therapy programme in India: A review.
PMID: 29128646
2018
International journal of infectious diseases
Abstract: The temporal trend analysis of individual DRM from sequences retrieved during 2004-2014 indicated a rising trend in K65R mutations (p=0.013).
Seroconversion on preexposure prophylaxis: a case report with segmental hair analysis for timed adherence determination.
Abstract: On day 2, HIV-1 RNA was 27 316 copies/ml, genotyping revealed M184V, K70T, K65R, and K103N mutations, plasma TFV and FTC concentrations were consistent with recent dosing.
Introduction: In that case, if the patient was not fully adherent to PrEP when exposed to HIV in the past, the patient could have developed the NRTI-resistant mutations (M184V, K70T, and K65R) through the selective pressure of FTC/TDF prophylaxis after acquiring a virus carrying the K103N mutation.
Introduction: On day 2, his HIV-1 RNA was 27 316 copies/ml, and genotyping (by population sequencing) subsequently revealed significant mutations in the reverse transcr
A Trial of a Single-tablet Regimen of Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate for the Initial Treatment of Human Immunodeficiency Virus Type 2 Infection in a Resource-limited Setting: 48-Week Results From Senegal, West Africa.
Abstract: The 1 subject with virologic failure had multidrug-resistant HIV-2 (reverse transcriptase mutation: K65R; integrase mutations: G140S and Q148R) detected at week 48.
Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases.
Abstract: An adapted version of the assay was used to obtain error rates of RNA-dependent DNA synthesis for several RTs, including wild-type HIV-1BH10, HIV-1ESP49, AMV and MLV RTs, and the high-fidelity mutants of HIV-1ESP49 RT K65R and K65R/V75I.
Abstract: Analysis of the RNA-dependent mutational spectra revealed a higher tendency to introduce large deletions at the initiation of reverse transcription by all HIV-1 RTs except the double-mutant K65R/V75I.
Discussion: For enzymes showing higher accuracy such as AMV RT, MLV RT and the mutant HIV-1ESP49 PMID: 29566538
2018
Antiviral chemistry & chemotherapy
Method: In total, 94 of 100 samples from patients failing ARV treatment also carried HIV-1 NRTI resistane mutations including M184V (82%), K65R (35%), L74I (19%), M41L (17%) or D67N (17%).
Rare emergence of drug resistance in HIV-1 treatment-naive patients receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide for 144 weeks.
Abstract: Resistant virus emerged in 24 patients who developed resistance to antiretrovirals in the regimens (E/C/F/TAF: M184V/I [1.3%], INSTI-RAMs [0.9%], K65R/N [0.2%]; E/C/F/TDF: M184V/I [1.0%], INSTI-RAMs [0.9%], K65R/N [0.5%]).
Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data.
Method: Presence or absence of the K65R mutation was also included as a predictor, and analyses were also conducted including the respective accessory mutations for Q151M and T69i.
Result: Only 3% of patients showed no other mutation, and the most common associated major reverse transcriptase mutations were M184V (47%), K103N (35%) and K65R (29%).
Result: There was no strong evidence that linked TAMs were associated with the probability of viral suppression, although negative effects cannot be ruled out, and there were no cases with a K65R mutation included in this analysis.
Table: K65R
HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study.
Characterization of HIV Seroconverters in a TDF/FTC PrEP Study: HPTN 067/ADAPT.
PMID: 28328548
2017
Journal of acquired immune deficiency syndromes (1999)
Introduction: M184I/V drug resistance mutations, which confer resistance to FTC, are seen more commonly in the setting of PrEP than the Result: This included two cases where participants had acute HIV infection at enrollment (Case 1: K65R was detected in 24.7% of sequences; Case 2: M184I was detected in 3.5% of sequences), and one case where the participant was randomized to the time-driven arm (Case 10: K65R was detected in 3.9% of sequences; M184I was detected in 62.3% of sequences).
Discussion: In two cases, resistance mutations were detected by NGS only; in the third case, one mutation was detected by routine HIV genotyping (M184I) and one was detected by NGS only (K65R).