Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria.
PMID: 34741609
2022
The Journal of antimicrobial chemotherapy
Result: One of the subtype G viruses had a K65N mutation (AAC), which causes intermediate resistance to tenofovir, abacavir, stavudine and didanosine.
Long-term efficacy of dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: Week 96 results of ART-PRO pilot study.
PMID: 33200210
2021
The Journal of antimicrobial chemotherapy
Abstract: Baseline proviral DNA NGS detected lamivudine RAMs (M184V/I and/or K65R/E/N) above a 5% threshold in 71.4% (15/21) and 15% (3/20) of participants with and without history of lamivudine resistance, respectively.
Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients.
PMID: 33734374
2021
The Journal of antimicrobial chemotherapy
Method: Inclusion criteria included vertically HIV-infected youths and young adults aged 10 years and olde
Result: All carried M184V mutation in their historic plasma (point 1 in Table 1), but no K65R/N/E mutations.
Discussion: Only 3/12 patients (25%) with pDNA sequence under study presented the M184V mutation in their pDNA and none presented K65R/E/N.
Discussion: This is the first study analysing the existence of lamivudine- or emtricitabine resistance-conferring mutations in pDNA (M184V/I and/or K65R/E/N) in historic plasma genotypes in a cohort of vertically HIV-infected patients under ART after at least 1 year of viraemia suppression.
Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure.
PMID: 33734374
2021
The Journal of antimicrobial chemotherapy
Result: None of the 12 patients presented K65R/N/E in their pDNA.
Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance.
Abstract: Among candidate NRTI-SDRMs, there were six tenofovir-associated mutations including three which increased in prevalence (K65N, T69deletion, K70G/N/Q/T).
Method: Tenofovir-associated mutations were defined as A62V, K65R/N/E, S68G/N/D, T69 deletions, and K70E/Q/N/T/S/G.
Result: Figure 1 shows the locations
Result: Three additional tenofovir-associated mutations (K65N and K70G/N) did not increase in prevalence.
Result: With the exception of K65N, which was on four expert lists, the remaining tenofovir-associated mutations were on just one or two lists.
Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study.
PMID: 34397746
2021
Journal of acquired immune deficiency syndromes (1999)
Method: Participants had an estimated glomerular filtration rate (eGFR) >=50 mL per minute (calculated by the Cockcroft-Gault equation) and no documented history of resistance to INSTIs or tenofovir (TFV) resistance defined as K65R/E/N mutations, >=3 thymidine analog mutations, or T69 insertions (See Appendix, Supplemental Digital Content, http://links.lww.com/QAI/B674).
Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice.
PMID: 34327247
2021
Open forum infectious diseases
Method: The role of any non-TAM was not specifically studied because of the low number of patients harboring the K65R/E/N mutation (the only other non-TAM associated with decreased susceptibility to 3TC) and its collinearity with M184V/I.
Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study.
Result: M184 V/I 87 (28.8%), K65R/E/N 27 (8.9%), L74 V 3 (1.0%), and Y115F 12 (4.0%) were the mutations conferring resistance to NRTIs, along with thymidine analog mutations (TAMs) M41L 14 (4.6%), D67N 17 (5.6%), K70R 20 (6.6%), L210W 10 (3.3%), T215Y/F 23 (7.6%), K219Q/E 32 (10.6%), and K65R/E/N 27 (8.9%).
Result: K65R/E/N and K70E mutations conferred resistance to TDF and M41L, D67N, PMID: 32265875
2020
Frontiers in microbiology
Result: The K65R/N mutation occurred in five (5%) patients; K65R occurred in two (2%) patients receiving AZT plus 3TC, and in one (1%) patient receiving TDF plus FTC.
Table: K65R/N
Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO).
Introduction: This is the first clinical trial specifically designed to address the efficacy of lamivudine and dolutegravir as dual therapy for maintenance of viral suppression in patients with historical lamivudine resistance as long as M184V/I and/or
Result: Among participants without historical lamivudine resistance, none presented the K65R/E/N mutation but in three and seven cases the M184I mutation was detected with over a 5% or 1% threshold, respectively, including one participant harboring the M184I mutation with a 99% frequency.
Result: Seven participants with historical lamivudine resistance had the M184V/I and/or K65R/E/N mutations detected over the 20% threshold at baseline by next generation sequencing.