HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa.
PMID: 28129253
2017
Journal of acquired immune deficiency syndromes (1999)
Result: After adjustment, participants on zidovudine at failure were more likely to have T215F, T215Y, M41L, K70R, D67N, L210W, type-1 thymidine analog, type-2 thymidine analog, and any thymidine analogue mutations (TAMs); those on tenofovir to have K65R, K70E, Y115F, and M184I; those on efavirenz to have K103N, P225H, Y188L, and L100I; and those on nevirapine to have Y181C and G190A.
Result: Supplemental Digital Content, Table 1a, htt
Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya.
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).
Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure.
Abstract: Resistance selection experiments using HIV-1 isolates harboring pre-existing tenofovir (TFV)-resistance (K65R, 3TAMs, and Q151M complex) were carried out with the novel tenofovir prodrug tenofovir alafenamide (TAF) as well as with tenofovir (TFV), to investigate the potential for additional resistance development in the presence of TAF or TFV.
Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration.
Abstract: Of the 33 NRTI-associated TRAMs, 12 - A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F - were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen.
Abstract: Tenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen.
Method: The mutational covariates included number of TRAMs, number of NRTI-associated TRAMs, number of
The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration.
Method: The generation of the R263K and H51Y/R263K integrase and K65R reverse transcriptase mutants from pNL4.3 has been described previously.
Result: This progressive decrease was not observed with the K65R mutant.
Result: We also used a virus bearing the K65R RT substitution as a control.
Discussion: This effect was specific, as infections with the K65R mutant did not result in diminished HIV-1 integration over time.
Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure.
PMID: 28379449
2017
The Journal of antimicrobial chemotherapy
Discussion: A further consideration is the fact that the K65R mutation could have disappeared due to the adverse effect it has on replication fitness of the virus upon stopping combination ART and could therefore be underrepresented in our database.
Discussion: A recent multicentre retrospective cohort study (TenoRes) that combined data from cohorts and clinical trials across 36 countries found K65R prevalence rates of more than 50% in sub-Saharan African patients with treatment failure on tenofovir- and NNRTI-based regimens.
Discussion: An explanation for the differences in treatment response and risk of K65R developing between subtypes could be that a single point mutation under an optimal treatment setting does not affect outcome.
Discussion: Data analysis from the UK CHIC Study, which is a representative cohort of the UK HIV populat
Comparative effectiveness of single versus multiple tablet antiretroviral therapy regimens in clinical HIV practice.
Method: Among VF patients we examined the frequency of common resistance mutations: K103N, M184 V/I, K65R, and thymidine analog mutations.
Result: Of these, 25 (69%) had a K103N, 4 (11%) a K65R, 14 (39%) an M184 V/I, and 7 (19%) had a thymidine analog mutation.
Commonly Transmitted HIV-1 Drug Resistance Mutations in Reverse-Transcriptase and Protease in Antiretroviral Treatment-Naive Patients and Response to Regimens Containing Tenofovir Disoproxil Fumarate or Tenofovir Alafenamide.
PMID: 28453836
2017
The Journal of infectious diseases
Abstract: Only 1 patient had K65R (0.01%) and 7 had M184V/I (0.1%), despite high use of tenofovir disoproxil fumarate (TDF), emtricitabine, and lamivudine and potential transmission of resistance to these drugs.