Result: Fifteen combinations were observed among 46 ARV drug-experienced subjects with 3 TAMs; where 39% of these subjects harbored the combination M41L + T215Y + L210W, followed in 11% by combination of D67N + K70R + K219Q.
Result: In ARV drug-experienced subjects, TAMs found were T215Y/F (26.8%), K70R (15.2%), M41L (13.7%), K219E/Q (12.2%), D67N (10.9%), and L210W (7.5%) (Fig 1A).
Resolution of Specific Nucleotide Mismatches by Wild-Type and AZT-Resistant Reverse Transcriptases during HIV-1 Replication.
Abstract: Outcomes for wild-type (WT) RT and an AZT-resistant (AZT(R)) RT containing a thymidine analog mutation set-D67N, K70R, D215F, and K219Q-were compared.
Method: To construct an AZTR RT-containing version of pCMVDeltaR8.2, the following amino acid substitutions that confer resistance to AZT: D67N, K70R, T215F, and K219Q were introduced into an HIV reverse transcriptase (RT) gene fragment using overlap extension PCR, sequenced, and used to replace wild-type sequences between AgeI and BclI in pCMVDeltaR8.2 to produce pCBN103-18, which
Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors.
Result: Finally, in July 2008 four out of six TAMs relevant for highly efficient AZTMP excision (M41L, D67N, T215Y and K219E, missing K70R and L210W) as well as four out of five discrimination mutations (A62V, V75I, F116Y and Q151M, lacking F77I) were present.
Result: First, the K70R mutation, which is the missing fifth TAM residue promoting excision, was introduced (MR-70R).
Result: In a third variant, the pivotal discrimination substitution Q151M was reversed to WT and combined with K70R (MR-
HIV-1 Transmitted Drug Resistance Mutations in Newly Diagnosed Antiretroviral-Naive Patients in Turkey.
PMID: 26414663
2016
AIDS research and human retroviruses
Abstract: However, TAMs were divided into three categories and M41L, L210W, and T215Y mutations were found for TAM1 in 97 (7.4%) patients, D67N, K70R, K219E/Q/N/R, T215F, and T215C/D/S mutations were detected for TAM2 in 52 (3.9%) patients, and M41L + K219N and M41L + T215C/D/S mutations were detected for the TAM1 + TAM2 profile in 22 (1.7%) patients, respectively.
Patterns of HIV-1 Drug-Resistance Mutations among Patients Failing First-Line Antiretroviral Treatment in South India.
PMID: 26385878
2016
Journal of the International Association of Providers of AIDS Care
Abstract: RESULTS: Of the study patients followed up for 6 months, 23 patients failed first-line therapy and the mutation of I135R/T/V/X, L178 I/M, M184V/I, D67N, K70R, and K103N was most common.
Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals.
Result: Protease (PR) RAMs detected from this outlier sample were M46I, I47V and I84V, and reverse transcriptase (RT) RAMs were A62V, D67N, K70R, V75I, F116Y, Q151M and K219Q.
Discussion: Other RT RAMs found in the CRF01_AE sample were thymidine analogue-associated mutations (TAMs) which included D67N, K70R and K219Q.
Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy.
Introduction: In this study, we used AS-PCR to analyze expression dynamics of eight drug resistance mutations (M41L, K65R, K70R, K103N, Y181C, M184V and T215F/Y) during the clinical course of ARV-treated individuals with documented virologic failures and drug-resistant HIV-1.
Method: Briefly, mutation-specific primers were designed for seven reverse transcriptase inhibitor resistance mutations, M41L, K65R, K70R, K103N, Y181C, M184V, and
Table: K70R
Compensatory substitutions in the HIV-1 capsid reduce the fitness cost associated with resistance to a capsid-targeting small-molecule inhibitor.
Abstract: Q67H, K70R, and T107N each conferred low-level resistance to PF74 and collectively conferred strong resistance.
Abstract: In the present study, we dissected the individual and combinatorial contributions of each of the five substitutions Q67H, K70R, H87P, T107N, and L111I to PF74 resistance, PF74 binding, and HIV-1 infectivity.
Abstract: PF74 binding to HIV-1 particles was reduced by the Q67H, K70R, and T107N substitutions, consistent with the location of these positions in the inhibitor-binding pocket.
Abstract: The substitutions K70R and PMID: 25582324
2015
AIDS research and human retroviruses
Discussion: In addition, we found that mutations E35D, N37DST, R57K, and K70R in the PR and D123N and I135TV in the RT were present at high rates in this cohort.
High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa.
Result: K70R was more frequently detected in d4T-exposed patients (15.0%, n = 12) as compared to the TDF-exposed group (8.8%, n = 7) but again, the difference was not significant.