Abstract: Several large-scale HIV-1 genotypic analyses have revealed that the most prevalent nucleos(t)ide analog RT inhibitor (NRTI)-resistance mutation is M184V/I followed by a series of thymidine analog-associated mutations: M41L, D67N, K70R, L210W, T215Y/F and K219Q/E.
Thymidine analogue excision and discrimination modulated by mutational complexes including single amino acid deletions of Asp-67 or Thr-69 in HIV-1 reverse transcriptase.
PMID: 21504903
2011
The Journal of biological chemistry
Abstract: Here, we show that the complex Delta67/T69G/K70R enhances ATP-dependent phosphorolytic activity on primers terminated with 3'-azido-3'-deoxythymidine (AZT) or 2',3'-didehydro-2',3'-dideoxythymidine (d4T) both in the presence or absence of TAMs.
Abstract: Molecular dynamics studies based on models of wild-type HIV-1 RT and mutant Delta69, Delta67/T69G/K70R, and D67N/K70R RTs support a relevant role for Lys/Arg-70 in the excision reaction.
Abstract: The deletion of Asp-67 together with mutations T69G and K70R (Delta67 complex) are usually associated with thymidine analog resistance mutations
High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo.
PMID: 21663632
2011
Journal of the International AIDS Society
Result: Two patients had virus mutations indicative of the TAM-1 profile (M41L, L210W, T215S), and two of the TAM-2 profile (D67N, K70R, T215F, K219Q/R/E).
Table: K70R
Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa.
PMID: 21694608
2011
Journal of acquired immune deficiency syndromes (1999)
Result: Four participants had at least one thymidine-associated mutation (TAM) - two recipients of ZDV+ddI had D67N + K70R, another ZDV+ddI recipient had K70R alone.
Result: Of the 32 individuals who never received EFV, 6 (18.8%, CI: 7.2-36.4%) had NRTI-associated mutations; five had M184V and one with K70R.
Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum.
PMID: 21765365
2011
Journal of acquired immune deficiency syndromes (1999)
Method: An OLA was performed on all amplicons derived from plasma and PBMC using probes that detect mutations
Result: In addition, OLA detected 4 resistance mutations in 4 women that were not detected by sequencing, including the mutations encoding K103N, Y181C, M184V, and K70R.
Result: She had ART-associated suppression of viral replication, but subsequently her virus rebounded with the L90M and K70R mutations and M184V was newly detected.
Result: The new NRTI mutations included M184V associated with resistance to 3TC/FTC, and K70R and T215Y associated with resistance to thymidine analogs.
The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket.
Result: have reported a concomitant increase in the processivity of the mutant enzyme D76N, K70R, T215F, and K219Q to compensate for the increased pyrophosphorolysis, which they attribute to alterations T215F and K219Q.
Result: have reported such enhanced pyrophosphorolysis in HIV-1 RT due to mutations D76N/K70R in the high-level resistance mutants D76N, K70R,
Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010.
Abstract: Major RT inhibitor resistance mutations K70R and A98G
Result: Patient SE37, naive for antiretroviral treatment, had A98G and K70R major mutations associated with resistance to non-nucleoside RT inhibitors (NNRTI), and nucleoside RT inhibitors (NRTI), respectively.
Table: K70R
Discussion: It is of note that one treatment naive patient, with G subtype, showed major RT mutations associated with resistance to NRTI (K70R) and NNRTI (A98G).
Drug resistance patterns and virus re-suppression among HIV-1 subtype C infected patients receiving non-nucleoside reverse transcriptase inhibitors in South Africa.
PMID: 21927716
2011
Journal of AIDS & clinical research
Discussion: Among eight patients with TAMs, the most common pathway (seen in 6/8 patients) was TAM-2 related (D67N, K70R, K219Q/R/E); and the rest (2/8) were mixed with the TAM-1 pathway (M41L, L210W, T215Y) extending similar prior Southern African observations.
A structural frame for understanding the role of thymidine analogue resistance mutations in resistance to zidovudine and other nucleoside analogues.
Introduction: With regard to subtype, in subjects infected with HIV-1 subtype B, the thymidine analogue mutations pathway 1 or TAM-1 (including mutations M41L, L210W and T215Y) is probably more frequent than the TAM-2 pathway (including mutations D67N, K70R, T215F and K219E/Q), although systematic studies of these pathways have not been done.
Method: RT mutations were identified from the International AIDS Society USA Drug (IAS-USA) mutation tables, spring 2008 (http://www.iasusa.org/resistance_mutations): M41L, K65R, D67N, insertion 69,