Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia.
Result: As expected, the most common NRTI DRM was M184V (selected by 3TC and FTC) present in 60 patient isolates (88%), followed by K65R (selected by TDF, d4T, abacavir [ABC], didanosine [DDI]) (n = 21, 31%).
Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations.
Introduction: These polymorphisms are reported to be associated with a more rapid selection of the K65R TFV-resistance mutation in HIV-1 subtype C compared to subtype B.
Introduction: This increased selection of K65R is mediated by a template-dependent dislocation mechanism during plus-strand DNA synthesis occurring on a homopolymeric run of six A-nucleotides at RT codons 63-65.
Subtype-specific analysis of the K65R substitution in HIV-1 that confers hypersusceptibility to a novel nucleotide-competing reverse transcriptase inhibitor.
PMID: 25779585
2015
Antimicrobial agents and chemotherapy
Abstract: Although the K65R substitution is more common in subtype C viruses, the impact of subtype variability on NcRTI susceptibility has not been studied.
Abstract: Compound A is a novel nucleotide-competing HIV-1 reverse transcriptase (RT) inhibitor (NcRTI) that selects for a unique W153L substitution that confers hypersusceptibility to tenofovir, while the K65R substitution in RT confers resistance against tenofovir and enhances susceptibility to NcRTIs.
Abstract: Steady-state kinetic analysis showed that K65R RTs enhanced the susceptibility to compound A by increasing binding of the inhibitor to the nucleotide binding site of RT in a subtype-independent manner,
AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase.
Result: This is similar to the results shown with the substitutions K65R and M184V/I in HIV-1 RT revealing an inverse correlation between fidelity and processivity or activity of the RT.
Repeated Vaginal SHIV Challenges in Macaques Receiving Oral or Topical Preexposure Prophylaxis Induce Virus-Specific T-Cell Responses.
PMID: 25886925
2015
Journal of acquired immune deficiency syndromes (1999)
Introduction: Finally, because the mechanisms of T cell induction are unknown, but could be dose dependent, could involve antigen-presentation through non-classical pathways that are independent of viral replication, and because persons receiving PrEP may be exposed to HIV variants with drug-resistance mutations, we evaluated the virus-specific responses in animals exposed to a replication-impaired virus with a K65R mutatio
Result: This indicated that SHIV with K65R mutation, although infectious, is not as efficient as wildtype virus in inducing SHIV-specific T cell responses (P=0.003, Fisher's exact test to compare the two proportions).
Result: We examined induction of SHIV-specific T cell responses in animals on topical PrEP with vaginal tenofovir gel and challenged with a drug-resistant virus containing the K65R point mutation (SHIVSF162P3-K65R).
A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission.
Discussion: In addition, no K65R mutation associated with resistance to TDF was observed.
Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations.
Result: It is noteworthy that several major mutations associated to high level resistance to NRTIs (K65R, L74V, Y115F, M184V and T215Y), to NNRTIs (l100I, K101E, K103N/S, V106M, Y181C, Y188L and G190A) and to PIs (D30N, M46I/L, I54V/T, L76V, V82A, I84V, N88D
Identification of mechanistically distinct inhibitors of HIV-1 reverse transcriptase through fragment screening.
Abstract: The dNTP competing RT inhibitor retains activity against the NRTI-resistant mutants K65R and M184V, demonstrating a drug resistance profile distinct from the nucleotide competing RT inhibitors indolopyridone-1 (INDOPY-1) and 4-dimethylamino-6-vinylpyrimidine-1 (DAVP-1).
Short Communication: In Vitro Accumulation of Drug Resistance Mutations in Chimeric Infectious Clones Containing Subtype B or C Reverse Transcriptase and Selected with Tenofovir or Didanosine.
PMID: 26075306
2015
AIDS research and human retroviruses
Abstract: Both patterns, M184V+K65R and Q151M+K65R, have a significant impact on NRTI resistance.
Abstract: Other primary mutations (M184V and Q151M) were selected with ddI treatment in conjunction with K65R only in RTC' viruses.
Abstract: The mutation K65R is selected more quickly in RTC' than in RTB' viruses with TDF and ddI, and additional mutations (positions 45, 62, and 68) were selected after K65R fixation.
Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia.
Abstract: VF was associated with emergence of usual nevirapine mutations (Y181C/I/D, K103N and V106A/I), M184V (n = 16; 12 with lamivudine vs. 4 with emtricitabine, p = 0.04), and K65R (n = 7).
Result: Seven patients had K65R (6 associated to M184V, none with thymidine-analogue mutations [TAMs]), 5 of them treated with 3TC and 2 with FTC.
Result: Six patients selected A62V, with K65R
Table: K65R
Discussion: The rate of K65R selection was low was, but appeared in approximately one of every three failures, usually with M184V, and more frequently in those treated with 3TC (vs FTC) .
HIV mutation literature information.
PMID: 
2015
Journal of medical virology
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