Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy.
PMID: 29084434
2018
AIDS research and human retroviruses
Introduction: As expected, patients failing AZT-based therapy did not develop mutations K65R, K70E, L74V, or Y115F, and only rarely were DRMs from the Q151M complex seen.
Introduction: However, in the 31 patients with no K65R present at S2, 6 had intermediate or high-level resistance to AZT: 4 were caused by TAM-2 DRMs, 1 by T215Y, and 1 by Q151M-complex mutations Q151M, A62V, V75I, F77L, F116Y.
Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases.
Abstract: In HIV-2, resistance to all approved nucleoside analogues is conferred by the combination of RT substitutions K65R, Q151M and M184V.
Abstract: We have determined the intrinsic fidelity of DNA synthesis of WT HIV-2 RT and mutants K65R and K65R/Q151M/M184V.
Introduction: An estimated prevalence of 9% has been reported for the combination of K65R, Q151M and M184V in a European cohort of HIV-2-infected patients treated with antiretroviral drugs.
Introduction: By themselves, amino acid substitutions K65R, PMID: 28099515
2017
PloS one
Table: Q151M
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)
Abstract: In general, DRMs were more common in subtype-C than in subtype-A and/or subtype-D (nucleoside reverse transcriptase inh
Result: In particular, Q151M was seen in 10% of the subtype-C vs <1% of subtype-A/subtype-D.
Result: Supplemental Digital Content, Table 1a, http://links.lww.com/QAI/A970), type-2 thymidine analog DRMs were more common in A and C than in D, K65R and Q151M were more common in C than in both A and D (K65R was more common in A than in D), whereas L210W was less common in C than in both A and D.
Discussion: Q151M, a rare mutation that confers cross-class NRTI resistance, was present in 11% of subtype-C, but negligible levels in other subtypes (not previously described).
Evolution of tenofovir-resistant HIV-1 isolates exposed to tenofovir alafenamide dose escalation.
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.
HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China.
Chemical system biology based molecular interactions to identify inhibitors against Q151M mutant of HIV-1 reverse transcriptase.
PMID: 28396546
2017
Antimicrobial agents and chemotherapy
Abstract: Q151M and four associated mutations, A62V, V75I, F77L, and F116Y, were detected in patients failing therapies with dideoxynucleosides (didanosine [ddI], zalcitabine [ddC]) and/or zidovudine (AZT).
Abstract: The cluster of the five mutations is referred to as the Q151M complex (Q151Mc), and an RT or virus containing Q151Mc exhibits resistance to multiple NRTIs.
Abstract: The single mutation Q151M introduces conformational perturbation at the deoxynucleoside triphosphate (dNTP)-binding pocket, and the mutated pocket may exist in multiple conformations.
Abstract: To understand the structural basis for Q151M and Q151Mc
Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128).
Result: A62V often occurs in combination with multi-resistance NRTI mutations K65R and Q151M.
Result: In this study, all the A62V mutations described were linked to K65R, but not to Q151M.
Result: The Q151M multi-drug resistant mutation was found in one subject while the transitional mutation (Q151L) which precedes the emergence of Q151M was observed in 2 patients.