Abstract: In contrast, mutant viruses exhibited strongly impaired RC relative to the wild type (WT) in macrophages, with the following RC order: WT > two TAMs > four TAMs = M184V > K65R.
Abstract: Strikingly, however, the M184V mutant, although fully resistant to 3TC in P4 cells, maintained some susceptibility to 3TC in macrophages from 8 of 11 donors.
Relative fitness and replication capacity of a multinucleoside analogue-resistant clinical human immunodeficiency virus type 1 isolate with a deletion of codon 69 in the reverse transcriptase coding region.
Abstract: In this work, we have measured the in vivo fitness of HIV-1 variants containing a deletion of 3 nucleotides affecting codon 69 (Delta69) of the viral RT as well as the replication capacity (RC) ex vivo of a series of recombinant HIV-1 variants carrying an RT bearing the Delta69 deletion or the T69A mutation in a multidrug-resistant (MDR) sequence background, including the Q151M complex and substitutions M184V, K103N, Y181C, and G190A.
Development and evaluation of an oligonucleotide ligation assay for detection of drug resistance-associated mutations in the human immunodeficiency virus type 2 pol gene.
PMID: 17329450
2007
Journal of clinical microbiology
Abstract: In this study, we designed oligonucleotide probes to detect the Q151M mutation, associated with phenotypic resistance to zidovudine, didanosine, zalcitabine, and stavudine, and the M184V mutation, associated with phenotypic resistance to lamivudine and emtricitabine, in HIV-2.
Abstract: OLA results were compared with sequencing to give high concordances of 98.4% (Q151M) and 97.5% (M184V).
Abstract: The overall sensitivity of the assay was 98.8%, with 99.2% for Q151M and 98.4% for M184V.
Emergence of the H208Y mutation in the reverse transcriptase (RT) of HIV-1 in association with nucleoside RT inhibitor therapy.
PMID: 17356061
2007
The Journal of antimicrobial chemotherapy
Abstract: The prevalence of H208Y was highest in genotypes harbouring M184V and the thymidine analogue mutations (TAMs) M41L, D67N, L210W and T215Y.
No response to first-line tenofovir+lamivudine+efavirenz despite optimization according to baseline resistance testing: impact of resistant minority variants on efficacy of low genetic barrier drugs.
Abstract: Retrospective single genome sequencing of the baseline sample revealed the presence of minority viral variants with additional mutations: a mutation conferring resistance to lamivudine (M184IV), a thymidine associated mutation (K219R) and mutations possibly associated with non-nucleoside reverse transcriptase resistance (F227S, M230IV).
D- and L-2',3'-didehydro-2',3'-dideoxy-3'-fluoro-carbocyclic nucleosides: synthesis, anti-HIV activity and mechanism of resistance.
PMID: 17373782
2007
Journal of medicinal chemistry
Abstract: According to the molecular modeling studies, cross-resistance of D-3'-F-C-d4G (35) to M184V mutant may be caused by the realignment of the primer and template in the HIV-RTM184V interaction, which destabilizes the RT-inhibitor triphosphate complex, resulting in a significant reduction in anti-HIV activity of the D-guanine derivative 35.
[Prevalence of mutations of resistance to HIV-I reverse transcriptase inhibitors among HIV-infected patients in the Southern Federal District].
Abstract: The group of patients receiving antiviral treatment was found to have different drug resistance mutations in the HIV-1 pol gene: K70R, M184V, K219Q, T215Y/F, L74V, etc.
Surveillance of genotypic resistance mutations in chronic HIV-1 treated individuals after completion of the National Access to Antiretroviral Program in Thailand.
Abstract: The reverse transcriptase genes M184V/I (919/1,880; 48.9%) and K103S/H (416/1,880; 22.1%) were the most frequent in nucleoside reverse transcriptase and non-nucleoside reverse transcriptase, respectively.
Biochemical studies on the mechanism of human immunodeficiency virus type 1 reverse transcriptase resistance to 1-(beta-D-dioxolane)thymine triphosphate.
PMID: 17403997
2007
Antimicrobial agents and chemotherapy
Abstract: For non-ATP-dependent discrimination toward DOT-TP, high levels of resistance were found for RT bearing the Q151M mutation with family mutations, while RT bearing only the M184V or the Y115F mutation conferred no resistance to DOT-TP.
Abstract: The results suggest that DOT, compared with other approved nucleoside analogs, is overall more resilient to mutations such as TAM, M184V, and K65R, which are commonly found in viruses derived from subjects failing multinucleoside therapy.
Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients.
Abstract: CONCLUSIONS: The simultaneous presence of K65R and M184V in reverse transcriptase has a negative impact with regard to the efficiency of initiation of (-)ssDNA synthesis and RNA usage, that exceeds the effect of either mutation on its own.
Abstract: OBJECTIVES: To determine the underlying biochemical mechanisms responsible for the diminished viral replicative capacity associated with K65R/M184V-containing viruses.
Abstract: RESULTS: We observed that the K65R/M184V mutations in reverse transcriptase caused reductions in the efficiency of initiation of (-)ssDNA synthesis by increasing pausing at positions +3 and +5 as well as diminished RNA usage.