Effects of the W153L substitution in HIV reverse transcriptase on viral replication and drug resistance to multiple categories of reverse transcriptase inhibitors.
PMID: 24867966
2014
Antimicrobial agents and chemotherapy
Abstract: Biochemical assays demonstrated that W153L alone or in combination with K65R, M184I, K101E, K103N, E138K, and Y181C impaired enzyme processivity and polymerization efficiency but did not diminish RNase H activity, providing mechanistic insights into the low replicative fitness associated with these substitutions.
Abstract: The nucleoside 3TC retained potency against W153L-containing viruses but not when the M184I substitution was also present.
Abstract: To investigate the impact of W153L, alone or in combination with the clinically relevant RT resistance substitutions
Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe.
Discussion: E138K and to a lesser extent K101E usually occur in combination with the nRTI resistance mutation M184I, which alone does not reduce rilpivirine susceptibility.
Discussion: When M184I is combined with E138K or K101E, rilpivirine susceptibility is reduced about 7-fold and 4.5-fold, respectively.
Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro.
Discussion: Computer modeling was performed to predict the binding of FNC and 3TC to RT and in turn elucidate the higher level of resistance of M184I and M184V mutants for 3TC than FNC.
Discussion: In FNC- induced HIV, mutation frequencies of M184I at P-5 and P11 were 3.03% and 66.67%, respectively, whereas in 3TC- induced HIV,M184I frequency at P-5 was 4.76% and M184I/V frequency of at P-11 was 91.66%.
Discussion: Since M184I was transient and replaced by M184V in 3TC-resistant patients, this suggests FNC might have different mechanisms for 3TC resistance.
Discussion: The dominant mutation site associated with FNC resistance was M184I (from 3.03% at P-5
A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses.
Result: M184V/I alone was the most common NRTI-resistance mutation pattern, occurring in 36% (79/218) of patients receiving just thymidine-analog containing regimens (ZDV and/or d4T and 3TC), 23% (14/61) receiving just nonthymidine-analog regimens (abacavir and/or ddI and 3TC), and 14% (12/87) receiving both thymidine-analog and nonthymidine-analog regimens.
A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load.
Result: M184I/V mutations abruptly decreased in the year 2009.
Result: Multiple logistic regression analysis indicated that the introduction of co-formulated emtricitabine/tenofovir or emtricitabine/tenofovir/efavirenz was positively associated with the decrease of M184I/V mutations (p 0.0004).
Result: The logistic regression model, logit(M184I/V)~beta0 + beta1x lamivudine + beta2 x emtricitabine, controlled for the presence of lamivudine, implemented a lag time of two years between mutation and prescription prevalence, and accounted for overdispersion.
Result: The most common primary mutations associated with ARV resistance in TE individuals ( Figure 2 ) were NRTIs: M184I/V (51.1%) and thymidine analog mutations (TAM) from TAM1 pathway (41L/210W/215Y; 17%), representing 76.2
Week 144 resistance analysis of elvitegravir/cobicistat/emtricitabine/tenofovir DF versus atazanavir+ritonavir+emtricitabine/tenofovir DF in antiretroviral-naive patients.
Abstract: Emergent substitutions were E92Q, N155H, or Q148R (n = 2 each) and T66I or T97A (n = 1 each) in IN and M184V/I (n = 7) and K65R (n = 1) in RT.
Abstract: In the ATV+RTV+FTC/TDF group, HIV-1 from 2 patients (0.6%; 2/355 treated patients; both at week 144) developed the resistance substitution M184V/I in RT.
Time to virologic failure for patients taking their first antiretroviral regimen and the subsequent resistance profiles.
PMID: 25397502
2014
Journal of the International AIDS Society
Abstract: Three patients taking PI-based regimens developed NRTI mutations (M184V, M184I, T215Y).
Early clinical response and presence of viral resistant minority variants: a proof of concept study.
PMID: 25397504
2014
Journal of the International AIDS Society
Abstract: One patient without baseline resistance selected for M184I+E138K+T215I (NGS) after four months of TDF/FTC/RPV therapy.
Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model.
Abstract: M184I/V mutations are known to have a profound effect on viral replication and tend to revert over time in the new host.
Abstract: As dendritic cells (DCs) play a pivotal role in HIV-1 transmission, we used a model containing primary human Langerhans cells (LCs) and DCs to compare the transmission efficacy M184 variants (HIV-M184V/I/T) to HIV wild type (HIV-WT).
Abstract: Especially the NRTI-related M184I/V variants, which are among the most frequently encountered mutations in treated patients, are underrepresented in the antiretroviral naive population.
HIV mutation literature information.
PMID: 
2014
Antimicrobial agents and chemotherapy
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