Introduction: In fact several biochemical defects in the M184I mutant RT have been reported.
Introduction: Structural studies also demonstrated that the M184I mutation alters the template-primer interactions of RT, which explains its reduced processivity.
Introduction: The beta-branched side chain of isoleucine in M184I reduces the binding affinity of RT for dNTP substrates and raises its Kd approximately 50-fold (from 1 microM of WT RT Kd to 56 microM).
Introduction: The transient nature of the M184I mutation is likely due to its limited replicational fitness, compared to the M184V mutation.
Introduction: Thus M184I
Partially active HIV-1 Vif alleles facilitate viral escape from specific antiretrovirals.
Abstract: Among these mutations, the lamivudine drug-resistance-associated mutation M184I in reverse transcriptase was detected in 25% of clones in the absence of any lamivudine exposure.
Proteochemometric modeling of the susceptibility of mutated variants of the HIV-1 virus to reverse transcriptase inhibitors.
Abstract: The most deleterious mutations were K65R, Q151M, M184V/I, and T215Y/F, each of them decreasing susceptibility to most of the NRTIs.
Result: For example, mutations M184V/I and K65R, which are the most deteriorating for 3TC and FTC, lead to significant increase in susceptibility to AZT, thus suggesting a benefit of combining these inhibitors.
Result: Similarly, mutation M184V/I confers high resistance to the two structurally very similar inhibitors 3TC and FTC; it also affects susceptibility to ABC, DDC, and DDI, but is unimportant or even beneficial for AZT, d4T, and TDF.
Allele-specific real-time PCR testing for minor HIV-1 drug resistance mutations: assay preparation and application to reveal dynamic of mutations in vivo.
Abstract: METHODS: We developed the allele-specific PCR assay, using the most common drug resistance mutations in Chinese AIDS patients, K103N, M184V/I, T215F/Y as a model system.
Abstract: RESULTS: The sensitivities of ASPCR assay were 0.04% for K103N, 0.30% for M184I, 0.40% for M184V, 0.03% for T215F and 0.02% for T215Y.
Selection of drug-resistant HIV-1 during the early phase of viral decay is uncommon in treatment-naive patients initiated on a three- or four-drug antiretroviral regimen including lamivudine.
Abstract: In patients on dual therapy, M184I/V mutants were found frequently.
Abstract: In this study, the extent to which selection of the HIV-1 reverse transcriptase M184I/V mutations occur during the initial phase of viral decay in treatment-naive HIV-1 infected patients receiving antiretroviral therapy (ART) was examined.
Abstract: Plasma virus from three cohorts of treatment-naive patients initiating quadruple (n = 43), triple (n = 14) or dual (n = 15) lamivudine-containing ART were analyzed for M184I/V during the first 6 months of therapy using direct sequencing and a sensitive selective real-time PCR method.
Abstract: Selection of M184I/V mutants was found to be rare during the initial phase of viral decay after initia
High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients.
PMID: 19036752
2009
The Journal of antimicrobial chemotherapy
Abstract: Resistance genotypes for the nine Group 2 failing patients showed the mutations M184V/I (n = 3), K65R (n = 6), one or more NNRTI resistance mutations in all cases.
Nucleoside and nucleotide analogs select in culture for different patterns of drug resistance in human immunodeficiency virus types 1 and 2.
PMID: 19064892
2009
Antimicrobial agents and chemotherapy
Abstract: In HIV-1 subtype B, TFV-3TC and ZDV-3TC selected for M184I and D67N, respectively.
Abstract: In contrast, selections with all four HIV-2 cultures favored the development of M184I in dual-drug combinations that included either 3TC or FTC.
Minority quasispecies of drug-resistant HIV-1 that lead to early therapy failure in treatment-naive and -adherent patients.
Abstract: Minority quasispecies with either the M184V mutation or the M184I mutation were detected in 3 of 18 control patients.
Abstract: The key mutations K65R, K103N, Y181C, M184V, and M184I in the reverse transcriptase were quantified by allele-specific real-time polymerase chain reaction performed on plasma samples before and during early virological treatment failure.
Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy.
Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa.
Result: In HIV-1, the M184I mutation produces high-level in vitro resistance to 3TC and FTC and low-level resistance to didanosine and abacavir, has been reported in virus strains in both ARV therapy-naive and ARV-treated HIV-2-infected patients, and appears to be under selective pressure to 3TC in HIV-2 in vitro.
Result: The M184I mutation (together with M184V) emerged in a virus strain from 1 patient.
Discussion: However, the authors did find high treatment failure rates, RT mutations M184V/I and Q151M, and the PR mutation L90M in the virus strains from 7 patients who received NRTI- and nelfinavir-based regimens.