A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus.
Discussion: A recent study comparing binary structures of WT and M184I RTs showed that Ile mutation at position 184 with a longer and more rigid beta-branched side chain possibly deforms the shape of the dNTP binding pocket which can restrict dNTP binding resulting in inefficient DNA synthesis at low dNTP concentrations.
Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity.
Introduction: The authors reported a faster rate of reversion for primary resistance mutations (K70R, M184I/V, T215Y/F in RT, and D30N, M46I/L, V82A, L90M in PR) compared to secondary mutations (M41L, D67N, T69D/N, L210W, K219Q/E in RT and L10I/V, L63P, A71V/T, V77I in PR)
Multi-nucleoside reverse transcriptase inhibitor resistant HIV type-1 in a patient from Sierra Leone failing stavudine, lamivudine and nevirapine.
Abstract: We report a 33-year-old HIV type-1 (HIV-1)-infected male from Sierra Leone who harboured extensive drug resistance mutations to all nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs, including the multi-NRTI-resistance Q151M complex, K65R, M184I and Y181I, after using standard first-line generic fixed-dose stavudine, lamivudine and nevirapine (Triomune ) for 36 months.
The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage?
Introduction: As example, M184V/I, the most prevalent NRTI-mutations selected under 3TC or FTC in the reverse transcriptase, do for instance revert partially the effect of thymidine-analogue mutation- (TAM) on resistance.
Rapid development of antiretroviral drug resistance mutations in HIV-infected children less than two years of age initiating protease inhibitor-based therapy in South Africa.
PMID: 21345162
2011
AIDS research and human retroviruses
Abstract: Of 41 children without virologic suppression with posttreatment HIV genotype data available, major resistance mutations were found in 32 (78%): 14 (36%) had PI mutations including V82A, M46I, and L90M; 29 (71%) had M184V/I; and three had NNRTI mutations (K103N, Y181C, and G190A).
Failure of initial therapy with two nucleosides and efavirenz is not associated with early emergence of mutations in the C-terminus of HIV-1 reverse transcriptase.
PMID: 21350368
2011
Journal of acquired immune deficiency syndromes (1999)
Abstract: Mutations in the polymerase but not in connection or RNase H domains of RT increased in frequency between pretherapy and failure (K103N, P = 0.001; M184I/V, P = 0.016).
Result: Only K103N and M184I/V were significantly more frequent at failure than pre-therapy (unadjusted p=0.001 and p=0.016, respectively).
Discussion: The only mutations that were significantly more frequent at virologic failure than pre-therapy were K103N (p=0.001) and M184I/V (p=0.016) in the polymerase domain, which confer resistance to the study drugs EFV and 3TC, respectively.
Clinical significance of HIV reverse-transcriptase inhibitor-resistance mutations.
Abstract: Several large-scale HIV-1 genotypic analyses have revealed that the most prevalent nucleos(t)ide analog RT inhibitor (NRTI)-resistance mutation is M184V/I followed by a series of thymidine analog-associated mutations: M41L, D67N, K70R, L210W, T215Y/F and K219Q/E.
Differential persistence of transmitted HIV-1 drug resistance mutation classes.
PMID: 21451005
2011
The Journal of infectious diseases
Abstract: CONCLUSIONS: The rapid replacement of M184V/I mutations is consistent with known fitness costs.
Abstract: RESULTS: Among 75 individuals with 195 TDR mutations, M184V/I became undetectable markedly faster than did nonnucleoside reverse-transcriptase inhibitor (NNRTI) mutations (hazard ratio, 77.5; 95% confidence interval [CI], 14.7-408.2; P<.0001), while protease inhibitor and NNRTI replacement rates were similar.
HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis.
Result: Of the 16 infants with HIV drug resistance mutations at 6 mo, 13 (81%) had at least one NRTI resistance mutation (M184 I/V [n = 12], K65R [n = 2], and D67G [n = 1]), and six (38%) had NNRTI resistance mutations (K103N [n = 2], Y181 [n = 2], and G190A [n = 2]) (sequences submitted to GenBank, http://www.ncbi.nlm.nih.gov/Genbank/index.html, accession numbers HM164112-HM164123, HM164127-HM164128, and HM164130-HM164131) (Table 3).
Table: M184I/V
Table: M184I
Reduced emergence of the M184V/I resistance mutation when antiretroviral-naive subjects use emtricitabine versus lamivudine in regimens composed of two NRTIs plus the NNRTI efavirenz.
Abstract: Among VF subjects at week 48, 5/26 (19.2%) FTC-treated subjects and 27/77 (35.5%) 3TC-treated subjects developed the M184V/I mutation (P = .145).
Abstract: CONCLUSIONS: The results of this pooled analysis of 3 clinical trials indicate a lower frequency of development of the M184V/I mutation in subjects treated with FTC versus 3TC when combined in regimens containing dual NRTIs and EFV.
Abstract: Multivariate analyses adjusting for baseline viral load, baseline CD4 cell counts, and baseline NRTI resistance showed that treatment with FTC had a significantly lower rate of M184V/I development than treatment with 3TC (odds ratio 0.32; P = .02).
Abstract: PURPOSE: To compare the development of the M184V/I substitution among antiretrov
HIV mutation literature information.
PMID: 
2011
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