N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations.
Result: Previous biochemical studies suggested that this phenotype was due to the Y181C mutation decreasing the AZT-MP excision activity of both WT and D67N/K70R/T215F/K219Q HIV-1 RT by directly impacting ATP binding and/or the rate of AZT-MP excision.
Short communication: selection of thymidine analogue resistance mutational patterns in children infected from a common HIV type 1 subtype G source.
PMID: 20334563
2010
AIDS research and human retroviruses
Abstract: At first sampling date, the T215Y-linked pattern was observed in five cases and the T215F cluster was seen in nine.
Abstract: In HIV-1, thymidine analogue mutations (TAMs) cluster in one of two groups (215Y, 41L, 210W, or 215F, 219E/Q), representing two independent mutational patterns (T215Y and T215F cluster, respectively).
Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations.
PMID: 20462946
2010
The Journal of antimicrobial chemotherapy
Method: We also examined the extent to which the 52 NNRTI-selected mutations covaried with mutations at 12 major nucleoside reverse transcriptase inhibitor (NRTI) resistance positions, including M41L, K65R, D67N, T69S_SS, K70E, K70R, L74V,
Result: The NNRTI-associated mutation A98G was also strongly positively correlated (corrected P < 0.01) with the thymidine analogue mutations M41L, D67N, L210W and T215F/Y.
Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study.
Discussion: For the same reason we would have expected to find M184V, Y181C and Y188C, but not T215Y/F since the latter are double mutants compared to wild-type.
Discussion: However, Johnson et al developed sensitive real-time PCRs and estimated the absolute assay sensitivities on a clone as well as the natural occurrence of several resistance mutations, including M184V, Y181C, T215Y and T215F, in 138 treatment naive patients with samples collected before the ART era.
Discussion: In contrast, we did not find any significant pre-existence of the major drug resistance mutations M184V,
Structural basis of HIV-1 resistance to AZT by excision.
Abstract: The most deleterious mutations were K65R, Q151M, M184V/I, and T215Y/F, each of them decreasing susceptibility to most of the NRTIs.
Result: E.g., a pathway that the virus uses often to escape from thymidine analogs is by the mutation T215Y (or T215F), followed by M41L, which in turn is followed by L210W.
Result: For example, mutations L210W and T215Y/F are the most deleterious for the thymidine analogues AZT and d4T, although they also reduce the susceptibility to the other NRTIs.
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.
Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa.
Abstract: HIV-1-associated thymidine analogue mutations (M41L, D67N, K70R, L210W, and T215Y/F) were not observed, with the exception of K70R
Result: HIV-1-associated thymidine analogue mutations (M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E) were not found, with the exception of K70R, which was present in a strain from 1 patient (in conjunction with K65R, Q151M, and 219E, the latter of which is commonly present in wild-type HIV-2 in ARV therapy naive patients).
HIV mutation literature information.
PMID: 
2010
AIDS (London, England)
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