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.
Result: All patients developed the M184V mutation, four patients developed T215Y and three developed L210W.
Result: However, after prolonged treatment interruption the prevalence of the resistance mutations rapidly decreased and after five month the M184V mutation was undetectable and the T215Y present at 0.10% (Table 5).
Result: However, during prolonged 3TC containing treatment the M184V variants were completely replaced by the M184V-T215Y variants, suggesting that the M184V-T215Y variants were more fit during selection pressure from 3TC, d4T and ddI.
Result: In pat
Table: T215Y
Mechanisms involved in the selection of HIV-1 reverse transcriptase thumb subdomain polymorphisms associated with nucleoside analogue therapy failure.
PMID: 20733040
2010
Antimicrobial agents and chemotherapy
Abstract: Here, we demonstrate that in the presence of zidovudine, HIV-1(BH10) RT mutations P272A/R277K/T286A produce a significant reduction of the viral replication capacity in peripheral blood mononuclear cells in both the absence and presence of M41L/T215Y.
Specific HIV-1 integrase polymorphisms change their prevalence in untreated versus antiretroviral-treated HIV-1-infected patients, all naive to integrase inhibitors.
PMID: 20817922
2010
The Journal of antimicrobial chemotherapy
Abstract: The mutation M154L, absent in drug-naive patients, was prevalent at 5.7% in antiretroviral-treated patients, and was positively associated with RT resistance mutations F227L and T215Y.
Frequency and diversity of human immunodeficiency virus type 1 mutations associated with antiretroviral resistance among patients from Southern Brazil failing highly active antiretroviral therapy (HAART).
PMID: 20818500
2010
International journal of molecular medicine
Abstract: The main mutations associated with nucleoside reverse transcriptase inhibitor (NRTI) resistance were M184V in 82 (64.6%), and the thymidine analog mutations were D67N in 51 (40.1%) tests, K70R in 45 (35.4%), T215Y in 40 (31.5%), and M41L in 38 (30.0%).
Structural basis of HIV-1 resistance to AZT by excision.
Abstract: We determined five crystal structures: wild-type reverse transcriptase-double-stranded DNA (RT-dsDNA)-AZTppppA; AZT-resistant (AZTr; M41L D67N K70R T215Y K219Q) RT-dsDNA-AZTppppA; AZTr RT-dsDNA terminated with AZT at dNTP- and primer-binding sites; and AZTr apo reverse transcriptase.
Introduction: The mutations commonly associated with excision-mediated AZT resistance are M41L, D67N, K70R, L210W, T215Y, PMID: 21179544
2010
PloS one
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: Figure 3 presents screenshots of outputs from the web page, illustrating the predicted susceptibilities for two patterns of mutations: K65R+M184V (Panel A) and M41L+L210W+