Safety and pharmacokinetic profile of multiple escalating doses of (+)-calanolide A, a naturally occurring nonnucleoside reverse transcriptase inhibitor, in healthy HIV-negative volunteers.
Abstract: BACKGROUND: (+)-Calanolide A is a naturally occurring nonnucleoside reverse transciptase inhibitor (NNRTI) that exhibits enhanced activity against HIV-1 isolates with the Y181C mutation and retains activity against HIV-1 isolates with dual Y181C and K103N mutations.
Genotypic and phenotypic resistance patterns in early-stage HIV-1-infected patients failing initial therapy with stavudine, didanosine and nevirapine.
Abstract: Seven patients (50%) had nevirapine resistance mutations (mainly K103N [4/7], Y181C/I [2/7], G190A/S [2/7] and V108I [1/7]) associated with phenotypic high-level resistance to nevirapine, delavirdine and efavirenz (nevirapine >47.4- to 58.1-fold, delavirdine >74.4- to 168.9-fold and efavirenz >56.0- to 347.2-fold).
The Y181C mutant of HIV-1 reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors alters the size distribution of RNase H cleavages.
Abstract: Studies with this substrate labeled at the RNA 3' end showed that Y181C is no more likely than wild type to cleave toward the RNA 3' end.
Abstract: Thus, Y181C RT has a strong preference to cleave in the direction of the RNA 5' end even when secondary cleavage is prevented, resulting in a disruption of the normal sequence of primary followed by secondary cleavages.
Abstract: Under these conditions, Y181C cleaved closer to the RNA 5' end than wild type.
Abstract: We investigated the effects of the nonnucleoside reverse transcriptase inhibitor-resistant mutant Y181C on RNA 5'-end-directed RNase H cleavage by HIV-1 reverse transcriptase, using an RNA.DNA hybrid in which a radiolabeled RNA 5' end was recessed.
4'-Ethynyl nucleoside analogs: potent inhibitors of multidrug-resistant human immunodeficiency virus variants in vitro.
PMID: 11302824
2001
Antimicrobial agents and chemotherapy
Abstract: The 4'-E analogs also blocked the replication of a non-nucleoside reverse transcriptase inhibitor-resistant clone, HIV-1(Y181C), and showed an HIV-1 inhibition profile similar to that of zidovudine in time-of-drug-addition assays.
Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from patients failing nonnucleoside reverse transcriptase inhibitor therapy.
Abstract: Further, certain secondary mutations (V106I, V108I, Y181C, Y188H, P225H, and F227L) conferred little resistance to efavirenz as single mutations but enhanced the level of resistance of viruses carrying these mutations in combination with K103N or Y188L.
An in vivo model for HIV resistance development.
PMID: 11375059
2001
AIDS research and human retroviruses
Abstract: This resulted in the selection of mutants with Y181C and K103N changes in RT, which correspond to the HIV-1 mutations in nevirapine-resistant HIV-1 patients.
2-Amino-6-arylsulfonylbenzonitriles as non-nucleoside reverse transcriptase inhibitors of HIV-1.
PMID: 11384233
2001
Journal of medicinal chemistry
Abstract: However, they showed a lack of activity against the K103N and Y181C mutant viruses.
High prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients receiving antiretroviral therapy in Abidjan, Cote d'Ivoire.
PMID: 11391173
2001
Journal of acquired immune deficiency syndromes (1999)
Abstract: The prevalence of mutations associated with resistance to ARV drugs was: 29 (42.6%) to zidovudine, 10 (14.7%) to lamivudine, one (1.5%) to didanosine, one K103N mutation (associated with resistance to delavirdine, nevirapine, and efavirenz), one Y181C mutation (associated with resistance to delavirdine and nevirapine), two to both indinavir (M46I/L and V82A) and saquinavir (G48V and L90M), and one each to ritonavir (V82A) and nelfinavir (D30N).
Distribution of K103N and/or Y181C HIV-1 mutations by exposure to zidovudine and non-nucleoside reverse transcriptase inhibitors.
PMID: 11418520
2001
The Journal of antimicrobial chemotherapy
Abstract: Group B patients had the highest prevalence of K103N+/Y181C.
Abstract: No difference was found in the exposure to zidovudine or major zidovudine mutations between the resistance patterns K103N-/Y181C+, K103N+/Y181C- and K103N+/ Y181C+, either in group A (patients on nevirapine and previously NNRTI naive) or in group B (on any NNRTI and experience of two or more NNRTIs including nevirapine).
Impact of clinical reverse transcriptase sequences on the replication capacity of HIV-1 drug-resistant mutants.
Abstract: In contrast, three of five clones that did not have P236L (but had either K103N or Y181C) replicated significantly better than NL4-3 with P236L.
Abstract: Other NNRTI-resistance mutations, such as K103N and Y181C, do not reduce the replication capacity of NL4-3 as much as P236L and develop more frequently in HIV-1 isolates from patients failing delavirdine.
HIV mutation literature information.
PMID: 
2002
HIV clinical trials
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