Discovery of 3-{5-[(6-Amino-1H-pyrazolo[3,4-b]pyridine-3-yl)methoxy]-2-chlorophenoxy}-5-chlorobenzonitrile (MK-4965): A Potent, Orally Bioavailable HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor with Improved Potency against Key Mutant Viruses

2008 ◽  
Vol 51 (20) ◽  
pp. 6503-6511 ◽  
Author(s):  
Thomas J. Tucker ◽  
John T. Sisko ◽  
Robert M. Tynebor ◽  
Theresa M. Williams ◽  
Peter J. Felock ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Transcriptase Inhibitor ◽  
Orally Bioavailable ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

scholarly journals Characterization of a Mutant HIV-1 Reverse Transcriptase Resistant to (+)-(5S)-4,5,6,7-tetrahydro-5-methyl-6-(3-methyl-2-butenyl)-imidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-thione (TIBO R82150)

1994 ◽  
Vol 5 (4) ◽  
pp. 278-281
Author(s):  
H. Samanta ◽  
R. Rose ◽  
A. K. Patick ◽  
C. M. Bechtold ◽  
J. Trimble ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Serial Passage ◽  
Transcriptase Inhibitor ◽  
Viral Resistance ◽  
Resistant Virus ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

A virus strain resistant to R82150, a non-nucleoside reverse transcriptase (NNRT) inhibitor (tetrahydro-imidazo [4,5, 1- jk] [1,4] benzodiazepine-2(1 H)-thione), was isolated following serial passage of HIV-1 RF in CEM-SS cells. The virus is cross-resistant to another non-nucleoside reverse transcriptase inhibitor, TGG-II-23A [1,4-dimethyl-1-[5,5-dimethyl-2-oxazoionyl]-naphthalen-2-one), but remains susceptible to AZT, DDI, D4T and phosphonoformate (PFA). DNA sequencing of reverse transcriptase genes from resistant virus indicated that R82150 selects for amino acid alterations Y181C and V108I. In vitro mutagenized reverse transcriptase and recombinant HIV-1 (pNL4-3) carrying either of the mutations have been generated. Genotypic and phenotypic analyses identified V108I as an unreported R82150-associated mutation. Both reverse transcriptase and viral resistance assays indicated that the resistance conferred by the V108I mutation is 7-fold less than that conferred by Y181C.

ChemInform Abstract: An Efficient Chiral Moderator Prepared from Inexpensive (+)-3-Carene: Synthesis of the HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor DPC 963.

ChemInform ◽  
2001 ◽  
Vol 32 (6) ◽  
pp. no-no
Author(s):  
Goss S. Kauffman ◽  
Gregory D. Harris ◽  
Roberta L. Dorow ◽  
Benjamin R. P. Stone ◽  
Rodney L. Parsons Jr. ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Transcriptase Inhibitor ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

scholarly journals Molecular Epidemiology of HIV-1 Infected Migrants Followed Up in Portugal: Trends between 2001–2017

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 268 ◽  
Author(s):  
Victor Pimentel ◽  
Marta Pingarilho ◽  
Daniela Alves ◽  
Isabel Diogo ◽  
Sandra Fernandes ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Molecular Epidemiology ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Country Of Origin ◽  
Transcriptase Inhibitor ◽  
Subtype B ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1 ◽  
Over Time

Migration is associated with HIV-1 vulnerability. Objectives: To identify long-term trends in HIV-1 molecular epidemiology and antiretroviral drug resistance (ARV) among migrants followed up in Portugal Methods: 5177 patients were included between 2001 and 2017. Rega, Scuel, Comet, and jPHMM algorithms were used for subtyping. Transmitted drug resistance (TDR) and Acquired drug resistance (ADR) were defined as the presence of surveillance drug resistance mutations (SDRMs) and as mutations of the IAS-USA 2015 algorithm, respectively. Statistical analyses were performed. Results: HIV-1 subtypes infecting migrants were consistent with the ones prevailing in their countries of origin. Over time, overall TDR significantly increased and specifically for Non-nucleoside reverse transcriptase inhibitor (NNRTIs) and Nucleoside reverse transcriptase inhibitor (NRTIs). TDR was higher in patients from Mozambique. Country of origin Mozambique and subtype B were independently associated with TDR. Overall, ADR significantly decreased over time and specifically for NRTIs and Protease Inhibitors (PIs). Age, subtype B, and viral load were independently associated with ADR. Conclusions: HIV-1 molecular epidemiology in migrants suggests high levels of connectivity with their country of origin. The increasing levels of TDR in migrants could indicate an increase also in their countries of origin, where more efficient surveillance should occur.

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