Matches in SemOpenAlex for { <https://semopenalex.org/work/W4225281036> ?p ?o ?g. }
- W4225281036 abstract "Doravirine (DOR), a non-nucleoside reverse transcriptase inhibitor (NNRTI), was approved for treatment of HIV-1 infection in 2018. In the pivotal phase 3 trials, DRIVE-FORWARD and DRIVE-AHEAD, 7 out of 747 (0.9%) treatment-naive participants treated with DOR plus two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) met protocol-defined virologic failure criteria and showed phenotypic resistance to DOR at week 48. The most common DOR resistance-associated mutation (RAM) detected in 5 of the 7 resistant isolates was F227C. Six isolates bearing NRTI RAMs (M184V and/or K65R) were resistant to lamivudine (3TC) and emtricitabine (FTC) but not to other approved NRTIs. All DOR-resistant isolates were susceptible or hypersusceptible (fold change of <0.25) to islatravir (ISL), a nucleoside reverse transcriptase translocation inhibitor (NRTTI). Isolate hypersusceptibility to ISL required F227C, in contrast to zidovudine, an NRTI, which required M184V. Based on the frequent emergence of F227C, we hypothesized that DOR and ISL would create a combination (DOR/ISL) with a high barrier to resistance. In de novo resistance selection studies in MT4-GFP cells (MT4 cells engineered to express green fluorescent protein), DOR/ISL synergistically prevented viral breakthrough at a threshold of 2× the half-maximal inhibitory concentration (IC50). DOR/ISL exhibited a higher barrier to resistance than DOR/3TC and dolutegravir (DTG)/3TC. Resistance analysis showed no emergence of substitutions at F227, an observation consistent with its ability to confer hypersusceptibility to ISL. Overall, the data demonstrate that DOR/ISL creates a 2-drug combination with a higher barrier to resistance, consistent with the reported clinical activity." @default.
- W4225281036 created "2022-05-04" @default.
- W4225281036 creator A5006285809 @default.
- W4225281036 creator A5007414433 @default.
- W4225281036 creator A5007841867 @default.
- W4225281036 creator A5008610083 @default.
- W4225281036 creator A5008971844 @default.
- W4225281036 creator A5012941009 @default.
- W4225281036 creator A5021255679 @default.
- W4225281036 creator A5030830066 @default.
- W4225281036 creator A5088571596 @default.
- W4225281036 date "2022-05-17" @default.
- W4225281036 modified "2023-10-06" @default.
- W4225281036 title "Doravirine and Islatravir Have Complementary Resistance Profiles and Create a Combination with a High Barrier to Resistance" @default.
- W4225281036 cites W1966225597 @default.
- W4225281036 cites W1991492628 @default.
- W4225281036 cites W2005821645 @default.
- W4225281036 cites W2008954911 @default.
- W4225281036 cites W2072041078 @default.
- W4225281036 cites W2077754502 @default.
- W4225281036 cites W2092786021 @default.
- W4225281036 cites W2102698854 @default.
- W4225281036 cites W2103766655 @default.
- W4225281036 cites W2109598777 @default.
- W4225281036 cites W2149148148 @default.
- W4225281036 cites W2165473677 @default.
- W4225281036 cites W2256825639 @default.
- W4225281036 cites W2318289184 @default.
- W4225281036 cites W2331244401 @default.
- W4225281036 cites W2508295414 @default.
- W4225281036 cites W2625924212 @default.
- W4225281036 cites W2792742326 @default.
- W4225281036 cites W2884122408 @default.
- W4225281036 cites W2889157553 @default.
- W4225281036 cites W2902172836 @default.
- W4225281036 cites W2976245304 @default.
- W4225281036 cites W2999016136 @default.
- W4225281036 cites W3133567607 @default.
- W4225281036 cites W3156341605 @default.
- W4225281036 cites W3160242901 @default.
- W4225281036 doi "https://doi.org/10.1128/aac.02223-21" @default.
- W4225281036 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35491829" @default.
- W4225281036 hasPublicationYear "2022" @default.
- W4225281036 type Work @default.
- W4225281036 citedByCount "3" @default.
- W4225281036 countsByYear W42252810362023 @default.
- W4225281036 crossrefType "journal-article" @default.
- W4225281036 hasAuthorship W4225281036A5006285809 @default.
- W4225281036 hasAuthorship W4225281036A5007414433 @default.
- W4225281036 hasAuthorship W4225281036A5007841867 @default.
- W4225281036 hasAuthorship W4225281036A5008610083 @default.
- W4225281036 hasAuthorship W4225281036A5008971844 @default.
- W4225281036 hasAuthorship W4225281036A5012941009 @default.
- W4225281036 hasAuthorship W4225281036A5021255679 @default.
- W4225281036 hasAuthorship W4225281036A5030830066 @default.
- W4225281036 hasAuthorship W4225281036A5088571596 @default.
- W4225281036 hasBestOaLocation W42252810362 @default.
- W4225281036 hasConcept C104317684 @default.
- W4225281036 hasConcept C114851261 @default.
- W4225281036 hasConcept C142462285 @default.
- W4225281036 hasConcept C156719811 @default.
- W4225281036 hasConcept C159047783 @default.
- W4225281036 hasConcept C182707283 @default.
- W4225281036 hasConcept C2522874641 @default.
- W4225281036 hasConcept C2776543447 @default.
- W4225281036 hasConcept C2777351918 @default.
- W4225281036 hasConcept C2777869810 @default.
- W4225281036 hasConcept C2779502633 @default.
- W4225281036 hasConcept C2779778239 @default.
- W4225281036 hasConcept C2779889181 @default.
- W4225281036 hasConcept C2780216070 @default.
- W4225281036 hasConcept C2780593183 @default.
- W4225281036 hasConcept C2780727368 @default.
- W4225281036 hasConcept C2909970146 @default.
- W4225281036 hasConcept C2993143319 @default.
- W4225281036 hasConcept C3013748606 @default.
- W4225281036 hasConcept C54355233 @default.
- W4225281036 hasConcept C67705224 @default.
- W4225281036 hasConcept C86803240 @default.
- W4225281036 hasConcept C89423630 @default.
- W4225281036 hasConcept C98274493 @default.
- W4225281036 hasConceptScore W4225281036C104317684 @default.
- W4225281036 hasConceptScore W4225281036C114851261 @default.
- W4225281036 hasConceptScore W4225281036C142462285 @default.
- W4225281036 hasConceptScore W4225281036C156719811 @default.
- W4225281036 hasConceptScore W4225281036C159047783 @default.
- W4225281036 hasConceptScore W4225281036C182707283 @default.
- W4225281036 hasConceptScore W4225281036C2522874641 @default.
- W4225281036 hasConceptScore W4225281036C2776543447 @default.
- W4225281036 hasConceptScore W4225281036C2777351918 @default.
- W4225281036 hasConceptScore W4225281036C2777869810 @default.
- W4225281036 hasConceptScore W4225281036C2779502633 @default.
- W4225281036 hasConceptScore W4225281036C2779778239 @default.
- W4225281036 hasConceptScore W4225281036C2779889181 @default.
- W4225281036 hasConceptScore W4225281036C2780216070 @default.
- W4225281036 hasConceptScore W4225281036C2780593183 @default.
- W4225281036 hasConceptScore W4225281036C2780727368 @default.
- W4225281036 hasConceptScore W4225281036C2909970146 @default.
- W4225281036 hasConceptScore W4225281036C2993143319 @default.
- W4225281036 hasConceptScore W4225281036C3013748606 @default.