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Basic Characteristics of Mutations
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Mutation Site
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K70H |
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Mutation Site Sentence
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Postbaseline resistance mutations to lenacapavir occurred in 8 participants (6 with M66I, 1 with K70H, 1 with Q67H + K70R) who were receiving unintended functional LEN monotherapy at the time of resistance selection. |
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Mutation Level
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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CA |
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Standardized Encoding Gene
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Gag
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Genotype/Subtype
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HIV-1 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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HIV Infections
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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LEN |
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Location
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- |
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Literature Information
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PMID
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36082606
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Title
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Resistance Analyses in Highly Treatment-Experienced People With Human Immunodeficiency Virus (HIV) Treated With the Novel Capsid HIV Inhibitor Lenacapavir
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Author
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Margot NA,Naik V,VanderVeen L,Anoshchenko O,Singh R,Dvory-Sobol H,Rhee MS,Callebaut C
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Journal
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The Journal of infectious diseases
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Journal Info
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2022 Nov 28;226(11):1985-1991
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Abstract
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BACKGROUND: Lenacapavir (LEN) is a first-in-class inhibitor of human immunodeficiency virus type 1 (HIV-1) capsid function in clinical development for the treatment of heavily treatment-experienced (HTE) people with HIV (PWH) harboring multidrug resistance (MDR) in combination with an optimized background regimen (OBR). Here we describe resistance analyses conducted in the pivotal phase 2/3 CAPELLA study. METHODS: CAPELLA enrolled viremic HTE PWH with resistance to >/=3 of 4 of the main antiretroviral (ARV) classes and resistance to >/=2 ARV drugs per class. Baseline resistance analyses used commercial assays (HIV-1 protease, reverse transcriptase, integrase genotypic/phenotypic tests). Postbaseline resistance was evaluated in participants experiencing virologic failure. RESULTS: At baseline, 46% of participants had resistance to the 4 main ARV drug classes, with one-third of participants having exhausted all drugs from >/=3 of the 4 main ARV classes. Treatment with LEN + OBR for 26 weeks led to viral suppression in 81% of participants. Postbaseline resistance mutations to lenacapavir occurred in 8 participants (6 with M66I, 1 with K70H, 1 with Q67H + K70R) who were receiving unintended functional LEN monotherapy at the time of resistance selection. CONCLUSIONS: LEN added to OBR led to high efficacy in this HTE patient population with MDR but could select for resistance when used unintentionally as functional monotherapy.
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Sequence Data
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-
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