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Basic Characteristics of Mutations
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Mutation Site
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N42T |
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Mutation Site Sentence
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Table 1.Clonal analysis of enfuvirtide resistance mutations in gp41 from plasma virus in subjects undergoing partial treatment interruption. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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gp41 |
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Standardized Encoding Gene
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Env
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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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CD4
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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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- |
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Location
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- |
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Literature Information
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PMID
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18645515
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Title
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Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide
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Author
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Marconi V,Bonhoeffer S,Paredes R,Lu J,Hoh R,Martin JN,Deeks SG,Kuritzkes DR
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Journal
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Journal of acquired immune deficiency syndromes (1999)
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Journal Info
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2008 Aug 15;48(5):572-6
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Abstract
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OBJECTIVES: To estimate the in vivo fitness cost of enfuvirtide (ENF) resistance, we analyzed dynamic shifts in the HIV-1 quasispecies under changing selective pressure in 3 subjects on failing ENF-based regimens who interrupted ENF while maintaining stable background regimens. Subsequently, ENF was readministered for 4 weeks as ""pulse intensification."" METHODS: The proportion of plasma virus carrying the V38A mutation in gp41 was quantified by allele-specific real-time polymerase chain reaction in serial samples collected from 3 subjects at 1- to 4-week intervals. Fitness differences were calculated using a method that corrected for time dependence of the viral replication rate. RESULTS: The V38A mutant made up >or=85% of the quasispecies at baseline and decayed to <5% over 12-24 weeks; plasma HIV-1 RNA levels remained stable during this time. Fitness differences for mutant versus wild type ranged from -25% to -65%, providing in vivo evidence for the reduced fitness of ENF-resistant HIV-1. The V38A mutant virus reemerged rapidly during the ENF pulse. CONCLUSIONS: These results demonstrate that the HIV-1 quasispecies undergoes dynamic changes in response to withdrawal and reinitiation of fusion inhibitor therapy. The relative stability of plasma HIV-1 titers during decay of V38A suggests that factors other than viral fitness likely define viral load set-point in patients with advanced disease.
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Sequence Data
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-
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