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Basic Characteristics of Mutations
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Mutation Site
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I135V |
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Mutation Site Sentence
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Integrase polymorphisms in cohort samples: Comparative analyses of cohort subjects infected with CRF02_AG and non-AG subtypes showed that the G134N, I135V, K136T, and T206S polymorphisms were present in a significantly higher proportion of samples with AG subtype (81% to 97%) compared to samples with non-AG subtypes (28-52%) (p < 0.00001, Table 5). |
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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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IN |
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Standardized Encoding Gene
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gag-pol:155348
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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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Y |
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Treatment
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INSTIs |
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Location
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Cameroon |
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Literature Information
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PMID
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32106437
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Title
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Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy
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Author
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Acharya A,Tagny CT,Mbanya D,Fonsah JY,Nchindap E,Kenmogne L,Jihyun M,Njamnshi AK,Kanmogne GD
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Journal
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International journal of molecular sciences
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Journal Info
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2020 Feb 25;21(5):1553
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Abstract
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: Integrase strand-transfer inhibitors (INSTIs) are now included in preferred first-line antiretroviral therapy (ART) for HIV-infected adults. Studies of Western clade-B HIV-1 show increased resistance to INSTIs following mutations in integrase and nef 3'polypurine tract (3'-PPT). With anticipated shifts in Africa (where 25.6-million HIV-infected people resides) to INSTIs-based ART, it is critical to monitor patients in African countries for resistance-associated mutations (RAMs) affecting INSTIs efficacy. We analyzed HIV-1 integrase and 3'-PPT sequences in 345 clinical samples from INSTIs-naive HIV-infected Cameroonians for polymorphisms and RAMs that affect INSTIs. Phylogeny showed high genetic diversity, with the predominance of HIV-1 CRF02_AG. Major INSTIs RAMs T66A and N155K were found in two (0.6%) samples. Integrase polymorphic and accessory RAMs found included T97A, E157Q, A128T, M50I, S119R, L74M, L74I, S230N, and E138D (0.3%-23.5% of samples). Ten (3.2%) samples had both I72V+L74M, L74M+T97A, or I72V+T97A mutations; thirty-one (9.8%) had 3'-PPT mutations. The low frequency of major INSTIs RAMs shows that INSTIs-based ART can be successfully used in Cameroon. Several samples had 1 INSTIs accessory RAMs known to reduce INSTIs efficacy; thus, INSTIs-based ART would require genetic surveillance. The 3'-PPT mutations could also affect INSTIs. For patients failing INSTIs-based ART with no INSTIs RAMs, monitoring 3'-PPT sequences could reveal treatment failure etiology.
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Sequence Data
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MK327828-MK327927;MK333810-MK333910
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