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Basic Characteristics of Mutations
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Mutation Site
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T215Y |
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Mutation Site Sentence
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The most prevalent (>20%) RT mutations included NRTI-associated M184V, T215Y/F/N/V, D67N/G, M41L and K219Q/R/N/E;and NNRTI-associated K103N/S, Y181C/V and G190A/S. |
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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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RT |
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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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NRTIs |
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Location
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Kenya |
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Literature Information
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PMID
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30134290
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Title
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HIV-1 second-line failure and drug resistance at high-level and low-level viremia in Western Kenya
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Author
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Kantor R,DeLong A,Schreier L,Reitsma M,Kemboi E,Orido M,Obonge S,Boinett R,Rono M,Emonyi W,Brooks K,Coetzer M,Buziba N,Hogan J,Diero L
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Journal
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AIDS (London, England)
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Journal Info
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2018 Nov 13;32(17):2485-2496
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Abstract
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OBJECTIVE: Characterize failure and resistance above and below guidelines-recommended 1000 copies/ml virologic threshold, upon second-line failure. DESIGN: Cross-sectional study. METHODS: Kenyan adults on lopinavir/ritonavir-based second-line were enrolled at AMPATH (Academic Model Providing Access to Healthcare). Charts were reviewed for demographic/clinical characteristics and CD4/viral load were obtained. Participants with detectable viral load had a second visit and pol genotyping was attempted in both visits. Accumulated resistance was defined as mutations in the second, not the first visit. Low-level viremia (LLV) was detectable viral load less than 1000 copies/ml. Failure and resistance associations were evaluated using logistic and Poisson regression, Fisher Exact and t-tests. RESULTS: Of 394 participants (median age 42, 60% women, median 1.9 years on second-line) 48% had detectable viral load; 21% had viral load more than 1000 copies/ml, associated with younger age, tuberculosis treatment, shorter time on second-line, lower CD4count/percentage, longer first-line treatment interruption and pregnancy. In 105 sequences from the first visit (35 with LLV), 79% had resistance (57% dual-class, 7% triple-class; 46% with intermediate-to-high-level resistance to >/=1 future drug option). LLV was associated with more overall and NRTI-associated mutations and with predicted resistance to more next-regimen drugs. In 48 second-visit sequences (after median 55 days; IQR 28-33), 40% accumulated resistance and LLV was associated with more mutation accumulation. CONCLUSION: High resistance upon second-line failure exists at levels above and below guideline-recommended virologic-failure threshold, impacting future treatment options. Optimization of care should include increased viral load monitoring, resistance testing and third-line ART access, and consideration of lowering the virologic failure threshold, though this demands further investigation.
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Sequence Data
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-
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