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Basic Characteristics of Mutations
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Mutation Site
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Y188L |
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Mutation Site Sentence
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In these studied population, 28.8% (17/59) had mutations in PI (M46L and N88K/T), 5.1% (3/59) had mutations in NRTI (K219N, S68G and T215TS), 83.1% had mutations in NNRTI (E138A/G, F227L/P/S, V179D/E, G190A, K101EP, V108I, Y181C, K103N, L100I, P225H, V106IM, and Y188L) and 1.7% (1/59) had a mutation against INSTI (S147G). |
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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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NNRTI |
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Location
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Mozambique |
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Literature Information
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PMID
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40109100
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Title
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Susceptibility to Lenacapavir Among Newly Diagnosed HIV-Positive Patients Followed Up in Mozambique That Presented With Primary Antiretroviral Resistance to Other Classes
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Author
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Sebastiao CS,Bathy J,Nhampossa T,Santos A,Miranda M,Manhica NM,Bila R,Vubil D,Seabra S,O Martins MR,Giovanetti M,Gomes P,Pingarilho M,Abecasis AB,Pimentel V
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Journal
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Journal of medical virology
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Journal Info
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2025 Mar;97(3):e70317
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Abstract
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Multidrug-resistant HIV patients have limited ART options. Lenacapavir (LEN) is a capsid inhibitor that exhibits substantial antiviral activity in patients with therapeutic failure but is also proposed for PrEP. Herein, we assessed LEN susceptibility among ART-naive HIV patients with drug resistance in Mozambique. In this study, 63 patients with DRM against PIs, NRTIs, NNRTIs, and INSTIs were included. The gag (p24) and env fragments were amplified with a low-cost in-house protocol and sequenced with nanopore. HIVDR database from Stanford University was used to assess LEN resistance and geno2pheno to assess viral tropism and protease/maturation inhibitor-associated mutations. A total of 59 patients were successfully sequenced. About 29% had DRMs to PIs, 5% to NRTI, 83% to NNRTI, and 2% to INSTI. No DRMs to LEN were detected. Additionally, 42% of the sequences presented protease/maturation inhibitor-associated mutations. A relationship was observed between the E138A/G mutation and protease/maturation inhibitors (p = 0.004). We identified changes at the first codon position of position 56 of the p24 gag gene, which represents a key site for resistance to LEN. Also, codon 66 was highly conserved. Our results support the potential effectiveness of lenacapavir as a PrEP regimen or rescue therapy for patients with at least one drug-resistance mutation.
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Sequence Data
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-
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