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- Title
Prevalence of gp160 polymorphisms known to be related to decreased susceptibility to temsavir in different subtypes of HIV-1 in the Los Alamos National Laboratory HIV Sequence Database.
- Authors
Gartland, Margaret; Arnoult, Eric; Foley, Brian T; Lataillade, Max; Ackerman, Peter; Llamoso, Cyril; Krystal, Mark
- Abstract
<bold>Background: </bold>Fostemsavir, a prodrug of the gp120-directed attachment inhibitor temsavir, is indicated for use in heavily treatment-experienced individuals with MDR HIV-1. Reduced susceptibility to temsavir in the clinic maps to discrete changes at amino acid positions in gp160: S375, M426, M434 and M475.<bold>Objectives: </bold>To query the Los Alamos National Laboratory (LANL) HIV Sequence Database for the prevalence of polymorphisms at gp160 positions of interest.<bold>Methods: </bold>Full-length gp160 sequences (N = 7560) were queried for amino acid polymorphisms relative to the subtype B consensus at positions of interest; frequencies were reported for all sequences and among subtypes/circulating recombinant forms (CRFs) with ≥10 isolates in the database.<bold>Results: </bold>Among 239 subtypes in the database, the 5 most prevalent were B (n = 2651, 35.1%), C (n = 1626, 21.5%), CRF01_AE (n = 674, 8.9%), A1 (n = 273, 3.6%) and CRF02_AG (n = 199, 2.6%). Among all 7560 sequences, the most prevalent amino acids at positions of interest (S375, 73.5%; M426, 82.1%; M434, 88.2%; M475, 89.9%) were the same as the subtype B consensus. Specific polymorphisms with the potential to decrease temsavir susceptibility (S375H/I/M/N/T/Y, M426L/P, M434I/K and M475I) were found in <10% of isolates of subtypes D, G, A6, BC, F1, CRF07_BC, CRF08_BC, 02A, CRF06_cpx, F2, 02G and 02B. S375H and M475I were predominant among CRF01_AE (S375H, 99.3%; M475I, 76.3%; consistent with previously reported low temsavir susceptibility of this CRF) and 01B (S375H, 71.7%; M475I, 49.5%).<bold>Conclusions: </bold>Analysis of the LANL HIV Sequence Database found a low prevalence of gp160 amino acid polymorphisms with the potential to reduce temsavir susceptibility overall and among most of the common subtypes.
- Subjects
HIV; GOVERNMENT laboratories; AMINO acids; DATABASES; HIV infection epidemiology; THERAPEUTIC use of proteins; HIV infections; ANTI-HIV agents; RESEARCH; RESEARCH methodology; LABORATORIES; MEDICAL cooperation; EVALUATION research; COMPARATIVE studies; DISEASE prevalence
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2021, Vol 76, Issue 11, p2958
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkab257