title: Drug resistance mutations of HIV type 1 non-B viruses to integrase inhibitors in treatment-naive patients from sub-saharan countries and discordant interpretations.
abstract: The routine use of integrase inhibitors in sub-Saharan Africa where HIV-1 non-B viruses predominate is limited, but evaluating their effectiveness on HIV-1 subtypes and CRFs that circulate in this region is essential. We here analyzed 97 integrase sequences from HIV-1 non-B-infected individuals from African countries. Using currently available interpretation algorithms (ANRS, HIVdb, and Rega), we identified the presence of mutations at nine resistance-associated positions including L74M (3.1%), T97A (9.3%), K156N (2.1%), E157Q (5.2%), G163K (1.0%), T206S (48.5%), S230N (1.0%), D232N (1.0%), and R236K (1.0%). All but one (E157Q) were considered as accessory resistant mutation by the algorithms. E157Q identified in 5% of patients tested (5/97) was selected by the ANRS algorithm as a primary mutation, which alone can confer resistance to raltegravir. These results illustrated the need of further in vitro and clinical studies involving non-B viruses to better understand the real significance of observed mutations and harmonize interpretations.
authors.affiliation: UMI –TransVIHMI, Institut de Recherche pour le Développement, Montpellier, France.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Monleau
authors.forename: Avelin F
authors.initials: AF
authors.lastname: Aghokeng
authors.forename: Benedicte A
authors.initials: BA
authors.lastname: Nkano
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chaix
authors.forename: Martine
authors.initials: M
authors.lastname: Peeters
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D000465:Algorithms; D000595:Amino Acid Sequence; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral; D005260:Female; D019427:HIV Integrase / Q000187:drug effects* / Q000235:genetics; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000068898:Raltegravir Potassium
chemical_list: D004279:DNA, Viral; D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D015363:Quinolones; D000068898:Raltegravir Potassium; C509700:elvitegravir; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1