title: The SnoB study: frequency of baseline raltegravir resistance mutations prevalence in different non-B subtypes.
abstract: The SnoB study analysed the variability of the integrase (IN) gene of non-B viruses from treatment-naïve patients to determine whether non-B subtypes carry natural resistance mutations to raltegravir (RAL). Plasma viral RNA from 427 patients was gained, and IN sequences were subtyped and screened for subtype-specific highly-variable residues. Seven viruses of different subtypes were phenotypically tested for RAL susceptibility; 359/427 samples could be sequenced. One hundred and seventy samples (47%) were classified as non-B subtypes. No primary RAL resistance-associated mutations (RRAMs) were detected. Certain secondary mutations were found, mostly related to specific non-B subtypes. L74 M was significantly more prevalent in subtype 02_AG, T97A in A and 06_cpx, V151I in 06_cpx, and G163R in 12_BF. Various additional mutations were also detected and could be associated with the subtype too. While K156 N and S230 N were correlated with B subtype, V72I, L74I, T112I, T125A, V201I and T206S were more frequent in certain non-B subtypes. The resistance factors (RF) of 7 viral strains of different subtypes ranged from 1.0 to 1.9. No primary or secondary but subtype-associated additional RRAMs were present. No correlation between RF and additional RRAMs was found. The prevalence of RRAMs was higher in non-B samples. However, the RFs for the analysed non-B subtypes showed lower values to those reported relevant to clinical failure. As the role of baseline secondary and additional mutations on RAL therapy failure is actually not known, baseline IN screening is necessary.
authors.affiliation: Institute of Virology, University of Cologne, Fürst-Pückler-Str. 56, 50935 Cologne, Germany. saleta.sierra-aragon@uk-koeln.de
authors.forename: Saleta
authors.initials: S
authors.lastname: Sierra
authors.forename: Nadine
authors.initials: N
authors.lastname: Lübke
authors.forename: Hauke
authors.initials: H
authors.lastname: Walter
authors.forename: Eugen
authors.initials: E
authors.lastname: Schülter
authors.forename: Stefan
authors.initials: S
authors.lastname: Reuter
authors.forename: Gerd
authors.initials: G
authors.lastname: Fätkenheuer
authors.forename: Markus
authors.initials: M
authors.lastname: Bickel
authors.forename: Hugo
authors.initials: H
authors.lastname: da Silva
authors.forename: Rolf
authors.initials: R
authors.lastname: Kaiser
authors.forename: Stefan
authors.initials: S
authors.lastname: Esser
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology; D019427:HIV Integrase / Q000235:genetics; D019428:HIV Integrase Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D015995:Prevalence; D011446:Prospective Studies; D011760:Pyrrolidinones / Q000494:pharmacology*; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D000068898:Raltegravir Potassium; D055815:Young Adult
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium; D019427:HIV Integrase