title: Prevalence and factors associated with darunavir resistance mutations in multi-experienced HIV-1-infected patients failing other protease inhibitors in a referral teaching center in Brazil.
abstract: Information about resistance profile of darunavir (DRV) is scarce in Brazil. Our objectives were to estimate the prevalence of DRV resistance mutations in patients failing protease inhibitors (PI) and to identify factors associated with having more DRV resistance mutations. All HIV-infected patients failing PI-based regimens with genotyping performed between 2007 and 2008 in a referral teaching center in São Paulo, Brazil, were included. DRV-specific resistance mutations listed by December 2008 IAS-USA panel update were considered. Two Poisson regression models were constructed to assess factors related to the presence of more DRV resistance mutations. A total of 171 HIV-infected patients with available genotyping were included. The number of patients with lopinavir, saquinavir, and amprenavir used in previous regimen were 130 (76%), 83 (49%), and 35 (20%), respectively. The prevalence of major DRV resistance mutations was 50V: 5%; 54M: 1%; 76V: 4%; 84V: 15%. For minor mutations, the rates were 11I: 3%; 32I: 7%; 33F: 23%; 47V: 6%; 54L: 6%; 74P: 3%; 89V: 6%. Only 11 (6%) of the genotypes had > 3 DRV resistance mutations. In the clinical model, time of HIV infection of > 10 years and use of amprenavir were independently associated with having more DRV resistance mutations. In the genotyping-based model, only total number of PI resistance mutations was associated with our outcome. In conclusion, the prevalence of DRV mutations was low. Time of HIV infection, use of amprenavir and total number of PI resistance mutations were associated with having more DRV mutations.
authors.affiliation: AIDS Clinic, School of Medicine, Universidade de São Paulo, São Paulo, Brazil. josevibe@gmail.com
authors.forename: Jose E
authors.initials: JE
authors.lastname: Vidal
authors.forename: Angela C
authors.initials: AC
authors.lastname: Freitas
authors.forename: Alice Tw
authors.initials: AT
authors.lastname: Song
authors.forename: Silvia V
authors.initials: SV
authors.lastname: Campos
authors.forename: Mirian
authors.initials: M
authors.lastname: Dalben
authors.forename: Adrian V
authors.initials: AV
authors.lastname: Hernandez
mesh_terms: D000328:Adult; D001938:Brazil; D018791:CD4 Lymphocyte Count; D000069454:Darunavir; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D015995:Prevalence; D013449:Sulfonamides / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D013449:Sulfonamides; D000069454:Darunavir