title: Drug resistance mutations in patients infected with HIV-2 living in Spain.
abstract: BACKGROUND
  In contrast with HIV-1, information about drug resistance in HIV-2 is scarce and mainly derived from small series of patients failing antiretroviral therapy.
  
  
  METHODS
  The spectrum of changes in the reverse transcriptase (RT), protease (PR) and integrase (INT) genes was examined in HIV-2 individuals enrolled in the HIV-2 Spanish register.
  
  
  RESULTS
  From a total of 236 HIV-2-infected individuals registered in Spain from 1989 to June 2010, 53 PR, 44 RT and 8 INT sequences were obtained. Low plasma viraemia precluded collection of this information from most of the remaining cases. No major mutations associated with drug resistance in HIV-1 were recognized in 29 PR, 20 RT and 5 INT sequences from antiretroviral-naive HIV-2 individuals, although natural polymorphisms with potential effects on susceptibility to PR inhibitors were recognized at 10 positions (L10V/I, V32I, M36I, M46I, I47V, Q58E, A71V/I, G73A, V82I and L89I/V) and for nucleoside reverse transcriptase inhibitors at three positions (T69N, V75I and K219E). In 24 antiretroviral-experienced patients with virological failure the most frequent major RT resistance mutations were M184V (58%), Q151M (33%) and K65R (21%), which are rarely seen thymidine analogue mutations. In PR the most frequent major changes were V47A (17%), I54M (17%), I82F (13%), L90M (29%) and L99F (29%). Two of the three patients who failed on raltegravir had N155H in the INT region.
  
  
  CONCLUSIONS
  Drug resistance mutations in HIV-2 are selected at the same positions as in HIV-1, although with different frequency. Polymorphisms in the RT and PR associated with drug resistance in HIV-1 as compensatory changes are common in untreated HIV-2 subjects. These findings highlight the need for specific guidelines for interpreting genotypic resistance patterns in HIV-2 infection.
authors.affiliation: Infectious Diseases Department, Hospital Carlos III, Madrid, Spain. ana.trevino.rc@gmail.com
authors.forename: Ana
authors.initials: A
authors.lastname: Treviño
authors.forename: Carmen
authors.initials: C
authors.lastname: de Mendoza
authors.forename: Estrella
authors.initials: E
authors.lastname: Caballero
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodríguez
authors.forename: Patricia
authors.initials: P
authors.lastname: Parra
authors.forename: Rafael
authors.initials: R
authors.lastname: Benito
authors.forename: Teresa
authors.initials: T
authors.lastname: Cabezas
authors.forename: Lourdes
authors.initials: L
authors.lastname: Roc
authors.forename: Antonio
authors.initials: A
authors.lastname: Aguilera
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015498:HIV-2 / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D019426:Integrases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D013030:Spain; D014764:Viral Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D014764:Viral Proteins; D019426:Integrases; C072416:reverse transcriptase, Human immunodeficiency virus 2; D054303:HIV Reverse Transcriptase; D016333:HIV Protease