title: Prevalence of C-terminal gag cleavage site mutations in HIV from therapy-naïve patients.
abstract: OBJECTIVE
  HIV protease - as well as gag cleavage site (CS) - mutations occur in HIV with PI resistance but little is known about the prevalence of CS mutations in drug-naïve patients.
  
  
  METHODS
  HIV samples (collected before 1997: n=94, after 1997: n=1617) from drug-naïve patients were analysed in the C-terminal gag and pol gene. Additionally, sequences from HIV Stanford database were included according to the collection date of the blood sample (before 1997: n=200, after 1997: n=375).
  
  
  RESULTS
  Only CS mutations 431V and 452S were correlated with primary PI resistance in drug-naïve HIV. Previously described therapy-associated CS mutations (431V/449F/449H/451T/452S/453A) were found in less than 0.5% of therapy-naïve HIV without primary drug resistance and were totally absent in HIV isolates collected before 1997. The detection of 431V in the absence of PR mutations was significantly correlated with the presence of 429K. The treatment-associated CS mutations (436R/437V/453L) were generally found in more than 1% of drug-naïve HIV with differences between HIV subtypes. Natural polymorphisms were frequently found and also differed between HIV subtype B and non-B subtypes.
  
  
  CONCLUSIONS
  The majority of therapy-associated CS mutations were rarely detected in drug-naïve HIV, but can be found in the absence of protease mutations. Moreover, the prevalence of these CS mutations seemed to have increased in recent years. The presence of treatment-associated CS mutations in drug-naïve patients might lower the genetic barrier of first-line therapies with protease inhibitors.
authors.affiliation: Institute of Virology, University of Cologne, Cologne, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Verheyen
authors.forename: Elena
authors.initials: E
authors.lastname: Knops
authors.forename: Bernd
authors.initials: B
authors.lastname: Kupfer
authors.forename: Osamah
authors.initials: O
authors.lastname: Hamouda
authors.forename: Sybille
authors.initials: S
authors.lastname: Somogyi
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schuldenzucker
authors.forename: Daniel
authors.initials: D
authors.lastname: Hoffmann
authors.forename: Rolf
authors.initials: R
authors.lastname: Kaiser
authors.forename: Herbert
authors.initials: H
authors.lastname: Pfister
authors.forename: Claudia
authors.initials: C
authors.lastname: Kücherer
mesh_terms: D024882:Drug Resistance, Viral; D006678:HIV / Q000235:genetics* / Q000302:isolation & purification*; D015658:HIV Infections / Q000821:virology*; D006801:Humans; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D054301:gag Gene Products, Human Immunodeficiency Virus