title: Investigation of baseline susceptibility to protease inhibitors in HIV-1 subtypes C, F, G and CRF02_AG.
abstract: OBJECTIVE
  To compare baseline susceptibility to protease inhibitors among HIV-1 isolates of subtypes C, F, G and CRF02_AG, and to identify polymorphisms that determine the differences in susceptibility.
  
  
  METHODS
  A total of 42 samples of drug-naive patients infected with subtypes G (n=19), CRF02_AG (n = 10), F (n = 6) and C (n = 7) were phenotyped and genotyped with the Antivirogram and the ViroSeq 2.0 genotyping system, respectively. A Bayesian network approach was used for a preliminary analysis of the collected data and the dependencies indicated by the network were statistically confirmed.
  
  
  RESULTS
  CRF02_AG samples were found to be more susceptible to nelfinavir and ritonavir than other subtypes. Hypersusceptibility to these drugs was associated with the 70R polymorphism. 37D/S/T was associated with reduced susceptibility to indinavir and 89M with reduced susceptibility to lopinavir. Susceptibility to tipranavir was the lowest among the subtype F samples and the highest for subtype G samples, with samples carrying 57R being more susceptible than samples carrying 57K.
  
  
  CONCLUSIONS
  Our study suggests that there are baseline susceptibility differences between subtypes and these differences are due to naturally occurring polymorphisms in these subtypes. The predictive value for phenotype of these polymorphisms was even valid in subtypes where these polymorphisms are less prevalent. Taking into account such polymorphisms should improve current algorithms for interpretation of genotyping results in a subtype-independent way.
authors.affiliation: Virology Laboratory, Hospital Egas Moniz, Lisbon, Portugal. ana.abecasis@uz.kuleuven.ac.be
authors.forename: Ana B
authors.initials: AB
authors.lastname: Abecasis
authors.forename: Koen
authors.initials: K
authors.lastname: Deforche
authors.forename: Lee T
authors.initials: LT
authors.lastname: Bacheler
authors.forename: Paula
authors.initials: P
authors.lastname: McKenna
authors.forename: Ana Patricia
authors.initials: AP
authors.lastname: Carvalho
authors.forename: Perpétua
authors.initials: P
authors.lastname: Gomes
authors.forename: Anne-Mieke
authors.initials: AM
authors.lastname: Vandamme
authors.forename: Ricardo Jorge
authors.initials: RJ
authors.lastname: Camacho
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D024882:Drug Resistance, Viral / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D019469:Indinavir / Q000494:pharmacology / Q000627:therapeutic use; D008957:Models, Genetic; D019888:Nelfinavir / Q000494:pharmacology / Q000627:therapeutic use; D010641:Phenotype; D011110:Polymorphism, Genetic; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D011753:Pyrones / Q000494:pharmacology / Q000627:therapeutic use; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides
chemical_list: D017320:HIV Protease Inhibitors; D011725:Pyridines; D011753:Pyrones; D013449:Sulfonamides; D019469:Indinavir; D016333:HIV Protease; D019888:Nelfinavir; D019438:Ritonavir; C107201:tipranavir