title: The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage?
abstract: BACKGROUND
  Although being considered as a rarely observed HIV-1 protease mutation in clinical isolates, the L76V-prevalence increased 1998-2008 in some European countries most likely due to the approval of Lopinavir, Amprenavir and Darunavir which can select L76V. Beside an enhancement of resistance, L76V is also discussed to confer hypersusceptibility to the drugs Atazanavir and Saquinavir which might enable new treatment strategies by trying to take advantage of particular mutations.
  
  
  RESULTS
  Based on a cohort of 47 L76V-positive patients, we examined if there might exist a clinical advantage for L76V-positive patients concerning long-term success of PI-containing regimens in patients with limited therapy options.Genotypic- and phenotypic HIV-resistance tests from 47 mostly multi-resistant, L76V-positive patients throughout Germany were accomplished retrospectively 1999-2009. Five genotype-based drug-susceptibility predictions received from online interpretation-tools for Atazanavir, Saquinavir, Amprenavir and Lopinavir, were compared to phenotype-based predictions that were determined by using a recombinant virus assay along with a Virtual Phenotype™(Virco). The clinical outcome of the L76V-adapted follow-up therapy was determined by monitoring viral load for 96 weeks.
  
  
  CONCLUSIONS
  In this analysis, the mostly used interpretation systems overestimated the L76V-mutation concerning Atazanavir- and SQV resistance. In fact, a clear benefit in drug susceptibility for these drugs was observed in phenotype analysis after establishment of L76V. More importantly, long-term therapy success was significantly higher in patients receiving Atazanavir and/or Saquinavir plus one L76V-selecting drug compared to patients without L76V-selecting agents (p = 0.002).In case of L76V-occurrence ATV and/or SQV may represent encouraging options for patients in deep salvage situations.
authors.affiliation: PZB Aachen, HIV&Hepatitis Research Group, Blondelstr,, 52062 Aachen, Germany. f.wiesmann@googlemail.com.
authors.forename: Frank
authors.initials: F
authors.lastname: Wiesmann
authors.forename: Jan
authors.initials: J
authors.lastname: Vachta
authors.forename: Robert
authors.initials: R
authors.lastname: Ehret
authors.forename: Hauke
authors.initials: H
authors.lastname: Walter
authors.forename: Rolf
authors.initials: R
authors.lastname: Kaiser
authors.forename: Martin
authors.initials: M
authors.lastname: Stürmer
authors.forename: André
authors.initials: A
authors.lastname: Tappe
authors.forename: Martin
authors.initials: M
authors.lastname: Däumer
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Gudrun
authors.initials: G
authors.lastname: Naeth
authors.forename: Patrick
authors.initials: P
authors.lastname: Braun
authors.forename: Heribert
authors.initials: H
authors.lastname: Knechten