title: Intensification of a failing regimen with zidovudine may cause sustained virologic suppression in the presence of resensitising mutations including K65R.
abstract: OBJECTIVE
  The reverse transcriptase (RT)-mutation K65R limits further therapeutic options and has been selected by unfavorable RT-combinations, e.g. tenofovir in combination with abacavir and/or didanosine.
  
  
  METHODS
  We identified HIV-1 infected patients from a large treatment cohort who experienced virological failure (HIV-1 RNA >1000 copies/mL) with evidence of resistance mutations including the K65R, but without thymidine analogue mutations (TAMs) in genotypic resistance assay. Phenotype was performed from previously collected frozen plasma. The patients were followed for clinical and resistance outcome after treatment intensification with only zidovudine.
  
  
  RESULTS
  Five patients had experienced antiretroviral treatment failure on various nucleoside analogue combinations, containing abacavir, didanosine, lamivudine, nevirapine, reverset and/or tenofovir. RT-sequence revealed mutations at position K65R in combination with other non-TAMs. The patients' median viral load prior to zidovudine intensification was 3.551 Log10 (range 3.053-4.681) and despite evidence for resistance to the failing drug regimen, all responded within 4 weeks to undetectable levels (<1.699 Log10 or <50 copies/mL) and remained virologically suppressed during follow-up (20 months through 6.5 years).
  
  
  CONCLUSIONS
  In virologically failing patients due to K65R- and other non-thymidine-mutations, simple regimen intensification with zidovudine resulted in sustained HIV-1 suppression. The finding of re-sensitized HIV-1 in patients may be clinically relevant.
authors.affiliation: HIVCENTER, Johann Wolfgang Goethe-University Hospital, Department of Internal Medicine II, Theodor-Stern-Kai 7, Frankfurt, Germany. c.stephan@em.uni-frankfurt.de
authors.forename: C
authors.initials: C
authors.lastname: Stephan
authors.forename: B
authors.initials: B
authors.lastname: Dauer
authors.forename: M
authors.initials: M
authors.lastname: Bickel
authors.forename: A
authors.initials: A
authors.lastname: Haberl
authors.forename: L
authors.initials: L
authors.lastname: Locher
authors.forename: A
authors.initials: A
authors.lastname: Müller
authors.forename: S
authors.initials: S
authors.lastname: Klauke
authors.forename: A
authors.initials: A
authors.lastname: Berger
authors.forename: H-W
authors.initials: HW
authors.lastname: Doerr
authors.forename: M
authors.initials: M
authors.lastname: Stürmer
authors.forename: S
authors.initials: S
authors.lastname: Staszewski
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D020125:Mutation, Missense; D016879:Salvage Therapy / Q000379:methods; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage*
chemical_list: D019380:Anti-HIV Agents; D015215:Zidovudine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase