title: Resistance analyses in HIV infected patients with a history of multiple antiretroviral treatment regimens.
abstract: OBJECTIVE
  To assess HIV-1 isolate based resistance profiles from extensively pretreated patients and effects of a resistance guided switch of antiretroviral therapy.
  
  
  METHODS
  In a prospective study phenotypic and genotypic resistance analyses were performed on HIV infected individuals with failure of the current therapy and history of at least three antiretroviral regimens. Antiretroviral therapy was changed according to the results. Viral load and CD4 lymphocyte counts were measured at baseline, after 10 (SD 2), and 24 (2) weeks.
  
  
  RESULTS
  All patients (n=52) failed their actual regimen. Currently versus ever previously taking the specific drug, resistance associated mutations and phenotypic resistance to AZT and 3TC were found in over 80% of individuals; resistance to DDI and D4T was detected in less than 10% of cases. A resistance guided switch of therapy was followed by a median decrease of viral load of 0.5 log10 units after 24 weeks. Individuals resistant to two or more drugs compared with patients with resistance to less than two drugs of ongoing treatment, were switched to a regimen containing DDI, D4T, and a PI or NNRTI. After 10 (SD 2) weeks viral load decrease was pronounced in patients with resistance to at least two drugs in the previous regimen.
  
  
  CONCLUSIONS
  Among different RTI, the profile of clinically relevant resistance indicates pronounced differences when looking at separate drugs. Regarding virological response, in the context of available drugs, resistance tested with currently used methods is of limited value in extensively pretreated patients and seems to have its value primarily in first or second switch of therapy.
authors.affiliation: General Hospital St Georg, Hamburg, Germany. plettenberg@ifi-infektiologie.de
authors.forename: A
authors.initials: A
authors.lastname: Plettenberg
authors.forename: D
authors.initials: D
authors.lastname: Albrecht
authors.forename: T
authors.initials: T
authors.lastname: Lorenzen
authors.forename: V
authors.initials: V
authors.lastname: Paech
authors.forename: H
authors.initials: H
authors.lastname: Petersen
authors.forename: T
authors.initials: T
authors.lastname: Fenner
authors.forename: T
authors.initials: T
authors.lastname: Meyer
authors.forename: R
authors.initials: R
authors.lastname: Arndt
authors.forename: K
authors.initials: K
authors.lastname: Hertogs
authors.forename: R
authors.initials: R
authors.lastname: Pauwels
authors.forename: T
authors.initials: T
authors.lastname: Weitzel
authors.forename: A
authors.initials: A
authors.lastname: Stoehr
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents