title: Persisting long-term benefit of genotype-guided treatment for HIV-infected patients failing HAART. The Viradapt Study: week 48 follow-up.
abstract: OBJECTIVE
  We report the 12 months follow-up of the patients who participated in the Viradapt study.
  
  
  METHODS
  A total of 108 HIV-infected patients failing antiretroviral (ARV) therapy (HIV RNA > 10,000 copies/ml, therapy > 6 months with nucleoside reverse transcriptase inhibitors, > 3 months with protease inhibitors (PIs) were randomized into two arms: standard of care in the control arm, and treatment according to the resistance mutations in the protease and reverse transcriptase genes in the study arm. After the first 6 months of the randomized study, open-label, genotype-guided treatment was offered in both arms. A multivariate analysis was performed to assess the predictive factors of treatment success (HIV RNA < 200 copies/ml).
  
  
  RESULTS
  The two arms were comparable in terms of risk factors, age, sex, previous treatments, CD4 cell count and log10 HIV-1 RNA at baseline. At week 24, an interim combined analysis showed a statistically significant difference in the drop in viral load at months 3 and 6 (P = 0.015, repeated measures analysis of variance) in favour of the genotype group. Patients in both arms were then offered open-label genotyping. Genotype analysis was performed every 3 months, and treatment changes could accordingly be made. As some of the patients in the control arm had already progressed to months 9 or 12, only 69% (30/43) of these patients received genotype-guided treatment changes. In the genotype arm, the mean drop in HIV RNA of 1.15 log10 copies/ml, obtained at month 6, persisted at months 9 and 12 (1.15 log10 copies/ml +/- 0.17). In the control arm, an additional drop in HIV RNA to 0.98 log10 +/- 0.22 copies/ml was observed by month 12. In control patients receiving open-label genotype, the percentage of patients with HIV-1 RNA levels below detection limit (200 copies/ml) rose from 14% at month 6 to 30.5% at month 12. This percentage in the study arm remained stable at 31.3% and 30% at months 9 and 12, respectively. Genotype-guided therapy, primary protease mutations and PI plasma concentrations were significantly correlated with virological success.
  
  
  CONCLUSIONS
  In this heavily pretreated patient population, genotype-guided therapy resulted in a sustained reduction in HIV RNA of greater than one log10 throughout a 1 year follow-up period. Performance of genotype-guided therapy may have contributed to the additional viral load reduction seen in patients in the control group who received open-label genotyping after the 6 months point. Multivariate analysis showed that the presence of primary protease mutations, performance of genotype-guided treatment changes and PI plasma concentrations independently affected virological response.
authors.affiliation: Department of Infectious Diseases, Nice University Hospital, France. clevenbergh.ph@easynet.fr
authors.forename: P
authors.initials: P
authors.lastname: Clevenbergh
authors.forename: J
authors.initials: J
authors.lastname: Durant
authors.forename: P
authors.initials: P
authors.lastname: Halfon
authors.forename: P
authors.initials: P
authors.lastname: del Giudice
authors.forename: V
authors.initials: V
authors.lastname: Mondain
authors.forename: N
authors.initials: N
authors.lastname: Montagne
authors.forename: J M
authors.initials: JM
authors.lastname: Schapiro
authors.forename: C A
authors.initials: CA
authors.lastname: Boucher
authors.forename: P
authors.initials: P
authors.lastname: Dellamonica
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease