title: Long-term virological response to multiple sequential regimens of highly active antiretroviral therapy for HIV infection.
abstract: OBJECTIVE
  Information about the virological response to sequential highly active antiretroviral therapy (HAART) for HIV infection is limited. The virological response to four consecutive therapies was evaluated in the Swiss HIV Cohort.
  
  
  METHODS
  Retrospective analysis in an observational cohort.
  
  
  METHODS
  1140 individuals receiving uninterrupted HAART for 4.8 +/- 0.6 years were included. The virological response was classified as success (<400 copies/ml), low-level (LF: 400-5000 copies/ml) or high-level failure (HF: >5000 copies/ml). Potential determinants of the virological response, including patient demographics, treatment history and virological response to previous HAART regimens were analysed using survival and logistic regression analyses.
  
  
  RESULTS
  40.1% failed virologically on the first (22.0% LF; 18.1% HF), 35.1% on the second (14.2% LF; 20.9% HF), 34.2% on the third (9.9% LF; 24.3% HF) and 32.7% on the fourth HAART regimen (9% LF; 23.7% HF). Nucleoside pre-treatment (OR: 2.34; 95% CI: 1.67-3.29) and low baseline CD4 T-cell count (OR: 0.79/100 cells rise; 95% CI: 0.72-0.88) increased the risk of HF on the first HAART. Virological failure on HAART with HIV-1 RNA levels exceeding 1000 copies/ml predicted a poor virological response to subsequent HAART regimens. A switch from a protease inhibitor- to a non-nucleoside reverse transcriptase inhibitor-containing regimen significantly reduced the risk of HF. Multiple switches of HAART did not affect the recovery of CD4 T lymphocytes.
  
  
  CONCLUSIONS
  Multiple sequential HAART regimens do not per se reduce the likelihood of long-term virological suppression and immunological recovery. However, early virological failure increases significantly the risk of subsequent unfavourable virological responses. The choice of a potent initial antiretroviral drug regimen is therefore critical.
authors.affiliation: Division of Infectious Diseases, University Hospital, Basel, Switzerland.
authors.forename: Gilbert R
authors.initials: GR
authors.lastname: Kaufmann
authors.forename: Nina
authors.initials: N
authors.lastname: Khanna
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.forename: Luc
authors.initials: L
authors.lastname: Perrin
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.forename: Pietro
authors.initials: P
authors.lastname: Vernazza
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Martin
authors.initials: M
authors.lastname: Rickenbach
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D012367:RNA, Viral