title: Long-term efficacy and safety of ritonavir/indinavir at 400/400 mg twice a day in combination with two nucleoside reverse transcriptase inhibitors as first line antiretroviral therapy.
abstract: OBJECTIVE
  To determine the long-term antiretroviral efficacy and tolerability of dual protease inhibitor (PI) therapy with indinavir (IDV)/ritonavir (RTV) at 400/400 mg twice a day (BID) in combination with two nucleoside reverse trancriptase inhibitors (NRTIs).
  
  
  METHODS
  In an open-label, uncontrolled multicentre clinical trial, antiretroviral therapy naive patients (n = 93) with a high median baseline HIV-1 RNA level of 210 000 copies/mL (range 17 000-2 943 000) and a median CD4 cell count of 195 copies/microL (range 4-656 copies/microL) were started on a regimen of either zidovudine (ZDV)/lamivudine (3TC) (49%), stavudine (d4T)/3TC (38%) or d4T/didanosine (ddI) (14%) plus RTV and IDV, each at 400 mg BID. CD4 cell counts and HIV RNA were determined at 4-week intervals for a duration of 72 weeks. Statistical analysis was performed on treatment as well as by intent to treat, where missing values were counted as failures.
  
  
  RESULTS
  HIV RNA levels below the limit of detection were achieved in 59.5% (< 80 copies/mL) and 63% (< 500 copies/mL) of patients according to the intent to treat analysis at week 72. In the on treatment analysis, the proportion of patients reaching an undetectable viral load was 94.5% (< 80 copies/mL) and 100% (< 500 copies/mL), respectively. Apart from diarrhoea and nausea, serum lipid abnormalities were identified as the most prominent adverse reaction. No cases of nephrotoxicity occurred during the entire observation period of 72 weeks.
  
  
  CONCLUSIONS
  Our results demonstrate that quadruple therapy with RTV/IDV and two NRTIs induces potent, durable and safe HIV suppression and might be particularly beneficial as a first line therapy for patients with a high baseline viral load.
authors.affiliation: Department of General Internal Medicine, University of Bonn, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Lichterfeld
authors.forename: H D
authors.initials: HD
authors.lastname: Nischalke
authors.forename: F
authors.initials: F
authors.lastname: Bergmann
authors.forename: W
authors.initials: W
authors.lastname: Wiesel
authors.forename: A
authors.initials: A
authors.lastname: Rieke
authors.forename: A
authors.initials: A
authors.lastname: Theisen
authors.forename: G
authors.initials: G
authors.lastname: Fätkenheuer
authors.forename: M
authors.initials: M
authors.lastname: Oette
authors.forename: H
authors.initials: H
authors.lastname: Carls
authors.forename: S
authors.initials: S
authors.lastname: Fenske
authors.forename: M
authors.initials: M
authors.lastname: Nadler
authors.forename: H
authors.initials: H
authors.lastname: Knechten
authors.forename: J-C
authors.initials: JC
authors.lastname: Wasmuth
authors.forename: J K
authors.initials: JK
authors.lastname: Rockstroh
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D015497:HIV-1; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019469:Indinavir; D019438:Ritonavir