title: Indinavir/ritonavir 800/100 mg bid and efavirenz 600 mg qd in patients failing treatment with combination nucleoside reverse transcriptase inhibitors: 96-week outcomes of HIV-NAT 009.
abstract: OBJECTIVE
  Nucleoside reverse transcriptase (NRTI) sparing is a favourable option for patients with NRTI failure or toxicity.
  
  
  METHODS
  Patients judged to be failing NRTI therapy were enrolled in a single-arm, open-label study of indinavir/ritonavir (IDV/r) 800/100 mg twice a day (bid)+efavirenz (EFV) 600 mg once a day (qd). The primary endpoint was the change in time-weighted average HIV RNA from baseline. The initial 48-week protocol was extended to 96 weeks by a single amendment. Analysis was by intention to treat.
  
  
  RESULTS
  Sixty-one patients (23 female) were enrolled in the study. Baseline median inter-quartile range (IQR) NRTI exposure was 4.4 (3.9-4.7) years; baseline median viral load was 4.09 log(10) HIV-1 RNA copies/mL (range 3.75-4.61 log(10) copies/mL); baseline median CD4 count was 169 cells/microL (range 60-277 cells/microL). The mean (SD) change in time-weighted average HIV RNA from baseline at 48 and 96 weeks was -2.1 (0.7) and -2.1 (0.8) log(10) copies/mL respectively, resulting in 87% and 69% of patients with HIV RNA <50 copies/mL. Sixteen per cent of patients permanently ceased therapy and 26% underwent temporary drug interruptions because of study drug-related adverse events. Fasted-lipid values rose significantly over the 96 weeks of study, as did median blood glucose and median serum creatinine levels. Twelve (20%) patients underwent IDV dose reduction, mainly because of nephrotoxicity (nine of 12 patients). Blood pressure values deteriorated following switch, but markers of nucleoside toxicity improved.
  
  
  CONCLUSIONS
  IDV/r 800/100 mg bid+EFV 600 mg qd gave a potent, durable response in these NRTI failures and was reasonably well tolerated. However, we observed adverse effects on renal, metabolic and blood pressure parameters. Lower doses of boosted IDV might improve toxicity while maintaining efficacy, and this possibility warrants further investigation.
authors.affiliation: The HIV Netherlands Australia Thailand Research Collaboration, the Thai Red Cross AIDS Research Centre, Bangkok, Thailand. mark.boyd@fmc.sa.gov.au
authors.forename: M A
authors.initials: MA
authors.lastname: Boyd
authors.forename: U
authors.initials: U
authors.lastname: Siangphoe
authors.forename: K
authors.initials: K
authors.lastname: Ruxrungtham
authors.forename: C J
authors.initials: CJ
authors.lastname: Duncombe
authors.forename: M
authors.initials: M
authors.lastname: Stek
authors.forename: J M A
authors.initials: JM
authors.lastname: Lange
authors.forename: D A
authors.initials: DA
authors.lastname: Cooper
authors.forename: P
authors.initials: P
authors.lastname: Phanuphak
mesh_terms: D000328:Adult; D000368:Aged; D000480:Alkynes; D000886:Anthropometry; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines; D001786:Blood Glucose / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D003404:Creatinine / Q000097:blood; D003521:Cyclopropanes; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D019469:Indinavir / Q000009:adverse effects / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000009:adverse effects / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D001786:Blood Glucose; D003521:Cyclopropanes; D008055:Lipids; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; D019469:Indinavir; D003404:Creatinine; D054303:HIV Reverse Transcriptase; C098320:efavirenz; D019438:Ritonavir