title: Pharmacokinetic evaluation and short-term activity of stavudine, nevirapine, and nelfinavir therapy in HIV-1-infected adults.
abstract: OBJECTIVE
  Evaluate pharmacokinetic interaction, short-term safety, and antiretroviral activity of stavudine (d4T), nevirapine (NVP), and nelfinavir (NFV) as combination HIV-1 therapy.
  
  
  METHODS
  Prospective, open-label study investigating the pharmacokinetic interactions between d4T, NVP, and NFV and documenting short-term tolerability and virologic and immunologic activity.
  
  
  METHODS
  Twenty-five HIV-1-infected adults, naive to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), < or = 6 months of d4T treatment, CD4 > or = 100 cells/mm, and viral load > = 5,000 copies/mL enrolled. All received NFV 750 mg 3 times daily and d4T 30-40 mg twice daily for 1 week, then added NVP at 200 mg once daily for 2 weeks and 200 mg twice daily thereafter. Steady-state pharmacokinetic parameters of NFV, AG1402 (metabolite of NFV), and d4T were compared before and after the addition of NVP.
  
  
  RESULTS
  No statistically significant changes in NFV or d4T pharmacokinetics were observed following the addition of NVP. Levels of AG1402 were suppressed 60-70%. Drug-related adverse events were seen at expected rates. At day 36, median viral load suppression was 2.0 log10 and absolute CD4 count increased by 111 cells/mm.
  
  
  CONCLUSIONS
  NVP administration did not significantly affect the steady-state pharmacokinetic parameters of NFV or d4T. The combination of d4T, NVP, and NFV induced rapid suppression of HIV-1 viral load and rises in CD4 cell count.
authors.affiliation: Division of Infectious Diseases, Roger Williams Medical Center, Providence, RI 02908, USA. Gail_Skowron@brown.edu
authors.forename: Gail
authors.initials: G
authors.lastname: Skowron
authors.forename: Gifford
authors.initials: G
authors.lastname: Leoung
authors.forename: David B
authors.initials: DB
authors.lastname: Hall
authors.forename: Patrick
authors.initials: P
authors.lastname: Robinson
authors.forename: Ronald
authors.initials: R
authors.lastname: Lewis
authors.forename: Robert
authors.initials: R
authors.lastname: Grosso
authors.forename: Mark
authors.initials: M
authors.lastname: Jacobs
authors.forename: Bradley
authors.initials: B
authors.lastname: Kerr
authors.forename: Thomas
authors.initials: T
authors.lastname: MacGregor
authors.forename: Michael
authors.initials: M
authors.lastname: Stevens
authors.forename: Alvan
authors.initials: A
authors.lastname: Fisher
authors.forename: Richard
authors.initials: R
authors.lastname: Odgen
authors.forename: Belinda
authors.initials: B
authors.lastname: Yen-Lieberman
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D018791:CD4 Lymphocyte Count; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019829:Nevirapine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018119:Stavudine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine; D018119:Stavudine; D019888:Nelfinavir