title: Clinical implications of the nelfinavir-proton pump inhibitor drug interaction in patients with human immunodeficiency virus.
abstract: OBJECTIVE
  To determine if the concomitant use of nelfinavir and proton pump inhibitors (PPIs) in patients with human immunodeficiency virus (HIV) infection results in the loss of virologic control.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Pharmacy, laboratory, and administrative databases of a large integrated health care system in northern California.
  
  
  METHODS
  A total of 1147 HIV-positive adults who started nelfinavir therapy between November 1, 1998, and June 20, 2003; within this cohort, 141 patients (12.3%) were also prescribed PPIs.
  
  
  RESULTS
  The effects on two virologic outcomes--achievement of undetectable HIV viral load and subsequent virologic rebound--were compared between patients receiving nelfinavir alone and those receiving nelfinavir with PPIs. Cox proportional hazards models were used, with adjustments for age, sex, race, HIV risk factors, hepatitis B or C coinfection, and other concurrent drugs known to affect the metabolism of nelfinavir. The use of PPIs had little effect on the ability to achieve an undetectable HIV viral load (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.58-1.19, p=0.29), but there was an approximate 50% increased risk of virologic rebound with the concurrent use of PPIs (adjusted HR 1.53, 95% CI 1.06-2.19, p=0.02). Short-term use of PPIs (defined as within 30 days of initial PPI dispensation) was not associated with increased risk of virologic rebound (HR 1.07, 95% CI 0.26-4.41, p=0.93) compared with no use of PPIs.
  
  
  CONCLUSIONS
  Use of PPIs should be minimized or avoided in patients who have attained an undetectable HIV viral load while taking a nelfinavir-based antiretroviral regimen. However, concomitant use of these drugs may be acceptable for indications where PPIs are required for fewer than 30 days.
authors.affiliation: Department of Medicine, University of California-San Francisco, San Francisco, California 94105, USA. parya.saberi@ucsf.edu
authors.forename: Parya
authors.initials: P
authors.lastname: Saberi
authors.forename: Dilrini K
authors.initials: DK
authors.lastname: Ranatunga
authors.forename: Charles P
authors.initials: CP
authors.lastname: Quesenberry
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Silverberg
mesh_terms: D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015331:Cohort Studies; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000009:adverse effects / Q000627:therapeutic use*; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012042:Registries; D012189:Retrospective Studies; D012306:Risk; D012307:Risk Factors; D013997:Time Factors; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D054328:Proton Pump Inhibitors; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D019888:Nelfinavir