Clinical implications of the nelfinavir-proton pump inhibitor drug interaction in patients with human immunodeficiency virus

Pharmacotherapy. 2011 Mar;31(3):253-61. doi: 10.1592/phco.31.3.253.

Abstract

Study 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.

Design: Retrospective cohort study.

Data source: Pharmacy, laboratory, and administrative databases of a large integrated health care system in northern California.

Patients: 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.

Measurements and main 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Cohort Studies
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP3A / metabolism
  • Drug Interactions
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease Inhibitors / adverse effects
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1 / drug effects*
  • HIV-1 / immunology
  • Humans
  • Male
  • Middle Aged
  • Nelfinavir / adverse effects
  • Nelfinavir / therapeutic use*
  • Proton Pump Inhibitors / adverse effects
  • Proton Pump Inhibitors / therapeutic use*
  • Registries
  • Retrospective Studies
  • Risk
  • Risk Factors
  • Time Factors
  • Viral Load*

Substances

  • HIV Protease Inhibitors
  • Proton Pump Inhibitors
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP3A
  • Nelfinavir