Clinically relevant drug-drug interactions between antiretrovirals and antifungals

Expert Opin Drug Metab Toxicol. 2014 Apr;10(4):561-80. doi: 10.1517/17425255.2014.883379. Epub 2014 Feb 12.

Abstract

Introduction: Complete delineation of the HIV-1 life cycle has resulted in the development of several antiretroviral drugs. Twenty-five therapeutic agents belonging to five different classes are currently available for the treatment of HIV-1 infections. Advent of triple combination antiretroviral therapy has significantly lowered the mortality rate in HIV patients. However, fungal infections still represent major opportunistic diseases in immunocompromised patients worldwide.

Areas covered: Antiretroviral drugs that target enzymes and/or proteins indispensable for viral replication are discussed in this article. Fungal infections, causative organisms, epidemiology and preferred treatment modalities are also outlined. Finally, observed/predicted drug-drug interactions between antiretrovirals and antifungals are summarized along with clinical recommendations.

Expert opinion: Concomitant use of amphotericin B and tenofovir must be closely monitored for renal functioning. Due to relatively weak interactive potential with the CYP450 system, fluconazole is the preferred antifungal drug. High itraconazole doses (> 200 mg/day) are not advised in patients receiving booster protease inhibitor (PI) regimen. Posaconazole is contraindicated in combination with either efavirenz or fosamprenavir. Moreover, voriconazole is contraindicated with high-dose ritonavir-boosted PI. Echinocandins may aid in overcoming the limitations of existing antifungal therapy. An increasing number of documented or predicted drug-drug interactions and therapeutic drug monitoring may aid in the management of HIV-associated opportunistic fungal infections.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy*
  • Alkynes
  • Anti-Retroviral Agents / therapeutic use*
  • Antifungal Agents / therapeutic use*
  • Benzoxazines / therapeutic use
  • Carbamates / therapeutic use
  • Cyclopropanes
  • Drug Interactions
  • Drug Monitoring
  • Echinocandins / therapeutic use
  • Furans
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / therapeutic use
  • Humans
  • Itraconazole / therapeutic use
  • Mycoses / complications
  • Mycoses / drug therapy*
  • Organophosphates / therapeutic use
  • Pyrimidines / therapeutic use
  • Ritonavir / therapeutic use
  • Sulfonamides / therapeutic use
  • Triazoles / therapeutic use
  • Voriconazole

Substances

  • Alkynes
  • Anti-Retroviral Agents
  • Antifungal Agents
  • Benzoxazines
  • Carbamates
  • Cyclopropanes
  • Echinocandins
  • Furans
  • HIV Protease Inhibitors
  • Organophosphates
  • Pyrimidines
  • Sulfonamides
  • Triazoles
  • Itraconazole
  • posaconazole
  • efavirenz
  • Voriconazole
  • Ritonavir
  • fosamprenavir