Clinically relevant drug–drug interactions between antiretrovirals and antifungals

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. Echino-candins 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.

Aspartic peptidase of Phialophora verrucosa as target of HIV peptidase inhibitors: blockage of its enzymatic activity and interference with fungal growth and macrophage interaction

“…Also, saquinavir and fluconazole promoted a similar action against C. albicans and C. neoformans 60 . The association of PIs and antifungal drugs can potentially modify pharmacokinetic parameters due to the drug-drug interactions 61 . This may for instance increase drugs absorption, inhibiting enzymes that are responsible for their degradation, and consequently enabling high levels and prolonged action of drugs.…”

Consensus guidelines for optimising antifungal drug delivery and monitoring to avoid toxicity and improve outcomes in patients with haematological malignancy, 2014

“…Drug interactions between the azole class and drugs commonly used in the haematology population are summarised in Table . Specific interactions with antiretroviral medications have recently been reviewed, and the University of Liverpool human immunodeficiency virus (HIV) drug interaction chart is also available for assessment of potential azole drug interactions in patients with HIV infection . Relevant drug–food interactions are outlined in Table .…”

CYP2C19 Genotype-Dependent Pharmacokinetic Drug Interaction Between Voriconazole and Ritonavir-Boosted Atazanavir in Healthy Subjects

“…For patients with HIV infection and their health care providers, drug–drug interactions are common concerns because of complex antiretroviral drug regimens that must be administered to provide potent and sustained viral suppression . Many first‐line antiretroviral therapies, notably protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors, interact with drug‐metabolizing enzymes such as the cytochrome P450 (CYP) family of enzymes and membrane transporters and can be victims or perpetrators of drug interactions . As HIV‐infected patients are often immunocompromised and highly susceptible to serious opportunistic fungal infections, there is a need to understand and manage drug–drug interactions between antiretroviral and antifungal agents, particularly the broad‐spectrum triazole antifungals …”