The intersection of drug interactions and adverse reactions in contemporary antiretroviral therapy

Abstract

Purpose of reviewAdvances in antiretroviral therapy (ART) have transformed HIV infection into a chronic and manageable condition. The introduction of potent and more tolerable antiretrovirals (ARVs) with favorable pharmacokinetic profiles has changed the prevalence and nature of drug-drug interactions (DDIs). Here, we review the relevance of DDIs in the era of contemporary ART. Recent findingsManagement of DDIs remains an important challenge with modern ART, primarily due to increased polypharmacy in older persons living with HIV. Significant DDIs exist between boosted ARVs or older nonnucleoside reverse transcriptase inhibitors and comedications for chronic comorbidities (e.g., anticoagulants, antiplatelets, statins) or complex conditions (e.g., anticancer agents, immunosuppressants). Newer ARVs such as unboosted integrase inhibitors, doravirine, and fostemsavir have reduced DDI potential, but there are clinically relevant DDIs that warrant consideration. Potential consequences of DDIs include increased toxicity and/or reduced efficacy of ARVs and/or comedications. Management approaches include switching to an ARV with less DDI potential, changing comedications, or altering medication dosage or dosing frequency. Deprescribing strategies can reduce DDIs and polypharmacy, improve adherence, minimize unnecessary adverse effects, and prevent medication-related errors.

2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines

“…4,18 Drug interactions are common among patients with HIV on antiretroviral therapy, which should be considered when starting or intensifying statin therapy for management of CCD. 6,7,19,20 Although pravastatin and pitavastatin are least likely to interact with antiretroviral therapy, rosuvastatin and atorvastatin may be preferred for more intense LDL-C reduction in patients with HIV and CCD. 20,21 Management of hypertriglyceridemia in patients with CCD and HIV should follow standard treatment pathways.…”

Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate for Nonoccupational HIV-1 Postexposure Prophylaxis: A Prospective Open-Label Trial (DORAVIPEP)

“…In our study cohort, 30% of PEP users reported engaging in chemsex; an additional third had comorbidities, with half of these individuals receiving psychiatric medications. The DOR/3TC/TDF regimen is associated with a lower risk of drug–drug interactions than many other PEP regimens [ 34 ]. This is relevant because of the potential for drug–drug interactions among different PEP regimens recommended in current guidelines, including pharmacokinetic enhancers such as protease inhibitors or EVG-based regimens.…”

Use of enfortumab vedotin in an HIV-positive patient with urothelial carcinoma

“…This was likely due to decreased plasma clearance of the antineoplastic agents as the CYP3A4 proteins were being used by the antiretroviral drugs. Previous drug interactions between ritonavir and docetaxel 13,14 as well as boosted antiretrovirals including darunavir boosted with ritonavir 15 have been reported. Strategies to diminish adverse reactions due to drug interactions include switching to antiretrovirals with decreased drug interaction potential, changing co-medications, and altering medication dosage or dosing frequency.…”

“…Strategies to diminish adverse reactions due to drug interactions include switching to antiretrovirals with decreased drug interaction potential, changing co-medications, and altering medication dosage or dosing frequency. 15 The patient's antiretroviral regimen was subsequently changed to dolutegravir (minor CYP3A4 substrate), doravirine (major CYP3A4 substrate), and valacyclovir (not a CYP3A4 substrate). With this antiretroviral combination, the patient was able to resume therapy with EV and has been tolerating it without major toxicity to date.…”