Date of report 13 Oct 2020

Reported case interaction between
Cobicistat and Voriconazole

Middle-aged male patient with HIV since 1987, treated since the early 1990s with several ARV regimens and experienced multiple virological failures causing an MDR strain (62V/65R/ 101E/181C/184I mutations, conferring resistance to lamivudine/ emtricitabine/didanosine/abacavir/nevirapine/efavirenz/rilpivirine/etravirine and partial resistance to tenofovir). Relevant medical history: COPD. He had an undetectable viral load high CD4 lymphocyte count on 800/100 mg of darunavir/ritonavir once daily and 400 mg of raltegravir twice daily at the time of consultation. He was admitted for a respiratory infection and treated with broad-spectrum antibiotics and high doses of systemic steroids with incomplete response. Then, invasive pulmonary aspergillosis was diagnosed. ARV regimen was changed to enfuvirtide, zidovudine, tenofovir and raltegravir at the usual doses, to avoid DDI between ritonavir and voriconazole 200mg twice daily (ritonavir induces the CYP2C19 isoenzyme, leading frequently to insufficient drug levels of voriconazole). Later, ART regimen was changed again (due to intolerance to enfuvirtide injections and to get a simplification) to elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate 150/150/200/300 mg once daily and 800 mg of darunavir once daily (cobicistat has a theoretically better drug–drug interaction profile, due to the more selective 3A4 isoenzyme inhibition than ritonavir) Vorizonazole levels were monitored (and a complete PK curve over 24 hs was performed), requiring increase in doses up to 400mg twice daily to maintain target levels (1 mg/mL). Patient completely resolved the pulmonary aspergillosis, with no relapse. This case has been already published: Ambrosioni J et al. J Antimicrob Chemother. 2016 Apr;71(4):1125-7. doi: 10.1093/jac/dkv449. https://pubmed.ncbi.nlm.nih.gov/26755498/