title: Long-term efficacy and safety of TDM-assisted combination of voriconazole plus efavirenz in an AIDS patient with cryptococcosis and liver cirrhosis.
abstract: OBJECTIVE
  To report the efficacy, tolerability, and pharmacokinetic effects of combined voriconazole and efavirenz treatment administered at therapeutic drug monitoring (TDM)-based adjusted doses to a patient with AIDS, cryptococcosis, and mild liver cirrhosis.
  
  
  METHODS
  A 40-year-old man with AIDS (hemophiliac, antiretroviral-naïve, plasma HIV-RNA = 290,000 copies/mL, CD4+ lymphocytes = 0), hepatitis C virus-related liver cirrhosis (Child-Pugh class A), and cryptococcal meningitis was failing standard antifungal therapies. He received an antifungal-antiretroviral combination treatment based on the association of voriconazole plus efavirenz. Doses of both drugs were serially adjusted based on their plasma concentrations, which were evaluated at steady-state of each dose combination at least once (week 3.1 or later) as full concentration-time profile (samples collected at 0, 1, 2, 3, 4, 6, 8, 12 h postdose). Adequate concentrations of voriconazole in both plasma and cerebrospinal fluid were obtained and target plasma concentrations of efavirenz were achieved at the final dose adjustment (voriconazole 200 mg twice daily plus efavirenz 300 mg once daily, both administered orally). The patient showed prompt and stable suppression of cryptococcosis and plasma viremia of HIV at long-term follow-up (66 wk), with no significant adverse events.
  
  
  CONCLUSIONS
  Standard therapies for cryptococcosis in patients with AIDS are often not effective. Voriconazole, despite its promising anticryptococcal efficacy, is currently not approved for cryptococcosis therapy in the US and Europe, nor is it recommended for combination with efavirenz due to the significant pharmacokinetic interactions between the 2 compounds. Thus far, published studies regarding the effects of voriconazole in human cryptococcosis are scarce and none has described the clinical and pharmacokinetic outcomes of a voriconazole/efavirenz combination in patients with AIDS, either with or without liver cirrhosis.
  
  
  CONCLUSIONS
  The combination of voriconazole and efavirenz at TDM-assisted doses may represent a valuable therapeutic option in AIDS patients with cryptococcosis and mild liver cirrhosis.
authors.affiliation: Clinic of Infectious Diseases, University of Bari, Bari, Italy. s_carbonara@yahoo.it
authors.forename: Sergio
authors.initials: S
authors.lastname: Carbonara
authors.forename: Mario
authors.initials: M
authors.lastname: Regazzi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Ciracì
authors.forename: Paola
authors.initials: P
authors.lastname: Villani
authors.forename: Francesca
authors.initials: F
authors.lastname: Stano
authors.forename: Maria
authors.initials: M
authors.lastname: Cusato
authors.forename: Manuela
authors.initials: M
authors.lastname: Heichen
authors.forename: Laura
authors.initials: L
authors.lastname: Monno
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000188:drug therapy; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage; D000935:Antifungal Agents / Q000008:administration & dosage; D048588:Benzoxazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003521:Cyclopropanes; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D016919:Meningitis, Cryptococcal / Q000150:complications* / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D065819:Voriconazole
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D000935:Antifungal Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D011743:Pyrimidines; D014230:Triazoles; C098320:efavirenz; D065819:Voriconazole