pyrimidinones and Histoplasmosis

To report the results of therapeutic drug monitoring of lopinavir/ritonavir and itraconazole concentrations in an HIV-infected male who was treated for histoplasmosis.. A 34-year-old HIV-infected man who had recently initiated efavirenz-based antiretroviral therapy was diagnosed with disseminated Histoplasma capsulatum infection. In the hospital, lopinavir/ritonavir 400 mg/100 mg twice daily replaced efavirenz to avoid efavirenz-itraconazole interactions. After 14 days of liposomal amphotericin B therapy, itraconazole solution was initiated at 150 mg twice daily for 3 days, followed by 200 mg daily. Prior to itraconazole initiation, lopinavir trough concentration was 7.4 mg/L. The lopinavir trough concentration 15 days later, after 14 days of itraconazole, was 6.8 mg/L. An itraconazole concentration measured 2 hours post-dose on day 15 of oral therapy was 1.9 microg/mL. After 2 weeks of liposomal amphotericin, urine Histoplasma antigen was 27.23 ng/mL; after 5 months of oral itraconazole therapy, it decreased to 5.24 ng/mL. Plasma HIV RNA decreased 4.26 log(10) in 5 months to less than 40 copies/mL. The patient has demonstrated marked clinical improvement.. In this case, dosing recommendations of itraconazole 200 mg daily with lopinavir/ritonavir were appropriate. Lopinavir trough concentrations were not significantly different following the addition of itraconazole and were above the minimum target of 1 mg/L in treatment-naïve patients. The itraconazole concentration was above the recommended concentration of at least 1 microg/mL.. The dose of itraconazole was reduced to 200 mg daily as recommended by current guidelines, and therapeutic drug monitoring of both itraconazole and lopinavir concentrations confirmed that no further dosage adjustments were necessary.

Topics: Adult; Antifungal Agents; Drug Combinations; Drug Interactions; Drug Monitoring; Histoplasmosis; HIV Infections; HIV Protease Inhibitors; Humans; Itraconazole; Lopinavir; Male; Pyrimidinones; Ritonavir

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Biopsy; Female; Histoplasma; Histoplasmosis; HIV Infections; HIV Protease Inhibitors; Humans; Itraconazole; Lopinavir; Pyrimidinones; Skin; Treatment Outcome

We describe a drug-drug interaction between coformulated lopinavir/ritonavir and itraconazole in a patient infected with human immunodeficiency virus type 1 who had disseminated histoplasmosis. Coadministration of these agents led to a strong increase in itraconazole concentrations and a decrease in concentrations of its metabolite, hydroxyitraconazole, which is equally active pharmacologically. The dosage of itraconazole was reduced when it was used in combination with lopinavir/ritonavir.

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Antiretroviral Therapy, Highly Active; Drug Interactions; Drug Therapy, Combination; Histoplasmosis; HIV Infections; HIV Protease Inhibitors; Humans; Itraconazole; Lopinavir; Male; Middle Aged; Pyrimidinones; Ritonavir