EFFECTIVENESS AND SAFETY OF ALTERNATIVE TREATMENT SCHEMES FOR PATIENTS WITH CRYPTOCOCCAL MENINGOENCEPHALITIS AND HIV INFECTION

Abstract

In Ukraine the problem of effective and safe treatment of HIV infected patients with cryptococcal meningoencephalitis has not been resolved due to the unavailability of flucytosine and the extremely limited use of amphotericin B deoxycholate.

The aim of our study was to evaluate the efficacy and safety of using fluconazole monotherapy in comparison with the combination of amphotericin B deoxycholate and fluconazole for the treatment of patients with cryptococcal meningoencephalitis associated with HIV infection.

Material and methods. We conducted a retrospective, cohort study that included 71 adult patients. The patients were divided into two groups – group 1 included 49 people who received treatment with a combination of amphotericin B deoxycholate (0.7–1 mg/kg body weight per day intravenously) and fluconazole (800 mg per day). Group 2 included 22 patients treated with high doses of fluconazole (800–1200 mg per day) as monotherapy. The duration of induction therapy was at least two weeks in both groups. In the consolidation phase patients received fluconazole 400 mg daily for eight weeks. The lethality count was used in the groups after 2 and 10 weeks of treatment to evaluate its efficacy. The safety assessment included the detection of toxic effects, severe adverse reactions and monitoring of laboratory parameters during the observation period.

Results and discussion. In 14 days of treatment the mortality rates in group 2 were 3.6 times less than in group 1 – 4.5 % (95 % CI: 0.1–22.8 %) and 16.3 % (95 % CI: 7.3–23.7 %), respectively, but they did not differ (P=0.17) statistically. On the day 25 of treatment 14/49 (28.5 %) died in group 1, while in group 2 only 2/22 (9 %), but by the end of the tenth week of observation, the mortality rates in both groups were equal (P=0.76) – 36.4 % (95 % CI: 17.2–59.3 %) versus 32.6 % (95 % CI: 20–47.5 % ). During this period the overall cumulative survival rate also did not differ (P=0.47) and amounted 67.1 % in group 1 and 57.2 % in group 2. A significant difference (P<0.01) in terms of the incidence of acute kidney injury was recorded among the adverse reactions during 10 weeks of treatment – 87 % in group 1 compared to 27 % in group 2.

Conclusions. The effectiveness of an alternative treatment regimen for patients with cryptococcal meningoencephalitis associated with HIV infection using fluconazole monotherapy does not differ (P=0.17) from the combination of amphotericin B deoxycholate plus fluconazole and 10-week mortality in groups is 36.4 % (95 % CI: 17.2–59.3 %) and 32.6 % (95 % CI: 20–47.5 %) respectively. The incidence of acute kidney injury with amphotericin B deoxycholate is 87 % compared to 27 % with fluconazole monotherapy.