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. 2018 Oct 23;5(11):ofy267.
doi: 10.1093/ofid/ofy267. eCollection 2018 Nov.

High Mortality in HIV-Associated Cryptococcal Meningitis Patients Treated With Amphotericin B-Based Therapy Under Routine Care Conditions in Africa

Raju K K Patel  1 , Tshepo Leeme  1 , Caitlin Azzo  1 , Nametso Tlhako  1 , Katlego Tsholo  1 , Ephraim O Tawanana  2 , Mooketsi Molefi  3 , Mosepele Mosepele  3   4 , David S Lawrence  4   5 , Margaret Mokomane  6 , Mark W Tenforde  1   7   8 , Joseph N Jarvis  1   4   5   9
Affiliations

High Mortality in HIV-Associated Cryptococcal Meningitis Patients Treated With Amphotericin B-Based Therapy Under Routine Care Conditions in Africa

Raju K K Patel et al. Open Forum Infect Dis. .

Abstract

Background: Cryptococcal meningitis (CM) causes 10%-20% of HIV-related deaths in Africa. Due to limited access to liposomal amphotericin and flucytosine, most African treatment guidelines recommend amphotericin B deoxycholate (AmB-d) plus high-dose fluconazole; outcomes with this treatment regimen in routine care settings have not been well described.

Methods: Electronic national death registry data and computerized medical records were used to retrospectively collect demographic, laboratory, and 1-year outcome data from all patients with CM between 2012 and 2014 at Botswana's main referral hospital, when recommended treatment for CM was AmB-d 1 mg/kg/d plus fluconazole 800 mg/d for 14 days. Cumulative survival was estimated at 2 weeks, 10 weeks, and 1 year.

Results: There were 283 episodes of CM among 236 individuals; 69% (163/236) were male, and the median age was 36 years. All patients were HIV-infected, with a median CD4 count of 39 cells/mm3. Two hundred fifteen person-years of follow-up data were captured for the 236 CM patients. Complete outcome data were available for 233 patients (99%) at 2 weeks, 224 patients (95%) at 10 weeks, and 219 patients (93%) at 1 year. Cumulative mortality was 26% (95% confidence interval [CI], 20%-32%) at 2 weeks, 50% (95% CI, 43%-57%) at 10 weeks, and 65% (95% CI, 58%-71%) at 1 year.

Conclusions: Mortality rates following HIV-associated CM treated with AmB-d and fluconazole in a routine health care setting in Botswana were very high. The findings highlight the inadequacies of current antifungal treatments for HIV-associated CM and underscore the difficulties of administering and monitoring intravenous amphotericin B deoxycholate therapy in resource-poor settings.

Keywords: HIV; amphotericin B; cryptococcal meningitis; resource-limited settings; sub-Saharan Africa.

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Figures

Figure 1.
Figure 1.
Kaplan-Meier survival curves showing the probability of survival following presentation with a first episode of HIV-associated cryptococcal meningitis in Botswana. A, Survival for all 236 patients, with vertical dotted lines indicating 2 weeks (26% mortality), 10 weeks (50% mortality), and 12 months (65% mortality). B, Survival stratified by antiretroviral therapy (ART) status at presentation. C, Survival stratified by mental status. D, According to number of missed amphotericin B deoxycholate doses.
See this image and copyright information in PMC

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