1. High mortality despite high dose oral fluconazole (1600 mg) and flucytosine, and serial lumbar punctures, for HIV-associated cryptococcal meningitis : ANRS study in Burundi and Côte d’Ivoire
Poster WEPDB0103
IAS Paris 2017
A Chabrol (1) , A Doumbia (2) , R Landman (3) , A Fontanet (4) , S Eholie (2,3) , T Niyongabo (5) , L Nizigama (5) , D Laureillard (6) , B Sylla (3) , H Menan (2) , C Padoin (7) , S Brun (7) , C Alloui (7) , A Kakou (2) , O Bouchaud (7)
And the ANRS Study Group
(1) CH Corbeil, France (2) CHU Treichville, Côte d’Ivoire (3) IMEA, CHU Bichat, France (4) Epidémiologie, Institut Pasteur, France (5) CHU Kamenge, Burundi (6) CHU Nîmes, France (7) CHU Avicenne, France

2. Methods / characteristics of patients
Cryptococcal meningitis in resource-limited countries
High burden : deaths per year in sub-Saharan Africa
Amphotericin B + flucytosine + serial lombar punctures (LP) = gold standard treatment but often unavailable
Treatment is usually fluconazole alone 800 to 1200 mg/day
Prospective pilot study of « optimal real life treatment » for induction phase :
41 patients : oral fluconazole 1600 mg + oral flucytosine + serial LP (2 weeks)
Excluded : children, relapse, comatose (Glasgow < 9)

3. Results : mortality rates
Results of ANRS study
In the litterature
Study / Arm
Mortality rate at 2 weeks
Mortality rate at 10 weeks
Mortality rate at 24 weeks
Fluco (1)
55%
Fluco (2)
37 %
48 %
Fluco flucytosine (2)
10 %
43 %
AmB (3)
25%
44%
53%
AmB + fluco (3)
20%
33%
45%
AmB + flucytosine (3)
15%
30%
34%
Fluco flucytosine (4)
18 %
35 %
AmB-based 7 days (4)
22 %
36 %
(1) Gaskell, PLoS One (2) Nussbaum, CID 2010 (Malawi) (3) Day, NEJM 2013 (Vietnam) (4) ACTA Trial, IAS 2017

4. Results : early fongicidal activity (EFA)
EFA = / logCFU/ml/day
In the litterature
Study / Arm
EFA (log CFU / ml / day)
Fluco (1)
- 0.11
Fluco flucytosine (1)
- 0.28
AmB (2)
- 0.31
AmB + fluco (2)
- 0.32
AmB + flucytosine (2)
- 0.42
Fluco flucytosine (3)
-0.26
AmB-based 7 days (3)
-0.40
(1) Nussbaum, CID 2010 (Malawi) (2) Day, NEJM 2013 (Vietnam) (3) ACTA Trial, IAS 2017

5. Conclusion CAN WE DO BETTER ? YES WE SHOULD
=> Urgent need of Amphotericin B (short course 7 days)
=> Fluconazole –based preemptive strategies
Acknowledgements : ANRS, IMEA, and every physician of the study in Côte d’Ivoire and Burundi