1271. High Dose Fluconazole Monotherapy is Inadequate for Cerebrospinal Fluid Cryptococcal Antigen Positive (CRAG+) Persons in a CRAG Screening Program in Ethiopia
Session: Oral Abstract Session: HIV Complications and Co-Infections
Friday, October 9, 2015: 3:00 PM
Room: 25--ABC
Background:  Cryptococcus is a major cause of deaths among HIV/AIDS patients who are antiretroviral treatment (ART)-naïve or ART-defaulters with low CD4+ T cell counts. Cryptococcosis is a neglected killer in Sub-Saharan Africa; however, meningitis can be prevented by early screening and giving preemptive treatment to a high-risk population.  The aim of our study was to evaluate integrating CRAG screening among ART naïve or defaulters HIV-infected with CD4+ count <150 cells/µL.

Methods:  In an ongoing prospective multisite study, we implemented cryptococcal antigen (CRAG) screening at Adama and Asella hospitals in Ethiopia at time of CD4 count testing. HIV-infected patients whose CD4+ count ≤150/µL underwent lab-based reflex CRAG screening, using the remaining plasma after CD4 testing. All CRAG+ patients were offered lumbar puncture (LP), and the cerebrospinal fluid (CSF) were also tested for the presence of the Cryptococcus by using CRAG lateral flow assay and India ink microscopy. CRAG+ patients without CNS disease (or suspicion of meningitis for those declining LP or have contraindication) were treated with fluconazole 800 mg/day until ART start and 400mg/day thereafter for 8 weeks. CSF CRAG+ patients were treated with fluconazole 1200mg/day and serial LPs were performed was until patients were asymptomatic.

Results: A total of 462 HIV-infected CD4+ count ≤150/µL ART naive or defaulters were CRAG screened starting from mid-August 2014 to mid-May 2015. Overall prevalence of cryptococcal antigenemia was 6.1% (28/462) and number needed to test (NNT) is 16.5 persons to detect one CRAG+ person.  Among 28 CRAG+ participants, the mean CD4+ count was 53 cells/µL and 60% (16/28) were women. LPs were performed in 26 plasma CrAg+ persons, of which 69% (18/26) were CSF CRAG+ positive. Patients with CSF CRAG+ were treated with high dose fluconazole monotherapy (1200mg/day, yet 72% (13/18) died.  Of those CRAG+ in plasma but CSF CRAG-negative, mortality 20% (2/10) died when receiving fluconazole 800mg/day preemptive treatment (P=.004).

Conclusion: Lab-based reflex CRAG screening could be prospectively implemented at two Ethiopian regional hospitals. Even though national treatment guideline recommend high dose fluconazole monotherapy for cryptococcal meningitis, we found this inadequate even in screening program.


Tafese Tufa, MSc, Microbiology, Asella Teaching Hospital, College of Health Sciences and Hirsch-Institute of Tropical Medicine (HITM) Research Center, Arsi University., Asella, Ethiopia, Abera Balcha, MD, Assela Teaching Hospital, Assela, Ethiopia, Fikadu Beyene, MD, Asella Teaching Hospital, College of Health Sciences, Asella, Ethiopia, Tadele Yitbarik, MD, Adama Referral Hospital, Adama, Ethiopia, Tashome Gabissa, MSc, Asella School of Health Sciences, Asella, Ethiopia, Anteneh Zewde, MD, University of Minnesota, Minneapolis, MN, Radha Rajasingham, MD, Medicine, University of Minnesota, Minneapolis, MN and David Boulware, MD, MPH, Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN

Disclosures:

T. Tufa, None

A. Balcha, None

F. Beyene, None

T. Yitbarik, None

T. Gabissa, None

A. Zewde, None

R. Rajasingham, None

D. Boulware, None

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