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Cryptococcal Antigenemia in Immunocompromised HIV Patients in Rural Tanzania:A Preventable Cause of Early Mortality

Letang, E., M, M. C., Ntamatungiro, A. J., Kimera, N., Faini, D., Furrer, H., Battegay, M., Tanner, M., Boulware, D. R., Glass, T. R. and Hatz, C. (2015) Cryptococcal Antigenemia in Immunocompromised HIV Patients in Rural Tanzania:A Preventable Cause of Early Mortality. Open Forum Infectious Diseases. ISSN 2328-8957

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Abstract

Cryptococcal meningitis is a leading cause of death in people living with HIV/AIDS. WHO recommends pre-antiretroviral (ART) cryptococcal antigen (CRAG) screening in persons with CD4 below 100 cells/μL. We assessed the prevalence and outcome of cryptococcal antigenemia in rural southern Tanzania. Retrospective study including all ART-naïve adults with CD4<150 cells/μL prospectively enrolled in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) between 2008 and 2012. CRAG was assessed in cryopreserved pre-ART plasma. Cox regression estimated the composite outcome of death or loss-to-follow-up (LFU) by CRAG status and fluconazole use. Of 750 ART-naive adults, 28 (3.7%) were CRAG-positive, corresponding to a prevalence of 4.4% (23/520) in CD4 <100, and 2.2% (5/230) in CD4 100-150 cells/μL. Within 1-year, 75% (21/28) of CRAG-positive and 42% (302/722) of CRAG-negative patients were dead/LFU (p<0.001), with no differences across CD4 strata. CRAGpositivity was an independent predictor of death/LFU after adjusting for relevantconfounders (Hazard ratio (HR) 2.50, 95%CI 1.29-4.83, p=0.006). Cryptococcal meningitis occurred in Accepted Manuscript 39% (11/28) of CRAG-positives, with similar retention-in-care regardless of meningitis diagnosis (p=0.8). CRAG titre >1:160 was associated with meningitis development (OddsRatio 4.83; 95%CI, 1.24-8.41, p=0.008).Fluconazole receipt decreased death/LFU in CRAG-positive (HR 0.18, 95% CI 0.04-0.78, p=0.022). Cryptococcal antigenemia predicted mortality/LFU among ART-naive HIVinfected persons with CD4<150 cells/μL and fluconazole increased survival/retention-incare, suggesting that targeted pre-ART CRAG screening may decrease early mortality/LFU. A CRAG screening threshold of CD4<100 cells/μL missed 18% of CRAGpositive patients suggesting guidelines should consider a higher threshold.

Item Type: Article
Keywords: Cryptococcal Antigenemia, HIV/AIDS, Antiretroviral(ART), Cryptococcal antigen(CRAG), CD4
Subjects: HIV > Treatment
Divisions: Ifakara Health Institute > Biomedical
Depositing User: Mr Joseph Madata
Date Deposited: 20 Apr 2015 06:47
Last Modified: 20 Apr 2015 06:47
URI: http://ihi.eprints.org/id/eprint/3204

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