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

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