Cryptococcal Antigenemia in Immunocompromised Human Immunodeficiency Virus Patients in Rural Tanzania: A Preventable Cause of Early Mortality

Letang, Emilio; Müller, Matthias C; Ntamatungiro, Alex J; Kimera, Namvua; Faini, Diana; Furrer, Hansjakob; Battegay, Manuel; Tanner, Marcel; Hatz, Christoph; Boulware, David R; Glass, Tracy R (2015). Cryptococcal Antigenemia in Immunocompromised Human Immunodeficiency Virus Patients in Rural Tanzania: A Preventable Cause of Early Mortality. Open Forum Infectious Diseases, 2(2), ofv046. Oxford University Press 10.1093/ofid/ofv046

[img]
Preview
Text
ofv046.full.pdf - Published Version
Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND).

Download (275kB) | Preview

Background.  Cryptococcal meningitis is a leading cause of death in people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome. The World Health Organizations recommends pre-antiretroviral treatment (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. Methods.  We conducted a retrospective study including all ART-naive adults with CD4 <150 cells/µL prospectively enrolled in the Kilombero and Ulanga Antiretroviral Cohort between 2008 and 2012. Cryptococcal antigen 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. Results.  Of 750 ART-naive adults, 28 (3.7%) were CRAG-positive, corresponding to a prevalence of 4.4% (23 of 520) in CD4 <100 and 2.2% (5 of 230) in CD4 100-150 cells/µL. Within 1 year, 75% (21 of 28) of CRAG-positive and 42% (302 of 722) of CRAG-negative patients were dead or LFU (P<.001), with no differences across CD4 strata. Cryptococcal antigen positivity was an independent predictor of death or LFU after adjusting for relevant confounders (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.29-4.83; P = .006). Cryptococcal meningitis occurred in 39% (11 of 28) of CRAG-positive patients, with similar retention-in-care regardless of meningitis diagnosis (P = .8). Cryptococcal antigen titer >1:160 was associated with meningitis development (odds ratio, 4.83; 95% CI, 1.24-8.41; P = .008). Fluconazole receipt decreased death or LFU in CRAG-positive patients (HR, 0.18; 95% CI, .04-.78; P = .022). Conclusions.  Cryptococcal antigenemia predicted mortality or LFU among ART-naive HIV-infected persons with CD4 <150 cells/µL, and fluconazole increased survival or retention-in-care, suggesting that targeted pre-ART CRAG screening may decrease early mortality or LFU. A CRAG screening threshold of CD4 <100 cells/µL missed 18% of CRAG-positive patients, suggesting guidelines should consider a higher threshold.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Furrer, Hansjakob

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2328-8957

Publisher:

Oxford University Press

Language:

English

Submitter:

Annelies Luginbühl

Date Deposited:

30 Jul 2015 10:08

Last Modified:

05 Aug 2015 03:02

Publisher DOI:

10.1093/ofid/ofv046

PubMed ID:

26213690

Uncontrolled Keywords:

cryptococcal antigen, cryptococcal meningitis, diagnosis, mortality prevention, retention in care, screening, sub-Saharan Africa

BORIS DOI:

10.7892/boris.70564

URI:

https://boris.unibe.ch/id/eprint/70564

Actions (login required)

Edit item Edit item
Provide Feedback