Asymptomatic cryptococcal antigenemia is associated with mortality among HIV‐positive patients in Indonesia

Ahmad Rizal Ganiem,Bachti Alisjahbana,Reinout Van Crevel,Andre Van Der Ven,Rudi Wisaksana,Agnes Rengga Indrati,Hinta Meijerink

doi:10.7448/ias.17.1.18821

Abstract

IntroductionPrevious studies, mostly from Africa, have shown that serum cryptococcal antigenemia may precede the development of cryptococcal meningitis and early death among patients with advanced HIV infection. We examined cryptococcal antigenemia as a risk factor for HIV-associated mortality in Indonesia, which is experiencing a rapidly growing HIV epidemic.MethodsWe included ART-naïve HIV patients with a CD4 cell count below 100 cells/μL and no signs of meningitis in an outpatient HIV clinic in Bandung, West Java, Indonesia. Baseline clinical data and follow-up were retrieved from a prospective database, and cryptococcal antigen was measured in stored serum samples using a semiquantitative lateral flow assay. Cox regression analysis was used to identify factors related to mortality.ResultsAmong 810 patients (median CD4 cell count 22), 58 (7.1%) had a positive cryptococcal antigen test with a median titre of 1:80 (range: 1:1 to 1:2560). Cryptococcal antigenemia at baseline was strongly associated with the development of cryptococcal meningitis and early death and loss to follow-up. After one year, both death (22.4% vs. 11.6%; p=0.016; adjusted HR 2.19; 95% CI 1.78–4.06) and the combined endpoint of death or loss to follow-up (67.2% vs. 40.4%; p<0.001; adjusted HR 1.57; 95% CI 1.12–2.20) were significantly higher among patients with a positive cryptococcal antigen test.ConclusionsCryptococcal antigenemia is common and clinically relevant among patients with advanced HIV in this setting. Routine screening for cryptococcal antigen followed by lumbar puncture and pre-emptive antifungal treatment for those who are positive may help in reducing early mortality.

Highlights

Previous studies, mostly from Africa, have shown that serum cryptococcal antigenemia may precede the development of cryptococcal meningitis and early death among patients with advanced HIV infection
Cryptococcal meningitis is a major cause of subacute meningitis and death in patients with advanced HIV infection, affecting an estimated one million people each year, especially in subSaharan Africa [1,2]
Cryptococcal meningitis is usually diagnosed by microscopic detection or culture of cryptococcus from cerebrospinal fluid (CSF), or detection of cryptococcal antigen in CSF or serum [3Á5]

Summary

Introduction

Mostly from Africa, have shown that serum cryptococcal antigenemia may precede the development of cryptococcal meningitis and early death among patients with advanced HIV infection. Cryptococcal antigenemia at baseline was strongly associated with the development of cryptococcal meningitis and early death and loss to follow-up. After one year, both death (22.4% vs 11.6%; p00.016; adjusted HR 2.19; 95% CI 1.78Á4.06) and the combined endpoint of death or loss to follow-up (67.2% vs 40.4%; p B0.001; adjusted HR 1.57; 95% CI 1.12Á2.20) were significantly higher among patients with a positive cryptococcal antigen test. In a cohort in South Africa, cryptococcal antigen screening adequately identified patients at risk for cryptococcal meningitis and death [6]. We determined the prevalence of serum cryptococcal antigenemia and its effect on mortality among ART-naıve patients with a CD4 count below 100 cells/mL

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