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. 2014 Jan 28;17(1):18821.
doi: 10.7448/IAS.17.1.18821. eCollection 2014.

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

Ahmad Rizal Ganiem  1 , Agnes Rengga Indrati  2 , Rudi Wisaksana  3 , Hinta Meijerink  4 , Andre van der Ven  4 , Bachti Alisjahbana  3 , Reinout van Crevel  4
Affiliations

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

Ahmad Rizal Ganiem et al. J Int AIDS Soc. .

Abstract

Introduction: 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. We examined cryptococcal antigenemia as a risk factor for HIV-associated mortality in Indonesia, which is experiencing a rapidly growing HIV epidemic.

Methods: We 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.

Results: Among 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.

Conclusions: Cryptococcal 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.

Keywords: AIDS; Indonesia; antigen testing; cryptococcal antigenemia; lateral flow assay; meningitis.

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Figures

Figure 1
Figure 1
Patient flow. *All HIV-positive patients included in the HIV clinic cohort during the study period (2007–2011).
Figure 2
Figure 2
(A) Death in one year and (B) combined death or loss to follow-up in one year of subjects with and without cryptococcal antigenemia. CrAg+=positive cryptococcal antigen test; CrAg−=negative cryptococcal antigen test. Date of death was missing for seven patients (one CrAg+ and six CrAg−), who are not included in the survival curve in Figure 2A.
See this image and copyright information in PMC

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