No Association of Cryptococcal Antigenemia with Poor Outcomes among Antiretroviral Therapy-Experienced HIV-Infected Patients in Addis Ababa, Ethiopia

Christopher C Smitson,Abere S Alemu,Mulugeta Tsegaye,Henry M Blumberg,Abraham Aseffa,Admasu Tenna,Daniel Fekade,Russell R Kempker,Alan Winston

doi:10.1371/journal.pone.0085698

Abstract

IntroductionThere are limited data on clinical outcomes of ART-experienced patients with cryptococcal antigenemia. We assessed clinical outcomes of a predominantly asymptomatic, ART-experienced cohort of HIV+ patients previously found to have a high (8.4%) prevalence of cryptococcal antigenemia.MethodsThe study took place at All Africa Leprosy, Tuberculosis and Rehabilitative Training Centre and Black Lion Hospital HIV Clinics in Addis Ababa, Ethiopia. A retrospective study design was used to perform 12-month follow-up of 367 mostly asymptomatic HIV-infected patients (CD4<200 cells/µl) with high levels of antiretroviral therapy use (74%) who were previously screened for cryptococcal antigenemia. Medical chart abstraction was performed approximately one year after initial screening to obtain data on clinic visit history, ART use, CD4 count, opportunistic infections, and patient outcome. We evaluated the association of cryptococcal antigenemia and a composite poor outcome of death and loss to follow-up using logistic regression.ResultsOverall, 323 (88%) patients were alive, 8 (2%) dead, and 36 (10%) lost to follow-up. Among the 31 patients with a positive cryptococcal antigen test (titers ≥1∶8) at baseline, 28 were alive (all titers ≤1∶512), 1 dead and 2 lost to follow-up (titers ≥1∶1024). In multivariate analysis, cryptococcal antigenemia was not predictive of a poor outcome (aOR = 1.3, 95% CI 0.3–4.8). A baseline CD4 count <100 cells/µl was associated with an increased risk of a poor outcome (aOR 3.0, 95% CI 1.4–6.7) while an increasing CD4 count (aOR 0.1, 95% CI 0.1–0.3) and receiving antiretroviral therapy at last follow-up visit (aOR 0.1, 95% CI 0.02–0.2) were associated with a reduced risk of a poor outcome.ConclusionsUnlike prior ART-naïve cohorts, we found that among persons receiving ART and with CD4 counts <200 cells/µl, asymptomatic cryptococcal antigenemia was not predictive of a poor outcome.

Highlights

There are limited data on clinical outcomes of antiretroviral therapy (ART)-experienced patients with cryptococcal antigenemia
In response to the high burden of cryptococcal disease in resource limited settings (RLS) including an estimated 720,000 cases of cryptococcal meningitis (CM) and 530,000 deaths annually in Sub-Saharan Africa [1], World Health Organization (WHO) recently released ‘‘rapid advice’’ guidelines for cryptococcal infection among persons living with HIV [3]
No persons with cryptococcal antigenemia received a lumbar puncture at baseline

Summary

Introduction

There are limited data on clinical outcomes of ART-experienced patients with cryptococcal antigenemia. A major emphasis of the guidelines is to consider implementation of cryptococcal antigen (CRAG) screening among antiretroviral therapy (ART)-naıve adults with a CD4 count ,100 cell/ml in areas with a high prevalence of cryptococcal infection, followed by preemptive anti-fungal therapy for those with a positive CRAG test [3]. This conditional recommendation was based on low quality evidence and more data are needed to optimize cryptococcal screening strategies. The purpose of this current study was to assess one-year clinical outcomes for this cohort in an effort to determine the utility of CRAG screening among an ART-experienced cohort

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