Prevalence of Cryptococcal Antigenemia and Cost-Effectiveness of a Cryptococcal Antigen Screening Program – Vietnam

Rachel M Smith,Julie R Harris,Robyn Neblett Fanfair,Hoang Thi Thanh Ha,Tuan Anh Nguyen,Truong Xuan Lien,Hien T Bui,Thai Hung Le,Pham Hong Thang,Bruce Struminger,Cao Thuy,Benjamin J Park,Michelle S Mcconnell

doi:10.1371/journal.pone.0062213

Abstract

BackgroundAn estimated 120,000 HIV-associated cryptococcal meningitis (CM) cases occur each year in South and Southeast Asia; early treatment may improve outcomes. The World Health Organization (WHO) recently recommended screening HIV-infected adults with CD4<100 cells/mm3 for serum cryptococcal antigen (CrAg), a marker of early cryptococcal infection, in areas of high CrAg prevalence. We evaluated CrAg prevalence and cost-effectiveness of this screening strategy in HIV-infected adults in northern and southern Vietnam.MethodsSerum samples were collected and stored during 2009–2012 in Hanoi and Ho Chi Minh City, Vietnam, from HIV-infected, ART-naïve patients presenting to care in 12 clinics. All specimens from patients with CD4<100 cells/mm3 were tested using the CrAg lateral flow assay. We obtained cost estimates from laboratory staff, clinicians and hospital administrators in Vietnam, and evaluated cost-effectiveness using WHO guidelines.ResultsSera from 226 patients [104 (46%) from North Vietnam and 122 (54%) from the South] with CD4<100 cells/mm3 were available for CrAg testing. Median CD4 count was 40 (range 0–99) cells/mm3. Nine (4%; 95% CI 2–7%) specimens were CrAg-positive. CrAg prevalence was higher in South Vietnam (6%; 95% CI 3–11%) than in North Vietnam (2%; 95% CI 0–6%) (p = 0.18). Cost per life-year gained under a screening scenario was $190, $137, and $119 at CrAg prevalences of 2%, 4% and 6%, respectively.ConclusionCrAg prevalence was higher in southern compared with northern Vietnam; however, CrAg screening would be considered cost-effective by WHO criteria in both regions. Public health officials in Vietnam should consider adding cryptococcal screening to existing national guidelines for HIV/AIDS care.

Highlights

Cryptococcal meningitis (CM) is one of the most common opportunistic infections (OI) among HIV-infected individuals, with an estimated 1 million cases of HIV-associated cryptococcal meningitis (CM) and 600,000 deaths each year [1]
Sera collected at study enrollment from patients with CD4,100 cells/ mm3 in both studies were stored at 220uC to 280uC at the National Institute for Hygiene and Epidemiology (NIHE) in Hanoi and Pasteur Institute (PI) in Ho Chi Minh City (HCMC), and were retrieved for cryptococcal antigen (CrAg) lateral flow assay (LFA) testing in this sub-study during 2012
Cost-effectiveness Evaluation and Assumptions We evaluated the incremental cost-effectiveness of a CrAg screening program among Vietnamese HIV-infected patients newly presenting for anti-retroviral therapy (ART) at an outpatient clinics (OPCs), and compared it to the current standard of care for HIV-infected patients in Vietnam [25]

Summary

Introduction

Cryptococcal meningitis (CM) is one of the most common opportunistic infections (OI) among HIV-infected individuals, with an estimated 1 million cases of HIV-associated CM and 600,000 deaths each year [1]. Otherwise healthy HIV-infected persons with detectable serum CrAg have increased mortality when compared to their CrAg-negative counterparts [10,11]; pre-emptive treatment of serum CrAg-positive patients with fluconazole and anti-retroviral therapy (ART) has been shown, in a small observational study, to improve survival [12], compared with ART alone, and has been recommended for consideration by the World Health Organization (WHO) [13]. This period of asymptomatic antigenemia before symptomatic meningitis provides a window of opportunity to treat patients and potentially prevent fatal cryptococcal disease.

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Conclusion