Prevalence of cryptococcal antigenemia and cost-effectiveness of a cryptococcal antigen screening program--Vietnam

Abstract

Background: An 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/mm(3) 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.

Methods: Serum 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/mm(3) 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.

Results: Sera from 226 patients [104 (46%) from North Vietnam and 122 (54%) from the South] with CD4<100 cells/mm(3) were available for CrAg testing. Median CD4 count was 40 (range 0-99) cells/mm(3). 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.

Conclusion: CrAg 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.

Figure 1. Cryptococcal screening algorithm.

This algorithm, adapted from the South African national cryptococcal screening program, shows the flow of evaluation of HIV-infected patients in a model cryptococcal screening program. First, all patients with CD4<100 cells/mm³ undergo cryptococcal antigen (CrAg) testing. Those patients with a positive CrAg test then return to clinic for a symptom screening, followed by lumbar puncture referral for patients with a positive symptom screen. The algorithm also outlines the appropriate treatment for different patients within the screening program. Patients who have a negative CrAg test do not receive fluconazole but instead initiate antiretroviral therapy (ART) as per usual clinic practice. Patients who have a positive CrAg test and have a negative symptom screen or who have a positive symptom screen but negative lumbar puncture are treated with oral fluconazole for prevention of cryptococcal meningitis. Patients who have a positive symptoms screen and positive lumbar puncture are treated for cryptococcal meningitis according to Vietnam’s national HIV guidelines, with amphotericin B followed by fluconazole. Persons who have a positive symptom screen but refuse lumbar puncture are treated presumptively for cryptococcal meningitis. All CrAg-positive patients are initiated on ART after a minimum of two weeks of cryptococcal treatment (either for asymptomatic antigenemia, diagnosed, or presumptive cryptococcal meningitis).

Figure 2. Cost-effectiveness of cryptococcal screening at a range of prevalences and cost scenarios.

This graph has prevalence of asymptomatic cryptococcal antigenemia on the x-axis and incremental cost-effectiveness ratio (ICER) (increased cost per life-year gained [LYG] in US dollars) on the y-axis. The blue line represents the cost curve of full-cost fluconazole for one year of treatment. The red line represents the cost curve of full-cost fluconazole for ten weeks of treatment; the green line represents the cost curve of if fluconazole is obtained at no-cost. For Vietnam, the World Health Organization considers any intervention with an ICER under $6,948 to be ‘highly cost-effective’. This graph shows that cryptococcal screening, at any prevalence and under each of the three cost scenarios, should be considered a highly cost-effective intervention in Vietnam.