Abstract
Background: Cryptococcal antigen (CrAg) screening in individuals with advanced HIV reduces cryptococcal meningitis (CM) cases and deaths. The World Health Organization recently recommended increasing screening thresholds from CD4 ≤100 cells/µL to ≤200 cells/µL. CrAg screening at CD4 ≤100 cells/µL is cost-effective; however, the cost-effectiveness of screening patients with CD4 101-200 cells/µL requires evaluation. Methods: Using a decision analytic model with Botswana-specific cost and clinical estimates, we evaluated CrAg screening and treatment among individuals with CD4 counts of 101-200 cells/µL. We estimated the number of CM cases and deaths nationally and treatment costs without screening. For screening we modeled the number of CrAg tests performed, number of CrAg-positive patients identified, proportion started on pre-emptive fluconazole, CM cases and deaths. Screening and treatment costs were estimated and cost per death averted or disability-adjusted life year (DALY) saved compared with no screening. Results: Without screening, we estimated 142 CM cases and 85 deaths annually among individuals with CD4 101-200 cells/µL, with treatment costs of $368,982. With CrAg screening, an estimated 33,036 CrAg tests are performed, and 48 deaths avoided (1,017 DALYs saved). While CrAg screening costs an additional $155,601, overall treatment costs fall by $39,600 (preemptive and hospital-based CM treatment), yielding a net increase of $116,001. Compared to no screening, high coverage of CrAg screening and pre-emptive treatment for CrAg-positive individuals in this population avoids one death for $2440 and $114 per DALY saved. In sensitivity analyses assuming a higher proportion of antiretroviral therapy (ART)-naïve patients (75% versus 15%), cost per death averted was $1472; $69 per DALY saved. Conclusions: CrAg screening for individuals with CD4 101-200 cells/µL was estimated to have a modest impact, involve additional costs, and be less cost-effective than screening populations with CD4 counts ≤100 cells/µL. Additional CrAg screening costs must be considered against other health system priorities.
Highlights
Cryptococcal antigen (CrAg) screening in individuals with advanced HIV reduces cryptococcal meningitis (CM) cases and deaths
This includes a sizable population with advanced HIV disease (CD4 ≤200 cells/μL) who are at an increased risk of opportunistic infections such as cryptococcal meningitis (CM)[2]
We previously found screening at this threshold to be highly cost-effective and likely to prevent a significant proportion of CM cases and deaths[4]
Summary
Overview We used a decision analytic model to evaluate the number of patients receiving CD4 testing in Botswana who are at risk of cryptococcal meningitis and (1) develop CM without CrAg screening and (2) with national reflex CrAg screening adoption, as previously described[4], but in this analysis focused on those with a CD4 count of 101–200 cells/μL. This is compared with the estimated number of CM cases, CM-related deaths and DALYs lost, and associated costs of screening and pre-emptive therapy as well as costs of CM management for incident cases occurring despite implementation of screening (Figure 1B) For these models, CD4 count distribution data were obtained from the Botswana-Harvard HIV Reference Laboratory[11], and local CrAg prevalence and titre data used to predict risk for progression to CM in the CD4 101–200 cells/μL population. Sensitivity analysis 1 (SA1): In this analysis, we assume that in some real world settings a lower proportion of CrAg-positive patients are started on pre-emptive fluconazole after laboratory testing (50% versus 90% in the base model) because of programmatic barriers such as inadequate communication of test results to clinics, a lack of fluconazole availability in clinics, lack of provider awareness of treatment guidelines, or for other reasons This analysis still assumes that 90% of patients attended in outpatient clinics and receiving CD4 testing will stay engaged in health care.
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