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Radha Rajasingham, David Meya, Melissa Rolfes, Kate Birkenkamp , David R Boulware

Cost-Benefit of Integrating Cryptococcal Antigen Screening and Preemptive Treatment into Routine HIV Care. Radha Rajasingham, David Meya, Melissa Rolfes, Kate Birkenkamp , David R Boulware Presented by: Radha Rajasingham, MD July 23, 2012. Background.

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Radha Rajasingham, David Meya, Melissa Rolfes, Kate Birkenkamp , David R Boulware

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  1. Cost-Benefit of Integrating Cryptococcal Antigen Screening and Preemptive Treatment into Routine HIV Care Radha Rajasingham, David Meya, Melissa Rolfes, Kate Birkenkamp, David R Boulware Presented by: Radha Rajasingham, MD July 23, 2012

  2. Background • Cryptococcal Meningitis causes ~20-25% of AIDS-related attributable mortality in sub-Saharan Africa • Cryptococcal Antigen (CrAg) can be detected >3 weeks before onset of symptoms • Asymptomatic CrAg+ persons have a high risk of subsequent CM and death, despite ART. • A new CrAg point of care lateral flow assay (LFA) is available with excellent sensitivity and specificity

  3. Methods • We assessed the cost-benefit of targeted CRAG screening for patients with CD4<100 using the LFA ($2.50/screen) coupled with preemptive fluconazole therapy for CRAG+ persons entering HIV care in sub-Saharan Africa • CRAG LFA Cost Components • CRAG LFA Assay $2.00 www.Immy.com • Lab Supplies $0.05 One pipette tip, one Eppendorf tube • Labor $0.25 • Overhead $0.20 • LFA can be shipped/stored at room temperature

  4. Performed CRAG screening at the Infectious Disease Institute in Kampala Uganda between 2004 and 2007 • CRAG latex agglutination was $16.75 per test • Among HIV+ with a CD4<100, 8.8% (26/295) had asymptomatic/subclinical cryptococcal antigenemia • 21 were treated with fluconazole (200-400mg x 2-4 weeks), 30-month survival was 71% • 5 were not treated with fluconazole, and all died within 2 months of starting ART Clinical Infectious Diseases 2010; 51:448-55.

  5. Cost-Effectiveness Analysis • Among CD4<100, the number needed to screen in order to detect one CRAG+ was 11.3 (95% CI: 7.9-17.1) • NNS = 1 / prevalence • NNS = 1 / 0.088 • The number needed to be screened and treated to prevent one death was 15.9 people • NNT life-saved = 1 / (prevalence * survival) • NNT life-saved = 1 / (0.088 * 0.71)

  6. Based on $16.75 CRAG, this translates to: • $190 (95% CI: $132-$286) to detect one asymptomatic person with cryptococcal antigenemia • $266 (95% CI: $185 to $402) to save one person’s life with preemptive fluconazole • Assuming an average increase in life expectancy of 18 years for a 30yo Ugandan initiating ART with a CD4<100,* this is $14.77 per DALY saved * Mills EJ, Bakanda C, Birungi J, et al. Life expectancy of persons receiving combination antiretroviral therapy in low-income countries: a cohort analysis from Uganda. Ann Intern Med 2011; 155: 209-216

  7. CRAG Lateral Flow Assay (LFA) Immunochromatographic LFA test FDA approved July 2011

  8. Using the same assumptions • Among HIV+ with CD4<100 cells/µL with CRAG+ prevalence of 8.8%: • To detect one CRAG+, the number need to screen was 11.3 (95% CI: 7.9-17.1) • To prevent one death, 15.9 people would need to be screened and treated

  9. Based on CRAG LFA cost of $2.50: • The cost of detecting one person with subclinical antigenemia with the LFA is $28.37 (95% CI: $20 to $43) • The cost of saving one life is $39.73 (95% CI: $28 to $60) • Assuming an average increase in life expectancy of 18 years for a 30yo Ugandan initiating ART with a CD4<100,* this is $2.21 per DALY saved * Mills EJ, Bakanda C, Birungi J, et al. Life expectancy of persons receiving combination antiretroviral therapy in low-income countries: a cohort analysis from Uganda. Ann Intern Med 2011; 155: 209-216

  10. Prevalence of asymptomatic antigenemia with corresponding cost per life saved based on LFA cost of $2.50 per test

  11. No CrAg Screening CrAg Latex Agglutination CrAg Lateral Flow Assay

  12. CRAG Screening is Cost Saving • Conversely, the cost of hospitalization and 14 days of amphotericin for treatment of cryptococcal meningitis is: • $425 per episode in Uganda • $2883 per episode in South Africa • Thus for the treatment costs of 1 cryptococcal meningitis episode, one could perform CRAG LFA screening on: • 170 persons in Uganda • 1153 persons in South Africa • Above a CRAG+ prevalence of 1%, pre-ART CRAG screening is Cost Savingcompared to the cost of amphotericin and CM treatment

  13. Conclusions • Targeted CRAG screening and preemptive fluconazole therapy is cost-saving to health care systems and should be integrated into routine HIV care for persons with CD4<100. • Better understanding of the implementation science is needed to determine how best to scale up CRAG screening and define optimal treatment.

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