cost effectiveness of cryptococcal antigen...

Cost effectiveness of Cryptococcalantigen screening in ART naïve PLWA

with CD4< 100cells/mm3

Dr.SriramaMedical Officer/ Research AssociateAsha Kirana Hospital, Mysore, India

Background

• Risk of Cryptococcal infection is high among PLHIV with CD4<100 cells/mm3.

[Oghomwen OF,et al,2012]

• Cryptococcal meningitis implies prolonged hospitalisation with mortality rate of 30-40% and thus high cost

[Lortholory O et al,2006]

• Cryptococcal antigen (CrAg), is detectable in the serum, 3 weeks before symptoms of meningitis appear

[David B et al,2010]

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Background Contd…

• HIV-infected persons with detectable serum CrAg have increased mortality when compared to CrAg-negative counterparts.

[“Liechty et al, 2007 ”]

• Pre-emptive treatment of serum CrAg-positive patients with fluconazole and anti-retroviral therapy has shown to improve survival

[“ Meya et al,2010’]

• This period of asymptomatic antigenemia provides opportunity to prevent fatal cryptococcal disease.

[“Rajasingham R et al,2012”]

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Presentator

Presentatienotities

However, the circumstances under which CrAg screening programs are cost effective are country-specific, as they depend not only on prevalence of cryptococcal disease, but also local drug costs and other aspects of treatment. Existing data demonstrating the cost effectiveness of CrAg screening programs are limited to studies from Uganda where costs and CrAg prevalence differ from those in Southeast Asia, and Cambodia, where a model with inputs that differ substantially from the WHO-recommended cryptococcal screening strategy was utilized. In India where cryptococcal infection is of medium prevalence there are no data on routine screening with cryptococcal antigen test, hence this is a study to do a cost effectiveness analysis of routine screening. However, the circumstances under which CrAg screening programs are cost effective are country-specific, as they depend not only on prevalence of cryptococcal disease, but also local drug costs and other aspects of treatment. Existing data demonstrating the cost effectiveness of CrAg screening programs are limited to studies from Uganda where costs and CrAg prevalence differ from those in Southeast Asia, and Cambodia, where a model with inputs that differ substantially from the WHO-recommended cryptococcal screening strategy was utilized. In India where cryptococcal infection is of medium prevalence there are no data on routine screening with cryptococcal antigen test, hence this is a study to do a cost effectiveness analysis of routine screening. However, the circumstances under which CrAg screening programs are cost effective are country-specific, as they depend not only on prevalence of cryptococcal disease, but also local drug costs and other aspects of treatment. Existing data demonstrating the cost effectiveness of CrAg screening programs are limited to studies from Uganda where costs and CrAg prevalence differ from those in Southeast Asia, and Cambodia, where a model with inputs that differ substantially from the WHO-recommended cryptococcal screening strategy was utilized. In India where cryptococcal infection is of medium prevalence there are no data on routine screening with cryptococcal antigen test, hence this is a study to do a cost effectiveness analysis of routine screening.

Background contd…

CrAg screening programs depend on - Prevalence of the disease- Cost effectiveness(country specific)- India – no data on routine screening with

CrAg test and cost effectiveness

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Objectives

• To assess the point prevalence of asymptomaticcryptococcal infection among ART naive ,CD4<100

cells/mm3

• To do a cost effectiveness analysis of routine

screening for cryptococcal antigen

Materials & MethodsRetrospective cross sectional chart review of all the

patients hospitalized with Cryptococcal Meningitis(N=35) –

ARM-A & 560 patients- ARM – B(Screened Group)

registered for HIV care from 01/07/2012 to 30/06/2015.

Inclusion criteria for ARM - B:• ART naïve• CD4<100cell/mm3• Asymptomatic Exclusion criteria for ARM-B:• <18 years of age• H/o Cryptococcal disease

Definitions• For the cost-effectiveness model, CM is defined as a

positive lumbar puncture (LP) in any patient, regardless of symptoms. Isolated serum CrAg positivity, or asymptomatic cryptococcal antigenemia, is defined as a positive serum LFA result for CrAg in the absence of a positive LP.

• We used WHO’s Choosing Interventions that are Cost Effective (CHOICE) guidelines to evaluate cost-effectiveness.

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Cost Estimates

Costs included

• clinic visits• personnel time –physician care, hospitalization & nursing• diagnostic tests, • follow-up

Costs not included• CD4 testing, • the initial clinic visit for enrollment in HIV care,• subsequent cost of ART were not included.

Presentator

Presentatienotities

Treatment of isolated serum CrAg positivity was based on the WHO guidelines and includes one year of fluconazole: 800 mg/day for two weeks, followed by 400 mg/day for eight weeks, followed by 200 mg/day maintenance . Clinical cost estimates, including the cost of clinic visits, personnel time, diagnostic tests, hospitalization, and follow-up were provided by Ashakirana Charitable trust managing the hospital All direct costs, including physician care, hospitalization, and nursing care, were incorporated into the model. Indirect costs were also included in this analysis. Costs of CD4 testing, the initial clinic visit for enrollment in HIV care, and subsequent cost of ART were not included, as those do not represent additional costs to the system. Costs were not discounted in this model as they accrued over less than a one-year time horizon

Statistical analysis

• Point prevalence of asymptomatic cryptococcal infection was

assessed.

• Number Needed to Screen(NNS) was calculated

• Incremental cost-effectiveness of a CrAg screening program

was compared to patients directly presenting with

Cryptococcal Meningitis

• Incremental Cost Effectiveness Ratio (ICER) determined

Presentator

Presentatienotities

= Total #of patients undergoing screening= { #of CM cases (or deaths) without screening - #of CM cases (or deaths) with screening} Average age at diagnosis of CM was derived from the literature [29], as was life expectancy of HIV-infected persons on ART with CD4,100 cells/mm3 [30,31]. Undiscounted life-years gained (LYG) were calculated by multiplying excess deaths from CM by years of life gained when a screened patient did not die from CM. We calculated the incremental cost effectiveness ratio (ICER) of screening as the excess cost associated with screening divided by the number of LYG through screening. ICER of screening as the excess cost associated with screening divided by the number of LYG through screening

Results

N= 560

Mean Age : 39.9yrs, Male: 63.8%, Female : 36.2%

• The prevalence of Cryptococcal antigenemia - 9.7%

4.5 % - Positive CSF CrAg

5.2%-Positive Serum CrAg (isolated Cryptococcal antigenemia)

Contd….

• The Incremental cost effectiveness ratio(ICER) for the

screening program is 616 US$ /death averted .

• The number needed to screen(NNS) to prevent

one case of Cryptococcal Meningitis is 56.

• The number needed to screen(NNS) to prevent

one death from Cryptococcal Meningitis is 3112

Cost in USD

Mead Duration of Hospital Stay

Treatment Outcome 3 month FollowupTreatment Outcome

Died Eventfulrecovery

Uneventful recovery

Died Eventfulrecovery

Uneventful recovery

ARM - A 10069 12.8 18(51%)

17(49%) 0 1(2.9%)

12(34.3%)

6(17.1%)

ARM - B 12331 5.13 0 0 54(100%)

1(1.8%)

0 53(98.15%)

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Summary• Prevalence rates of Cryptococcal infection in asymptomatic

HIV infected patients in India - 9.8% .

• In our study ICER of 616 US$/death averted is far less than India’s average Gross Domestic Product(GDP) per capita by the world bank for the same period (1,498.87 US$) making the screening program very cost effective as per WHO CHOICE guidelines.

• We recommend Cryptococcal antigen screening to be included in India’s National AIDS Program

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Presentator

Presentatienotities

WHO-CHOICE guidelines consider a very cost-effective intervention to be one in which the incremental cost-effectiveness ratio is less than the GDP per capita in the respective WHO region [23}

Cr Ag screening(in CD4 < 100) will save lives & minimize morbidity at a reduced cost because it is very cost effective…

DisclosurePresenting author or Co-authors do not have any stake holding nor

have availed financial grants from any pharmaceutical companies.

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My special thanks to Team Asha Kirana

References:

1. David B Meya YCM, Barbara Castelnuovo, Bethany A Cook, Ali M. Elbireer1,, AndrewKambugu1,, Moses R Kamya1,, Paul R Bohjanen4, and David RBoulware. SerumCryptococcal Antigen (CRAG) Screening is a Cost-Effective Method to Prevent Death inHIV- infected persons withCD4 ≤100/μL starting HIV therapy in Resource-Limited SettingsClin Infect Dis 2010; 51(4): 448–55.

2. Jarvis JN, Lawn SD, Vogt M, Bangani N, Wood R, Harrison TS. Screening for cryptococcalantigenemia in patients accessing an antiretroviral treatment program in South Africa.Clinical infectious diseases : an official publication of the Infectious Diseases Society ofAmerica 2009; 48(7): 856-62.

3. Smith RM, Nguyen TA, Ha HT, et al. Prevalence of cryptococcal antigenemia and cost-effectiveness of a cryptococcal antigen screening program--Vietnam. PloS one 2013; 8(4):e62213.

4. World Health Organisation. Prevention, screening and management of commoncoinfections. Consolidated ARV guidelines. 2013.

5. 5. Govender N, Chetty V, Roy M, Chiller T, Oladoyinbo S, et al. (2012) PhasedImplementation of Screening for Cryptococcal Disease in South Africa. South AfricanMedical Journal 102: 914–917.

6. Liechty CA, Solberg P, Were W, Ekwaru JP, Ransom RL, et al. (2007) Asymptomatic serumcryptococcal antigenemia and early mortality during antiretroviral therapy in rural Uganda.Trop Med Int Health 12: 929–935.

7. Jarvis JN, Lawn SD, Vogt M, Bangani N, Wood R, et al. (2009) Screening for cryptococcalantigenemia in patients accessing an antiretroviral treatment program in South Africa. ClinInfect Dis 48: 856–862.

8. Meya DB, Manabe YC, Castelnuovo B, Cook BA, Elbireer AM, et al. (2010) Cost-effectiveness of serumcryptococcal antigen screening to prevent deaths among HIV-infected persons with a CD4+ cell count ,or = 100 cells/microL who start HIV therapy in resource-limited settings. Clin Infect Dis 51: 448–455.

9. Rajasingham R, Meya DB, Boulware DR (2012) Integrating cryptococcal antigen screening and pre-emptive treatment into routine HIV care. J Acquir Immune Defic Syndr 59: e85–91.

10. Micol R, Tajahmady A, Lortholary O, Balkan S, Quillet C, et al. (2010) Cost-effectiveness of primaryprophylaxis of AIDS associated cryptococcosis in Cambodia. PLoS One 5: e13856.

11. Micol R, Lortholary O, Sar B, Laureillard D, Ngeth C, et al. (2007) Prevalence, determinants ofpositivity, and clinical utility of cryptococcal antigenemia in Cambodian HIV-infected patients. J AcquirImmune Defic Syndr 45: 555–559.

12. Kendi C, Penner J, Otieno B, Odhiambo N, Bukusi E, et al. Routine cryptococcal screening and treatmentin Kenya: outcomes after six months of follow up; 2011; Rome, Italy.

13. Osazuwa F, Dirisu JO, Okuonghae PE, Ugbebor O (2012) Screening for cryptococcal antigenemia in anti-retroviral naive AIDS patients in benin city, Nigeria. Oman Med J 27: 228–231

14. Roy M, Chiller T (2011) Preventing deaths from cryptococcal meningitis: from bench to bedside. ExpertRev Anti Infect Ther 9: 715–717.

15. Organization WH (2001) Macroeconomics and health: investing in health for economic development. Report of the commission on macroeconomics and health.

16. Organization WH (2012) Table: Threshold values for intervention cost-effectiveness by Region.

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cost effectiveness of cryptococcal antigen...

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