Economic analysis of voluntary testing, counselling and referral (VTCR) for HIV in Portugal Julian Perelman, Joana Alves Escola Nacional de Saúde Pública Universidade Nova de Lisboa

Research team A project commissioned by the Coordenação Nacional para a Infecção VIH/SIDA Harvard Medical School Kenneth Freedberg, MD, MSc Elena Losina, PhD Rochelle Walensky, MD, MPH Madeline Di Lorenzo Ji-Eun Park Yale School of Public Health David Paltiel, PhD University of Lille Yazdan Yazdanpanah, MD, PhD Escola Nacional de Saúde Pública – UNL Julian Perelman, PhD Joana Alves, MA Céu Mateus, PhD João Pereira, PhD NHS hospitals - Portugal Kamal Mansinho, MD, and Ana Cláudia Miranda, MD (CH Lisboa Ocidental) Francisco Antunes, MD, PhD, and Manuela Doroana, MD (CH Lisboa Norte) Rui Marques, MD (H São João) José Saraiva da Cunha, MD, PhD, and Joaquim Oliveira, MD (HUC) José Poças, MD (CH Setubal) Eugénio Teófilo, MD (CH Lisboa Central)

Contribution of economic analysis Resources are scarce Choices must be made concerning their deployment Using resources in one setting: opportunity costs Economic evaluation of health care programs Economic analysis makes explicit the efficiency criteria Systematic comparison of costs and consequences “Value for money”

Contribution of economic analysis COSTA Treatment A CONSEQUENCESA Choice COSTB Treatment B CONSEQUENCESB Cost-effectiveness analysis links costs to a medical outcome: cost of achieving one additional unit of medical outcome, “cost per life-year gained”, “cost per QALY”

Contribution of economic analysis Some examples for HIV/AIDS Cost/QALY ZDV+3TC vs ZDV (Chancellor et al., 1997) £6,276 ZDV+3TC+ABC vs ZDV+3TC (Trueman et al., 2000) £10,254 HAART (2 NRTI + 1 PI) vs no treatment (Freedberg et al., 2001) $23,000 Personal risk assessment, counselling and education – gay and bissexual male adolescents (Tao et al., 1998) $6,180 Condom distribution – national US population (Pinkerton et al., 1999) Cost-saving Antenatal HIV screening (Ades et al., 1999) <£10,000 Expansion methadone maintenance program - IV drug users(Zaric et al., 2000) $10,900 Needle exchange program – IV drug users (Laufer et al., 2001) $20,947/case avoided

Rationale for a new HIV testing strategy Portugal Situation 31/12/2010: 39,347 diagnosed cases Diagnosed prevalence 18-69 yo: 0.48% Estimated undiagnosed prevalence 18-69 yo: 0.21% Europe 740,000 people living with HIV or AIDS No decrease in HIV incidence in the recent past Estimation: 30% undiagnosed cases

Source: European Commission - Public Health, 2010

Source: Health at a glance, OECD 2010 New cases per million, 2007

Rationale for a new HIV testing strategy Source: Health at a glance, OECD 2010

Rationale for a new HIV testing strategy Portugal France Mean CD4 at care initiation 292 372 Viral load at care initiation > 100,000 42.10% 18.75% 30,0001 - 100,000 23.71% 21.15% 10,001 - 30,000 14.03% 15.19% 3,001 - 10,000 8.22% 13.88% 501 - 3,000 4.76% 11.19% 20-500 19.84% < 20 2.41% 0.00%

Rationale for a new HIV testing strategy Proposal of a new HIV testing strategy in Portugal Testing at all health care settings as part of routine care All population Provider-initiated test (rapid test) Counselling of positive cases and linkage to care Voluntary (opting-out approach) Confidentiality and anonymity Voluntary provider-initiated HIV testing, counselling and referral (here-below “expanded testing”)

Rationale for a new HIV testing strategy Proposal of a new HIV testing strategy in Portugal Necessity to evaluate different strategies All population versus high-risk groups Whole country versus high-prevalence areas Screen once versus every year versus every 3, 5 or 10 years Screen at primary care centres versus emergency units Research project: evaluate the cost-effectiveness of different expanded testing strategies in Portugal

Cost-effectiveness of expanded testing Balancing costs and benefits Expanded testing Higher cost of testing, counselling and referral Earlier detection: Earlier treatment: Lower viral replication Less drug-related AE Lower costs (?) Higher life expectancy Better quality of life Lower rate of transmission Background strategy Lower cost of testing, counselling and referral Later detection: Later treatment: Higher costs (?) Lower efficacy Lower life expectancy Lower quality of life Higher rate of transmission

Cost-effectiveness of expanded testing Other less documented and measurable issues: HIV as “normal” disease Costs of waiting and costs of knowing How the test is performed (versus opportunity of testing) Confidentiality and anonymity Counselling and referral Anti-discrimination laws

Cost-effectiveness of expanded testing Widely published CEPAC* Monte Carlo simulation model of HIV acquisition/detection/care (see eg Paltiel et al., N Engl J Med 2005) Examine the impact of expanded screening in Portugal, compared to current risk-factor-based screening The model captures data on HIV screening: HIV prevalence and incidence, test offer/acceptance rates, returns for test results, linkage to care, and HIV counseling and testing costs HIV disease: incidence of opportunistic diseases, HIV treatment, mortality rates, and all associated costs and quality of life effects *Cost-effectiveness of Preventing AIDS Complications

Cost-effectiveness of expanded testing Primary HIV Infection Chronic HIV Infection Acute Clinical Event This figure depicts four general HIV disease states defined within this model, primary HIV infection, Chronic Infection, Acute Clinical Events, like an OI or a drug-related toxicity, and Death. Patients enter the model with primary infection as depicted in the upper left hand corner. After 1-2 months they transition to chronic HIV infection. In each month, they can remain in the Chronic State or transition to an acute clinical event or death. Patients who transition to the Acute State due to acute events, may likewise return to the Chronic HIV State, develop another acute event in the following month, or die. Within each state, the model tracks HIV RNA (current on therapy and setpoint); CD4 cell count (current and nadir); antiretroviral therapy (including success, failure, and prior regimen failure); use of resistance tests; history of opportunistic infections and use of prophylaxis; and treatment-related toxicity. Death The CEPAC Int’l Model Freedberg et al. Supported by NIAID 6

Cost-effectiveness of expanded testing Inputs required to estimate the CE of HIV expanded testing in Portugal Epidemiology of HIV: incidence/prevalence, undiagnosed prevalence, CD4 and viral load at detection Progression of disease and efficacy of treatments: international literature Treatment costs of HIV (by stage of disease), cost of testing and counselling, prices of anti-retroviral and prophylaxis drugs Behaviours: test acceptance and return rate, linkage to care, attitude towards risk and transmission of disease

Treatment cost of HIV/AIDS in Portugal

Cost-effectiveness of expanded testing Inputs for the CEPAC Model (1)

Cost-effectiveness of expanded testing Inputs for the CEPAC Model (2)

Cost-effectiveness of expanded testing Base Case Results (Costs and life expectancy discounted at 5%) All population (undiagnosed prevalence 0.21%) Scenario Life months Quality-adjusted life months Costs (€) 1 ICER (€/LY) 2 (€/QALY) 2 Current practice 193.11 192,98 980 - Screen once 193.14 193.01 1,070 33,865 38,601 Screen every 5 years 193.16 193.02 1,150 46,531 51,818 Screen annually 193.19 193.05 1,320 62,769 80,632 1. Costs rounded to nearest 10€. 2. ICERs rounded to nearest €/LY or €/QALY.

Cost-effectiveness of expanded testing Base Case Results (Costs and life expectancy discounted at 5%) Lisboa (undiagnosed prevalence 0.39%) Scenario Life months Quality-adjusted life months Costs (€) 1 ICER (€/LY) 2 (€/QALY) 2 Current practice 192.86 192.63 1,820 - Screen once 192.92 192.68 1,990 32,937 37,309 Screen every 5 years 192.96 192.71 2,120 43,120 46,627 Screen annually 193.02 192.77 2,390 52,357 61,002 1. Costs rounded to nearest 10€. 2. ICERs rounded to nearest €/LY or €/QALY.

Cost-effectiveness of expanded testing Cost-effectiveness of one-time expanded testing improves with higher estimated undiagnosed prevalence Lisboa 0.39%, Setúbal 0.33%, Porto 0.26%, Faro 0.26% Highly cost-effective among high-risk groups (undiagnosed prevalence >1%): MSM, IDUs Additional preliminary results for IDUs: testing cost-effective every 5 years

Undiagnosed Prevalence Yearly Incidence

Cost-effectiveness of expanded testing Cost-effectiveness of one-time HIV testing at different undiagnosed HIV prevalence values* Base Case *Costs and life expectancy discounted at 5%

Cost-effectiveness of screening strategies Cost/QALY Screening hypertension, asymptomatic men 20+ (Littenberg, Ann Intern Med 90) $80,400 Colon cancer, FOBT + SIG q5y, adults 50-85 (Frazier, JAMA 2000) $57,700 Biennal breast cancer screening, women 50-69 Biennal breast cancer screening, women 40-49 (Salzmann, Ann Intern Med 1997) (Salzmann, Ann Intern Med 1997) $21,400/LYG $105,000/LYG HPV vaccine at 12 and cytologic screening every 3y after 25 (Goldie, Journal Nacional Cancer Institute, 2004) $58,500

Cost-effectiveness of expanded testing Main limitations Disease transmission not accounted for. US results: 37,100$/QALY without transmission effect 30,800$/QALY with transmission effect Uncertainty for undiagnosed prevalence & incidence Use international published literature for quality of life Use data for specific settings: emergency rooms

Implicações para a tomada de decisão Valores razoáveis para um rastreio único e alargado, proposto pelo médico, acompanhado de aconselhamento e referenciação Valores aceitáveis para populações e regiões alvo IDUs de 5 em 5 anos MSM Regiões de alta prevalência: Lisboa, Setúbal, Porto, Faro Características do teste alargado Teste único e teste rápido ‘Opting-out’ e aconselhamento limitado a seropositivos Centros de saúde, internamentos e urgências Estimativas para o grupo 18-69 anos

Implicações para a tomada de decisão O que poderia ainda melhorar o custo-efectividade? Ter em conta a questão da transmissão Diminuição dos preços da medicação ART e teste confirmatório Melhor referenciação

International: US recommendations Source: CDC Recommendations 2006, Morbidity and Mortality Weekly Report, 22/9/2006, vol. 55, RR-14

International: French recommendations Source: Dépistage de l’infection VIH en France, Recommendations en Santé Publique, Haute Autorité de Santé, October 2009.

International: 3-country comparison Portugal France USA Undiagnosed prevalence 0.00210 0.00098 0.000768 Cost comparison CD4 test 36.20€ 21.60€ 48.57€ Viral load test 51.00€ 59.40€ 87.97€ Confirmation test 99.50€ 53.10€ 23.68€ Counselling 31.00€ 22.00€ 8.14€

International: 3-country comparison Line Portugal France USA 1. EFV + TDF/FTC 732.05 € 745.85 € 1,058.32 € 2. ATV/r + TDF/FTC 1,025.04 € 927.99 € 1,518.05 € 3. LPV/r + TDF/FTC + AZT 1,191.04 € 1,118.93 € 1,507.29 € 4a. RAL + OBR (2 NRTIs) + DRV/r - with truvada 2,086.11 € 1,999.79 €   1,946.92 € 4b. RAL + OBR (2 NRTIs) + DRV/r - with kivexa 1,942.40 € 5a.i. ENF + OBR (DRV/r + 2NRTIs) - with truvada 2,758.03 € 2,496.54 € 2,963.13 € 5a.ii. ENF + OBR (DRV/r + 2NRTIs) - with kivexa 2,614.32 € 5b. MVC + OBR (1 PI/r + 2NRTIs) +/- ENF - with trivuda 2,865.50 € 2,384.02 € 5b. MVC + OBR (1 PI/r + 2NRTIs) +/- ENF- with kivexa 2,721.79 € 6a. OBR (1 PI/r + 2NRTIs) - with trivuda 1,933.61 € 1,191.47 € 1,288.53 € 6b. OBR (1 PI/r + 2NRTIs) - with kivexa 1,789.90 €