1. The clinical and economic impact of interventions to prevent loss to follow- up (LTFU) in resource-limited settings Elena Losina, Hapsatou Touré, Lauren Uhler, Xavier Anglaret, A. David Paltiel, Eric Balestre, Rochelle Walensky, Eugène Messou, Milton Weinstein, François Dabis, Kenneth Freedberg for the CEPAC International and ART-LINC investigators Supported by NIAID and the ANRS

2. Background Nearly 4 million people have started ART 10-51% of patients in ART programs in Africa have been lost to follow up at one year Most interventions focus on patients lost after starting ART Many of these patients develop OIs or die before returning to care

3. Background Preventing LTFU could be more effective than efforts to find patients No LTFU prevention studies have been reported from resource-limited settings –Questions of efficacy and cost

4. Cost-effectiveness analysis and modeling Evaluating clinical trial results for policy “What if” analyses –Provide targets for efficacy and cost, before studies are done –To understand how interventions might have a role in HIV care

5. Objective To conduct a “what if” analysis to project the survival gains and cost-effectiveness of interventions to prevent LTFU in Côte d’Ivoire

6. Cost-effectiveness of Preventing AIDS Complications (CEPAC) International Model Detailed simulation model of HIV disease Key elements of natural history and treatment Outcome is the cost-effectiveness ratio – a measure of value for money ($/YLS) “Value” highlighted by Stefano Bertozzi

7. WHO Commission on Macroeconomics and Health – –If ratio <3x per capita GDP, cost-effective – –If ratio <1x per capita GDP, “very” cost-effective – –Côte d’Ivoire per capita GDP (2007) was $940 – –3X GDP was $2820 What is a Cost-effective Intervention? IMF 2007

8. Clinical Data Aconda program, Côte d’Ivoire –CePReF, Abidjan, dedicated HIV treatment center 3,500 HIV-infected patients –18 primary health centers, not HIV-specific 6,700 HIV-infected patients Mean CD4 at presentation: 140/μl Cumulative LTFU 1 year after ART initiation –11% at CePReF –18% in the primary health centers Touré, AIDS 2008

9. Cost Data Aconda program ART regimens –$60/year 1st-line NNRTI-based –$670/year 2nd-line PI-based Mean medical cost/person/year on ART $820

10. Four LTFU Prevention Interventions Intervention Individual ($/person/year) Combined ($/person/year) 1.Elimination of ART co- payments $22 2.Providing OI medications free to patients $19$ 41 3.Increased training for health care workers $12$ 53 4.Transportation to clinic and breakfast $24$ 77

11. Results: Projected Life Expectancy with HIV

13. 6.36

14. Results: Years of Life Lost from LTFU in Aconda General health clinics –6,700 patients –18% LTFU at 1 year –6.36 years per person lost –6,700 X 18% X 6.36 years = 7,670 years of life lost

15. Results: No ART co-payments, $22 Strategy Life Expectancy (years) Lifetime Costs ($) C-E Ratio ($/YLS) No intervention10.928,800--- $22 Intervention efficacy* 10%11.039,1003,100 25%11.209,3001,800 50%11.499,6001,400 75%11.789,9001,200 *% reduction in LTFU at 1 year (baseline LTFU = 18%)

16. Results: Efficacy and Cost of the Interventions Reduction in LTFU Cost-effectiveness ratio ($/YLS) X

17. Baseline Rates of LTFU Settings with highest rates of LTFU have the most to gain from effective interventions. Even in settings with moderate LTFU rates, interventions to decrease LTFU may be cost- effective.

18. Limitations Costs were projected from estimates of interventions in Abidjan, not from tested interventions Analysis did not include: –LTFU after the 1 st year –Sustainability 3X GDP threshold: –International commitment and partnerships in HIV care and financing

19. Conclusions Loss to follow-up from HIV treatment programs in resource-limited settings results in substantial decreases in life expectancy. Interventions to prevent LTFU in these settings, if moderately effective, would be cost- effective by international criteria.

20. The ART-LINC Collaboration of IeDEA PrincipaI investigators : François Dabis, Matthias Egger, Mauro Schechter Central Team: Eric Balestre, Martin Brinkhof, Claire Graber, Olivia Keiser, Catherine Seyler, Hapsatou Touré, Charlotte Lewden Steering Group: Kathryn Anastos (Kigali); David Bangsberg (Mbarara/ Kampala); Andrew Boulle (Cape Town); Jennipher Chisanga (Lusaka); Eric Delaporte (Dakar); Diana Dickinson (Gaborone); Ernest Ekong (Lagos); Kamal Marhoum El Filali (Casablanca); Mina Hosseinipour (Lilongwe); Silvester Kimaiyo (Eldoret); Mana Khongphatthanayothin (Bangkok); N Kumarasamy (Chennai); Christian Laurent (Yaounde); Ruedi Luthy (Harare); James McIntyre (Johannesburg); Timothy Meade (Lusaka); Eugene Messou (Abidjan); Denis Nash (New York); Winstone Nyandiko Mokaya (Eldoret); Margaret Pascoe (Harare); Larry Pepper (Mbarara); Papa Salif Sow (Dakar); Sam Phiri (Lilongwe); Mauro Schechter (Rio de Janeiro); John Sidle (Eldoret); Eduardo Sprinz (Porto Alegre); Besigin Tonwe-Gold (Abidjan); Siaka Touré (Abidjan); Stefaan Van der Borght (Amsterdam); Ralf Weigel (Lilongwe); Robin Wood (Cape Town)

21. The CEPAC International Team United States Elena Losina, PhD Rochelle Walensky, MD, MPH Melissa Bender, MD John Chiosi, BS Andrea Ciaranello, MD, MPH Jennifer Chu, BSc Kenneth Freedberg, MD, MSc Sue Goldie, MD, MPH April Kimmel, MSc Julie Levison, MD, MPhil Bethany Morris, BA A. David Paltiel, PhD Mai Pho, MD Erin Rhode, MS Callie Scott, MSc George Seage, III, PhD Caroline Sloan, AB Adam Stoler, MA Lauren Uhler, BA Milton Weinstein, PhD Côte d’Ivoire Xavier Anglaret, MD, PhD Eugène Messou, MD Catherine Seyler, MD, MSc Christine Danel, MD, PhD Eric Ouattara, MD, MPH Siaka Touré, MD, MPH Hapsatou Touré, MD, MPH France Yazdan Yazdanpanah, MD, PhD Sylvie Deuffic-Burban, PhD Delphine Gabillard, PhD South Africa Neil Martinson, MBBCh, MPH Robin Wood, MD India Nagalingeswaran Kumarasamy, MD Kenneth Mayer, MD Soumya Swaminathan, MD Supported by NIAID and the ANRS

23. Results: Efficacy and Cost of the Interventions Reduction in LTFU Cost-effectiveness ratio ($/YLS)

24. Two different outcome measures – –Cost: $, other currency – –Effectiveness: years of life saved (YLS) or quality-adjusted life-years (QALYs) Cost-effectiveness ratio: Additional Resource Use Additional Health Benefits Represents the value of resources spent ($/YLS) Cost-effectiveness Analysis