1. Results Introduction Background and Objectives  Identifying effective and cost-effective ways to improve adherence to antiretroviral therapy (ART) is critical to maximize the benefits of therapy and use scarce resources most efficiently  Few rigorous ART adherence interventions have been evaluated in low-resource settings; even when effective, few include a cost-effectiveness analysis  Reviews indicate that previous cost-effectiveness analyses of adherence-enhancing interventions are too few in number, use weak methods and poor cost data, and fail to provide complete, clear results 1,2  We aimed to analyze the costs and cost- effectiveness of a highly effective ART adherence intervention conducted in a low-resource setting Methods  We found that an intervention using EDM feedback to inform counseling can improve ART adherence to optimal levels in Chinese patients at a low incremental cost ($247/patient)  Compared to average annual cost of providing ART to a patient in China (estimated at over $2,000), and the social costs of poor adherence, this intervention may be considered a good use of scarce resources  We recommend further analysis of ART adherence interventions and scale-up of those found to be cost-effective in order to treat rising numbers of ART patients most efficiently Cost-effectiveness of Improving Adherence to Antiretroviral Therapy Using Electronic Drug Monitor Feedback among HIV-Positive Patients in China: The Adherence for Life (AFL) Study Lora Sabin, 1,2 Mary Bachman DeSilva, 1,2 Xu Keyi, 3 Davidson H Hamer, 1,2,4,5 Kee Chan, 6 and Christopher J. Gill 1,2 1 Center for Global Health and Development, Boston University, Boston, MA, U.S.A.; 2 Department of International Health, Boston University School of Public Health, Boston, MA, U.S.A.; 3 WHO Collaborating Center for Comprehensive Management of HIV Treatment and Care, Ditan Hospital, Beijing, China; 4 Zambia Centre for Applied Health Research and Development, Lusaka, Zambia; 5 Infectious Diseases Section, Department of Medicine, Boston University School of Medicine, Boston, MA, U.S.A.; 6 Department of Health Sciences, Sargent College of Health and Rehabilitation, Boston University, Boston, MA, U.S.A.  China has one of Asia’s most serious HIV epidemics, with ≈ 740,000 people living with HIV and tens of thousands of new infections occurring annually  Few rigorous ART adherence intervention studies have been assessed in China  In the “Adherence for Life” (AFL) study, we assessed an intervention that involved integrating electronic drug monitor (EDM, via eCAPs) data into HIV clinical care—a process we term ‘EDM feedback’—on ART adherence  The results showed a significant improvement in mean ART adherence in intervention patients 3 AFL Study Site  Dali 2nd People’s Hospital HIV Clinic, in Dali Old City, Yunnan Province, China  Semi urban area, population mainly from Bai minority  Most HIV infections contracted via injection drug use (IDU) AFL Intervention Design  80 ART patients were enrolled, given eCAPs  Subjects stratified into high vs. low adherence groups (based on mean adherence ≥95% in Months 1-5), and randomized in each stratum to intervention or control  Intervention subjects: received EDM adherence data at 6 monthly visits; if adherence was ‘sub-optimal’ (<95%) in previous month, counseled by a clinician using EDM report; otherwise, counseling was optional  Controls: continued standard of care, received counseling if self-reported adherence in previous month was <95%  Adherence measure: incorporated +/- 1 hour dose window, found to be best predictor of CD4 and undetectable VL 4 AFL Intervention Effect  At month 12, mean adherence was 96.5% in intervention subjects vs. 84.5% in controls (P-value = 0.003)  Intervention effect largely due to a sharp increase in adherence in previously low adherers (Figure 1)  EDM feedback associated with mean CD4 change (+90 cells/ul in intervention subjects vs. -9 cells/ul in controls (P-value = 0.020)) Analytic Methods  Calculated AFL’s financial and economic costs, forecasted economic cost of a 1-year intervention in 2012 among 500 patients, typical size of an ART clinic in China Financial analysis: included all project expenditures: 1) equipment & supplies (EDM scanner, eCAPs, user guide); 2) training in eCAP use; 3) shipping; 4) price cuts provided by eCAP supplier  Excluded: 1) all research-related costs; 2) control group costs; 3) clinicians’ time (counseling fit into regular workday)  China-based costs were converted to US$ (2007 exchange rate), then added to nominal US$ costs Economic analyses: to capture societal costs, included: 1) project coordinator/clinicians’ time; 2) opportunity cost of patients’ time for orientation and counseling, valued at mean patient income; 3) full costs (no price cuts) Economic analysis of forecasted 1-year program: 1) no US personnel; 2) addition of local project manager; 3) addition of counselors to orient and counsel patients  All costs adjusted to 2012 prices Cost effectiveness analysis (CEA):  Estimated incremental cost per change from sub-optimal to optimal adherent patient during 6-month program using standard formula: ICEA=(C I –C C )/(A I –A C ), (C=total costs; A=change in optimal adherent patients (≥95%); and I/C =intervention/control  Change in adherence based on AFL’s effect size (difference between intervention and control groups in net change in patients with optimal adherence, capturing both increase in intervention arm and avoided loss in control arm  Uncertainty assessed using sensitivity analysis Acknowledgements Thanks to: Mary Jordan, Billy Pick, David Stanton, Neal Brandes, Connie Osborne, Ray Yip, Ira Wilson, and staff at Med-ic, and our deep appreciation to the medical staff at the Dali Second People’s Hospital and the Dali-based HIV/AIDS patients who participated in the AFL study. Conclusions Dali China Costs  Estimated financial and economic costs of AFL were $7,943 and $9,065 (2007 US$), respectively, or $732 and $836 per patient  Fixed costs accounted for 75% of total costs  For 2012 scaled-up 1-year program, total and per patient costs were $42,222 and $84 (2012 US$) (Table 1) Sensitivity Analysis  Cost-effectiveness most sensitive to variation in effect size, number of patients participating, and cost of eCAPs  If intervention effect increased to 45%, cost per adherent patient falls by 25%  If unit price of eCAPs increased by 1/3, to $80, cost per adherent patient rises 25%.  Other cost variables, such as cost of EDM scanner, and assumptions such as time spent on counseling, do not greatly affect cost-effectiveness Figure 1: Monthly mean adherence in AFL subjects, stratified by mean adherence in pre- intervention period: high (≥95%) vs. low (<95%) Table 2: Results of one-way sensitivity analysis on the incremental cost of moving an ART patient from sub- optimal adherence to optimal adherence (≥95%) Citations 1.Elliott RA, Barber N, Horne R. Cost-effectiveness of adherence-enhancing interventions: a quality assessment of the evidence. Ann Pharmacother 2005;39(3):508-15. 2.Rosen AB, Spaulding AB, Greenberg D, Palmer JA, Neumann PJ. Patient adherence: a blind spot in cost-effectiveness analyses? Am J Manag Care 2009;15(9):626-32. 3.Sabin LL, Desilva MB, Hamer DH, et al. Using Electronic Drug Monitor Feedback to Improve Adherence to Antiretroviral Therapy Among HIV-Positive Patients in China. AIDS Behav 2009. 4.Gill CJ, Sabin LL, Hamer DH, et al. Importance of dose timing to achieving undetectable viral loads. AIDS Behav 2009; Published online: April 8, 2009. Cost-effectiveness (see Table 1)  Cost per newly optimally adherent patient in AFL trial: $732 (financial analysis) and $836 (economic analysis)  Cost per newly optimally adherent patient in projected 10–year program: $249 Table 1: Costs and cost-effectiveness of AFL intervention