1. Antiretroviral Treatment Monitoring: A Canadian Case Example Antiretroviral Treatment Monitoring: A Canadian Case Example Robert Hogg, PhD BC Centre for Excellence in HIV/AIDS Dept. of Health Care and Epidemiology University of British Columbia

2. British Columbia HIV/AIDS Drug Treatment Program In BC antiretrovirals have been centrally distributed free of charge to eligible HIV+ individuals since 1986 In October 1992, the HIV/AIDS Drug Treatment Program became the responsibility of the BC Centre for Excellence Ever enrolled over 6,500 and 2,800 currently on therapy

3. Monitoring and Evaluation Patient, Physician and geographical characteristics Antiretroviral therapy dispensing information Sociodemographic and adherence-related data Clinical and laboratory data, including CD4 and plasma viral load Morbidity and mortality data updated through linkages Antiretroviral resistance Adherence measures

6. Percent of persons first starting antiretroviral therapy on NNRTIs (Aug 1998 to Jan 2003)

7. Nevirapine use in British Columbia (Jan 2002 to Jan 2003)

9. Percent frequency distribution of initial antiretroviral regimens in British Columbia (1993-2001) Frequency Distribution (%) Therapy Start Time (year) N 614317398 963 764456397291284

10. Progression to AIDS/Death Months % of patients progressing JAMA 1998 & CMAJ 1999 No therapy Mono-therapy Dual-therapy Triple therapy

11. Deaths per 1,000 pts ever on therapy Number of Deaths Year By Quarters Updated from Hogg et al, Lancet, 1999

12. Drug Costs Cost: 1992/93: $500,000 US 2003/3004: $30,000,000 US

13. Antiretroviral cohorts International (PLATO, ART collaborative study) First start (HOMER) Mega HAART Women STI IDU (BART)

14. HAART Observational Medical Evaluation and Research (HOMER) Study Population-based study of HIV+ men and women in the Drug Treatment Program Aged 18 years and over Antiretroviral naive First prescribed triple therapy (2 NRTIs and either a PI or an NNRTI) between August 1, 1996 and September 30, 1999 HOMER

15. Disease Type Disease Type Recommendations Recommendations Cells/mm3 < 5 K 5 to 30 K > 30 K < 350 350 to 500 > 500 Recommend Recommend Based on CD4 decline, high viral load, patient interest, adherence potential, and risk of side effects Symptomatic  200 cells/mm 3 > 200 cells/mm 3 IAS-USA, JAMA, July 2002 When to start therapy in 2002

16. Combined CD4 & HIV-RNA groups Hogg et al JAMA, 2001 Probablity of Survival (%) Time from Start of ARVs (mths)

17. CD4 groups stratified by adherence Time Since Start of ARVs Probability of Survival (%) Wood et al. AIDS, 2003 < 75% Adherent> 75% Adherent Probability of Survival (%)

18. Wood et al. AIDS, 2003

19. NNRTI vs. PI: Time to DeathPI NNRTI Initial Regimen Probability of Survival (%) p = 0.252 Log-rank Time from Start of ARVs (months) Hogg et al., IAS, 2002

20. Time to Switching Therapy Probability of Adding/Switching ARV (%) Time from Start of ARVs (months) log rank p<0.001

21. Time to First Simultaneous Resistance to Antiretrovirals Probability of Detecting Resistance (%) 4C >=3C >=2C >=1C N= 1219 959873772623 1219 954 861752602 1219 873743621488 1219 932822702559 Time from Start of Antiretrovirals(months) Harrigan et al., IAS, 2003

22. Time to First Detection of Resistance to Each Class of Antiretrovirals Probability of Detecting Resistance (%) (Lamiv) (NNRTI) (NRTI) (PI) N= 1219 899783662528 1219937826 712 570 1219 947848 741 591 1219935839 730 580 Time from Start of Antiretrovirals(months) Harrigan et al., IAS, 2003

23. Donald Rumsfeld Clarifying US Policy on the war on terror Newsweek, March 10, 2003 “There are known knows. These are things we know that we know. There are known unknowns. That is to say, there are things that we know we don’t know. But these are also unknown unknowns. There are things we don’t know we don’t know.”

24. Human security?

25. Based on E Wood and P Braitstein et al. Lancet 2000 June 17;vol 355:2095-2100 1999200020012002200320042005 46 47 48 49 50Year Life Expectancy at Birth No Therapy 25% Antiretroviral Therapy Use Impact of Various ART Strategies in South Africa

26. Acknowledgements Michael O’Shaughnessy Paula Braitstein Richard Harrigan Nada Gataric Julio Montaner Benita Yip Keith Chan Evan Wood Michael Smith Foundation for Health Research The Canadian Institutes of Health Research BC Centre for Excellence in HIV/AIDS