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Antiretroviral Treatment M onitoring: A Canadian Ca se Example. Robert Hogg, PhD BC Centre for Excellence in HIV/AIDS Dept. of Health Care and Epidemiology University of British Columbia. British Columbia HIV/AIDS Drug Treatment Program.
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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
British ColumbiaHIV/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
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
Percent of persons first starting antiretroviral therapy on NNRTIs (Aug 1998 to Jan 2003)
Frequency Distribution (%) N 614 317 398 764 456 397 291 284 963 Therapy Start Time (year) Percent frequency distribution of initial antiretroviral regimens in British Columbia (1993-2001)
Progression to AIDS/Death No therapy Mono-therapy Dual-therapy % of patients progressing Triple therapy Months JAMA 1998 & CMAJ 1999
Updated from Hogg et al, Lancet, 1999 Deaths per 1,000 pts ever on therapy Number of Deaths Year By Quarters
Drug Costs Cost: 1992/93: $500,000 US 2003/3004: $30,000,000 US
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
When to start therapy in 2002 Recommendations > 30 K 5 to 30 K < 5 K Cells/mm3 Recommend < 350 Symptomatic Disease Type Recommend 350 to 500 200 cells/mm3 Based on CD4 decline, high viral load, patient interest, adherence potential, and risk of side effects > 200 cells/mm3 > 500 IAS-USA, JAMA, July 2002
Combined CD4 & HIV-RNA groupsHogg et al JAMA, 2001 Probablity of Survival (%) Time from Start of ARVs (mths)
CD4 groups stratified by adherence > 75% Adherent < 75% Adherent Probability of Survival (%) Probability of Survival (%) Time Since Start of ARVs Time Since Start of ARVs Wood et al. AIDS, 2003
NNRTI vs. PI: Time to Death Log-rank Probability of Survival (%) p = 0.252 Initial Regimen NNRTI PI Time from Start of ARVs (months) Hogg et al., IAS, 2002
Time to Switching Therapy log rank p<0.001 Probability of Adding/Switching ARV (%) Time from Start of ARVs (months)
Time to First Simultaneous Resistance to Antiretrovirals Probability of Detecting Resistance (%) Time from Start of Antiretrovirals(months) >=1C 1219 N= 873 743 621 488 N= 1219 >=2C 932 822 702 559 954 >=3C N= 1219 861 752 602 4C 959 873 772 623 N= 1219 Harrigan et al., IAS, 2003
Time to First Detection of Resistance to Each Class of Antiretrovirals Probability of Detecting Resistance (%) Time from Start of Antiretrovirals(months) N= 1219 (Lamiv) 899 783 662 528 (NNRTI) N= 712 1219 937 826 570 (NRTI) 730 N= 1219 935 839 580 (PI) N= 1219 741 947 848 591 Harrigan et al., IAS, 2003
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Impact of Various ART Strategies in South Africa 50 49 48 47 46 1999 2000 2001 2002 2003 2004 2005 Based on E Wood and P Braitstein et al. Lancet 2000 June 17;vol 355:2095-2100 25% Antiretroviral Therapy Use Life Expectancy at Birth No Therapy Year
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