Treatment as Prevention: HAART Expansion - A Powerful Strategy to Reduce AIDS Morbidity and Mortality and HIV Incidence - World Health ...
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Treatment as Prevention: HAART Expansion - A Powerful Strategy to Reduce AIDS Morbidity and Mortality and HIV Incidence Julio Montaner MD, FRCPC, FCCP, FRSC Director, BC-Centre for Excellence on HIV/AIDS, Providence Health Care Professor of Medicine and Head, Division of AIDS, University of British Columbia President, International AIDS Society UNAIDS, Geneva, March 24th 2010 British Columbia Centre for Excellence in HIV/AIDS
USA - Trends in Annual Rates of Death Ages 25 to 44 40 Unintentional Deaths per 100,000 Population injury 35 Cancer 30 Heart 25 disease Suicide 20 15 HIV infection 10 Homicide 5 Chronic liver disease 0 Stroke 82 84 86 88 90 92 94 Diabetes Year
Vancouver 1996 “One World One Hope” % Progression to AIDS in 3 yrs Plasma Viral Load, a strong Predictor of outcome in CD4+ 100 cells/µL > 750 HIV Infected Individuals 80 501-750 351-500 60 201-350 < 200 40 High Plasma Viral Load: Poor Prognosis 20 Low Plasma Viral Load: Good Prognosis 0 > 30 10-30 3-10 0.5-3 < 0.5 Plasma HIV RNA (thousand copies/mL) J Mellors et al. Annals 1997
Montaner et al JAMA, March 25th 1998 Vancouver 1996 “One World One Hope” AZT + NVP AZT + ddI % Progression to AIDS in 3 yrs 100 CD4+ cells/µL Triple Therapy: AZT + ddI + NVP > 750 80 501-750 351-500 60 201-350 < 200 Gulick et al; JAMA, July 1, 1998 40 0 20 Change in Viral Load 0 > 30 10-30 3-10 0.5-3 < 0.5 -1 Plasma HIV RNA (thousand copies/mL) Dual Therapy Regimens J Mellors et al. Annals 1997 -2 Triple Therapy: AZT+3TC+IDV -3 0 52 Study Weeks
Impact of HAART in BC-CfE 140 Death Rate per 1000 120 Greater than 85% reduction 100 in death rate among those 80 engaged in care 60 40 20 0 1993-94 1995-96 1997-98 1999-00 2001-02 2003-04 Modified from Hogg et al, Lancet. 2009
Impact of HAART in BC-CfE 140 Death Rate per 1000 35 Life Expectancy at age 20 120 30 100 25 80 20 60 15 40 10 20 5 0 0 1993-94 1995-96 1997-98 1999-00 2001-02 2003-04 1993-94 1995-96 1997-98 1999-00 2001-02 2003-04 Modified from Hogg et al, Lancet. 2009
HAART Can Reduce HIV Transmission HAART stops HIV replication ↓ HIV levels fall to undetectable in blood as well as in sexual fluids ↓ Sharp reduction in HIV transmission
Prevention Strategies - Education - Change in behavoir - Harm reduction - New strategies/technology - Vaccines Existing strategies have failed to contain the global HIV pandemic
Vertical Transmission Canada, 1990 to 2008 Modified from Alimenti et al CAHR, 2009
Discordant Couples S Attia, M Egger, M Muller, M Zwahlen and N Lowa. AIDS. 2009 Jul 17;23(11):1397-404
Discordant Couples Studies of heterosexual discordant couples observed no transmission in patients treated with ART and with viral load below 400 c/ml, but data were compatible with one transmission per 79 person-years. S Attia, M Egger, M Muller, M Zwahlen and N Lowa. AIDS. 2009 Jul 17;23(11):1397-404
B&M Gates Fdn: HIV Transmission Risk in Heterosexual Serodiscordant Couples 3,400 couples In 7 African countries All counseled and given free condoms HAART initiated based on CD4 count eligibility Over the next 1 to 3 years, 103 new HIV infections All but 1 infection occurred in the untreated couples Estimated 92% reduction of HIV transmission by HAART Unadjusted relative risk: 0.17 (95% CI: 0.004-0.94; P = .037) Adjusted relative risk: 0.08 (95% CI: 0.002-0.57; P = .004) Adjusted for visit and CD4+ cell count at initiation Donnell D, et al. CROI 2010. Abstract 136.
B&M Gates Fdn: HIV Transmission Risk in Heterosexual Serodiscordant Couples 3,400 Morecouples recentlyInan7email Africanhascountries been circulated saying that: All “counseled The singleand case of transmission given free condoms involved a man who initiated ARVs 18 days before his 12-month HAART study initiated visit. At this based visit hisonpartner CD4 count testedeligibility positive for HIV, Over the next having 1 tobeen negative 3 years, at month 103 new 9.” HIV infections All but 1 infection occurred in the untreated couples Estimated 92% reduction of HIV transmission by HAART Unadjusted relative risk: 0.17 (95% CI: 0.004-0.94; P = .037) Adjusted relative risk: 0.08 (95% CI: 0.002-0.57; P = .004) Adjusted for visit and CD4+ cell count at initiation Donnell D, et al. CROI 2010. Abstract 136.
Wood et al, BMJ, 2009
Wood et al, BMJ, 2009 Whiskers represent 95% confidence intervals.
Wood et al, BMJ, 2009 Whiskers represent 95% confidence intervals.
Wood et al, BMJ, May 16, 2009
Impact of HAART in BC-CfE Frequency of people 6 months Baseline Plasma Viral Load (log10 copies/mL) Distribution Modified from Anema et al. EIDJ 2009
Impact of HAART in BC-CfE Frequency of people Baseline 24 months Plasma Viral Load (log10 copies/mL) Distribution Modified from Anema et al. EIDJ 2009
New HIV and Syphilis in BC Rate per 100,000 population M REKART, BC-CDC, 2006
New HIV and Syphilis in BC Rate per 100,000 population M REKART, BC-CDC, 2006
Cost-Effectiveness of HAART BC-DTP “HIV deficit” in BC in 2005: 400 Cost of Medical Management of 1 HIV infection over a lifetime = $250,000 800 cases per year Averted lifetime Rx cost up to 2001 US $96.4M A total of 3,963 pts were on HAART in BC in 2005 400 cases per year Total actual drug cost (using patented drugs) in 2005 $49 million US
Cost-Effectiveness of HAART BC-DTP “HIV deficit” in BC in 2005: 400 Cost of Medical Management of 1 HIV infection over a lifetime = $250,000 Averted lifetime Rx cost up to U$A 100M A total of 3,963 pts were on HAART in BC in 2005 Total actual drug cost (using patented drugs) in 2005 U$A 50M
The Bc-CfE Mathematical Model Viviane D. Lima et al JID 2008
Adhe re nc e : 0 % -
Incremental net benefit (Millions of CDN $) over 30 years Overall population and patient-centered Net Benefit (million $ Can 2005) 800 Overall Population Patient-Centered incremental net benefit of 600 increasing uptake of HAART from 50% to 75% 400 over 30 years, based on a 200 willingness-to-pay thresholds of $50,000 per 0 0 5 10 15 20 25 30 quality-adjusted life year. Time (years) K Johnston et al, submitted, 2010
Summary HAART is widely regarded as a cost effective, life- saving strategy ↓ Mortality of treated HIV/AIDS patients ↓ Morbidity of treated HIV/AIDS patients ↓ Health Resource utilization ↓ Vertical Transmission of HIV infection Furthermore, when the impact of HAART on HIV transmission is considered, HAART expansion becomes a cost-averting strategy
The third approach, though, is the most intriguing. This is to do nothing more than press ahead faster with the treatment program. Since treatment reduces viral load, it should, in theory, make those being treated less infectious. Of course, theory is one thing and practice another. But studies in Taiwan and British Columbia (the latter by Julio Montaner, the incoming president of the International AIDS Society, which organizes the conference) have shown big falls in transmission rates as ARVs have been rolled out.
The Power of HAART: Demographic Model Treat 30% HIV prevalence Cost of treatment Treat all Treat 30% Treat all Number of infections prevented Montaner et al, Lancet 2006
R Granich, C Gilks, C Dye, K De Cock, B Williams. The Lancet Nov 26th 2008
AIDS Nov 27th 2008, The Economist Deploying the drugs used to treat AIDS may be the way to limit its spread Illustration by Peter Schrank Thank you
AIDS Nov 27th 2008, The Economist Deploying the drugs used to treat AIDS may be the way to limit its spread Illustration by Peter Schrank Thank you
An Alternative Approach Preliminary Results
Methods Prospective ecological study in BC, Canada Used administrative records to evaluate the association between expansion of HAART coverage, population level plasma HIV-1-viral load and new HIV diagnoses HIV testing, CD4 & viral load testing and HAART distribution are centralized and free in BC Data for second half of 2009 is preliminary due to delayed reporting, therefore only the first half of 2009 was used for statistical analyses Montaner et al, CROI 2010
January 2004 Summer of 1996 The second expansion of HAART occurred prior to the new 2008 IAS-USA Guidelines, which were adopted in BC at the end of 2008 The first expansion of HAART occurred as a result of the new 1996 IAS-USA Guidelines, which were adopted in BC in the summer of 1996 Year Montaner et al, CROI 2010
1.00 Incidence/yr 0.20 0.10 0.04 Acquired resistance 1.00 falling 0.02 0.01 0.201995 2000 2005 2010 < 50/mL (%) 90 Viral load 0.10 80 Plasma viral load 0.04 suppression rising 70 0.02 0.01 60 1995 2000 2005 2010
Number of Active HAART Participants and Number of New Number of Active HAART Participants HIV+ Diagnoses per Year Number of New HIV+ Diagnoses p=0.015 New HIV+ Diagnoses (All) Active on HAART New HIV+ Diagnoses (IDU) Year Montaner et al, CROI 2010
Number of Active HAART Participants and Number of New Number of Active HAART Participants HIV+ Diagnoses per Year Number of New HIV+ Diagnoses p=0.015 New HIV+ Diagnoses (All) Active on HAART p=0.085 New HIV+ Diagnoses (IDU) p=0.026 Year Montaner et al, CROI 2010
“True” New Yearly HIV Diagnoses in BC BC-CDC Updated March 2010
HIV testing in BC, 1985 to 2008 Year # of HIV Tests Jan 2004 BC-CDC Report, 2009
Hepatitis C, 1999-2008 Infectious Syphilis, 1999-2008 • BC 2004 • BC 2004 x Canada x Canada Genital Chlamydia, 1999-2008 Gonorrhea, 1999-2008 • BC x Canada x Canada 2004 • BC 2004
Highest Non IDU HIV-1- Plasma Viral load per Year IDU Ever on Treatment & Censoring at the time of Death or Move The proportion of HIV infected IDUs engaged in care in BC with plasma viral load >1500 c/mL, as a surrogate for “high” community HIV-1-viral load, decreased from ~50% in 2000-04 to ~20% in 2009 (p
“Provincial Viral Load” All Patients Ever Tested for Plasma HIV-1-Viral Load in BC Censoring at the time of Death or Move
New Data: Pre HAART CD4 Count Montaner et al, 2010, Preliminary Data
Community pVL and New HIV Diagnoses San Francisco 30,000 P = .005 for Mean CVL Mean Community Viral Load (copies/mL) association* Number of Newly Diagnosed HIV Cases 1200 Newly diagnosed and 25,000 reported HIV cases 1000 20,000 800 798 15,000 600 642 10,000 523 518 434 400 5000 200 0 0 2004 2005 2006 2007 2008 *Data insufficient to prove significant association with reduced HIV incidence. Das-Douglas M, et al. CROI 2010. Abstract 33.
A Formidable Challenge A Unique Opportunity
When to Start HAART? A matter of Perspective Viral Load CD4 Count years
When to Start HAART? A matter of Perspective Viral Load CD4 Count years years
When to Start HAART? A matter of Perspective Viral Load CD4 Count years years years
When to Start HAART? A matter of Perspective Viral Load CD4 Count years years years
Person years on ART (M) Cost: 2010 to 2050 70 7 60 6 50 5 Deaths (M) Cost (Bn$) 40 4 30 3 20 2 10 1 0 0 0 Current 1 200 2 350 3 500 4 Immediate 5 6 Economics of ART up to 2050 in South Africa Current policy vs. Universal Access at different CD4 counts Granich. CROI 2010
STOP HIV & AIDS: AIDS Seek and Treat to Optimally Prevent HIV & AIDS* * Supported through a $2.5M five year Avant Garde Award by the National Institute for Drug Abuse (NIDA) at the NIH in 2008 and $48M (+ drugs) four year outreach grant by BC Govt in 2010
STOP HIV & AIDS: AIDS Seek and Treat to Optimally Prevent HIV & AIDS* Prospectively Evaluate the Impact of HAART Expansion on AIDS Morbidity and Mortality and HIV Incidence in BC Intervention Primary Endpoint HAART Expansion HIV Incidence within medical guidelines at years 3 to 5 Secondary Endpoints: MORBIDITY AND MORTALITY, CD4 COUNTS, HIV-1-RNA LEVELS, RESISTANCE, ADVERSE EVENTS, SAFETY, ADHERENCE, HOSPITALIZATIONS, RESOURCE UTILIZATION * Supported through a $2.5M five year Avant Garde Award by the National Institute for Drug Abuse (NIDA) at the NIH in 2008 and $48M (+ drugs) four year outreach grant by BC Govt in 2010
HAART Expansion to Reduce AIDS Morbidity & Mortality, and HIV Incidence HAART has a substantial added preventive value The magnitude of this effect is not yet fully characterized, and may well vary in different settings Seek and Treat among those who have a medical indication for HAART cannot wait for the above to be resolved Many lives will be saved and much insight will be gained from closely monitoring a more “aggressive”roll out of HAART within Rx Guidelines Seek and Treat outside the range where treatment is medically indicated remains a research question However, Rx Guidelines leave few outside the “treatment envelope” TAP should serve to re-energize Universal Access
Combination prevention Biomedical Interventions HIV testing, Structural linkage to care Interventions and expanded HAART HIV coverage Prevention Individual Community and small Interventions group behavioral interventions Modified from T. Coates
A Statistician’s Opinion All scientific work is incomplete - whether it be observational or experimental. All scientific work is liable to be upset or modified by advancing knowledge. That does not confer upon us a freedom to ignore the knowledge we already have, or to postpone the action that it appears to demand at a given time. Bradford-Hill, A. 1965 The environment and disease: Association or Causation? President address at January 14 meeting. Proceedings of the Royal Society of Medicine 163 (seriesB): 295-300
Seek and Treat to Optimally Prevent HIV & AIDS STOP HIV & AIDS R Hogg, E Wood, T Kerr, M Tyndall, A Levy, PR Harrigan, Viviane Lima, Aranka Anema, Stephen Smith, Warren O’Brien Pedro Cahn, Jose Esparza, Craig Mc Clure, Robin Gorna Jacques Normand, Nora Volkow IAS - USA ART Guidelines Panel, IAS, WHO and UNAIDS BC-MoH and MHL&S SPH Foundation Merck, Gilead, ViiV MSHRF, CIHR, NIDA and NIH H&W, Ottawa Research Staff and Study Participants British Columbia Centre for Excellence in HIV/AIDS
British Columbia Centre for Excellence in HIV/AIDS Thank You
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