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UNAIDS Final Exp of HAART March 2010

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UNAIDS Final Exp of HAART March 2010 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 injury 35 Cancer 30 Population Heart 25 disease Suicide 20 15 HIV infection 10 Homicide Deaths per 100,000 5 Chronic liver disease 0 Stroke 82 84 86 88 90 92 94 Diabetes Year Harald zur Hausen Françoise Barré-Sinoussi Luc Montagnier Announced Oct 6th 2008 Vancouver 1996 “One World One Hope” Vancouver 1996 “One World One Hope” % Progression to AIDS in 3 yrs Plasma Viral Load, a strong CD4+ 100 cells/µL > 750 Predictor of outcome in 80 501-750 351-500 60 201-350 HIV Infected Individuals < 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 CD4+ 100 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 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 Change in Viral Load 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 . 3,400More couples recently Inan 7 email African has countries been circulated saying that: . All “counseledThe single and case given of transmission free condoms involved a man who initiated ARVs 18 days before his 12-month . studyHAART visit. initiated At this basedvisit his on partner CD4 count tested eligibility positive for HIV, . Over the nexthaving 1 to been 3 years, negative 103 new at month HIV infections9.” . 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 6 months Baseline Frequency of people of Frequency Plasma Viral Load (log10 copies/mL) Distribution Modified from Anema et al. EIDJ 2009 Impact of HAART in BC-CfE Baseline 24 months Frequency of people of Frequency 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 Adherence: 0% - <40% Adherence: 0% - <40% Guideline: !200 cells/mm 3 Guideline: !350 cells/mm 3 550 500 500 50% 50% 450 450 400 400 350 75% Infections Infections 350 75% CD4 350/mm3 300 New CD4 200/mm3 New 300 of of 250 90% 250 90% Adh <40% 200 200 Number Adh <40% Number 150 150 100% 100% 100 100 1995 2000 2005 2010 2015 2020 2025 2030 2035 1995 2000 2005 2010 2015 2020 2025 2030 2035 Year Year Coverage: Coverage: 50% 75% 90% 100% 50% 75% 90% 100% Current Adherence: 78.5% Current Adherence: 78.5% Guideline: !200 cells/mm 3 Guideline: !350 cells/mm 3 550 550 500 500 450 50% 450 50% 400 400 CD4 350/mm3 CD4 200/mm3 Infections 350 75% Infections 350 New 300 New 300 of of 75% Adh 40 - 80% Adh 40 - 80% 250 90% 250 Number 200 Number 200 90% 150 150 100 100% 100 100% 1995 2000 2005 2010 2015 2020 2025 2030 2035 1995 2000 2005 2010 2015 2020 2025 2030 2035 Year Year Coverage: 50% 75% 90% 100% Coverage: 50% 75% 90% 100% Adherence: 80% - <95% Adherence: 80% - <95% Guideline: !200 cells/mm 3 Guideline: !350 cells/mm 3 550 550 500 500 450 50% 450 400 400 50% CD4 350/mm3 CD4 200/mm3 Infections 350 75% Infections 350 New 300 New 300 of of 75% Adh 80 - 95% Adh 80 - 95% 250 90% 250 Number 200 Number 200 90% 150 150 100 100% 100 100% 1995 2000 2005 2010 2015 2020 2025 2030 2035 1995 2000 2005 2010 2015 2020 2025 2030 2035 Year Year Coverage: 50% 75% 90% 100% Coverage: 50% 75% 90% 100% Adherence: 95% - 100% Adherence: 95% - 100% Guideline: !200 cells/mm 3 Guideline: !350 cells/mm 3 550 550 500 500 450 50% 450 400 400 50% CD4 350/mm3 CD4 200/mm3 Infections 350 75% Infections 350 New 300 New 300 of of 75% Adh 95 - 100% Adh 95 - 100% 250 90% 250 Number 200 Number 200 90% 150 100% 150 100 100 100% 1995 2000 2005 2010 2015 2020 2025 2030 2035 1995 2000 2005 2010 2015 2020 2025 2030 2035 V D Lima et al Year Year JID 2008 Coverage: 50% 75% 90% 100% Coverage: 50% 75% 90% 100% Incremental net benefit (Millions of CDN $) over 30 years Overall population and patient-centered 800 Overall Population Patient-Centered incremental net benefit of 600 increasing uptake of Net Benefit (million $ Can 2005) 400 HAART from 50% to 75% over 30 years, based on a 200 willingness-to-pay 0 thresholds of $50,000 per 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.
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