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Wafaa El-Sadr, MD, MPH ICAP-Columbia University

The World Before SMART. Wafaa El-Sadr, MD, MPH ICAP-Columbia University. Think Back. HIV eradication . “...2.3 - 3.1 years of a completely inhibitory treatment would be required to eradicate HIV completely.”. HIV-Associated Lipodystrophy.

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Wafaa El-Sadr, MD, MPH ICAP-Columbia University

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  1. The World Before SMART Wafaa El-Sadr, MD, MPH ICAP-Columbia University
  2. Think Back
  3. HIV eradication “...2.3 - 3.1 years of a completely inhibitory treatment would be required to eradicate HIV completely.”
  4. HIV-Associated Lipodystrophy New England Journal of Medicine (1998:339;1296). International Journal of STD and AIDS (1198;9:596).
  5. Myocardial Infarction and ART Exposure MIs per 1,000 PY (95% CI) Test for trend p<0.00001 Years on CART Total 126 36,199 No. MIs 3 9 14 22 31 47 No. PY 5,714 4,140 4,801 5,847 7,220 8,477 D:A:D, NEJM, 2003
  6. Why Treatment Interruption? Lifelong use of ART inevitable in absence of cure Risk of complications low at lower CD4+ cell counts Adverse events from ART Serious complications e.g. CVD, hepatic and renal Difficulty in maintaining high rates of adherence HIV resistance likely with prolonged ART Pill-taking onerous and may be associated with decrease in quality of life Cost of ART is substantial, particularly in resource-limited countries
  7. The Story of SMARTThe Beginning April 8, 2000 - Meeting in New York City Who: Cal Cohen, Wafaa El-Sadr, Fred Gordin, Birgit Grund, Carlton Hogan, Jim Neaton, Claire Rappaport, Debby Wentworth Where: 535 West 110th Street, Apt 14H Outcome: Outline of the SMART design Study name identified
  8. SMART--The Beginning
  9. The SMART Study Question What is the optimal way to use ART?
  10. Weighing Pros and Cons VS DC
  11. SMART Study Design CD4+ cell count >350 cells/mm3 n = 3000 n = 3000 Drug Conservation (DC) Strategy [Stop or defer ART until CD4+ < 250; then episodic ART based on CD4+ cell count to increase counts to > 350] Virologic Suppression (VS) Strategy [Use of ART to maintain viral load as low as possible throughout follow-up] Plan: 910 primary endpoints, 8 years average follow-up
  12. Primary Endpoint HIV clinical disease progression or death Other Key Endpoints Death Serious HIV progression events Severe complications: cardiovascular, renal and hepatic
  13. SMART Study CPCRA RCC Sydney RCC London RCC Copenhagen RCC Brazil Canada Peru United States Argentina Australia Japan New Zealand Austria Belgium Denmark Finland Germany Norway Poland Portugal Spain France Greece Ireland Italy Morocco Switzerland United Kingdom
  14. Baseline Characteristics Total enrollment: 5472 1% 3% Countries: 33 Sites: 318 3% 10% 57% 26% Age: 46 years Women: 27% Blacks: 30%
  15. SMART MeetingJanuary 2006
  16. FOR IMMEDIATE RELEASEWednesday, Jan. 29, 2006 Media Contact:Laurie K. Doepel(301) 402-1663niaidnews@niaid.nih.gov
  17. SMART Primary Outcome SMART, NEJM 2006
  18. SMART-Non-AIDS Events SMART, NEJM 2006
  19. Definitive Evidence from SMART- Treatment Interruption Smith, Phillips et al
  20. Reasons for ART Interruption Smith, Phillips et al
  21. Paradigm ShiftPathogenesis of HIV Disease
  22. A New Paradigm Ongoing Morbidity from HIV 1000 800 600 400 200 0 Opportunistic Diseases CD4+ cells Count 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Time in Years Infection
  23. Conclusions SMART challenged the status quo Seeking definitive answers to tough questions is not easy, requires patience, may be costly, but is well worth it Getting an unexpected answer to a question is often more profound than getting the expected answer Other tough questions of the hour remain, and will require similar efforts to answer them
  24. SMART - A Paradigm ShiftSTART - Another One?
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