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C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients
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C1_2 Michael Saag Chronic Disease in Longer-Term HIV Patients

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  • 1. Strategies forAntiretroviral Therapy:When to Start, How to Finish <br />Michael S. Saag, MDProfessor of MedicineThe University of Alabama at Birmingham<br />The International AIDS Society–USA<br />
  • 2. M Saag, UAB<br />
  • 3.
  • 4. Latently Infected CD4+ Lymphocytes<br />HIV Infected Cells<br />HIV virions<br />Antiretroviral Rx<br />Uninfected Activated CD4+ Lymphocytes<br />Uninfected Resting CD4+ Lymphocytes<br />M Saag, UAB<br />
  • 5.
  • 6. At steady state, when an actively producing cell dies, it is replaced by how many newly infected cells?<br />One<br />Twenty-five<br />One hundred<br />One thousand<br />It depends on the viral load<br />[Default]<br />[MC Any]<br />[MC All]<br />
  • 7. M Saag, UAB<br />
  • 8. VL = 100,000<br />
  • 9. VL < 50<br />
  • 10.
  • 11.
  • 12.
  • 13.
  • 14.
  • 15.
  • 16. Goals of Antiretroviral Therapy<br />Prevent Clinical Progression<br />Prevent Resistance<br />
  • 17.
  • 18.
  • 19. NEJM, 1993<br />
  • 20. Impact of Replication on Resistance<br />Likelihood of Resistance<br />High<br />Degree of Suppression<br />
  • 21. Case 1<br />30 yo white man<br />Diagnosed on routine insurance examination<br />PMHx remarkable for HTN, diet controlled<br />No medications<br />Understands treatment issues and wants to begin therapy if you think it is appropriate<br />
  • 22. If his viral load is 30,000 c/ml, at which CD4 count would you recommend starting therapy?<br />750 cells / ul<br />500 cells / ul<br />350 cells / ul<br />300 cells / ul<br />250 cells / ul<br />≤ 200 cells / ul<br />Would observe <br />Would treat at any CD4 count<br />[Default]<br />[MC Any]<br />[MC All]<br />
  • 23. When To Start Treatment? – Summary of Current Guidelines<br />symptoms<br />
  • 24. CD4 Count at Initiation of ARV 2003-2005<br />Egger M, 14th CROI; 2007; Abstract 62.<br />
  • 25. Which of the following convinces you MOST to start therapy earlier in course of HIV infection?<br />Cohort Study Results (NA-ACCORD / ART-CC<br />Consequences of unchecked viral replication (Inflammation / Harm)<br />Improved tolerability / convenience of newer ARV regimens<br />Treatment reduces transmission of HIV <br />Cost Savings<br />I have my own personal reasons!<br />[Default]<br />[MC Any]<br />[MC All]<br />
  • 26. Inverse Probability Weighted Cox Regression Multivariate Analysis<br /><ul><li> Results were similar when restricting the analysis to the 77% of </li></ul> participants with baseline HIV RNA data<br /><ul><li> Adjusted RH for deferral vs. immediate treatment was also 1.7</li></ul> 95% C.I. 1.4, 2.2; p <0.0001<br /><ul><li> HIV RNA was not an independent predictor of mortality</li></li></ul><li>4<br />2<br /> Hazard Ratio for AIDS or Death<br />1<br />.5<br /> 0<br /> 100<br /> 200<br /> 300<br /> 400<br /> 500<br />CD4 threshold (cells/mm3)<br />Hazard ratios for AIDS or death, adjusted for lead times and unseen events<br />
  • 27. A Randomized Clinical Trial of Early Versus Standard Antiretroviral Therapy for HIV-infected Patients with a CD4 T Cell Count of 200 – 350 cells/ml (CIPRAHT001)<br />Daniel Fitzgerald, MD<br />The GHESKIO Centers, Haiti<br />Weill Cornell Medical College, USA<br />
  • 28. Baseline Characteristics<br />
  • 29. Clinical Endpoints<br />
  • 30.
  • 31. Case 1<br />30 yo white man<br />Diagnosed on routine insurance examination<br />PMHx remarkable for HTN, diet controlled<br />No medications<br />Understands treatment issues and wants to begin therapy if you think it is appropriate<br /> VL is 30,000 c/mL<br /> CD4 is 650 cells/ul<br />
  • 32. If his viral load is 30,000 c/ml, and his CD4 count is 650 cells/ul, at what age would you recommend starting therapy?<br />20 yrs<br />30 yrs<br />40 yrs<br />50 yrs<br />60 yrs<br />70 yrs<br />Would treat at any age<br />Would not treat<br />[Default]<br />[MC Any]<br />[MC All]<br />
  • 33. Relative Time on Treatment…<br />40 years on Rx<br />CD4 650/ul<br />35 years on Rx<br />5 years<br />CD4 500/ul<br /> 30 35 40 45 50 55 60 65 70<br />AGE (years)<br />
  • 34. <ul><li>Cohort Study Results (NA-ACCORD / ART-CC)
  • 35. Consequences of unchecked viral replication (Inflammation / Harm)
  • 36. Improved tolerability / convenience of newer ARV regimens
  • 37. Treatment reduces transmission of HIV
  • 38. Cost Savings
  • 39. I have my own personal reasons!</li></li></ul><li>Relative Time on Treatment…<br />40 years on Rx<br />HARM?<br />CD4 650/ul<br />35 years on Rx<br />5 years<br />CD4 500/ul<br /> 30 35 40 45 50 55 60 65 70<br />AGE (years)<br />
  • 40. So ….what is the harm?(Pick the most compelling reason)<br />Destruction of lymphoid tissue<br />Inflammation<br />Increased Cardiovascular events<br />Increased incidence of certain malignancies<br />Increased ‘aging’<br />Accelerated cognitive decline<br />Another reason<br />[Default]<br />[MC Any]<br />[MC All]<br />
  • 41. Question 1 – Cognitive Differences Detected?<br />*<br />*<br />Lower scores reflect better function.<br />Trails A - Sig. Dif. for Age and HIV<br />Trails B – Sig. Dif. For HIV<br />
  • 42. Question 1 – Cognitive Differences Detected?<br />*<br />Higher scores reflect better function.<br />Finger Tapping - Sig. Dif. for HIV<br />
  • 43. Question 2 – Differences in TIADLs in Older and Younger Adults with and without HIV?<br />*<br />*<br />Lower scores reflects better function.<br />Age, HIV, and AgeXHIV effects observed.<br />
  • 44. Question 2 – Differences in TIADLs in Older and Younger Adults with and without HIV?<br />*<br />*<br />Lower scores reflects better function.<br />Age, HIV, and AgeXHIV effects observed for Total Score.<br />
  • 45. <ul><li>Cohort Study Results (NA-ACCORD / ART-CC)
  • 46. Consequences of unchecked viral replication (Inflammation / Harm)
  • 47. Improved tolerability / convenience of newer ARV regimens
  • 48. Treatment reduces transmission of HIV
  • 49. Cost Savings
  • 50. I have my own personal reasons!</li></li></ul><li>Willig, et al, AIDS, 2008<br />
  • 51. 1st Line ARV Therapy: 2003- 2007<br />McKinnell, et al, AIDS Pt Care & STDs, 2010<br />
  • 52. Does treating HIV lead to reduced transmission of HIV?<br />Yes<br />No<br />Depends on the sexual practices!<br />[Default]<br />[MC Any]<br />[MC All]<br />
  • 53. Most New Infections Transmitted by Persons who Do Not Know Their Status<br />account for…<br />~25% Unaware of Infection<br />~54% New Infections<br />~75% Aware of Infection<br />~46% of New Infections<br />Source: G. Marks et al. AIDS 2006<br />
  • 54. <400<br /><400<br /><400<br />>50 000<br />>50 000<br />>50 000<br />400-3499<br />400-3499<br />400-3499<br />3500-9999<br />3500-9999<br />3500-9999<br />10 000-49 999<br />10 000-49 999<br />10 000-49 999<br />TNT: Based on the association of viral load and HIV transmission risk<br />30<br />Female-to-Male<br />Transmission<br />Male-to-Female<br />Transmission<br />All subjects<br />25<br />20<br />15<br />Transmission rate per 100 Person-Years <br />10<br />5<br />0<br />Viral load (HIV-1 RNA copies/mL) and HIV transmission<br />Quinn TC, et al.NEJM 2000; also Fideli U, et al. AIDS Res Hum Retrovir 2001<br />
  • 55. <ul><li>Cohort Study Results (NA-ACCORD / ART-CC)
  • 56. Consequences of unchecked viral replication (Inflammation / Harm)
  • 57. Improved tolerability / convenience of newer ARV regimens
  • 58. Treatment reduces transmission of HIV
  • 59. Cost Savings
  • 60. I have my own personal reasons!</li></li></ul><li>Prevention of Transmission<br />TEST and TREAT <br />Testing and Linkage to Care (TLC+)<br />National AIDS Strategy…<br />
  • 61. <ul><li>Cohort Study Results (NA-ACCORD / ART-CC)
  • 62. Consequences of unchecked viral replication (Inflammation / Harm)
  • 63. Improved tolerability / convenience of newer ARV regimens
  • 64. Treatment reduces transmission of HIV
  • 65. Cost Savings
  • 66. I have my own personal reasons!</li></li></ul><li>Cost-Effectiveness of Early vs. Deferred ART<br /> “Starting ART earlier … rather than later … is a cost-effective strategy (by the generally accepted benchmark in the US).”<br />Mauskopf JA, et al. JAIDS 2005;39:562-569.<br />
  • 67. Case 1<br />30 yo white man<br />Diagnosed on routine insurance examination<br />PMHx remarkable for HTN, diet controlled<br />No medications<br />Understands treatment issues and wants to begin therapy if you think it is appropriate<br />
  • 68. If his viral load is 30,000 c/ml, at which CD4 count would you recommend starting therapy?<br />750 cells / ul<br />500 cells / ul<br />350 cells / ul<br />300 cells / ul<br />250 cells / ul<br />≤ 200 cells / ul<br />Would observe<br />Would treat at any CD4 count<br />[Default]<br />[MC Any]<br />[MC All]<br />
  • 69. START (Strategic Timing of ART) Study<br />INSIGHT Network: multinational<br />Study population: adults with CD4 >500<br />Study treatment:<br />Immediate ART<br />CD4 <350<br />Study endpoints:<br />Serious AIDS-defining illness, non-AIDS illness, death<br />Sample size:<br />N=900 (pilot for feasibility)<br />N=4000 (definitive)<br />Duration: ~6 yrs.<br />http://insight.ccbr.umn.edu/official_documents/START/protocol_documents/START_ProtocolSynopsis.pdf<br />
  • 70. CD4 Count at Initiation of ARV 2003-2005<br />Egger M, 14th CROI; 2007; Abstract 62.<br />
  • 71. Which of the following convinces you MOST to start therapy earlier in course of HIV infection?<br />Cohort Study Results (NA-ACCORD / ART-CC)<br />Consequences of unchecked viral replication (inflammation / harm)<br />Improved tolerability / convenience of newer ARV regimens<br />Treatment reduces transmission of HIV<br />Cost savings<br />I have my own personal reasons!<br />[Default]<br />[MC Any]<br />[MC All]<br />
  • 72. Case 1<br />30 yo White Male<br />Diagnosed on routine insurance examination<br />PMHx remarkable for HTN, diet controlled<br />No medications<br />Understands treatment issues and wants to begin therapy if you think it is appropriate<br />
  • 73. If his viral load is 30,000 c/ml, at which CD4 count would you recommend starting therapy?<br />750 cells / ul<br />500 cells / ul<br />350 cells / ul<br />300 cells / ul<br />250 cells / ul<br />≤200 cells / ul<br />Would observe<br />Would treat at any CD4 count<br />[Default]<br />[MC Any]<br />[MC All]<br />
  • 74. END of SESSION 1<br />

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