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