Opportunistic disease and mortality in patients coinfected with hepatitis C virus HCV andor hepatiti

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Opportunistic disease and mortality in patients
co-infected with hepatitis C virus (HCV) and/or
hepatitis B virus (HBV) in the SMART (Strategic
Management of Antiretroviral Therapy) Study

• SMART Hepatitis Group
• 4th IAS Conference, Sydney
• July 2007

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SMART study design
CD4 cell count gt 350 cells/mm³ N5472
Drug Conservation (DC) Strategy ?defer ART
until CD4 lt250 then episodic ART until CD4
gt350? N 2720
Virologic Suppression (VS) Strategy ?continuous
ART? N2752
Study halted prematurely Jan 06 16 month average
follow-up, 1.5 lost to follow-up
SMART Study Group, N Engl J Med 2006
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Primary and Major Secondary End Points
Hazard ratio DC vs. VS (95 CI)
No. of Patients with Events
Event
2.6
Opportunistic disease or death 167
1.7
Major CV, hepatic or renal disease 104
1.6
Fatal or non-fatal CV disease 79
1.4
Fatal or non-fatal hepatic disease 17
4.5
Fatal or non-fatal renal disease 11
Favors VS ?
CV cardio vascular
SMART Study Group, N Engl J Med 2006
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Rationale and Objective of this Presentation

• Co-infection with hepatitis B and/or C and HIV
  can be associated with adverse effects on
  morbidity and survival.
• Did co-infection with hepatitis B and/or C impact
  the outcomes of opportunistic disease (OD),
  morbidity or mortality seen in SMART?
• To compare the rate of total OD/death, OD and
  non-OD death by baseline hepatitis status and
  DC/VS group .

OD opportunistic disease
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Definitions

• Chronic HBV (HBV)
• if HBV surface antigen positive over 6 months
• Chronic HCV (HCV)
• if HCV antibody positive.
• HBV and/or HCV
• Chronic HBV and/or HCV

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of SMART population being HBV and/or HCV
of total SMART population
Time of follow-up HBV and/or HCV 1467
person-years HBV/HCV uninfected 5901
person-years
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Baseline Characteristics of Co-infected
Participants
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Risk of OD/Death by hepatitis status for VS
versus DC group
n of events, rate events/100 person-years
(PY) unadjusted
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Risk of OD by hepatitis status for VS versus DC
group
n of events, rate events/100 person-years
(PY) unadjusted
10
Risk of Non-OD Death by hepatitis status for VS
versus DC group
n of events, rate events/100 person-years
(PY) unadjusted
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Risk of OD/Death, OD and non-OD Death by baseline
hepatitis status
Hazard ratio (infected/uninfected) 95 CI
2.0
2.0
1.9
1.1
1.2
0.7
3.8
3.9
3.5
Favors Infected
Favors Uninfected ?
?
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Rate of OD and non-OD death by baseline hepatitis
status
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Rate of non-OD death (/100 PY) by baseline
hepatitis status (DC and VS combined)
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Causes of non-OD deaths in HBV and/or HCV
infected in DC and VS groups
Number of persons with cause of death
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Summary

• The risk of Opportunistic Disease (OD) was
  comparable regardless of hepatitis status.
• Conversely, whereas HCV and/or HBV infected
  constituted 17 of pts in SMART, almost half of
  all non-OD deaths occurred in this population
• i.e., the co-infected population had an
  underlying higher risk of non-OD deaths than the
  uninfected population (3.8-fold)
• The relative harm of experiencing OD or non-OD
  deaths by being randomized to the DC versus the
  VS strategy was comparable regardless of
  hepatitis status
• As the risk of non OD-deaths was higher in the
  co-infected population, the strategy of ART
  interruption is particularly unsafe in these
  patients

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Acknowledgements

• SMART Hepatitis Group
• Ellen Tedaldi
• Massimo Puoti
• Jacqueline Neuhaus
• Lars Peters
• Jürgen Rockstroh
• Marina Klein
• Greg Dore
• Amanda Mocroft

• Vicente Soriano
• Buenaventura Clotet
• Jens Lundgren, Chair
• SMART Participants
• SMART Investigators
• SMART Executive Committee
• NIH/NIAID