Jorge A. Tavel, MD

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Study of Aldesleukin with and without
Antiretroviral Therapy
Jorge A. Tavel, MD On behalf of the STALWART
Protocol Team of the INSIGHT Network 5th IAS
Conference on HIV Pathogenesis, Treatment and
Prevention 19-22 July 2009
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STALWART Study Design
Patients ART-naïve (or off ART 1 year) with
CD4 T cells 300 /mm3
Control No IL-2 or ART
IL-2 IL-2 alone
IL-2 IL-2 with peri-cycle ART
N91
N87
N89
Follow-up Every 4 weeks until week 32, q 4 mo.
thereafter Primary Endpoint CD4 cell count at
week 32
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IL-2 Cycles

• Subcutaneous injections twice daily for 5
  consecutive days
• Starting dose 7.5 MIU reduce in decrements of
  1.5 MIU as necessary to control toxicities
• 3 cycles, 8 weeks apart

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Peri-cycle ART in the IL-2 group

• 1 PI and 2 nRTIs

IL-2
Cycle 1
5 days
2 days
14 days
Subsequent Cycles
3 days
2 days
5 days
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STALWART Study Closure

• Two large HIV studies, ESPRIT and SILCAAT, were
  unblinded January 8, 2009
• IL-2 did not result in a reduction of
  opportunistic disease or mortality but was
  associated with an increased risk of adverse
  events
• Because of these findings
• STALWART IL-2 cycling was stopped
• STALWART results were unblinded early
• Planned follow-up ended February 28, 2009

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Participant Characteristics
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Frequency of Cycling
At least 3 cycles IL-2 76 IL-2
67
Percent
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IL-2 with or without peri-cycle ART increases
CD4 cell counts
IL-2
IL-2
CD4
Control
Study Week
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CD4 Changes from Baseline to Week 32
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A greater number of participants assigned to no
therapy started ART
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HIV RNA (log10) Changes from Baseline to Week 32
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IL-2 use is associated with a greater number of
adverse events
Patients with Events
HR (95 CI)
Event
HR
p .03
p lt .001
Favors Control ?
?
Favors IL-2
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Opportunistic Events and Deaths
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SUMMARY

• The groups assigned to receive IL-2
• Experienced CD4 cell count increases
• Started continuous ART less frequently
• Experienced a greater number of opportunistic
  events or deaths
• Combined with the results of ESPRIT and SILCAAT,
  this calls into question the functionality of
  CD4 cells induced by IL-2

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STALWART PROTOCOL TEAM
ICC Representatives Washington Barbara
Standridge Copenhagen Daniela Gey London Nick
Paton, Nicki Smith Sydney Cate Carey, David
Courtney-Rodgers Statisticians Abdel
Babiker Deb Wentworth SDMC Coordinator Nicole
Wyman Community Rep Dave Munroe Protocol
Clinicians Gustavo Lopardo Norm
Markowitz Juan Carlos Lopez Kiat
Ruxrungtham Martin Fisher