Transcript History of Opportunistic Complications: Should This Remain An

History of Opportunistic Complications:
Should This Remain An Exclusionary
Criterion?
Kathleen E. Squires, M.D.
Associate Professor of Medicine
Keck School of Medicine
University of Southern California
Opportunistic Complications:
Current Situation
• History of opportunistic complications (infections
or neoplasia) is an absolute reason for exclusion
• Reason: immunosuppression required for
transplantation will put these patients at increased
risk of experiencing recurrence or a new
complication
• Studies do indicate that history of one OI confers
increased risk of developing a novel OI
Opportunistic Complications:
Proposal to Change Eligibility Criteria
• Reevaluate this requirement after the first 20
transplants:
- if total number if OC’s in this group is </= 1,
criteria would be changed to allow subjects
with history of an OC to enroll
- OC occurred some defined period of time prior
to enrollment
• Is there data to support this proposal?
Changing Spectrum of Opportunistic
Complications in the HAART Era
• There has been a marked decline in the incidence
of nearly all AIDS-defining opportunistic
complications in the US and Europe
• This decline has been linked temporally to advent
of potent triple drug antiretroviral therapy
• Several OC’s for which there is no definitive
therapy (e.g. cryptosporidiosis, PML) have
responded to HAART alone
• Atypical presentations of well-characterized OC’s
(vitritis, CMV; fever, regional adenopathy; MAC)
Changing Spectrum of Opportunistic
Complications in HAART ERA
• Many lines of evidence indicate that immune
reconstitution does occur:
– evidence of increase in thymic mass in patients
receiving HAART
– gradual rise in naïve T cell populations
– documentation of organism-specific host
defense mechanisms
• UPHS Guidelines now recommend
discontinuation of primary and secondary
prophylaxis for essentially all OI’s
Changing Spectrum of Opportunistic
Complications in HAART Era
• Clinicians are now considering stopping ART in
patients who have evidence of
– sustained suppression of viral replication
– CD4 counts >350 cells/mm3 for 1.5-2 years
– SMART trial
• There are concerns with this approach:
– Incidence of lymphoma
– Chronic viral infections (HPV)
Opportunistic Complications in the
Setting of Transplantation:
What Should We Do?
• The data supports allowing individuals with
history of OI to undergo transplantation
• Possible eligibility criteria:
– viral load <400 (50) copies/mL for 6-12 months
– CD4 cell counts >/=350 cells/mm3 for how
long?
• Maintain ART
• Maintain or consider restarting prophylaxis
• Monitor chronic conditions