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 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