Faculty Bibliography

BACKGROUND:Organ transplantation from donors with HIV to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV+ donors is critical for safety. METHODS:We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) testing within the HOPE in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262; NCT03500315; NCT03734393). We compared clinical characteristics in HIV+ versus FP donors. We measured CD4+ T cells, HIV viral load (VL), drug resistance mutations (DRMs), co-receptor tropism, and serum antiretroviral therapy (ART) detection using mass spectrometry in HIV+ donors. RESULTS:Between 03/2016-03/2020, 92 donors (58 HIV+, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidney, 46 liver). Each year the number of donors increased. Prevalence of hepatitis B (16% vs. 0%), syphilis (16% vs. 0%), and cytomegalovirus (91% vs. 58%) was higher in HIV+ versus FP donors; hepatitis C viremia was similar (2% vs. 6%). Most HIV+ donors (71%) had known HIV diagnosis, of whom 90% were prescribed ART and 68% had VL<400 copies/mL. Median CD4 count was 194 cells/uL (IQR=77-331); median CD4% was 27.0 (IQR=16.8-36.1). Major HIV DRMs were detected in 42%, including non-nucleoside reverse transcriptase inhibitors (33%), integrase strand transfer inhibitor (INSTI, 4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history. CONCLUSION/CONCLUSIONS:Utilization of HIV+ donor organs is increasing. HIV DRMs are common, yet resistance that would compromise INSTI-based regimens is rare, which is reassuring regarding safety.

Patient and graft survival are similar following whole versus split liver transplants (SLT) among pediatric and adult recipients, yet SLTs are rarely used. We sought to determine the survival benefit associated with accepting a splittable offer for SLT versus declining and waiting for a subsequent offer using 2010-2018 SRTR data on 928 pediatric and 1814 adult LT candidates who were ever offered a splittable graft. We compared eventual mortality, regardless of subsequent transplants, between those who accepted versus declined a splittable liver offer with adjustment for PELD/MELD, diagnosis, and weight among pediatric candidates, and matching for MELD, height, and offer among adult candidates. Among pediatric candidates ≤7kg, splittable offer acceptance versus decline was associated with a 63% reduction in mortality (aHR _0.17 0.37_0.80 , p=0.01; 93.1% versus 84.0% one-year survival post-decision). Within one year of decline for those ≤7kg, 6.4% died and 31.1% received a whole liver transplant. Among pediatric candidates >7kg, there was no significant difference associated with acceptance of a splittable offer (aHR _0.63 1.07_1.82 , p=0.81; 91.7% vs 94.4% one-year survival post-decision). Within one year of decline for those >7kg, 1.8% died and 45.8% received a whole liver. Among adult candidates, splittable offer acceptance was associated with a 43% reduction in mortality (aHR _0.39 0.57_0.83, p=0.005; 92.2% vs 84.4% one-year survival post-decision). Within one year of decline for adult candidates, 7.9% died and 39.3% received a whole liver. Conclusion: Accepting splittable offers for SLT could significantly improve survival for small children and adults on the waitlist.

BACKGROUND:Medicaid expansion has led to earlier stage diagnoses in several cancers but has not been studied in hepatocellular carcinoma (HCC), a disease with complex risk factors. We examined the effect of Medicaid expansion on the diagnosis of HCC and associations with county-level social vulnerability. METHODS:Patients with HCC <65 years of age were identified from the SEER database (2010-2016). County-level social vulnerability factors were obtained from the CDC SVI and BRFSS. A Difference-in-Difference analysis evaluated change in early-stage diagnoses (stage I-II) between expansion and non-expansion states. A Difference-in-Difference-in-Difference analysis evaluated expansion impact among counties with higher proportions of social vulnerability. RESULTS:Of 19,751 patients identified, 81.5% were in expansion states. Uninsured status decreased in expansion states (6.3%-2.4%, p < 0.0001) and remained unchanged in non-expansion states (12.7%-14.8%, p = 0.43). There was no significant difference in the incidence of early-stage diagnoses between expansion states and non-expansion states. Results were consistent when accounting for social vulnerability. CONCLUSION/CONCLUSIONS:Medicaid expansion was not associated with earlier stage diagnoses in patients with HCC, including those with higher social vulnerability. Unlike other cancers, expanded access did not translate into higher utilization of care in HCC, suggesting barriers on a multitude of levels.

Background/UNASSIGNED:Posttransplant diabetes (PTD), a major complication after kidney transplantation (KT), is often attributable to immunosuppression. The risk of PTD may increase with more potent steroid maintenance and older recipient age. Methods/UNASSIGNED:Using United States Renal Data System data, we studied 12 488 adult first-time KT recipients (2010-2015) with no known pre-KT diabetes. We compared the risk of PTD among recipients who underwent early steroid withdrawal (ESW) versus continued steroid maintenance (CSM) using Cox regression with inverse probability weighting to adjust for confounding. We tested whether the risk of PTD resulting from ESW differed by recipient age (18-29, 30-54, and ≥55 y). Results/UNASSIGNED:). Conclusions/UNASSIGNED:The beneficial association of ESW with decreased PTD was more pronounced among recipients aged ≥55, supporting an age-specific assessment of the risk-benefit balance regarding ESW.

Background/UNASSIGNED:The development of cytomegalovirus (CMV) infection after kidney transplant remains a significant cause of posttransplant morbidity, graft loss, and mortality. Despite appropriate antiviral therapy, recipients without previous CMV exposure can currently be allocated a kidney from a donor with previous CMV infection (D+R-) which carries the greatest risk of posttransplant CMV infection and associated complications. Preferential placement of CMV D- organs in negative recipients (R-) has been shown to reduce the risk of viral infection and associated complications. Methods/UNASSIGNED:To assess the long-term survival and economic benefits of allocation policy reforms, a decision analytic model was constructed to compare receipt of CMV D- with CMV D+ organ in CMV R- recipients using data from transplant registry, Medicare claims, and pharmaceutical costs. Results/UNASSIGNED:For CMV R- patients, receipt of a CMV D- organ was associated with greater average survival (14.3 vs 12.6 years), superior quality-adjusted life years (12.6 vs 9.8), and lower costs ($529 512 vs $542 963). One-way sensitivity analysis demonstrated a survival advantage for patients waiting as long as 30 months for a CMV D- kidney. Conclusions/UNASSIGNED:Altering national allocation policy to preferentially offer CMV D- organs to CMV R- recipients could improve survival and lower costs after transplant if appropriately implemented.