Assessing the global threat from Zika virus.

First discovered in 1947, Zika virus (ZIKV) infection remained a little-known tropical disease until 2015, when its apparent association with a considerable increase in the incidence of microcephaly in Brazil raised alarms worldwide. There is limited information on the key factors that determine the extent of the global threat from ZIKV infection and resulting complications. Here, we review what is known about the epidemiology, natural history, and public health effects of ZIKV infection, the empirical basis for this knowledge, and the critical knowledge gaps that need to be filled

HIV and End-Stage Renal Disease: Disparities and Opportunities to Improve Outcomes

Racial disparities in patients with end-stage renal disease (ESRD) are well documented: young black patients die on dialysis at up to twice the rate of their white counterparts, while being half as likely to achieve access to the waitlist or a live donor. HIV-associated nephropathy (HIVAN) is the third leading cause of renal failure in black patients; its impact on racial disparities in ESRD outcomes is unknown. The goals of this dissertation were to characterize the mechanisms underlying racial disparities in ESRD, specifically the role of HIVAN, and develop strategies to improve outcomes. In the first paper of this thesis, we establish that cause of renal failure modifies the relationship between race and mortality on dialysis, with racial disparities attenuated in patients with ESRD caused by diabetes and hypertension. We show that excess mortality in young black dialysis patient is largely driven by a combination of 1) an increased burden of HIVAN and lupus, which are associated with poor outcomes, and 2) decreased access to transplantation. Furthermore, having access to nephrology care prior to ESRD onset is associated with improved survival in patients with HIVAN. In the second section, we discuss ongoing work showing that black patients with HIVAN are less likely to receive a kidney from a live donor, join the deceased donor waiting list, or receive an organ once listed; however, those who are transplanted derive a significant survival benefit from kidney transplant compared to remaining on dialysis or the waitlist. As such improving access to transplant for this population is critical to improve disparities in mortality on dialysis. In the third paper, we show that the use of induction immunosuppression is not associated with increased infections in HIV (+) kidney transplant recipients as was feared, and is in fact associated with fewer hospitalizations and better patient and graft survival. Given that HIV (+) kidney transplant recipients have 2-4 times the rate of rejection, the use of induction immunosuppression may be beneficial. In papers 4 and 5, we examine practices related to the use of donors classified as CDC increased infectious risk (IRD) for HIV. Currently, 20% of kidneys are from donors labeled IRD; while these are not appropriate for some patients due to the increased risk of HIV, HIV (+) kidney candidates stand to derive significant benefit from them. In part 4, we find that changes to national guidelines have led to a significant increase in the number of donors labeled CDC increased infectious risk, and that black donors are now significantly more likely to receive this label. Given that IRD kidneys are more likely to be discarded compared to similar organs without the label, this may reduce the supply of organs available for black, HIV (+) candidates. In part 5, we found that, while most nephrologists had been asked by patients about whether to accept an IRD kidney offer, knowledge of these donors was very low, and low knowledge was associated recommending decline of these organs. As such better education for nephrologists regarding IRD kidneys may facilitate shared decision making and increase utilization of IRD kidneys

Age and Comorbidities Are Effect Modifiers of Gender Disparities in Renal Transplantation

Women have less access to kidney transplantation than men, but the contributions of age and comorbidity to this disparity are largely unknown. We conducted a national cohort study of 563,197 patients with first-onset ESRD between 2000 and 2005. We used multivariate generalized linear models to evaluate both access to transplantation (ATT), defined as either registration for the deceased-donor waiting list or receiving a live-donor transplant, and survival benefit from transplantation, defined as the relative rate of survival after transplantation compared with the rate of survival on dialysis. We compared relative risks (RRs) between women and men, stratified by age categories and the presence of common comorbidities. Overall, women had 11% less ATT than men. When the model was stratified by age, 18- to 45-yr-old women had equivalent ATT to men (RR 1.01), but with increasing age, ATT for women declined dramatically, reaching a RR of 0.41 for those who were older than 75 yr, despite equivalent survival benefits from transplantation between men and women in all age subgroups. Furthermore, ATT for women with comorbidities was lower than that for men with the same comorbidities, again despite similar survival benefits from transplantation. This study suggests that there is no disparity in ATT for women in general but rather a marked disparity in ATT for older women and women with comorbidities. These disparities exist despite similar survival benefits from transplantation for men and women regardless of age or comorbidities

Changes in Utilization and Discard of Hepatitis C Infected Donor Livers in the Recent Era.

The impact of interferon (IFN)-free direct acting antiviral (DAA) hepatitis C virus treatments on utilization and outcomes associated with HCV+ deceased-donor liver transplantation (DDLT) is largely unknown. Using SRTR, we identified 25,566 HCV+ DDLT recipients from 2005 to 2015, and compared practices according to the introduction of DAA therapies using modified Poisson regression. The proportion of HCV+ recipients who received HCV+ livers increased from 6.9% in 2010 to 16.9% in 2015. HCV+ recipients were 61% more likely to receive an HCV+ liver after 2010 (early DAA/IFN era) [aRR:(1.45)1.61(1.79), p<0.001] and almost three times more likely to receive one after 2013 (IFN-free DAA era) [aRR:(2.58)2.85(3.16), p<0.001]. Compared to HCV− livers, HCV+ livers were 3 times more likely to be discarded from 2005–2010 [aRR:(2.69)2.99(3.34), p<0.001], 2.2 times more likely after 2010 [aRR:(1.80)2.16(2.58), p<0.001], and 1.7 times more likely after 2013 [aRR:(1.37)1.68(2.04), p<0.001]. Donor HCV status was not associated with increased risk of all-cause graft loss (p=0.1), and this did not change over time (p=0.8). Use of HCV+ livers has increased dramatically, coinciding with the advent of DAAs. However, the discard rate remains nearly double that of HCV− livers. Further optimization of HCV+ liver utilization is necessary to improve access for all candidates