Rhiannon D. Reed

A National Study of Outcomes among HIV-Infected Kidney Transplant Recipients

Kidney transplantation is a viable treatment for select patients with HIV and ESRD, but data are lacking regarding long-term outcomes and comparisons with appropriately matched HIV-negative patients. We analyzed data from the Scientific Registry of Transplant Recipients (SRTR; 2002-2011): 510 adult kidney transplant recipients with HIV (median follow-up, 3.8 years) matched 1:10 to HIV-negative controls. Compared with HIV-negative controls, HIV-infected recipients had significantly lower 5-year (75.3% versus 69.2%) and 10-year (54.4% versus 49.8%) post-transplant graft survival (GS) (hazard ratio [HR], 1.37; 95% confidence interval [95% CI], 1.15 to 1.64; P<0.001) that persisted when censoring for death (HR, 1.43; 95% CI, 1.12 to 1.84; P=0.005). However, compared with HIV-negative/hepatitis C virus (HCV)-negative controls, HIV monoinfected recipients had similar 5-year and 10-year GS, whereas HIV/HCV coinfected recipients had worse GS (5-year: 64.0% versus 52.0%, P=0.02; 10-year: 36.2% versus 27.0%, P=0.004 [HR, 1.38; 95% CI, 1.08 to 1.77; P=0.01]). Patient survival (PS) among HIV-infected recipients was 83.5% at 5 years and 51.6% at 10 years and was significantly lower than PS among HIV-negative controls (HR, 1.34; 95% CI, 1.08 to 1.68; P<0.01). However, PS was similar for HIV monoinfected recipients and HIV-negative/HCV-negative controls at both times. HIV/HCV coinfected recipients had worse PS compared with HIV-negative/HCV-infected controls (5-year: 67.0% versus 78.6%, P=0.007; 10-year: 29.3% versus 56.23%, P=0.002 [HR, 1.57; 95% CI, 1.11 to 2.22; P=0.01]). In conclusion, HIV-negative and HIV monoinfected kidney transplant recipients had similar GS and PS, whereas HIV/HCV coinfected recipients had worse outcomes. Although encouraging, these results suggest caution in transplanting coinfected patients.

Surgical Site Infection After Arthroplasty: Comparative Effectiveness of Prophylactic Antibiotics: Do Surgical Care Improvement Project Guidelines Need to Be Updated?

BACKGROUND Prophylactic antibiotics decrease surgical site infection (SSI) rates, and their timing, choice, and discontinuation are measured and reported as part of the Surgical Care Improvement Project (SCIP). The aim of this study was to assess the comparative effectiveness of the SCIP-approved antibiotics for SSI prevention. METHODS This retrospective cohort study utilized national Veterans Affairs (VA) data on patients undergoing elective hip or knee arthroplasty from 2005 to 2009. Data on prophylactic antibiotics were merged with VA Surgical Quality Improvement Program data to identify patient and procedure-related risk factors for SSI. Patients were stratified by documented penicillin allergy. Chi-square and Wilcoxon rank-sum tests were used to compare SSI rates among patients receiving SCIP-approved prophylactic antibiotics. RESULTS A total of 18,830 elective primary arthroplasties (12,823 knee and 6007 hip) were included. Most patients received prophylactic cefazolin as the sole agent (81.9%), followed by vancomycin as the sole agent (8.0%), vancomycin plus cefazolin (5.6%), and clindamycin (4.5%). Documented penicillin allergy accounted for 54.1% of cases involving vancomycin administration compared with 94.6% of cases involving clindamycin. The overall thirty-day SSI rate was 1.4%, and the unadjusted rate was 2.3% with vancomycin only, 1.5% with vancomycin plus cefazolin, 1.3% with cefazolin only, and 1.1% with clindamycin. Unadjusted analysis of penicillin-allergic patients revealed an SSI rate of 2.0% with vancomycin only compared with 1.0% with clindamycin (p = 0.18). For patients without penicillin allergy, the SSI rate was 2.6% with vancomycin only compared with 1.6% with vancomycin plus cefazolin (p = 0.17) and 1.3% with cefazolin only (p < 0.01). CONCLUSIONS Current SCIP guidelines address antibiotic timing but not antibiotic dosage. (The generally accepted recommendation for vancomycin is 15 mg/kg.) Although vancomycin is a narrower-spectrum antibiotic than either cefazolin or clindamycin, our finding of higher SSI rates following prophylaxis with vancomycin only may suggest a failure to use an appropriate dosage rather than an inequality of antibiotic effectiveness. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Long-term Outcomes After Liver Transplantation Among Human Immunodeficiency Virus-Infected Recipients.

Background Early outcomes after human immunodeficiency virus (HIV) + liver transplantation (LT) are encouraging, but data are lacking regarding long-term outcomes and comparisons with matched HIV− patients. Methods We examined outcomes among 180 HIV+ LT, and compared outcomes to matched HIV− counterfactuals (Scientific Registry of Transplant Recipients 2002-2011). Iterative expanding radius matching (1:10) on recipient age, race, body mass index, hepatitis C virus (HCV), model for end-stage liver disease score, and acute rejection; and donor age and race, cold ischemia time, and year of transplant. Patient survival and graft survival were estimated using Kaplan-Meier methodology and compared using log-rank and Cox proportional hazards. Subgroup analyses were performed by transplant era (early: 2002-2007 vs modern: 2008-2011) and HCV infection status. Results Compared to matched HIV− controls, HIV+ LT recipients had a 1.68-fold increased risk for death (adjusted hazard ratio [aHR], 1.68, 95% confidence interval [95% CI], 1.28-2.20; P < 0.001), and a 1.70-fold increased risk for graft loss (aHR, 1.70; 95% CI, 1.31-2.20; P < 0.001). These differences persisted independent of HCV infection status. However, in the modern transplant era risk for death (aHR, 1.11; 95% CI, 0.52-2.35; P = 0.79) and graft loss (aHR, 0.89; 95% CI, 0.42-1.88; P = 0.77) were similar between monoinfected and uninfected LT recipients. In contrast, independent of transplant era, coinfected LT recipients had increased risk for death (aHR, 2.24; 95% CI, 1.43-3.53; P < 0.001) and graft loss (aHR, 2.07; 95% CI, 1.33-3.22; P = 0.001) compared to HCV+ alone LT recipients. Conclusions These results suggest that outcomes among monoinfected HIV+ LT recipients have improved over time. However, outcomes among HIV+ LT recipients coinfected with HCV remain concerning and motivate future survival benefit studies.

Hospital Acquired Conditions Are the Strongest Predictor for Early Readmission: An Analysis of 26,710 Arthroplasties

Hospital readmission is a metric of hospital quality of care, yet little is known what factors predict hospital readmission following arthroplasty. Our aim was to identify variables associated with early readmission following knee and hip arthroplasty, with focus upon hospital acquired conditions (HACs). Retrospective cohort analysis using Surgical Care Improvement Project (SCIP) and Veterans Affairs Surgical Quality Improvement Program (VASQIP) data was performed over a five-year period. Following 26,710 total and partial primary arthroplasties (16,808 knees and 9902 hips), the overall 30-day readmission was 7.3% (1940) with readmission rates of 6.6% for knee arthroplasty and 8.4% for hip arthroplasty. HACs accounted for 42% of all complications and were the strongest predictor of readmission. Efforts to reduce these events may improve cost and safety of arthroplasty.

Center-Level Experience and Kidney Transplant Outcomes in HIV-Infected Recipients

Excellent outcomes among HIV+ kidney transplant (KT) recipients have been reported by the NIH consortium, but it is unclear if experience with HIV+ KT is required to achieve these outcomes. We studied associations between experience measures and outcomes in 499 HIV+ recipients (SRTR data 2004–2011). Experience measures examined included: (1) center‐level participation in the NIH consortium; (2) KT experiential learning curve; and (3) transplant era (2004–2007 vs. 2008–2011). There was no difference in outcomes among centers early in their experience (first 5 HIV+ KT) compared to centers having performed >6 HIV+ KT (GS adjusted hazard ratio [aHR]: 1.05, 95% CI: 0.68–1.61, p = 0.82; PS aHR: 0.93; 95% CI: 0.56–1.53, p = 0.76), and participation in the NIH‐study was not associated with any better outcomes (GS aHR: 1.08, 95% CI: 0.71–1.65, p = 0.71; PS aHR: 1.13; 95% CI: 0.68–1.89, p = 0.63). Transplant era was strongly associated with outcomes; HIV+ KTs performed in 2008–2011 had 38% lower risk of graft loss (aHR: 0.62; 95% CI: 0.42–0.92, p = 0.02) and 41% lower risk of death (aHR: 0.59; 95% CI: 0.39–0.90, p = 0.01) than that in 2004–2007. Outcomes after HIV+ KT have improved over time, but center‐level experience or consortium participation is not necessary to achieve excellent outcomes, supporting continued expansion of HIV+ KT in the US.

Access to Kidney Transplantation among HIV-Infected Waitlist Candidates

BACKGROUND AND OBJECTIVES Kidney transplantation among HIV-infected patients with ESRD confers a significant survival benefit over remaining on dialysis. Given the high mortality burden associated with dialysis, understanding access to kidney transplantation after waitlisting among HIV+ candidates is warranted. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Data from the Scientific Registry of Transplant Recipients were linked to Intercontinental Marketing Statistics pharmacy fills (January 1, 2001 to October 1, 2012) so that we could identify and study 1636 HIV+ (defined as having filled one or more antiretroviral medications unique to HIV treatment) and 72,297 HIV- kidney transplantation candidates. RESULTS HIV+ waiting list candidates were more often young (<50 years old: 62.7% versus 37.6%; P<0.001), were more often men (75.2% versus 59.3%; P<0.001), were more often black (73.6% versus 27.9%; P<0.001), had longer time on dialysis (years: 2.5 versus 0.8; P<0.001), were more often coinfected with hepatitis C virus (9.0% versus 3.9%; P<0.001), and were less likely to remain active on the waiting list (37.7% versus 49.4%; P<0.001). Waitlist mortality among HIV+ candidates was similar compared with HIV- candidates (adjusted hazard ratio, 1.03; 95% confidence interval, 0.89 to 1.20; P=0.67). In contrast, likelihood of living donor kidney transplantation was 47% lower (adjusted hazard ratio, 0.53; 95% confidence interval, 0.44 to 0.64; P<0.001), and there was a trend toward lower likelihood of deceased donor kidney transplantation (adjusted hazard ratio, 0.87; 95% confidence interval, 0.74 to 1.01; P=0.07) compared with in HIV- candidates. CONCLUSIONS Our findings highlight the need for additional study to better understand disparities in access to kidney transplantation, particularly living donor kidney transplantation, among HIV+ kidney waitlist candidates.

Impact of Protease Inhibitor–Based Anti‐Retroviral Therapy on Outcomes for HIV+ Kidney Transplant Recipients

Excellent outcomes have been demonstrated among select HIV‐positive kidney transplant (KT) recipients with well‐controlled infection, but to date, no national study has explored outcomes among HIV+ KT recipients by antiretroviral therapy (ART) regimen. Intercontinental Marketing Services (IMS) pharmacy fills (1/1/01–10/1/12) were linked with Scientific Registry of Transplant Recipients (SRTR) data. A total of 332 recipients with pre‐ and posttransplantation fills were characterized by ART at the time of transplantation as protease inhibitor (PI) or non–PI‐based ART (88 PI vs. 244 non‐PI). Cox proportional hazards models were adjusted for recipient and donor characteristics. Comparing recipients by ART regimen, there were no significant differences in age, race, or HCV status. Recipients on PI‐based regimens were significantly more likely to have an Estimated Post Transplant Survival (EPTS) score of >20% (70.9% vs. 56.3%, p = 0.02) than those on non‐PI regimens. On adjusted analyses, PI‐based regimens were associated with a 1.8‐fold increased risk of allograft loss (adjusted hazard ratio [aHR] 1.84, 95% confidence interval [CI] 1.22–2.77, p = 0.003), with the greatest risk observed in the first posttransplantation year (aHR 4.48, 95% CI 1.75–11.48, p = 0.002), and a 1.9‐fold increased risk of death as compared to non‐PI regimens (aHR 1.91, 95% CI 1.02–3.59, p = 0.05). These results suggest that whenever possible, recipients should be converted to a non‐PI regimen prior to kidney transplantation.

Survival Benefit of Kidney Transplantation in Hiv-infected Patients

Objective: To determine the survival benefit of kidney transplantation in human immunodeficiency virus (HIV)-infected patients with end-stage renal disease (ESRD). Summary Background Data: Although kidney transplantation (KT) has emerged as a viable option for select HIV-infected patients, concerns have been raised that risks of KT in HIV-infected patients are higher than those in their HIV-negative counterparts. Despite these increased risks, KT may provide survival benefit for the HIV-infected patient with ESRD, yet this important clinical question remains unanswered. Methods: Data from the Scientific Registry of Transplant Recipients were linked to IMS pharmacy fills (January 1, 2001 to October 1, 2012) to identify and study 1431 HIV-infected KT candidates from the first point of active status on the waiting list. Time-dependent Cox regression was used to establish a counterfactual framework for estimating survival benefit of KT. Results: Adjusted relative risk (aRR) of mortality at 5 years was 79% lower after KT compared with dialysis (aRR 0.21; 95% CI 0.10–0.42; P <0.001), and statistically significant survival benefit was achieved by 194 days of KT. Among patients coinfected with hepatitis C, aRR of mortality at 5 years was 91% lower after KT compared with dialysis (aRR 0.09; 95% CI 0.02–0.46; P < 0.004); however, statistically significant survival benefit was not achieved until 392 days after KT. Conclusions: Evidence suggests that for HIV-infected ESRD patients, KT is associated with a significant survival benefit compared with remaining on dialysis.

Kidney transplantation and waitlist mortality rates among candidates registered as willing to accept a hepatitis C infected kidney

HCV‐infected (HCV+) ESRD patients derive significant survival benefit from kidney transplantation (KT) over remaining on dialysis. Given high mortality rates on dialysis and the unique ability to accept HCV+ and HCV‐ donor kidneys, understanding their access to KT is essential.

Lymphocyte-depleting induction therapy lowers the risk of acute rejection in African American pediatric kidney transplant recipients.

The use of lymphocyte‐depleting induction immunosuppression has been associated with a reduction in risk of AR after KT among adult recipients, particularly among high‐risk subgroups such as AAs. However, data on induction regimen and AR risk are lacking among pediatric KT recipients. We examined outcomes among 7884 first‐time pediatric KT recipients using SRTR data (2000‐2014). Characteristics were compared across race using Wilcoxon rank‐sum tests for continuous and chi‐square tests for categorical variables. Risk of AR was estimated using modified Poisson regression, stratified by recipient race, adjusting for recipient age, gender, BMI, primary diagnosis, number of HLA mismatches, maintenance immunosuppression, and donor type. Risk of AR within 1 year was lower in AA recipients receiving lymphocyte‐depleting induction (ATG or alemtuzumab; RR, 0.66; 95% CI, 0.52‐0.83 P < .001) compared to AA recipients receiving anti‐IL‐2 receptor antibody induction. This difference was not seen in non‐AA recipients receiving lymphocyte‐depleting induction (RR, 0.93; 95% CI, 0.81‐1.06, P = .26) compared to IL‐2 induction. These findings support a role for lymphocyte‐depleting induction agents in AA pediatric patients undergoing KT and continued use of IL‐2 inhibitor induction in non‐AA pediatric KT recipients.