Chromosome-level assembly of the gray fox (Urocyon cinereoargenteus) confirms the basal loss of PRDM9 in Canidae.

Reference genome assemblies have been created from multiple lineages within the Canidae family; however, despite its phylogenetic relevance as a basal genus within the clade, there is currently no reference genome for the gray fox (Urocyon cinereoargenteus). Here, we present a chromosome-level assembly for the gray fox (U. cinereoargenteus), which represents the most contiguous, non-domestic canid reference genome available to date, with 90% of the genome contained in just 34 scaffolds and a contig N50 and scaffold N50 of 59.4 and 72.9 Megabases, respectively. Repeat analyses identified an increased number of simple repeats relative to other canids. Based on mitochondrial DNA, our Vermont sample clusters with other gray fox samples from the northeastern United States and contains slightly lower levels of heterozygosity than gray foxes on the west coast of California. This new assembly lays the groundwork for future studies to describe past and present population dynamics, including the delineation of evolutionarily significant units of management relevance. Importantly, the phylogenetic position of Urocyon allows us to verify the loss of PRDM9 functionality in the basal canid lineage, confirming that pseudogenization occurred at least 10 million years ago.

Association between HbA1C (Glycated Hemoglobin) and Clinical Outcomes in Patients with Subarachnoid Hemorrhage After Neuro-intervention.

OBJECTIVE: Our study investigated the association between the level of HbA1c (glycated hemoglobin) at admission and the prognosis of aneurysmal subarachnoid hemorrhage (SAH). METHODS: A total of 510 patients treated with neuro-intervention for aneurysmal SAH and with data for admission HbA1c (glycated hemoglobin) were included. Favorable clinical outcome was defined as modified Rankin Scale (mRS) score of 0-2 at 3 months. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff value of HbA1C for unfavorable clinical outcomes. Logistic regression was used to evaluate the association between HbA1C level and outcomes. RESULTS: The optimal cutoff value of HbA1C was identified as 6.0% (P < 0.001), and patients with a high HbA1C (≥ 6.0%) had a lower prevalence of favorable clinical outcomes than patients with low HbA1C (< 6.0%) (P < 0.001). High HbA1C (≥ 6.0%) was independently associated with unfavorable clinical outcome (OR 2.84; 95% CI: 1.52-5.44; P = 0.004). The risk of unfavorable clinical outcome was significantly increased in patients with HbA1C (≥ 7.0%, < 8%) and HbA1C (≥ 8.0%) compared with lower baseline HbA1C (≥ 6.0%, < 7%) values (OR 2.17; 95% CI: 1.87-5.13; P = 0.011 and OR 4.25; 95% CI: 3.17-8.41; P = 0.005). CONCLUSION: Our study showed that HbA1C could be an independent predictor of worse outcomes following neuro-intervention for aneurysmal SAH. High HbA1C (≥ 6.0%) was associated with unfavorable clinical outcomes, and gradual elevation of HbA1C contributed to an increase in the risk of worse clinical outcomes after SAH.

Isoflavone-enriched soybean leaves attenuate ovariectomy-induced osteoporosis in rats by anti-inflammatory activity.

BACKGROUND: With an increasing aging population, postmenopausal osteoporosis has become a global public health problem. Previous evidence has shown that postmenopausal osteoporosis is a skeletal disease mainly caused by estrogen deficiency, generally accompanied by inflammation, and dietary isoflavones may ameliorate postmenopausal osteoporosis by anti-inflammatory activity. We have generated isoflavone-enriched soybean leaves (IESLs), but their anti-inflammatory activity and effect on attenuating osteoporosis are still obscure. Here, we determined the isoflavone profiles of IESLs and evaluated their anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 cells and anti-osteoporotic effects on ovariectomy-induced osteoporosis in rats. RESULTS: IESLs had a high content of total isoflavone. Hydrolysate of IESLs (HIESLs) was rich with the aglycones daidzein and genistein, and HIESLs can significantly inhibit lipopolysaccharide-induced inflammation by reducing messenger RNA expression of iNOS, COX-2, IL6, and IL1ß. Moreover, ovariectomized rats receiving aqueous extracts of IESLs (HIESLs) orally maintained more bone mass than control rats did, which was attributed to inhibition of osteoclastogenesis by downregulating the messenger RNA expression of the bone-specific genes RANKL/OPG, OC, and cathepsin K, and the inflammation-related genes IL6, NFκB, and COX-2. CONCLUSION: IESLs may attenuate postmenopausal osteoporosis by suppressing osteoclastogenesis with anti-inflammatory activity and be a potential source of functional food ingredients for the prevention of osteoporosis. © 2020 Society of Chemical Industry.

Autologous CD4 T Lymphocytes Modified with a Tat-Dependent, Virus-Specific Endoribonuclease Gene in HIV-Infected Individuals.

MazF is an Escherichia coli-derived endoribonuclease that selectively cleaves ACA sequences of mRNA prevalent in HIV. We administered a single infusion of autologous CD4 T lymphocytes modified to express a Tat-dependent MazF transgene to 10 HIV-infected individuals (six remaining on antiretroviral therapy [ART]; four undergoing treatment interruption post-infusion) in order to provide a population of HIV-resistant immune cells. In participants who remained on ART, increases in CD4 and CD8 T cell counts of ~200 cells/mm3 each occurred within 2 weeks of infusion and persisted for at least 6 months. Modified cells were detectable for several months in the blood and trafficked to gastrointestinal lymph tissue. HIV-1 Tat introduced ex vivo to the modified CD4+ T cells induced MazF expression in both pre- and post-infusion samples, and MazF expression was detected in vivo post-viral-rebound during ATI. One participant experienced mild cytokine release syndrome. In sum, this study of a single infusion of MazF-modified CD4 T lymphocytes demonstrated safety of these cells, distribution to lymph tissue and maintenance of Tat-inducible MazF endoribonuclease activity, as well as sustained elevation of blood CD4 and CD8 T cell counts. Future studies to assess effects on viremia and latent proviral reservoir are warranted.

Association of diet with circulating trimethylamine-N-oxide concentration.

BACKGROUND: Trimethylamine-N-oxide (TMAO) is a compound that is present in seafood and produced through human gut microbial metabolism of its precursors. Previous studies have suggested that elevated TMAO concentrations are associated with an increased risk of cardiovascular events. However, the association between diet and TMAO concentrations in free-living adult populations has not been adequately described. OBJECTIVES: The objective of this study was to identify dietary predictors of plasma TMAO concentrations. METHODS: TMAO concentrations were assessed in 2 fasting plasma samples collected 6 mo apart among 620 healthy men. Short-term and long-term dietary intakes were assessed during the same time-frame of blood collections via repeated 7-d dietary records (7DDRs) and a semiquantitative food-frequency questionnaire (SFFQ), respectively. We grouped individual food items into 21 groups and regressed against averaged TMAO concentrations. We also assessed the association between dietary scores and TMAO concentrations. RESULTS: In models adjusted for demographic characteristics and mutually adjusted for food groups, SFFQ-assessments of fish and egg intakes were significantly associated with increased TMAO concentration (ß = 0.082; 95% CI: 0.021, 0.14; P = 0.009 for fish; ß = 0.065; 95% CI: 0.004, 0.13; P = 0.039 for egg). The positive association between fish consumption and TMAO concentration was replicated in the 7DDR-assessments (ß = 0.12; 95% CI: 0.060, 0.18; P < 0.001). There was no association between red meat intake and TMAO concentrations. The unhealthful plant-based diet index (uPDI) was inversely associated (ß = -0.013; 95% CI: -0.021, -0.005; P = 0.001) and healthy dietary scores were positively correlated with TMAO concentration. CONCLUSIONS: TMAO concentration was significantly associated with fish intake, but not with red meat consumption. uPDI, an unhealthy dietary pattern, was inversely related to TMAO concentration. As such, this study suggests that in free-living populations, higher circulating concentrations of TMAO cannot simply be interpreted as a marker of unhealthy food intake or an unhealthy dietary pattern.

Brief Report: Willingness to Accept HIV-Infected and Increased Infectious Risk Donor Organs Among Transplant Candidates Living With HIV.

BACKGROUND: HIV-infected (HIV+) donor to HIV+ recipient (HIV D+/R+) transplantation might improve access to transplantation for people living with HIV. However, it remains unknown whether transplant candidates living with HIV will accept the currently unknown risks of HIV D+/R+ transplantation. METHODS: We surveyed transplant candidates living with HIV from 9 US transplant centers regarding willingness to accept HIV+ donor organs. RESULTS: Among 116 participants, the median age was 55 years, 68% were men, and 78% were African American. Most were willing to accept HIV+ living donor organs (87%), HIV+ deceased donor organs (84%), and increased infectious risk donor organs (70%). Some (30%) were concerned about HIV superinfection; even among these respondents, 71% were willing to accept an HIV D+ organ. Respondents from centers that had already performed a transplant under an HIV D+/R+ transplantation research protocol were more willing to accept HIV+ deceased donor organs (89% vs. 71%, P = 0.04). Respondents who chose not to enroll in an HIV D+/R+ transplantation research protocol were less likely to believe that HIV D+/R+ transplantation was safe (45% vs. 77%, P = 0.02), and that HIV D+ organs would work similar to HIV D- organs (55% vs. 77%, P = 0.04), but more likely to believe they would receive an infection other than HIV from an HIV D+ organ (64% vs. 13%, P < 0.01). CONCLUSIONS: Willingness to accept HIV D+ organs among transplant candidates living with HIV does not seem to be a major barrier to HIV D+/R+ transplantation and may increase with growing HIV D+/R+ transplantation experience.

Impact of HbA1C (Glycated Hemoglobin) and Glucose on Outcomes of Mechanical Thrombectomy in Patients with Large Artery Occlusion.

OBJECTIVE: This study evaluated the relationship between HbA1c (glycated hemoglobin), admission serum glucose levels and outcomes in patients with large artery occlusion (LAO) treated with mechanical thrombectomy (MT). METHODS: A total of 413 patients were enrolled, and the following outcomes were reviewed: successful recanalization, symptomatic hemorrhage, favorable outcome (modified Rankin Scale, mRS scores of 0-2), and mortality at 3 months. Receiver operating characteristic (ROC) curve analysis was undertaken to identify the cutoff values for HbA1C and glucose to discriminate between favorable and unfavorable outcomes. The association of HbA1c and glucose levels with outcomes was evaluated using logistic regression. RESULTS: The best cutoff values to discriminate between favorable and unfavorable outcome after 3 months were identified by an HbA1C value of 6.0% and an admission serum glucose level of 131 mg/dL (P = <0.001 and <0.001, respectively). Patients with HbA1C ≥6.0% had a lower ratio of favorable mRS, more symptomatic hemorrhage, and higher mortality than those of HbA1C <6.0% (P = 0.002, 0.001, and <0.001, respectively). In multivariate analysis, high HbA1C (≥6.0%) and serum glucose on admission (≥131 mg/dL) were significantly associated with unfavorable outcomes at 3 months (P = 0.006 and 0.009, respectively). CONCLUSION: This study demonstrated that patients with HbA1C ≥6.0% had more unfavorable 3- month mRS, higher symptomatic hemorrhage, and a higher degree of mortality than those with HbA1C <6.0%. Higher HbA1C and admission serum glucose levels are independent predictors of unfavorable clinical outcomes in LAO patients treated with MT.

Association of High-sensitivity C-reactive Protein with Patient Prognosis Following Mechanical Thrombectomy for Acute Ischemic Stroke.

OBJECTIVE: The aim of this investigation was to examine the association of hsCRP (highsensitivity C-reactive protein) with outcomes and prognosis of patients who underwent mechanical thrombectomy (MT) for large vessel occlusion (LVO) after acute ischemic stroke (AIS). METHODS: A total of 404 patients were enrolled, and outcomes included unfavorable clinical outcome at three months (modified Rankin Scale, mRS scores 3-6), the occurrence of symptomatic intracerebral hemorrhage (sICH) and hemorrhagic transformation (HT) of the infarct. Receiver operating characteristic (ROC) curve analysis was performed to identify the cutoff value of hsCRP to discriminate between favorable and unfavorable outcomes. The association of hsCRP with outcomes was evaluated using a logistic regression model. RESULTS: The best cutoff value of hsCRP to distinguish between favorable and unfavorable outcomes at three months was identified as 3.0 mg/L (area under the curve, [AUC] 0.641, 95% confidence interval, [CI] 0.535-0.748; P = 0.014). In, multivariate analysis, patients with hsCRP ≥3 mg/L had more unfavorable outcome (odds ratio [OR] 1.72, 95% CI 1.42-2.02; P = 0.010), sICH (OR 2.64, 95% CI 1.62-3.66; P = 0.004), and HT of infarct (OR 1.72, 95% CI 1.42-2.02; P = 0.008) compared to those with hsCRP <1 mg/L. CONCLUSION: Our study demonstrates that patients with higher CRP levels had more unfavorable outcome, and exhibited higher sICH, and HT of infarct than those with lower CRP levels. Elevated hsCRP level, especially when higher than 3 mg/L, is an independent predictor for poor clinical prognosis in patients with MT for LVO.

Impact of deceased donor multidrug-resistant bacterial organisms on organ utilization.

The extent to which donor multidrug-resistant organisms (MDROs) affect organ utilization remains unclear. We performed a retrospective cohort study at 4 transplant centers between 2015 and 2016 to evaluate this question. All deceased donors who donated at least one organ were included. Exposed donors had at least one MDRO on culture. Unexposed donors had no MDRO-positive cultures. Only cultures obtained during the donor's terminal hospitalization were evaluated. Multivariable regression was used to determine the association between donor MDRO and (1) number of organs transplanted per donor and (2) the match run at which each organ was accepted. Subsequently, we restricted the analysis to donors with MDR-Gram-negative (GN) organisms. Of 440 total donors, 29 (7%) donors grew MDROs and 7 (2%) grew MDR-GNs. There was no significant association between donor MDRO and either measure of organ utilization. However, donor MDR-GNs were associated with a significant reduction in the number of organs transplanted per donor (incidence rate ratio 0.43, 95% confidence interval [CI] 0.39-0.48, P < .01), and organs were accepted significantly further down the match list (relative count 5.08, 95% CI 1.64-15.68, P = .01). Though donor MDR-GNs were infrequent in our study, their growing prevalence could meaningfully reduce the donor pool over time.

NO• /RUNX3/kynurenine metabolic signaling enhances disease aggressiveness in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy and is refractory to available treatments. Delineating the regulatory mechanisms of metabolic reprogramming, a key event in pancreatic cancer progression, may identify candidate targets with potential therapeutic significance. We hypothesized that inflammatory signaling pathways regulate metabolic adaptations in pancreatic cancer. Metabolic profiling of tumors from PDAC patients with a high- (>median, n = 31) and low-NOS2 (inducible nitric oxide synthase;

Safety and Efficacy of Intra-arterial Tirofiban Injection During Mechanical Thrombectomy for Large Artery Occlusion.

OBJECTIVE: The safety and effect of intra-arterial (IA) tirofiban, a glycoprotein IIb/IIIa inhibitor, during the stent retriever mechanical thrombectomy (MT) was investigated. METHODS: From January 2015 to May 2019, a total of 327 patients underwent mechanical thrombectomy of large artery occlusions (LAO). Patients were classified into two groups: MT with IA tirofiban (MTT) group and MT only (MTO, without IA tirofiban) group. Clinical outcomes, radiological results, and various complications, such as post thrombectomy hemorrhage, symptomatic hemorrhage, other systemic bleeding, and hemorrhagic transformation of infarct were evaluated by comparing the MTT group and MTO group. In addition, subgroup analysis was performed for patients who underwent MT with prior intravenous (IV) tissue plasminogen activator (t-PA). RESULTS: The MTT group needed a lower mean number of stent passes and showed a re-occlusion rate as compared with the MTO group (P=0.038 and 0.022, respectively). Between the two groups, there were no statistically significant differences in post thrombectomy hemorrhage, symptomatic hemorrhage, other systemic bleeding complications, or hemorrhagic transformation of infarct (P = 0.511, 0.397, 0.429, and 0.355, respectively). In the subgroup analysis, similar findings were observed. CONCLUSION: The use of IA tirofiban during MT seems to be safe and potentially more effective than only MT without IA tirofiban, even in patients who used IV t-PA before MT.

Risk factors for multidrug-resistant organisms among deceased organ donors.

Donor infection or colonization with a multidrug-resistant organism (MDRO) affects organ utilization and recipient antibiotic management. Approaches to identifying donors at risk of carrying MDROs are unknown. We sought to determine the risk factors for MDROs among transplant donors. A multicenter retrospective cohort study was conducted at four transplant centers between 2015 and 2016. All deceased donors who donated at least one organ were included. Cultures obtained during the donor's terminal hospitalization and organ procurement were evaluated. The primary outcome was isolation of an MDRO on culture. Multivariable Cox regression was used to determine risk factors associated with time to donor MDRO. Of 440 total donors, 64 (15%) donors grew an MDRO on culture. Predictors of an MDRO on donor culture included hepatitis C viremia (hazard ratio [HR] 4.09, 95% confidence interval [CI] 1.71-9.78, P = .002), need for dialysis (HR 4.59, 95% CI 1.09-19.21, P = .037), prior hematopoietic cell transplant (HR 7.57, 95% CI 1.03-55.75, P = .047), and exposure to antibiotics with a narrow gram-negative spectrum (HR 1.13, 95% CI 1.00-1.27, P = .045). This is the first study to determine risk factors for MDROs among deceased donors and will be important for risk stratifying potential donors and informing transplant recipient prophylaxis.

Herpes simplex virus infections in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of HSV in the pre- and post-transplant period. A majority of transplant recipients are seropositive for HSV-1 or 2. Compared with immunocompetent persons, SOT recipients shed HSV more frequently, have more severe clinical manifestations, and are slower to respond to therapy. Most HSV infection is diagnosed on clinical grounds, but patients may present with atypical lesions and/or other clinical manifestations. Acquisition from the donor is rare. Polymerase chain reaction is the preferred diagnostic test unless culture is needed for resistance testing. For limited mucocutaneous lesions, oral therapy can be used; however, in severe, disseminated, visceral or CNS involvement, acyclovir doses of up to 10 mg/kg every 8 hours intravenously should be initiated. Acyclovir-resistant HSV is less common in SOT patients than in HSCT and can be treated with foscarnet, though other novel therapies are currently under investigation. HSV-specific prophylaxis should be considered for all HSV-1 and HSV-2-seropositive organ recipients who are not receiving antiviral medication for CMV prevention that has activity against HSV.

Favorable outcomes of culture-based Helicobacter pylori eradication therapy in a region with high antimicrobial resistance.

BACKGROUND: The eradication rate of Helicobacter pylori has declined, mainly due to antimicrobial resistance. To overcome resistance-associated treatment failure, the efficacy of culture-based, susceptibility-guided therapy was demonstrated as the first-line eradication therapy for H pylori infection. AIMS: To evaluate the efficacy of culture-based therapy as the first-line eradication therapy in regions with high levels of antimicrobial resistance. METHODS: Helicobacter pylori-positive patients without previous eradication treatment history were recommended to undergo culture to determine the minimal inhibitory concentration (MIC). If they consented, 7-day clarithromycin-containing PPI triple; 7-day esomeprazole, moxifloxacin, and amoxicillin (MEA) therapy; or 7- or 14-day esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapy were administered based on the agar dilution-determined MIC. Eradication, treatment compliance, and adverse events were examined. RESULTS: In total, 74 patients were enrolled, and 69 patients completed the protocols. The overall resistance rates to amoxicillin, clarithromycin, metronidazole, and moxifloxacin were 6.7%, 31.0%, 41.8%, and 39.2%, respectively. The patients were allocated to the PPI triple (n = 50), MEA (n = 8) or quadruple (n = 16) therapy. The eradication rate in the intention-to-treat analysis was 93.1% (69 of 74 patients). The eradication rates in the per-protocol analysis were 100.0% (69 of 69 patients). Epigastric pain, nausea, and vomiting were less common than those of other empirical therapies. CONCLUSIONS: Culture-based, susceptibility-guided therapy is effective first-line eradication therapy, especially in regions with high levels of antimicrobial resistance.

Kidney Transplantation in HIV-Positive Patients: A Single-Center, 16-Year Experience.

Hahnemann University Hospital has performed 120 kidney transplantations in human immunodeficiency virus (HIV)-positive individuals during the last 16 years. Our patient population represents ∼10% of the entire US population of HIV-positive kidney recipients. In our earlier years of HIV transplantation, we noted increased rejection rates, often leading to graft failure. We have established a multidisciplinary team and over the years have made substantial protocol modifications based on lessons learned. These modifications affected our approach to candidate evaluation, donor selection, perioperative immunosuppression, and posttransplantation monitoring and resulted in excellent posttransplantation outcomes, including 100% patient and graft survival at 1 year and patient and graft survival at 3 years of 100% and 96%, respectively. We present key clinical data, including a granular patient-level analysis of the associations of antiretroviral therapy regimens with long-term survival, cellular and antibody-mediated rejection rates, and the causes of allograft failures. In summary, we provide details on the evolution of our approach to HIV transplantation during the last 16 years, including strategies that may improve outcomes among HIV-positive kidney transplantation candidates throughout the United States.

ADHFE1 is a breast cancer oncogene and induces metabolic reprogramming.

Metabolic reprogramming in breast tumors is linked to increases in putative oncogenic metabolites that may contribute to malignant transformation. We previously showed that accumulation of the oncometabolite, 2-hydroxyglutarate (2HG), in breast tumors was associated with MYC signaling, but not with isocitrate dehydrogenase (IDH) mutations, suggesting a distinct mechanism for increased 2HG in breast cancer. Here, we determined that D-2HG is the predominant enantiomer in human breast tumors and show that the D-2HG-producing mitochondrial enzyme, alcohol dehydrogenase, iron-containing protein 1 (ADHFE1), is a breast cancer oncogene that decreases patient survival. We found that MYC upregulates ADHFE1 through changes in iron metabolism while coexpression of both ADHFE1 and MYC strongly enhanced orthotopic tumor growth in MCF7 cells. Moreover, ADHFE1 promoted metabolic reprogramming with increased formation of D-2HG and reactive oxygen, a reductive glutamine metabolism, and modifications of the epigenetic landscape, leading to cellular dedifferentiation, enhanced mesenchymal transition, and phenocopying alterations that occur with high D-2HG levels in cancer cells with IDH mutations. Together, our data support the hypothesis that ADHFE1 and MYC signaling contribute to D-2HG accumulation in breast tumors and show that D-2HG is an oncogenic metabolite and potential driver of disease progression.

Spatial distribution of polycyclic aromatic hydrocarbon and polychlorinated biphenyl sources in the Nakdong River Estuary, South Korea.

Our research team investigated the elemental composition and the presence of various toxic organic compounds, such as polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), in estuary surface sediments to trace the spatial distribution of the sources of pollution deposited in Nakdong River, Busan, South Korea. The spatial patterns of elemental composition and toxic organic compounds were determined from the measurements of total organic carbon (TOC), total nitrogen, total sulfur, PAHs, and PCBs. The sediments had TOC contents of between 0.02 and 1.80 wt% (avg. 0.34 wt%), depending on the amount of clay-sized particles. The concentrations of PAHs and PCBs (10.8-167.7 ng g-1 dry wt and 197.0-754.0 pg g-1 dry wt, respectively) in surface sediments revealed different spatial patterns for these compounds, suggesting that they partially originated from the combustion of fossil fuels and from the use of commercial PCB products at adjacent industrial complexes. Although these concentrations were far below the Sediment Quality Guideline (SQG) of the National Oceanic and Atmospheric Administration (NOAA), the sediments at one site contained PCBs at concentrations close to the response level (754.0 pg g-1 dry wt), and were dominated by low-molecular-weight PAHs. The PAHs and PCBs in Nakdong River Estuary sediments were likely to have originated from the combustion of fossil fuels and biomass at the adjacent industrial complexes. The primarily analyzed results determined that PAHs originated from the combustion of fossil fuels and biomass, and overall concentrations were related to the contributions of individual PAHs in most sediment samples. Based on the SQG of the NOAA, our results indicate that the anthropogenic activity should be considered on the future-sustainable management of this estuary system.

HIV in the dialysis population: Current issues and future directions.

Antiretroviral therapy has significantly reduced mortality due to HIV infection, but the aging HIV-positive patient population now faces a growing burden of comorbidity. This review describes the changing epidemiology of chronic kidney disease and end-stage renal disease in this population, and highlights recent advances in antiretroviral therapy and kidney transplantation that directly impact the care of patients with HIV infection and end-stage renal disease.

Association of tenofovir disoproxil fumarate with primary allograft survival in HIV-positive kidney transplant recipients.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is an antiretroviral agent frequently used to treat human immunodeficiency virus (HIV). There are concerns regarding its potential to cause acute kidney injury, chronic kidney disease, and proximal tubulopathy. Although TDF can effectively suppress HIV after kidney transplantation, it is unknown whether use of TDF-based antiretroviral therapy (ART) after kidney transplantation adversely affects allograft survival. METHODS: We examined 104 HIV+ kidney transplant (KT) recipients at our center between 2001 and 2014. We generated a propensity score for TDF treatment using recipient and donor characteristics. We then fit Cox proportional hazards models to investigate the association between TDF treatment and 3-year, death-censored primary allograft failure, adjusting for the propensity score and delayed graft function (DGF). RESULTS: Of the 104 HIV+ KT candidates who underwent transplantation during the study period, 23 (22%) were maintained on TDF-based ART at the time of transplantation, and 81 (78%) were on non-TDF-based ART. Median age of the cohort was 48 years; 87% were male; 88% were black; and median CD4 count at transplantation was 450 cells/mm3 . Median kidney donor risk index was 1.2. At 3 years post transplantation, primary allograft failure occurred in 26% of patients on TDF-based ART and in 28% of patients on non-TDF-based ART (P=.5). TDF treatment was not associated with primary allograft failure at 3 years post transplant after adjusting for DGF and a propensity score for TDF use (hazard ratio 2.12, 95% confidence interval 0.41-10.9). CONCLUSIONS: In a large single-center experience of HIV+ kidney transplantation, TDF use following kidney transplantation was not significantly associated with primary allograft failure. These results may help inform management for HIV+ KT recipients in need of TDF therapy for adequate viral suppression.