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BACKGROUND: Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population. METHODS: Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D - [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS: HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P

Kidney transplantation from donors with HIV to recipients with HIV (HIV [D.sup.+]/[R.sup.+]) is an emerging practice that has shown substantial clinical benefit. Sustained HIV superinfection, whereby a transplant recipient acquires a new strain of HIV from their organ donor, is a theoretical risk, which might increase chances of viral failure. In this issue of theJCI, Travieso, Stadtler, and colleagues present phylogenetic analysis of HIV from kidney tissue, urine, plasma, and cells from 12 HIV [D.sup.+]/[R.sup.+] kidney transplants out to five years of follow-up. Early after transplant, donor HIV was transiently detected in five of 12 recipients, primarily from donors with untreated HIV and high-level viremia, consistent with a viral inoculum. Long-term, donor HIV was not detected in any recipients, demonstrating no sustained HIV superinfection. These reassuring data support earlier findings from South Africa and the United States and further confirm the safety of HIV [D.sup.+]/[R.sup.+] transplantation., The HOPE Act Solid organ transplantation is considered the optimal therapy for end-stage organ disease, including in people with HIV (PWH). However, a lack of donated organs constitutes a public [...]

BACKGROUND: Living kidney donation is possible for people living with HIV (PLWH) in the United States within research studies under the HIV Organ Policy Equity (HOPE) Act. There are concerns that donor nephrectomy may have an increased risk of end-stage renal disease (ESRD) in PLWH due to HIV-associated kidney disease and antiretroviral therapy (ART) nephrotoxicity. Here we report the first 3 cases of living kidney donors with HIV under the HOPE Act in the United States. METHODS: Within the HOPE in Action Multicenter Consortium, we conducted a prospective study of living kidney donors with HIV. Pre-donation, we estimated the 9-year cumulative incidence of ESRD, performed genetic testing of apolipoprotein L1 (APOL1), excluding individuals with high-risk variants, and performed pre-donation kidney biopsies (HOPE Act requirement). The primary endpoint was ≥grade 3 nephrectomy-related adverse events (AEs) in year one. Post-donation, we monitored glomerular filtration rate (measured by iohexol/Tc-99m DTPA [mGFR] or estimated with serum creatinine [eGFR]), HIV RNA, CD4 count, and ART. FINDINGS: There were three donors with two-four years of follow-up: a 35 year-old female, a 52 year-old male, and a 47 year-old male. Pre-donation 9-year estimated cumulative incidence of ESRD was 3.01, 8.01, and 7.76 per 10,000 persons, respectively. In two donors with APOL1 testing, no high-risk variants were detected. Biopsies from all three donors showed no kidney disease. Post-donation, two donors developed nephrectomy-related ≥grade 3 AEs: a medically-managed ileus and a laparoscopically-repaired incisional hernia. GFR declined from 103 to 84 mL/min/1.73 m2 at four years (mGFR) in donor 1, from 77 to 52 mL/min/1.73 m2 at three years (eGFR) in donor 2, and from 65 to 39 mL/min/1.73 m2 at two years (eGFR) in donor 3. HIV RNA remained

BackgroundOrgan transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety.MethodsWe performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors.ResultsBetween March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL

BACKGROUND: Few reports have focused on newer coronavirus disease 2019 (COVID-19) therapies (remdesivir, dexamethasone, and convalescent plasma) in solid organ transplant recipients; concerns had been raised regarding possible adverse impact on allograft function or secondary infections. METHODS: We studied 77 solid organ transplant inpatients with COVID-19 during 2 therapeutic eras (Era 1: March-May 2020, 21 patients; and Era 2: June-November 2020, 56 patients) and 52 solid organ transplant outpatients. RESULTS: In Era 1, no patients received remdesivir or dexamethasone, and 4 of 21 (19.4%) received convalescent plasma, whereas in Era 2, remdesivir (24/56, 42.9%), dexamethasone (24/56, 42.9%), and convalescent plasma (40/56, 71.4%) were commonly used. Mortality was low across both eras, 4 of 77 (5.6%), and rejection occurred in only 2 of 77 (2.8%) inpatients; infections were similar in hypoxemic patients with or without dexamethasone. Preexisting graft dysfunction was associated with greater need for hospitalization, higher severity score, and lower survival. Acute kidney injury was present in 37.3% of inpatients; renal function improved more rapidly in patients who received remdesivir and convalescent plasma. Post-COVID-19 renal and liver function were comparable between eras, out to 90 d. CONCLUSIONS: Newer COVID-19 therapies did not appear to have a deleterious effect on allograft function, and infectious complications were comparable.

A successful multidisciplinary research center depends on the quality of the science being conducted and the quality of the center's design, culture, infrastructure, and institutional support. In this perspective, we describe our experience building and maintaining a multidisciplinary transplant research center with a large focus on transplant infectious diseases. We identify principles that we believe contributed to our success including: taking inventory, defining culture, creating a multidisciplinary shared leadership model, establishing expertise in a multiple method approach, investing in operations and management, building and sharing resources, and securing institutional support. We share our experience putting these principles into practice and highlight potential roadblocks. [ABSTRACT FROM AUTHOR]

Purpose: Kidney transplantation has a survival benefit for people with human immunodeficiency virus (HIV) and end‐stage kidney disease, however increased rates of rejection remain an issue. Questions remain regarding the impact of induction immunosuppression therapy and antiretroviral (ARV) choice on long‐term outcomes. Methods: We performed a multicenter retrospective analysis of outcomes in recipients with HIV who received kidneys from donors without HIV transplanted between 2004 and 2019. The association between induction and ARV regimens and long‐term outcomes including rejection, graft, and recipient survival over 5 years was investigated using Cox regression modeling. Results: Seventy‐eight kidney transplants (KT) performed in 77 recipients at five US transplant centers were included, with median follow up of 7.1 (4.3–10.7) years. Overall recipient and graft survival were 83% and 67%, respectively. Rejection occurred in 37% (29/78). Recipients with rejection were more likely to be younger, recipients of deceased donor organs, and Black. Receipt of rabbit anti‐thymocyte globulin (rATG) induction without protease‐inhibitor (PI)‐based ARVs was associated with 83% lower risk of rejection (adjusted hazard ratio (aHR) 0.17 (95% CI 0.05–0.63), p =.007) and a non‐statistically significantly lower risk of graft failure (aHR 0.18 (0.03–1.16), p =.07) when compared to those who received other induction and ARV combinations. Conclusions: In this multicenter retrospective study, we found a trend toward lower rejection and improved graft survival among those who received both rATG for induction and PI‐sparing ARVs. [ABSTRACT FROM AUTHOR]

Background: Solid organ transplant recipients are at an increased risk for anogenital Human Papillomavirus (HPV)‐related disease, including anal high‐grade squamous intraepithelial lesions (HSIL) and anal squamous cell cancer (ASCC). Guidelines for ASCC screening in transplant recipients are limited. Our aim was to understand current practice of ASCC screening in adult liver transplant (LT) candidates and recipients at transplant centers across the United States. Methods: We surveyed medical directors of 113 LT centers across the United States which had publicly available contact information. The survey evaluated center perceptions on cancer and HPV disease risk in transplant populations, ASCC screening, barriers and facilitators for ASCC screening and HPV vaccination practices. Results: We received 26/113 (23%) responses, of which 24 were complete and included in the analysis. Eleven of 24 (46%) centers reported screening for ASCC and 3/24 (12.5%) centers reported having formal guidelines. Centers who perform ASCC screening were more likely to perform transplants in people living with HIV and were more aware of the burden of HPV disease in transplant populations. All respondents believed that additional data on the impact of screening on ASCC incidence would support screening decisions. Increased access to specialists for screening/high‐resolution anoscopy was also perceived as a facilitator. Only 7/24 (29%) centers regularly evaluated HPV vaccination status of their patients. Conclusion: This national survey of LT centers reveals non‐standardized ASCC screening practices, and identified data, educational and resource needs to improve prevention of ASCC in this population. [ABSTRACT FROM AUTHOR]

Kidney transplant recipients (KTRs) develop decreased antibody titers to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination compared to healthy controls (HCs), but whether KTRs generate antibodies against key epitopes associated with neutralization is unknown. Plasma from 78 KTRs from a clinical trial of third doses of SARS-CoV-2 vaccines and 12 HCs underwent phage display immunoprecipitation and sequencing (PhIP-Seq) to map antibody responses against SARS-CoV-2. KTRs had lower antibody reactivity to SARS-CoV-2 than HCs, but KTRs and HCs recognized similar epitopes associated with neutralization. Thus, epitope gaps in antibody breadth of KTRs are unlikely responsible for decreased efficacy of SARS-CoV-2 vaccines in this immunosuppressed population. Clinical Trials Registration.  NCT04969263. [ABSTRACT FROM AUTHOR]

Anti-spike antibody (Ab) assays were authorized to determine prior exposure to SARS-CoV-2 and have since been adopted by some clinicians to measure humoral response to vaccination and estimate vulnerability to infection.[[1]] As such, many commercial assays currently in use for clinical and research purposes have not undergone validation in the setting of high antibody concentrations which may be achieved through repeat antigen exposure or monoclonal antibody (mAb) therapies.[3] This is noteworthy because immunoassays used in other settings have been observed to return imprecise or artifactually low quantitative results due to a "hook" or prozone effect in undiluted samples at their upper limits of quantification, that is, in the setting of very high binding antibody titers.[4] We sought to determine whether a hook effect occurs in a semi-quantitative binding assay (Roche-Elecsys anti-SARS-CoV-2 S) which is widely used by medical providers and researchers, given potential clinical implications, particularly for vulnerable populations such as solid organ transplant recipients (SOTRs). Participants in the clinical trial were SOTRs with known poor response to vaccination, and developed lower peak Ab titers, therefore, the reported hook effect proportion may be an underestimate as compared to the general vaccinated SOTR population. Letter to the editor: "hook" (prozone) effect in sars-cov-2 anti-spike binding antibody levels following vaccination, infection, or monoclonal antibody in solid organ transplant recipients. [Extracted from the article]