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The limited effectiveness of rituximab plus intravenous immunoglobulin (IVIG) in desensitization may be due to incomplete B cell depletion. Obinutuzumab is a type 2 anti-CD20 antibody that induces increased B cell depletion relative to rituximab and may therefore be more effective for desensitization. This open-label phase 1b study assessed the safety, pharmacokinetics, and pharmacodynamics of obinutuzumab in highly sensitized patients with end-stage renal disease. Patients received 1 (day 1, n = 5) or 2 (days 1 and 15; n = 20) infusions of 1000-mg obinutuzumab followed by 2 doses of IVIG on days 22 and 43. Eleven patients received additional obinutuzumab doses at the time of transplant and/or at week 24. The median follow-up duration was 9.4 months. Obinutuzumab was well tolerated, and most adverse events were grade 1-2 in severity. There were 11 serious adverse events (SAEs) in 9 patients (36%); 10 of these SAEs were infections and 4 occurred after kidney transplant. Obinutuzumab plus IVIG resulted in profound peripheral B cell depletion and appeared to reduce B cells in retroperitoneal lymph nodes. Reductions in anti-HLA antibodies, number of unacceptable antigens, and the calculated panel reactive antibody score as centrally assessed using single-antigen bead assay were limited and not clinically meaningful for most patients (NCT02586051).

The limited effectiveness of rituximab plus intravenous immunoglobulin (IVIG) in desensitization may be due to incomplete B cell depletion. Obinutuzumab is a type 2 anti-CD20 antibody that induces increased B cell depletion relative to rituximab and may therefore be more effective for desensitization. This open-label phase 1b study assessed the safety, pharmacokinetics, and pharmacodynamics of obinutuzumab in highly sensitized patients with end-stage renal disease. Patients received 1 (day 1, n = 5) or 2 (days 1 and 15; n = 20) infusions of 1000-mg obinutuzumab followed by 2 doses of IVIG on days 22 and 43. Eleven patients received additional obinutuzumab doses at the time of transplant and/or at week 24. The median follow-up duration was 9.4 months. Obinutuzumab was well tolerated, and most adverse events were grade 1-2 in severity. There were 11 serious adverse events (SAEs) in 9 patients (36%); 10 of these SAEs were infections and 4 occurred after kidney transplant. Obinutuzumab plus IVIG resulted in profound peripheral B cell depletion and appeared to reduce B cells in retroperitoneal lymph nodes. Reductions in anti-HLA antibodies, number of unacceptable antigens, and the calculated panel reactive antibody score as centrally assessed using single-antigen bead assay were limited and not clinically meaningful for most patients (NCT02586051).

ImportancePolicy makers, transplant professionals, and patient organizations agree that there is a need to increase the number of kidney transplants by facilitating living donation. Vouchers for future transplant provide a means of overcoming the chronological incompatibility that occurs when the ideal time for living donation differs from the time at which the intended recipient actually needs a transplant. However, uncertainty remains regarding the actual change in the number of living kidney donors associated with voucher programs and the capability of voucher redemptions to produce timely transplants.ObjectiveTo examine the consequences of voucher-based kidney donation and the capability of voucher redemptions to provide timely kidney allografts.Design, setting, and participantsThis multicenter cohort study of 79 transplant centers across the US used data from the National Kidney Registry from January 1, 2014, to January 31, 2021, to identify all family vouchers and patterns in downstream kidney-paired donations. The analysis included living kidney donors and recipients participating in the National Kidney Registry family voucher program.ExposuresA voucher was provided to the intended recipient at the time of donation. Vouchers had no cash value and could not be sold, bartered, or transferred to another person. When a voucher was redeemed, a living donation chain was used to return a kidney to the voucher holder.Main outcomes and measuresDeidentified demographic and clinical data from each kidney donation were evaluated, including the downstream patterns in kidney-paired donation. Voucher redemptions were separately evaluated and analyzed.ResultsBetween 2014 and 2021, 250 family voucher-based donations were facilitated. Each donation precipitated a transplant chain with a mean (SD) length of 2.3 (1.6) downstream kidney transplants, facilitating 573 total transplants. Of those, 111 transplants (19.4%) were performed in highly sensitized recipients. Among 250 vouc

BackgroundDespite the institution of a new Kidney Allocation System in 2014, A2/A2B to B transplantation has not increased as expected. The current Organ Procurement and Transplantation Network policy requires subtyping on two separate occasions, and in the setting of discrepant results, defaulting to the A1 subtype. However, there is significant inherent variability in the serologic assays used for blood group subtyping and genotyping is rarely done.MethodsThe National Kidney Registry, a kidney paired donation (KPD) program, performs serological typing on all A/AB donors, and in cases of non-A1/non-A1B donors, confirmatory genotyping is performed.ResultsBetween 2/18/2018 and 9/15/2020, 13.0% (145) of 1,111 type A donors registered with the NKR were ultimately subtyped as A2 via genotyping. Notably, 49.6% (72) of these were subtyped as A1 at their donor center, and in accordance with OPTN policy, ineligible for allocation as A2.ConclusionInaccurate A2 subtyping represents a significant lost opportunity in transplantation, especially in KPD where A2 donors can not only facilitate living donor transplantation for O and highly sensitized candidates, but can also facilitate additional living donor transplants. This study highlights the need for improved accuracy of subtyping technique, and the need for policy changes encouraging optimal utilization of A2 donor kidneys.

Adrian Majid, Robert R Redfield, Bruce L GilliamInstitute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USAAbstract: Infection with human immunodeficiency virus remains a global concern with a significant number of incident infections still reported worldwide. The use of prophylaxis prior to exposure to the virus to prevent infection has been a growing area of recent research. Results in nonhuman primates and clinical trials in high-risk patient populations using preexposure prophylaxis have shown promising results in terms of efficacy and safety, especially relating to oral preexposure prophylaxis. The potential use of oral antiretroviral agents traditionally used for human immunodeficiency virus treatment as prophylaxis raises interesting considerations, such as the best agents available for such a role, long-term safety in healthy individuals, and the potential development of resistance to these agents should infection occur. From a public health perspective, the cost-effectiveness of implementing this preventive strategy has not been fully defined at this point in time.Keywords: preexposure prophylaxis, human immunodeficiency virus, tenofovir, maraviroc

Characterization of the capacity of human polyclonal antibody to neutralize wild-type patient isolates has important implications for vaccine development. We report the development of a polymerase chain reaction-based neutralization assay that quantitatively measures each infection using HIV proviral formation, These molecular end points identified the absence or quantitative diminution of DNA provirus formation as well as a delay in the kinetics of HIV DNA provirus formation. Using both laboratory strain prototype isolates (HIV-1-MN, HIV-Illb) and primary wild-type patients' isolates. neutralization end points were reproducibly determined. End points were reached within 72 h, thereby minimizing the impact of subsequent rounds of infection on interpretation of results. Although the neutralization titer of polyclonal sera was usually comparable using standard technology, this assay did find isolate- dependent variation in the relationship between p24 production and HIV proviral DNA formation. Finally, we noted the disparity between the ability of human sera to neutralize prototype and wild-type isolates in primary peripheral blood mononuclear cell targets. We believe this assay provides unique opportunities to characterize the initial events of virus-antibody interaction and will help to elucidate clinically relevant neutralization immunoregulatory mechanisms., Pub. in Jnl. of Acquired Immune Deficiency Syndromes, v5 p1224-1229, 1992.

Interleukin-6(IL-6), a multifunctional cytokine produced in monocytes, fibroblasts, and other cell types, is induced by a variety of stimuli, including bacteria, viruses, and other cytokines. When normal monocyte cultures were exposed to a monocytotropic strain of human immunodeficiency virus (HIV), HTLV-III significant levels of IL-6 bioactivity were detected in the culture supernatants after 12 and 43 days of incubation, at a time when there was associated evidence of HIV production. Similarly, when normal monocyte cultures were cocultured with peripheral blood mononuclear cells from HIV-infected individuals, HIV replication in these cultures was associated with production of IL-6. Interleukin-6, (IL-6), a recently identified phospho-glycoprotein, is emerging as a multifunctional cytokine induced by a variety of stimuli. Monocytes, fibroblasts, keratinocytes, and endometrial stromal cells produce IL-6 in vitro on stimulation with different signals, such as bacteria, bacterial products, viruses, and certain cytokines., Published in Blood, v76 n11 p2303-2310, 1 December 1990. ISBN 0006-4971.

In October 1985 the US Department of Defense instituted a program for screening all civilian applicants for military service for evidence of infection with HIV. Data for the first six months of the program for the entire United States and its territories are summarized elsewhere. Of the 14 counties with the highest seroprevalence rates in the continental United States, four were contiguous counties in the New York area (New York, Kings, Queens, and Bronx). This report is a preliminary summary of current data on demographic factors associated with HIV infection in these four counties. Reprints., Pub in New York State Jnl. of Medicine, v87 p262-264 May 1987

This editorial points out the different purposes for Center For Disease Control (CDC) case definition and the Walter Reed (WR) staging classification of HIV infection. CDC classification having a primarily epidemiological and public health bias while WR classification a prognostic and severity of illness indicator for a specific patient. Authors agree with Dr. Justice who wants a classification system for patients with end stage disease, but believe her system fall short in four areas, 1) use of CDC definition as starting place, 2) possibility of biased patient population as basis, 3) use of broad measures of physiologic deficits, 4) inability of system to predict survivability of end stage patients. Keywords: Acquired immunodeficiency syndrome; Human immunodeficiency virus; Disease stages; Human immunodeficiency virus infection. Reprints., Pub. in the New England Jnl. of Medicine, v320 p1414-1416, 25 May 1989.

Serum samples from 27 patients infected with human T -cell lymphotropic virus type III (14 with acquired immune deficiency syndrome AIDS and 13 with AIDS-related complex) were examined for antibodies to viral poteins by the Western blot method and with four different commercial solid-phase enzyme-linked immunosorbent assays (ELISAs). Virus-specific bands on blots at molecular masses 64, 55, 53, 41, 31, 24, and 17 kilodaltons were observed. Rank collelation matrices were calculated to relate the intensity of viral bands, stage of illness, and ELISA kit optical densities (ODs). Groups of bands tended to covary in intensity: p17, p24, and p55 (gang gene products); p53 and p64 (pol gene products); and p31 (pol/endonuclease gene product ) and p41 (env gene product). Blots of sera from AIDS-related complex patients usually showed strong activity against all viral poteins, while those of sera from AIDS patients characteristically showed strong reactivity only at the pol/endonuclease and env bands. For one ELISA kit (Abbott Laboratories, North Chicage, Ill.), ODs correlated well with the env and pol band intensity scores, while ELISA ODs with other kit (from Litton Industries, Sunnyvale, Calif; Electro-Nucleonics, Inc., Fairfeild, N.J.; and E.I. du Pont de Nemours & Co., Inc., Wilmington, Del.) correlated closely with gag band intensity scores. We concluded that human T-cell lymphotopic virus type III Western blot patterns are determined by (i) viral protein processing pathways and (ii) the stage of illness of the patient and may reflect (iii) the ELISA method used for serum screening. Reprints.