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HIV broadly neutralizing antibodies (bnAbs) have been shown to occasionally display unusual virus neutralization profiles with nonsigmoidal slopes and plateaus at <100% neutralization against a variety of viruses. The significance of incomplete neutralization for the ability of bnAbs to mediate protective effects vo, however, is undetermined. In the current study, we selected two bnAbs, PGT121 and 3BNC117, as they incompletely neutralize the clade C simian-human immunodeficiency virus (SHIV) stock (SHIV-327c) at 85% and 70%, respectively, and performed a protection study in rhesus macaques. The animals were intravenously (i.v.) administered PGT121 or 3BNC117 at 10 and 2 mg/kg of body weight before being rectally challenged with a single high dose of SHIV-327c. PGT121 protected 6 out of 7 monkeys, while 6 out of 7 3BNC117-pretreated animals became infected, although with significantly delayed plasma viremia compared to the control animals. These data suggest that complete neutralization is not imperative for bnAbs to prevent infection but that with increasing levels of incomplete neutralization the sterilizing activity diminishes. Multiple antibodies have been identified that potently neutralize a broad range of circulating HIV strains. However, not every virus-antibody combination results in complete neutralization of the input virus, suggesting that a fraction of virus particles are resistant to antibody neutralization despite high antibody concentrations. This observation of "incomplete neutralization" is associated with nonsigmoidal neutralization curves plateauing below 100% neutralization, but the significance of the phenomenon for the ability of neutralizing antibodies to mediate protective effects is undetermined. In this study, we show that the broadly neutralizing antibody PGT121, which neutralized only up to 85% of the SHIV-327c challenge stock, protected 6 out of 7 rhesus macaques against infection while the antibody 3BNC117, which neutralized up to 70% of SHIV-327c , did not prevent, though it significantly delayed, establishment of infection, suggesting that with increasing levels of incomplete neutralization the ability of a bnAb to mediate sterilizing protection diminishes.

Introduction The advent of direct‐acting antivirals (DAAs) has created an avenue for transplantation of hepatitis C virus (HCV)‐infected donors into uninfected recipients (D+/R−). The donor transmission of HCV is then countered by DAA administration during the post‐operative period. However, initiation of DAA treatment is ultimately dictated by insurance companies. Methods A retrospective chart review of 52 D+/R− kidney recipients who underwent DAA treatment post‐transplant was performed. Patients were grouped according to their prescription coverage plans, managed by either commercial or government pharmacy benefit managers (PBMs). Results Thirty‐nine patients had government PBMs and 13 had commercial PBMs. Demographics were similar between the two groups. All patients developed HCV viremia, but cleared the virus after treatment with DAA. Patients with government PBMs were treated earlier compared to those with commercial PBMs (11 days vs 26 days, P = .01). Longer time to DAA initiation resulted in higher peak viral loads (β = 0.39, R2 = .15, P = .01) and longer time to HCV viral load clearance (β = 0.41, R2 = .17, P = .01). Conclusions D+/R− transplantation offers patients an alternative strategy to increase access. However, treatment can be profoundly delayed by a third‐party payer authorization process that may be subjecting patients to unnecessary risks and worsened outcomes.

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Background: Transplant recipients are susceptible to cardiovascular complications, obesity, and increased insulin resistance after transplant. Here we assess weight gain in diabetic recipients after pancreas transplantation. Methods: This is a single-center study of 32 simultaneous pancreas and kidney and 5 pancreas after kidney transplant recipients from 2014 to 2018. Starting C-peptide levels ≤ 0.1 ng/mL were used to denote insulin nondetectability (n = 25) and C-peptide levels > 0.1 ng/mL as insulin detectability (n = 12). Hemoglobin A1c, body mass index (BMI), and weight following transplantation were assessed. Results: Hemoglobin A1c at 1 year was 5.9% in the insulin nondetectable recipients and 5.6% in the insulin detectable group ( P = .56). Average BMI after transplant was higher in the insulin detectable group 28.6 versus 24.4 kg/m2 ( P = .03) despite no difference in starting BMIs (24.9 versus 24.0 kg/m2, P = .42). The insulin detectable group also had a larger percentage weight change from their starting weight 13.1% versus 0.9 % at 1 year ( P = .02). Linear regression demonstrated that starting C-peptide was a significant predictor of weight gain posttransplant. Conclusions: Patients with elevated C-peptides at time of transplant are susceptible to rapid weight gain postoperatively. These patients may benefit from aggressive nutritional management.

The advent of direct‐acting antivirals (DAAs) has provided the impetus to transplant kidneys from hepatitis C virus‐positive donors into uninfected recipients (D+/R−). Thirty D+/R− patients received DAA treatment. Sustained virologic response (SVR12) was defined as an undetectable viral load in 12 weeks after treatment. An age‐matched cohort of uninfected donor and recipient pairs (D−/R−) transplanted during same time period was used for comparison. The median day of viral detection was postoperative day (POD) 2. The detection of viremia in D+/R− patients was 100%. The initial median viral load was 531 copies/μL (range: 10‐1 × 108 copies/μL) with a median peak viral load of 3.4 × 105 copies/μL (range: 804‐1.0 × 108 copies/μL). DAAs were initiated on median POD 9 (range: 5‐41 days). All 30 patients had confirmed SVR12. During a median follow‐up of 10 months, patient and graft survival was 100%, and acute rejection was 6.6% with no major adverse events related to DAA treatment. Delayed graft function was significantly decreased in D+/R− patients as compared to the age‐matched cohort (27% vs 60%; P = .01). D+/R− transplantation offers patients an alternative strategy to increase access.

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