HOPE Heart study: A Clinical Trial of HIV to HIV Transplantation

About This Grant

PROJECT SUMMARY/ABSTRACT We led the landmark trials in kidney (U01AI134591; NEJM 2024) and liver (U01AI138897) to establish the safety and efficacy of HOPE transplants, resulting in the 2024 HHS decision to expand HIV D+/R+ kidney and liver transplantation beyond research protocols to clinical practice. Yet the HOPE Act promise of heart transplants remains unrealized. People with HIV have twice the risk of clinical heart failure as the general population (6.5% prevalence), and HIV-associated cardiomyopathy is a major long-term complication of HIV infection. Transplanting hearts from donors with HIV (HIV D+) could lead to substantial public health benefit by decreasing the organ shortage, wait times, and waitlist mortality for people with and without HIV on the heart waitlist. Heart transplantation from donors without HIV to recipients with HIV (HIV D-/R+) confers a substantial survival advantage (77% vs 33% at 5 years), with post-transplant survival comparable to recipients without HIV. We performed the world’s first HIV D+/R+ heart transplants, and our 6 recipients are alive with follow-up as long as 3 years. In the proposed multicenter trial, we will evaluate the safety and efficacy of HIV D+/R+ heart transplantation. Furthermore, we will conduct important mechanistic studies to characterize dysregulated adaptive immune responses common to HIV and transplantation, linking them with allograft inflammation/fibrosis and clinical endpoints in the trial. Participants with HIV will be offered HIV D+ and HIV D- (including false positive) hearts as they become available in a quasi-random process mimicking a randomized trial. We will compare outcomes in 40 HIV D+/R+ and 40 HIV D-/R+ heart transplant recipients, enrolled over 5 years at 25 transplant centers. We aim: (1) to compare heart transplant outcomes (rejection, graft failure, and mortality) between HIV D+/R+ and HIV D-/R+, (2) to investigate whether dysregulated adaptive immune responses are associated with increased progression of inflammation and rejection after transplantation, in HIV D+/R+ recipients versus HIV D-/R+ recipients, and (3) to investigate whether HIV D+/R+, versus HIV D-/R+ recipients, demonstrate more intragraft inflammation and fibrosis, particularly whether inflammation and subclinical fibrosis in HIV D+ donor hearts is associated with clinical endpoints of the trial, and whether rejection in HIV D+/R+ has a distinct phenotype from rejection in HIV D-/R+. The proposed trial will determine whether the use of hearts from HIV D+ donors is safe and effective. If HIV D+/R+ transplantation can be implemented, the additional donors will help save the lives of both patients with and without HIV. The mechanistic studies have been designed to complement clinical endpoints, ensuring the knowledge gained will be novel and informative regardless of outcomes.