Hope heart study: a clinical trial of HIV to HIV transplantation

Award Details: New York University School of Medicine received a $1.72M Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), awarded April 20, 2026, with completion targeted for March 31, 2033.

Deliverables and Scope: This grant funds the HOPE Heart Study, a multicenter clinical trial evaluating the safety and efficacy of heart transplantation from human immunodeficiency virus (HIV)-positive donors to HIV-positive recipients (HIV D+/R+). The research will enroll 40 HIV D+/R+ and 40 HIV D-/R+ (HIV-negative donor) heart transplant recipients across 25 transplant centers over five years. Primary deliverables include comparative outcome analyses examining rejection, graft failure, and mortality between the two cohorts, mechanistic studies characterizing dysregulated adaptive immune responses linking to allograft inflammation and fibrosis, and clinical endpoint correlations. The trial builds on the investigator team's prior landmark kidney and liver HOPE transplant trials and their experience performing the world's first HIV D+/R+ heart transplants, with recipients demonstrating survival outcomes comparable to non-HIV recipients. This research directly supports clinical expansion of HIV organ transplantation beyond research protocols to broader clinical practice, thereby addressing critical organ shortage and waitlist mortality challenges for both HIV-positive and HIV-negative transplant candidates.

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.