# Kidney Transplantation from Donors with HIV: Impact on Rejection and Long-term Outcomes

> **NIH NIH U01** · JOHNS HOPKINS UNIVERSITY · 2024 · $1,727,039

## Abstract

Under the HIV Organ Policy Equity (HOPE) Act, early studies show that kidney transplantation (KT) from
donors with HIV to recipients with HIV (HIV D+/R+) expands the donor pool, reduces wait-times, and yields
excellent short-term patient and graft survival. However, significant rates of rejection were observed with a
trend towards higher rates in D+ recipients compared to HIV-uninfected donor (D-) recipients. Understanding
the impact of D+ on rejection, underlying mechanisms, and the impact on long-term outcomes is critical.
There are potential virologic and immunologic explanations for higher rejection in HIV D+/R+ vs D-/R+ KT. D+
kidneys harbor HIV and are more likely to harbor other co-infections such as CMV. These pathogens may
trigger an inflammatory response, enhancing T-cell or antibody(Ab)-mediated pathways of rejection.
Understanding the type of rejection and risk factors will inform interventions to improve outcomes, e.g. HIV D+
selection criteria, immunosuppression, or targeted monitoring and prophylaxis for co-infections.
We propose Expanding HOPE, a multicenter trial comparing outcomes in 100 HIV D+/R+ KT and 100 D-/R+
KT at 15 transplant centers. We will combine this cohort with prior cohorts of HIV D+ and D- KT from our
HOPE in Action Consortium, established in 2015. HOPE in Action has accrued approximately 325 HIV+ KT
recipients to date; this larger cohort provides sufficient statistical power to determine the impact of HIV D+
organ on rejection and it will also allow us to determine long-term patient and graft outcomes beyond 5 years.
Within this trial, we will perform comprehensive mechanistic studies to examine both T-cell and Ab-mediated
rejection pathways. We will quantify changes in donor-specific and viral-specific (HIV CMV) T cells using an
activated induced marker (AIM) assay in D+ and D- recipients, with and without rejection, over time. We will
perform TCRβ immunosequencing on sorted AIM+ cells vs unsorted T cells to track T cell receptor dynamics.
With VDJ-specific PCR, we will quantify expanded clones, including donor or viral AIM+ cells, post-KT.
We will also characterize inflammation and the humoral response to infections and human proteins (donor,
self). We will use a multiplexed electrochemiluminescence detection assay to quantify >30 cytokine and
chemokines to characterize inflammation, and phage display and immunoprecipitation sequencing to
characterize Abs to >1300 viruses, >14,000 microbial toxins/virulence factors, and >27,000 human autoAbs.
Our HOPE in Action Multicenter Consortium has an established track record, successfully completing
multicenter transplantation trials, including HIV D+/R+ KT. We will leverage our existing infrastructure to
oversee operations, data management, analysis, and safety monitoring.
In summary, the proposed research will determine the impact of HIV+ donor kidneys on rejection, will quantify
long term outcomes, and elucidate risks and mechanisms of rejection. This knowledge can i...

## Key facts

- **NIH application ID:** 10848468
- **Project number:** 5U01AI177211-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Christine Marie Durand
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,727,039
- **Award type:** 5
- **Project period:** 2023-05-25 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848468

## Citation

> US National Institutes of Health, RePORTER application 10848468, Kidney Transplantation from Donors with HIV: Impact on Rejection and Long-term Outcomes (5U01AI177211-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10848468. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*