Clinical trial NCT06659952: HIV+ Deceased Donor Heart Transplant Study for HIV+ Recipients
Official title: A Prospective Study of HIV+ Deceased Donor Heart Transplant for HIV+ Recipients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: HIV Infection
Advanced End Stage Heart Failure
Keywords: HIV positive donor
HIV positive recipient
Heart transplant
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2024-10-26
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: "Natural randomization" will take place as OPTN organ offers become available and will be assigned to either arm based on whether the subject accepts/ declines the HIV+ donor heart.
Primary purpose: TREATMENT

Brief summary: This will be a prospective single-center interventional trial to compare the outcomes of HIV-positive heart transplant recipients by the HIV status of the donor; HIV-positive vs. HIV-negative and learn whether heart organ transplantation from HIV+ deceased donors is as safe and effective in HIV+ recipients as transplants from HIV- deceased donors.

Patient will undergo standard evaluation for eligibility of transplantation by the primary heart transplant team. If patient meets eligibility criteria, they will be informed about the study and consent will be obtained. Informed consent will be obtained in a private clinic or inpatient hospital room in a confidential setting. HIV-positive or HIV-negative offers will be made by Organ Procurement and Transplantation Network (OPTN) (serving as a means of "natural randomization" and this information will also be collected, along with the information regarding any information for primary offer declines from the patients as well as other clinical indications to decline an organ offer. As a result of this, there will be two main groups in the study participants that will undergo analysis:

1. patients/recipients that are HIV+ who receive an organ from an HIV+ donor (HIV D+/R+ group)
2. patients/recipients that are HIV+ who receive an organ from an HIV negative donor (HIV D-/R+ group)

Only study participants will be able to receive organ offers from both HIV-positive and HIV-negative organ donors whichever is available first regardless of HIV status. This is the only study intervention. Baseline visit parameters will be obtained during a routine heart transplant visit. There will be no additional procedures or blood collection after the baseline study visit.

Study data will be collected from chart review of routine post-transplant follow-up visits at weeks 52 (1 year), 104 (2 years), and 152 (3 years) after the transplant.

Detailed description: The primary objective is to evaluate the safety of heart transplantation in HIV-positive recipients and to study any potential complications of solid organ transplantation in the recipient, as well as assess the long-term health and mortality.

Secondary objectives are to compare other clinical outcomes between HIV+ transplant recipients of hearts from HIV+ and HIV- donors.

HIV D+/R+ transplantation is still less common than HIV D-/R+ transplantation due to the overall availability of donor organs. Additionally, most of the HIV D+/R+ transplants have been done for kidney transplants. Overall, there is more data accruing regarding transplantation and HIV disease, but most of the procedures are done in the kidney and liver organ systems. Not only is it important to further expand the donor pool for patients with HIV and heart failure, further data is needed in thoracic organ transplantation and HIV-positive recipients. The HIV Organ Policy Equity Act (HOPE Act - enacted on November 21, 2013), made it possible for an HIV+ recipient to receive an HIV+ organ as a part of a research study.

HIV+ Deceased Donor Criteria:

1. Donation after brain death or cardiac death.
2. HIV+ donors have confirmed or suspected HIV infection\* (by medical record history and/or a licensed HIV test.) If HIV infection is diagnosed during the donor evaluation process, a second confirmatory test will be required).
3. Donor has no active opportunistic infections, neoplasms, or severe acute retroviral syndrome; if previous history of an opportunistic infection, donor has received appropriate treatment.
4. Donors may have any HIV-1 RNA viral load provided a safe, tolerable and effective post-transplant antiretroviral regimen to be prescribed for the recipient is anticipated, described and justified.
5. Donors with active hepatitis C virus (HCV) infection (detectable HCV nucleic acid by licensed assay in a Clinical Laboratory Improvement Amendments (CLIA) certified lab are acceptable based on local site practice.

Eligibility criteria: Inclusion Criteria:

All individuals with advanced heart failure and HIV infection who meet the study inclusion and exclusion criteria will be eligible for participation in the study.

* Participant meets the standard criteria for heart transplant at the local center.
* Participant is able to understand and provide informed consent.
* Participant meets with an independent advocate per the HOPE Act Safeguards and Research Criteria.
* Documented HIV infection (by any licensed assay, or documented history of detectable HIV-1 RNA).\*
* Participant is ≥ 18 years old.
* Opportunistic complications: if prior history of an opportunistic infection, the participant has received appropriate therapy and has no evidence of active disease. Medical record documentation should be provided whenever possible.\*
* CD4+ (cluster of differentiation 4+) T-cell count: ≥ 200/μL within 16 weeks of transplant.\*
* HIV-1 RNA is below 50 copies RNA/mL.\*/\*\* Viral blips between 50-400 copies will be allowed as long as there are not consecutive measurements \> 200 copies/mL. \*\*Organ recipients who are unable to tolerate ART due to organ failure or recently started Antiretroviral Therapy (ART) may have detectable viral load and still be eligible if a safe and effective antiretroviral regimen to be used by the recipient after transplantation is described.
* Participant is willing to comply with all medications related to their transplant and HIV management.
* For participants with a history of aspergillus colonization or disease, no evidence of active disease.
* The participant must have or be willing to start seeing a primary medical care provider with expertise in HIV management.
* Agreement to use contraception; according to the FDA Office of Women's Health (http://www.fda.gov/birthcontrol), there are a number of birth control methods that are more than 80% effective. Female participants of child-bearing potential must consult with their physician and determine the most suitable method(s) from this list to be used from the time that study treatment begins until after study completion.
* Participant is not suffering from significant wasting (e.g. body mass index \< 21) thought to be related to HIV disease.

Exclusion Criteria:

Individuals who meet any of these criteria are not eligible for enrollment as study participants:

* Participant has a history of progressive multifocal leukoencephalopathy (PML) or primary central nervous system (CNS) lymphoma.\*
* Participant is pregnant or breastfeeding. (Note: Participants who become pregnant post-transplant will continue to be followed in the study and will be managed per local site practice. Women that become pregnant should not breastfeed.)
* Past or current medical problems or findings from medical history, physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

Primary outcomes:
measure: Time to a composite event of all-cause-mortality, graft failure, graft function
timeFrame: 4 years post-transplant
Secondary outcomes:
measure: Number of participants who survived
timeFrame: 4 years post-transplant
measure: Incidence of Graft survival
timeFrame: 4 years post-transplant
measure: Number of Participants With One or More Serious Adverse Experience (SAE)
timeFrame: 4 years post-transplant
measure: Number of participants with graft rejection
timeFrame: 4 years post-transplant
measure: Incidence of graft function
timeFrame: 4 years post-transplant
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Ricardo La Hoz, M.D.
role: PRINCIPAL_INVESTIGATOR
References: