Final Revised Human Immunodeficiency Virus (HIV) Organ Policy Equity Act Safeguards and Research Criteria for Transplantation of Organs From Donors With HIV, 106542-106548 [2024-31265]

Agencies

• DEPARTMENT OF HEALTH AND HUMAN SERVICES
• National Institutes of Health

[Federal Register Volume 89, Number 249 (Monday, December 30, 2024)]
[Notices]
[Pages 106542-106548]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-31265]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Final Revised Human Immunodeficiency Virus (HIV) Organ Policy 
Equity Act Safeguards and Research Criteria for Transplantation of 
Organs From Donors With HIV

AGENCY: National Institutes of Health, Department of Health and Human 
Services.

ACTION: Final notice.

-----------------------------------------------------------------------

SUMMARY: Kidney and liver transplants from donors with HIV no longer 
require institutional review board (IRB)-approved research protocols or 
compliance with HHS research criteria per a November 27, 2024, final 
rule. Through this notice, the U.S. Department of Health and Human 
Services (HHS) announces the publication of this accompanying Final 
Revised Safeguards and Research Criteria for Transplantation of Organs 
from Donors with HIV to apply to non-kidney and non-liver organs from 
donors with HIV for transplantation in recipients with HIV. Under the 
HOPE Act, these transplants must still occur under an IRB-approved 
research protocol that is compliant with federal regulations governing 
human subjects' research. The goal of this research is to increase 
knowledge about the safety, efficacy, and effectiveness of transplants

[[Page 106543]]

other than liver and kidney, from donors with HIV, thereby expanding 
access to organs for patients with HIV in need of transplants. HHS 
published Draft Revised Safeguards and Research Criteria on December 
12, 2024. A summary of the public comments and HHS' responses follows. 
As explained below, NIH adopts revised research criteria as proposed 
except that NIH removed residual stigmatizing language from the title 
of the Research Criteria.

FOR FURTHER INFORMATION CONTACT: Dr. Jonah Odim, Chief Clinical 
Transplantation Section, Transplantation Branch, 5601 Fishers Lane, 
Room 6B21, MSC 9827, Rockville, MD 20892-9827; by email at 
[email protected]; by telephone at (301) 828-7220.

SUPPLEMENTARY INFORMATION:

Background

A. HHS Oversight of Organ Allocation and Transplantation

    HHS is responsible for overseeing the operation of the nation's 
OPTN, including assisting in the equitable allocation of donor organs 
for transplantation. 42 U.S.C. 274(b)(2)(D). The OPTN is a network of 
transplant centers, organ procurement organizations, and other 
providers who work collectively to develop, implement, and monitor 
organ allocation policy and performance of the organ transplant system. 
The OPTN is also charged with developing policies on many subjects 
related to organ donation and transplantation, which include 
establishing standards of quality pertaining to organs procured for use 
in transplantation. 42 U.S.C. 274(b)(2)(E).

B. HOPE Act Requirements and Implementation

    The enactment of the HOPE Act in 2013, Public Law 113-51, 
eliminated the prohibition in the United States on transplantation of 
organs from persons with HIV, allowing transplantation of these organs 
if certain requirements are satisfied. Under the HOPE Act, organs from 
donors with HIV may be transplanted only in recipients living with HIV 
prior to receiving such an organ. 42 U.S.C. 274(b)(3)(A). Further, the 
HOPE Act requires that transplants of HIV-positive organs occur only in 
recipients with HIV who are participating in institutional review board 
(IRB)-approved research protocols that adhere to certain criteria, 
standards, and regulations. 42 U.S.C. 274(b)(3)(B)(i). However, the 
Secretary may lift the research and IRB requirements if the Secretary 
has determined that participation in such clinical research, as a 
requirement for such transplants, is no longer warranted. 42 U.S.C. 
274(b)(3)(B)(ii).
    The HOPE Act outlines the process by which the Secretary may make 
such a determination under 42 U.S.C. 274(b)(3)(B)(ii). Specifically, 
the Secretary must routinely review the results of scientific research, 
in conjunction with the OPTN, to determine whether the results warrant 
revision of the OPTN standards of quality regarding organs from donors 
with HIV. If the Secretary determines that those standards of quality 
should be revised, the Secretary must direct the OPTN to revise the 
standards. 42 U.S.C. 274f-5(c)(2). The Secretary is also required to 
revise the regulatory provision implementing the HOPE Act, 42 CFR 
121.6, upon determining that revisions to the OPTN standards of quality 
are warranted. 42 U.S.C. 274f-5(c)(3).

C. Research Criteria for HOPE Act Transplants

    In 2015, NIH published proposed research criteria for HOPE Act 
transplants in the Federal Register and solicited public comment. 80 FR 
34912 (June 18, 2015). After consideration of public comments received, 
NIH published the ``Final Human Immunodeficiency Virus (HIV) Organ 
Policy Equity (HOPE) Act Safeguards and Research Criteria for 
Transplantation of Organs Infected With HIV'' (``2015 Research 
Criteria''). 80 FR 73785 (November 25, 2015). The goals of the 2015 
Research Criteria were to ensure that research using organs from donors 
with HIV was conducted under conditions protecting the safety of 
research participants and the public and that the results of this 
research provide a basis for evaluating the safety of transplants of 
organs from donors with HIV in recipients with HIV. 80 FR 73785.

Introduction

    The HOPE Act requires the Secretary of Health and Human Services 
(the Secretary) to develop and publish criteria for research involving 
transplantation of organs from donors with HIV to recipients with HIV. 
In 2015, the National Institutes of Health (NIH), U.S. Department of 
Health and Human Services (HHS) published the initial Research Criteria 
applicable to such transplants, which was in effect for all transplants 
involving organs from donors with HIV as authorized by the HOPE Act. 
Through a final rule published in the Federal Register on November 27, 
2024 (89 FR 93484), the Secretary determined that participation in 
clinical research should no longer be a requirement for transplantation 
of kidneys and livers from donors with HIV to recipients with HIV and 
amended the HHS regulations governing the operation of the Organ 
Procurement and Transplantation Network (OPTN) to reflect this 
determination. As a result, HOPE Act transplants involving kidneys and 
livers from donors with HIV no longer need to comply with the NIH 
Research Criteria. Given this regulatory change, NIH proposed revised 
Research Criteria and solicited public comments on such revisions by 
publication in the Federal Register on November 27, 2024 (89 FR 93616). 
NIH proposed deleting aspects of the Research Criteria that are 
specific to kidney and liver transplantation. NIH made additional 
proposed changes to the Research Criteria based on its review of 
scientific evidence and in consideration of prior public feedback 
concerning the criteria, including comments provided in the recent 
rulemaking procedure that modified the OPTN regulations. There were 4 
public comments to the Draft Revised HOPE Safeguards and Research 
Criteria. After considering the public comments, NIH now finalizes the 
Revised HOPE Safeguards and Research Criteria. As explained below, NIH 
adopts revised research criteria as proposed except that NIH removed 
residual stigmatizing language from the title of the 2015 Research 
Criteria.

Overview of and Response to Comments

Recipient Eligibility Criteria

    One commenter supported eliminating the organ-specific experience 
criteria of 5 HIV D-/R+ transplants over 4 years. Per the commenter, 
this benchmark was too high a bar for U.S. heart and lung transplant 
programs to satisfy; thereby, prohibiting participation in HOPE Act 
transplantation. This commenter proposed eliminating the recipient 
eligibility criteria of an HIV viral load <50 copies/mL in deference to 
investigator clinical judgement. NIH chose to maintain the undetectable 
viral load threshold (<50 copies/mL) that aligns with strong expert 
opinion from the Guidelines for the use of antiretroviral agents in 
adults and adolescents with HIV: Transplantation in people with HIV 
current as of 24 September 2024, https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/transplantation. This criteria, which applies to transplants involving 
donors with HIV, does not preclude transplant programs from

[[Page 106544]]

listing suitable recipients for organs from donors without HIV.

Removal of Clinical Research Criteria for Living Donors With HIV

    One commenter raised concerns over removal of clinical research 
criteria for living donors with HIV given needs for longer term outcome 
data. As described above, the final rule issued by the Secretary has 
removed the mandated IRB-approved research protocol requirements for 
HOPE Act kidney and liver transplantation. Living heart and lung donors 
with HIV are rare occurrences in today's transplant practice. In the 
event of an intended living donation other than liver and kidney from a 
person with HIV, we include protections for living donors in the 
Revised Research Criteria. The revised criteria provide that for such 
transplants, the deceased donor eligibility criteria will apply. 
Further, the OPTN collects data on all living donors and transplants, 
which allows for additional oversight.

Removal of Stigmatizing Language (e.g., Donors Infected With HIV)

    One commenter requested the removal of residual stigmatizing 
language from the title of the 2015 Research Criteria, which has been 
modified in this final document.

Elimination of Mandatory Pre-Implantation Donor Biopsies

    This commenter endorsed the elimination of mandatory pre-
implantation donor biopsies, since this is not routinely required for 
solid organ transplants, and the trend towards standardizing the 
evaluation of donors with HIV to that of donors without HIV.
    A final commenter supported the proposed changes to Research 
Criteria for HOPE Act kidney and liver transplants and applauded 
measures taken to improve kidney transplant access for people with HIV.

Conclusion

    HHS appreciates the time and effort responding to the Request for 
Comments. The comments represented the efforts of truly dedicated 
individuals and organizations in transplantation. The deliberations 
over the last 3 years and the responses surrounding the NPRM and the 
Draft Revised Research Criteria were helpful in completing the Final 
Revised Human Immunodeficiency Virus (HIV) Organ Policy Equity (HOPE) 
Act Safeguards and Research Criteria for Transplantation of Organs from 
Donors with HIV.

Changes to the 2015 Research Criteria

    NIH has made several changes to the 2015 Research Criteria to 
reflect the Secretary's determination, published by regulation on 
November 27, 2024 that HOPE Act kidney and liver transplants are no 
longer required to be conducted as research subject to the 2015 
Research Criteria, and to continue to further the goals shared in 2015 
with respect to HOPE Act transplants of other organs from donors with 
HIV that remain subject to the Research Criteria. NIH has removed the 
requirements from the 2015 Research Criteria applicable to HOPE Act 
kidney and liver transplants.
    NIH has also made other changes to the 2015 NIH Research Criteria 
for conducting HOPE Act transplants of organs other than kidneys and 
livers (primarily heart and lung transplants) in IRB-approved research. 
These changes are intended to accelerate research, ensure research 
participant safety, and maintain stakeholder confidence in clinical 
research conducted under the HOPE Act. Notable revisions include the 
elimination of (i) the transplant program experience requirement of 
five organ-specific transplants of organs from a donor without HIV in a 
recipient with HIV conducted over 4 years; (ii) mandated pre-implant 
biopsies; and iii) the requirement for HIV independent advocates for 
living donors with HIV and recipients with HIV. Other organs (including 
multi visceral organs such as small intestine, stomach, liver, pancreas 
and colon) and multi organ transplants (e.g., heart-kidney) must comply 
with the Revised Research Criteria for inclusion of any non-kidney or 
non-liver organs from donors with HIV and subject to IRB approval.
    The revisions to the 2015 Research Criteria are as follows:

Final Revised Human Immunodeficiency Virus (HIV) Organ Policy Equity 
(HOPE) Act Safeguards and Research Criteria for Transplantation of 
Organs From Donors With HIV

Table of Contents

Abbreviations
Definitions
Final Revised Hope Act Safeguards and Research Criteria
Table 1--Final Revised Human Immunodeficiency Virus (HIV) Organ 
Policy Equity (Hope) Act Safeguards and Research Criteria for 
Transplantation of Organs From Donors With HIV
References

Abbreviations

------------------------------------------------------------------------
 
------------------------------------------------------------------------
AIDS.......................  Acquired Immunodeficiency Syndrome.
ART........................  Antiretroviral Therapy.
CD4........................  Cluster of differentiation 4.
D-.........................  Donor Human Immunodeficiency Virus
                              negative.
D+.........................  Donor Human Immunodeficiency Virus
                              positive.
HBV........................  Hepatitis B virus.
HCT/Ps.....................  Human Cells, Tissues, and Cellular and
                              Tissue-Based Products (HCT/Ps).
HCV........................  Hepatitis C virus.
HIV........................  Human Immunodeficiency Virus.
HIV-.......................  Human Immunodeficiency Virus negative
                              (using serology and/or nucleic acid
                              testing using FDA-licensed, approved or
                              cleared devices).
HIV+.......................  Human Immunodeficiency Virus positive
                              (using serology and/or nucleic acid
                              testing using FDA-licensed, approved or
                              cleared devices).
HOPE Act...................  HIV Organ Policy Equity Act.
HRSA.......................  Health Resources and Services
                              Administration.
IRB........................  Institutional review board.
NIH........................  National Institutes of Health.
NPRM.......................  Notice of proposed rule making.
OI.........................  Opportunistic infection.
OPO........................  Organ procurement organization.
PML........................  Progressive multifocal leukoencephalopathy.
R-.........................  Recipient HIV negative.
R+.........................  Recipient HIV positive.
RNA........................  Ribonucleic acid.
SOPs.......................  Standard operating procedures.
------------------------------------------------------------------------


[[Page 106545]]

Definitions

------------------------------------------------------------------------
 
------------------------------------------------------------------------
Antiretroviral therapy (ART)        When an HIV strain develops drug
 resistance.                         resistance and/or genetic mutations
                                     associated with drug resistance.
HIV superinfection................  Systemic HIV superinfection is
                                     defined as the detection of HIV
                                     viral sequences that
                                     phylogenetically cluster with the
                                     donor's viral population at two or
                                     more time points in circulating
                                     blood cells, plasma, or recipient
                                     tissues other than the allograft.
Suppressed viral load.............  HIV RNA below 50 copies per mL with
                                     current technology at time of
                                     publication of this research
                                     criteria document.
------------------------------------------------------------------------

    The NIH Research Criteria are set forth in six broad categories 
(Donor Eligibility, Recipient Eligibility, Transplant Hospital 
Criteria, Organ Procurement Organization (OPO) Responsibilities, 
Prevention of Inadvertent Transmission of HIV, and Study Design/
Required Data Elements and Outcome Measures). Table 1 summarizes the 
Final Revised HOPE Act Research Criteria in each category and compares 
them to the 2015 Research Criteria.
---------------------------------------------------------------------------

    \1\ Consistent with the final rule amending the OPTN 
regulations, transplants using kidneys and livers from donors with 
HIV no longer need to comply with the HOPE Act Research Criteria. 
When multiple organs from donors with HIV are implanted 
simultaneously (e.g., dual heart-kidney or dual lung-kidney), the 
Research Criteria apply to such multiple organ transplants if the 
transplant of any of the organs are subject to the revised Research 
Criteria. For example, while a kidney transplant from a donor with 
HIV no longer is required to be conducted in accordance with the 
Research Criteria, a dual heart-kidney or dual lung-kidney 
transplant with organs from donors with HIV is required to be 
conducted in accordance with the Research Criteria and in accordance 
with an IRB-approved research protocol. A dual liver-kidney 
transplant with from donors with HIV is not required to be conducted 
in accordance with the Research Criteria, as neither liver 
transplants nor kidney transplants from donors with HIV are required 
to be conducted as research.

 Table 1--Final Revised Human Immunodeficiency Virus (HIV) Organ Policy
 Equity (HOPE) Act Safeguards and Research Criteria for Transplantation
                   of Organs From Donors With HIV \1\
------------------------------------------------------------------------
                                                    Revised criteria [No
                                                     longer pertains to
          Category              Previous criteria     kidney and liver
                                                      transplants \1\]
------------------------------------------------------------------------
Donor Eligibility:
    All deceased donors with  No evidence of        No evidence of
     HIV.                      invasive              invasive
                               opportunistic         opportunistic
                               complications of      complications of
                               HIV infection.        HIV infection.
                              Pre-implant donor     There is no
                               organ biopsy.         requirement for a
                                                     pre-implantation
                                                     biopsy.*
                              Viral load: no        Viral load: no
                               requirement.          requirement.
    Deceased donor with       The study team must   The study team must
     known history of HIV      describe the          describe the
     and prior                 anticipated post-     anticipated post-
     antiretroviral therapy    transplant            transplant
     (ART).                    antiretroviral        antiretroviral
                               regimen(s) to be      regimen(s) to be
                               prescribed for the    prescribed for the
                               recipient and         recipient and
                               justify its           justify its
                               conclusion that the   conclusion that the
                               regimen will be       regimen will be
                               safe, tolerable,      safe, tolerable,
                               and effective.        and effective.
    Living donor with HIV...  Well-controlled HIV   Thoracic Organs
                               infection defined     Exception: The
                               as:                   living donor
                               Cluster of    standards are not
                               Differentiation 4     relevant for
                               (CD4) + T-cell        thoracic organ
                               count >=500/          transplant except
                               [micro]L for the 6-   in the rare
                               month period before   instances of living
                               donation.             donor lung
                               HIV-1         transplant or
                               ribonucleic acid      ``domino'' heart
                               (RNA) <50 copies/mL.  transplant. In such
                               No evidence   circumstances, the
                               of invasive           deceased donor
                               opportunistic         eligibility
                               complications of      criteria should be
                               HIV infection.        followed.
                              Pre-implant donor     Other Organs: If a
                               organ biopsy..        living donor with
                                                     HIV donates another
                                                     type or organ
                                                     (other than kidney
                                                     and liver), the
                                                     deceased donor
                                                     eligibility
                                                     criteria should be
                                                     followed.*
Recipient Eligibility.......  CD4+ T-cell count     CD4+ T-cell count:
                               >=200/[micro]L        no minimum
                               (kidney).             threshold when all
                              CD4+ T-cell count      other recipient
                               >=100 [micro]L        eligibility
                               (liver) within 16     criteria are met.*
                               weeks prior to
                               transplant and no
                               history of
                               opportunistic
                               infection (OI); or
                               >=200 [micro]L if
                               history of OI is
                               present..
                              HIV-1 RNA <50 copies/ HIV-1 RNA <50 copies/
                               mL and on a stable    mL and on a stable
                               antiretroviral        antiretroviral
                               regimen.              regimen.
                              No evidence of        No evidence of
                               active                active
                               opportunistic         opportunistic
                               complications of      complications of
                               HIV infection.        HIV infection.
                              No history of         No history of
                               primary central       primary central
                               nervous system        nervous system
                               (CNS) lymphoma or     (CNS) lymphoma or
                               progressive           progressive
                               multifocal            multifocal
                               leukoencephalopathy   leukoencephalopathy
                               (PML).                (PML).
Transplant Hospital Criteria  Transplant hospital   Transplant hospital
                               with established      with established
                               program for care of   program for care of
                               subjects with HIV.    patients with HIV.
                              HIV program           HIV program
                               expertise on the      expertise on the
                               transplant team.      transplant team.
                              Organ-specific        There is no longer a
                               experience with       center specific
                               transplants of        case experience
                               organs from donors    requirement with
                               without HIV to        transplants of
                               recipients with HIV   organs from donors
                               (5 D-/R+ transplant   without HIV to
                               cases over 4 years).  recipients with
                                                     HIV.* Transplant
                                                     patients with
                                                     organs from donors
                                                     with HIV must be
                                                     managed with a
                                                     multidisciplinary
                                                     team before,
                                                     during, and after
                                                     transplant. The
                                                     multidisciplinary
                                                     team must include
                                                     transplant
                                                     surgeons,
                                                     physicians, HIV
                                                     specialists,
                                                     nurses, social
                                                     workers, and
                                                     pharmacists capable
                                                     of therapeutic drug
                                                     monitoring to
                                                     minimize drug-drug
                                                     interactions.
                              Standard operating    Standard operating
                               procedures (SOPs)     procedures (SOPs)
                               and training for      and training for
                               the organ             the organ
                               procurement,          procurement,
                               implanting/           implanting/
                               operative, and        operative, and
                               postoperative care    postoperative care
                               teams for handling    teams for handling
                               subjects with HIV,    HIV-infected
                               and organs and        subjects with HIV,
                               tissues from          and organs and
                               individuals with      tissues from
                               HIV.                  individuals with
                                                     HIV.
                              IRB-approved          IRB-approved
                               research protocol     research protocol
                               for transplantation   for transplantation
                               of organs from        of organs from
                               donors with HIV in    donors with HIV in
                               recipients with HIV.  recipients with HIV
                                                     for the applicable
                                                     organs.*

[[Page 106546]]

 
                              Institutional         Institutional
                               biohazard plan        biohazard plan
                               outlining measures    outlining measures
                               to prevent and        to prevent and
                               manage inadvertent    manage inadvertent
                               exposure to and/or    exposure to and/or
                               transmission of HIV.  transmission of
                                                     HIV.
                              Provide each living   There is no longer a
                               donor with HIV and    requirement to
                               recipient with HIV    provide an HIV
                               with an               independent
                               ``independent         advocate beyond
                               advocate''.           standard site
                                                     practices.*
                              Policies and SOPs     Policies and SOPs
                               governing the         governing the
                               necessary             necessary
                               knowledge,            knowledge,
                               experience, skills,   experience, skills,
                               and training for      and training for
                               independent           independent
                               advocates.            advocates.
OPO Responsibilities........  SOPs and staff        SOPs and staff
                               training procedures   training procedures
                               for working with      for working with
                               deceased donors       deceased donors
                               with HIV and their    with HIV and their
                               families in           families in
                               pertinent history     pertinent history
                               taking; medical       taking; medical
                               chart abstraction;    chart abstraction;
                               the consent           the consent
                               process; and          process; and
                               handling blood,       handling blood,
                               tissues, organs,      tissues, organs,
                               and biospecimens.     and biospecimens.
                              Biohazard plan to     Biohazard plan to
                               prevent and manage    prevent and manage
                               HIV exposure and/or   HIV exposure and/or
                               transmission.         transmission.
Prevention of Inadvertent     Each participating    Each participating
 Transmission of HIV.          Transplant Program    Transplant Program
                               and OPO shall         and OPO shall
                               develop an            develop an
                               institutional         institutional
                               biohazard plan for    biohazard plan for
                               handling organs       handling organs
                               from HIV-positive     from HIV-positive
                               donors that is        donors that is
                               designed to prevent   designed to prevent
                               and/or manage         and/or manage
                               inadvertent           inadvertent
                               transmission or       transmission or
                               exposure to HIV.      exposure to HIV.
                              Procedures must be    Procedures must be
                               in place to ensure    in place to ensure
                               that human cells,     that human cells,
                               tissues, and          tissues, and
                               cellular and tissue-  cellular and tissue-
                               based products (HCT/  based products (HCT/
                               Ps) are not           Ps) are not
                               recovered from        recovered from
                               donors with HIV for   donors with HIV for
                               implantation,         implantation,
                               transplantation,      transplantation,
                               infusion, or          infusion, or
                               transfer into a       transfer into a
                               human recipient;      human recipient;
                               however, HCT/Ps       however, HCT/Ps
                               from a donor          from a donor
                               determined to be      determined to be
                               ineligible may be     ineligible may be
                               made available for    made available for
                               nonclinical           nonclinical
                               purposes.             purposes.
Required Data Elements and
 Outcome Measures **
    Wait List Candidates....  HIV status..........  HIV status.
                              CD4+ T-cell counts..  CD4+ T-cell counts.
                              Co-infection          Co-infection:
                               (hepatitis C virus    Hepatitis C
                               [HCV], hepatitis B    (HCV RNA).
                               virus [HBV]).         Hepatitis B
                                                     (HBV
                                                     deoxyribonucleic
                                                     acid, HBV
                                                     antibody).
                                                    
                                                     Cytomegalovirus
                                                     (CMV immunoglobulin
                                                     G [IgG]).*
                              HIV viral load......  HIV viral load.
                              ART resistance......  ART resistance.
                              Removal from wait     Removal from wait
                               list (death or        list (death or
                               other reason).        other reason).
                              Time on wait list...  Time on wait list.
                                                    Renal dysfunction.*
                                                    Liver dysfunction.*
                                                    Indication for
                                                     transplant.*
                                                    Use of mechanical
                                                     circulatory
                                                     devices.*
                                                    Use of
                                                     extracorporeal
                                                     membrane
                                                     oxygenation, intra-
                                                     aortic balloon
                                                     pump, ventricular
                                                     assist device.*
    Donors (all)............  Type (Living or       Type Donation after
                               deceased).            Brain Death vs.
                                                     Donation after
                                                     Circulatory Death
                                                     vs. Living Donor.*
                              HIV status (new       HIV status (new
                               diagnosis of HIV,     diagnosis of HIV,
                               or known diagnosis    or known diagnosis
                               of HIV).              of HIV).
                              CD4+ T-cell count...  CD4+ T-cell count.
                              Co-infection (HCV,    Co-infection (HCV,
                               HBV).                 HBV).
                              HIV viral load......  HIV viral load.
                              ART resistance......  ART resistance.
                                                    Ex-vivo perfusion.*
                                                       
                                                        Duration.
                                                        Warm and
                                                        cold ischemia
                                                        time.
                                                       Normothermic
                                                        regional
                                                        perfusion.*
                                                       
                                                        Duration.
                                                        Warm and
                                                        cold ischemia
                                                        time.
    Living Donors...........  Progression to renal  These data elements
                               insufficiency in      no longer apply
                               kidney donors.        since kidney or
                                                     liver donation from
                                                     a living donor with
                                                     HIV no longer falls
                                                     under the Research
                                                     Criteria except
                                                     that these data
                                                     elements apply to
                                                     simultaneous
                                                     multiple organ
                                                     transplants.
                              Progression to
                               hepatic
                               insufficiency in
                               liver donors.
                              Change in ART         Change in ART
                               regimen as a result   regimen as a result
                               of organ              of organ
                               dysfunction.          dysfunction.
                              Progression to        Progression to AIDS.
                               acquired
                               immunodeficiency
                               syndrome (AIDS).
                              Failure to suppress   Failure to suppress
                               viral replication     viral replication
                               (persistent HIV       (persistent HIV
                               viremia).             viremia).
                              Death...............  Death.
    Transplant Recipients...  Rejection rate        Rejection rate
                               (annual up to 5       (annual through 5
                               years).               years).
                              Progression to AIDS.  Progression to AIDS.
                              New OI..............  New OI.
                              Failure to suppress   Failure to suppress
                               viral replication     viral replication
                               (persistent HIV       (persistent HIV
                               viremia).             viremia).
                              HIV-associated organ  HIV-associated organ
                               failure.              failure.
                              Malignancy..........  Malignancy.
                              Graft failure.......  Graft failure.

[[Page 106547]]

 
                              Mismatched ART        Mismatched ART
                               resistance versus     resistance versus
                               donor.                donor.
                              Death...............  Death.
                                                    Type of rejection
                                                     (antibody mediated
                                                     versus cellular
                                                     rejection).*
                                                    Chronic heart
                                                     allograft
                                                     vasculopathy.*
                                                    Chronic lung
                                                     allograft
                                                     dysfunction.*
                                                    Hospitalized
                                                     infections.*
                                                    Estimated glomerular
                                                     filtration rate.*
                                                    HIV superinfection.*
                                                    Re-transplantation.*
                                                    Simultaneous
                                                     multiple organ
                                                     transplants.
------------------------------------------------------------------------
* Denotes a revision of the 2015 Research Criteria.
** The previous category of outcome measures (from the original 2015
  Research Criteria) is modified to also include data elements.

    A summary of the revisions in each category of the Research 
Criteria is provided below as compared with the 2015 Research Criteria.
Donor Eligibility
    The only change to this category applies to all deceased donors 
with HIV. NIH has removed the requirement for a pre-implantation donor 
organ biopsy. Although pre-implantation biopsies for kidneys and livers 
have occurred regularly, pre-implant donor heart and lung biopsies are 
not routinely performed. Likewise, donor biopsies for other organs are 
not routine. Given that kidney and liver transplants are no longer 
subject to the Research Criteria, NIH has removed the requirement for 
pre-implantation biopsies. Any pre-implant biopsies obtained, as part 
of future IRB-approved research protocols, should be stored in 
accordance with local institutional requirements and the federal 
regulations applicable to slides, tissues and blocks, if applicable. 42 
CFR 493.1105 (https://www.ecfr.gov/current/title-42/chapter-IV/subchapter-G/part-493/subpart-J/section-493.1105).
    With respect to living donors with HIV, the 2015 Research Criteria 
defined a well-controlled HIV infection and required pre-implant donor 
organ biopsies. The last living lobar lung transplant procedure in the 
U.S. was performed in 2013. NIH has removed this element as not 
relevant for heart and lung transplantation except in the rare 
instances of living donor lung transplant or ``domino'' heart 
transplants. In such circumstances, the deceased donor eligibility 
criteria apply. If another type of organ is donated by a living donor 
with HIV, the deceased donor eligibility criteria apply.
Recipient Eligibility
    The only change in this category concerns CD4+ T-cell counts. The 
2015 Research Criteria imposed requirements with respect to the CD4+ T-
cell counts specific to livers and kidneys. Given that kidney and liver 
transplants are no longer required to comply with the Research 
Criteria, there is no minimum threshold CD4+ T-cell counts for other 
organs when all other eligibility criteria are met.
Transplant Hospital
    NIH made several changes to this category. The requirement for 
prior experience with transplantation of organs from donors without HIV 
in recipients with HIV. The 2015 Research Criteria required experience 
with five transplants over the four preceding years involving organs 
from donors without HIV transplanted into recipients with HIV. NIH has 
removed this requirement, which was perceived by many as burdensome and 
a barrier to entry to transplant hospitals wishing to perform HOPE Act 
transplants. To maximize favorable outcomes and effectively prevent and 
manage adverse events, NIH has specified that all patients with 
transplants involving donors with HIV be managed by multidisciplinary 
teams before, during, and after transplantation. NIH outlines specific 
members of this multidisciplinary team.
    NIH has removed the requirement that each living donor with HIV and 
each transplant recipient with HIV be provided with an HIV independent 
advocate. NIH advises that standard site practices apply. Based on a 
decade of HOPE Act clinical experience, stakeholder surveys have 
indicated that a requirement for an independent advocate is widely 
perceived as a redundant layer of consent and a potential barrier for 
some HIV patients who would otherwise benefit from an HIV donor 
transplant. The NIH notes that per current OPTN policy and guidance, 
all living donors, including those with HIV, have an independent 
advocate. NIH's change to the 2015 Research Criteria will not alter 
that.
Organ Procurement Organization (OPO) Responsibilities
    NIH did not make any changes to this category.
Prevention of Inadvertent Transmission of HIV
    NIH did not make any changes to this category.
Required Outcome Measures and Data Elements
    The 2015 Research Criteria referenced required outcome measures. 
NIH is using the more precise ``Required Data Elements and Outcome 
Measures.'' NIH notes that data on these existing and new outcome 
measures is collected by the OPTN as specified by the Secretary. NIH 
does not intend to incorporate data collection requirements beyond 
those collected by the OPTN.
    Waitlist Candidates: NIH has added several data elements for 
waitlist candidates. NIH has added cytomegalovirus (CMV immunoglobulin 
G [IgG]) as a required outcome measure for co-infection. NIH also 
included the following additional data elements and outcome measures: 
renal dysfunction, liver dysfunction, indication for transplant, use of 
mechanical circulatory devices, and use of extracorporeal membrane 
oxygenation, intra-aortic balloon pump, and ventricular assist device.
    Donors (All): First, NIH included additional elements related to 
type of deceased donation: after brain death (DBD) or after circulatory 
death (DCD) given the increasing use of the latter technique in the 
U.S. In addition, NIH has added the following data elements for all 
donors (if applicable): ex-vivo perfusion and normothermic regional 
perfusion including durations of warm and cold ischemia.
    Living Donors: The 2015 Research Criteria included as required 
outcome measures progression to renal insufficiency in kidney living 
donors.

[[Page 106548]]

Because kidney and liver transplants are no longer subject to the 
Research Criteria, NIH plans to retain these outcomes only where 
applicable (e.g., for deceased donor heart-living donor kidney 
transplants, deceased donor heart-living donor liver transplants, and 
for other organs subject to the Research Criteria).
    Transplant Recipients: NIH has added several additional data 
elements and outcome measures to those included for transplant 
recipients in the 2015 Research Criteria. NIH has added the following 
outcome measures: type of rejection (antibody mediated versus cellular 
rejection), chronic allograft vasculopathy (heart), chronic lung 
allograft dysfunction (lung), hospital infections, estimated glomerular 
filtration rate (heart and lung), HIV superinfection, graft failure 
(heart and lung), re-transplantation, and simultaneous multiple organ 
transplants.
    While not included as a requirement of the Research Criteria, NIH 
has included the following recommendation regarding patient management:
    NIH recommends that transplant programs and healthcare providers 
follow current and updated practice management guidelines. For specific 
guidance, transplant programs and healthcare providers should consult 
vaccination guidance (https://www.cdc.gov/acip-recs/hcp/vaccine-specific/) and expert guidance for the management of patients 
with HIV pre-, during-, and post-transplant summarized in: 
Transplantation in people with HIV (https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new).

References

1. Department of Health and Human Services (DHHS). Human 
Immunodeficiency Virus (HIV) Organ Policy Equity (HOPE) Act 
Safeguards and Research Criteria for Transplantation of Organs 
Infected With HIV. 80 FR 34912. June 18, 2015.
2. Doberne J.W., et al. (2021). Heart transplantation survival 
outcomes of HIV positive and negative recipients. Annals of Thoracic 
Surgery, 111:1465-71.
3. Durand C., et al. (2024). Safety of kidney transplantation from 
donors with HIV infection. N Engl J Med, 391:1390-401.
4. HIV Organ Policy Equity (HOPE) Act of 2013. Public Law 113-51.
5. Kern, R., Seethamraju, H., Blanc, P., Sinha, N., Loebe, M., 
Golden, J., et al. (2014). Lung Transplantation in HIV Seropositive 
Patients. Chest, 145(3 Suppl), 642A.
6. Koval C., et al. (2018). Heart and lung transplantation outcomes 
in HIV-positive recipients.
7. Koval, C.E., Farr, M., Krisl, J., Haidar, G., Pereira, M.R., 
Shrestha, N., Malinis, M.F., Mueller, N.J., Hannan, M.M., Grossi, 
P., & Huprikar, S. (2019). Heart or lung transplant outcomes in HIV-
infected recipients. The Journal of heart and lung transplantation: 
the official publication of the International Society for Heart 
Transplantation, 38(12), 1296-1305. https://doi.org/10.1016/j.healun.2019.09.011.
8. Madan S., et al, (2019). Outcomes of heart transplantation in 
patients with human immunodeficiency virus. Am J Transplant. 
19:1529-35.
9. Rouzaud C., et al., (2022). Lung transplantation in HIV-positive 
patients: a European retrospective cohort study. Eur Respir J. 
60(1):2200189.
10. Storm, K., & Durand, C.M. (2024). Overcoming barriers and 
stigma: new frontiers in solid organ transplantation for people with 
HIV. Clinical microbiology reviews, 37(1), e0011122. https://doi.org/10.1128/cmr.00111-22.
11. Wairimu, F., Ward, N.C., Liu, Y., & Dwivedi, G. (2021). Cardiac 
Transplantation in HIV-Positive Patients: A Narrative Review. 
Journal of acquired immune deficiency syndromes (1999), 87(2), 763-
768. https://doi.org/10.1097/QAI.0000000000002647.

    Dated: December 20, 2024.
Lawrence A. Tabak,
Principal Deputy Director, National Institutes of Health.
[FR Doc. 2024-31265 Filed 12-27-24; 8:45 am]
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