`[Federal Register Volume 89, Number 229 (Wednesday, November 27, 2024)]
[Notices]
[Pages 93616-93623]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-27733]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


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

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

ACTION: Request for comments.

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

SUMMARY: The HOPE Act requires the Secretary of Health and Human 
Services (the Secretary) to develop and publish criteria for research 
involving the transplantation of organs from donors with HIV to 
recipients with HIV. In 2015, the National Institutes of Health (NIH), 
and the U.S. Department of Health and Human Services (HHS) published 
research criteria applicable to such transplants, which have been in 
effect for all transplants involving organs from donors with HIV as 
authorized by the HOPE Act. As amended in an HHS final rule published 
elsewhere in this issue of the Federal Register, the Secretary 
determined that participation in clinical research should no longer be 
a requirement for the 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 research criteria. Given this regulatory 
change, NIH proposes to delete aspects of the research criteria that 
are specific to kidney and liver transplantation. NIH proposes 
additional 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. NIH invites 
the public to submit comments regarding the proposed changes to the 
research criteria.

DATES: To ensure that comments will be considered, comments must be 
received no later than 5 p.m. on December 12, 2024.

ADDRESSES: Comments may be submitted by any of the following methods:
     Email: [email protected].
     Fax: 301-451-5671.
     Regular Mail: Dr. Jonah Odim, 5601 Fishers Lane, Room 
6B21, MSC 9827, Bethesda, MD 20892-9827.
     Hand Delivery, Overnight Mail, FedEx, and UPS: Dr. Jonah 
Odim, 5601 Fishers Lane, Room 6B21, MSC 9827, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Dr. Jonah Odim, Chief Clinical 
Transplantation Section, Transplantation Branch, 5601 Fishers

[[Page 93617]]

Lane, Room 6B21, MSC 9827, Rockville, MD 20892-9827; by email at 
[email protected]; by telephone at (301) 828-7220.

SUPPLEMENTARY INFORMATION:

I. 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.
1. Proposed Changes to the 2015 Research Criteria
    NIH is now proposing 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 proposes to 
remove requirements from the Research Criteria applicable to HOPE Act 
kidney and liver transplants.
    NIH also proposes 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. 
The proposed 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.
2. Consideration of Public Comment Received on the HOPE Act NPRM
    In proposing these changes, NIH has considered the public 
participation in the HOPE Act rulemaking process through which the 
Secretary's determination was made. In response to the September 21, 
2024, notice of proposed rulemaking that proposed the Secretary's 
determination with respect to HOPE Act kidney and liver transplants, 89 
FR 74174, HHS received multiple comments that were relevant to the NIH 
Research Criteria, and some comments provided specific suggestions for 
the content of the revised NIH Research Criteria. All comments relating 
to the content of the revised Research Criteria were provided to NIH 
for consideration in the development of the proposed revised Research 
Criteria that appear later in this document. NIH has considered these 
comments and proposes changes to the Research Criteria responsive to 
specific comments received, as described here.
     Several commenters noted that referring to organs 
``infected with HIV'' or ``HIV positive organs'' may be stigmatizing, 
and one commenter requested that references to ``organs with HIV'' be 
revised to ``organ(s) from donors with HIV.'' The commenters indicated 
a strong preference for the use of stigma-reducing, and person-first 
language. In response to these comments, NIH proposes to revise 
references in the Research Criteria to refer to donors with HIV, 
recipients with HIV, and organs from donors with HIV. This is 
consistent with the Centers for Disease Control and Prevention's (CDC) 
Stigma Language Guide \1\ and with language adopted in the final rule.
---------------------------------------------------------------------------

    \1\ Centers for Disease Control and Prevention. Let's Stop HIV 
Together: Stigma Language Guide. https://www.cdc.gov/stophivtogether/hiv-stigma/ways-to-stop.html. Accessed 2/23/2024.
---------------------------------------------------------------------------

     Commenters also requested the elimination of the current 
requirement that a transplant team perform at least five transplants 
within a four-year period between any donor and a recipient with HIV 
for all organs, as, in the commenters' estimation, this

[[Page 93618]]

requirement is not necessary for organs from donors with HIV to be used 
safely. In response to these comments and based on its review of the 
evidence, NIH proposes to remove this requirement from the proposed 
revised Research Criteria.
     Commenters suggested that each transplant team should 
include infectious disease specialists with expertise in HIV care. In 
response to these comments and based on its review of the evidence, NIH 
proposes that this requirement of the 2015 NIH Research Criteria be 
retained in the revised Research Criteria.
     One commenter requested the elimination of the biopsy 
requirement. In response to this comment and based on its review of the 
evidence, NIH proposes to eliminate the requirement for a pre-
implantation biopsy.
     One commenter noted that, in revising the Research 
Criteria, NIH should maintain the strong patient safety record for HOPE 
Act transplants, while actively seeking to reduce burdens that may be 
slowing the establishment of non-kidney and non-liver HOPE Act 
transplant programs. In response to this comment and based on its 
review of the evidence, NIH believes that the proposed revisions to the 
Research Criteria appropriately strike this balance.
    NIH's rationale for these specific proposed revisions to the 
Research Criteria is provided in more detail in Section III, below.
    The Secretary delegated to the Director, NIH, the responsibility to 
revise the 2015 Research Criteria. The proposed revised Research 
Criteria proposed below were developed by NIH staff in collaboration 
with representatives of the Centers for Disease Control and Prevention, 
the Food and Drug Administration, the Health Resources and Services 
Administration, and the Office of the Assistant Secretary for Health.
    If adopted as proposed, it is anticipated that the revised Research 
Criteria would expand access to transplantation for recipients with 
HIV, provide benefits to organ donors; ensure safety of ongoing HOPE 
Act transplants of organs other than kidneys and livers; and provide 
for the systematic collection of safety and efficacy data related to 
transplants of hearts, lungs, and other organs from donors with HIV in 
recipients with HIV.
3. Other Considerations
(a) Research Results--Heart and Lung Transplants in Recipients With HIV
    As the Secretary has decided that HOPE Act transplants of organs 
other than kidneys and livers should remain subject to the Research 
Criteria until additional scientific research demonstrates the safety 
and efficacy of such transplants, NIH wishes to highlight the current 
state of the science with regard to transplantation of hearts and lungs 
from donors without HIV in recipients with HIV. The early outcomes data 
for such transplants may provide a foundation for future HOPE Act 
thoracic organ transplants (Koval 2018, 2019; Madan 2019). For example, 
in a retrospective analysis utilizing the OPTN database to compare 
outcomes of 75 heart transplant recipients with HIV to those of 29,848 
heart transplant recipients without HIV, survival rates were similar 
across the comparator groups, while rejection rates were approximately 
2-fold higher in recipients with HIV (38.7% vs. 17.7%, respectively) 
(Doberne 2021). Similar findings were reported in studies based on the 
International Society for Heart and Lung Transplantation (ISHLT) and 
Scientific Registry of Transplant Recipients (SRTR) databases (Wairmu 
2021; Storm 2024; Madan 2019). Fewer transplants of lungs from donors 
without HIV in recipients with HIV have been reported (Koval 2019; Kern 
2014; Rouzaud 2022).
    NIH recognizes that additional research in this area will advance 
the state of the relevant science, and the results of such research 
will increase the evidence basis needed to support any future 
determination by the Secretary that participation in clinical research 
is no longer a requirement for transplants of hearts or lungs from 
donors with HIV in recipients with HIV.
(b) Education Regarding the HOPE Act
    While no related proposals are included in the proposed revision to 
the 2015 Research Criteria, NIH further notes that expanding awareness 
and continuing education of potential organ donors, transplant centers, 
organ procurement organizations (OPOs), healthcare providers, and 
people living with HIV will be important to fully realize the medical 
and societal benefits envisioned under the HOPE Act. Success in these 
endeavors will expand the supply of quality donor HIV organs, enhance 
transplant access, improve quality of life, and increase longevity for 
potential transplant recipients with HIV. Reducing longstanding stigma 
and increasing access to organ transplantation will be particularly 
important for communities disproportionately impacted by HIV (https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/who-is-at-risk-for-hiv).
(D) Secretary's Review of Research Results
    As stated above, the HOPE Act requires that the Secretary, in 
conjunction with the OPTN, periodically review the results of 
scientific research to determine whether the results warrant revision 
to the OPTN standards of quality with respect to organs from donors 
with HIV and the safety of transplanting an organ from a donor with a 
particular strain of HIV into a recipient with a different strain of 
HIV. 42 U.S.C. 274f-5(c)(1). This review allows the Secretary to 
determine if the safety and efficacy of HOPE Act transplants are 
comparable to non-HOPE Act transplants and, if warranted, to further 
determine whether such transplants may be conducted outside of a 
research setting.
    Past procedures for this review are described in detail in the 
final rule amending the OPTN regulation. Past reviews involved 
deliberations by bodies that provided recommendations to the Secretary, 
including the OPTN (which solicited and considered public comments) 
2 3 the HHS Advisory Committee on Blood and Tissue Safety 
and Availability (ACBTSA) \4\ and the HHS Blood, Organ, and Tissue 
Senior Executive Council (BOTSEC) (an advisory forum for senior 
leadership from HHS entities involved in blood, organ, and tissue 
safety and availability. The recommendations of the OPTN, ASBTSA, and 
BOTSEC, as well as subsequent research results, were considered in the 
Secretary's decision as to whether participation in clinical research, 
as a requirement for certain types of transplants of organs from donors 
with HIV, is no longer warranted.
---------------------------------------------------------------------------

    \2\ Organ Procurement and Transplantation Network. Public 
Comment Proposal: Modify the HOPE Act Variance to Include Other 
Organs. 2019 Jan 22: https://optn.transplant.hrsa.gov/media/2800/dtac_publiccomment_20190122.pdf.
    \3\ Cooper M. ``OPTN Letter to Secretary Becerra on the HOPE 
Act.'' 2021 Oct 29. https://optn.transplant.hrsa.gov/media/ueyjdfnd/hope-act-letter.pdf.
    \4\ HHS Advisory Committee on Blood and Tissue Safety and 
Availability. 2022. Fifty-Sixth ACBTSA Meeting November 17, 2022--
Meeting Summary. https://www.hhs.gov/oidp/advisory-committee/blood-tissue-safety-availability/meeting-summary/2022-11-17/index.html.
---------------------------------------------------------------------------

    Although not incorporated into the 2015 Research Criteria or the 
proposed revised criteria, HHS intends to conduct a regular review of 
such scientific research to enable evidence-based recommendations, 
including any changes to the Research Criteria, and any determinations 
on transitioning additional HOPE Act organ transplants to medical 
practice and standard-of-care

[[Page 93619]]

(i.e., removing the clinical research and IRB requirements for such 
transplants) if appropriate in the future. NIH seeks public comment on 
this approach, and on the procedures through which this review should 
be conducted.

II. Instructions for Submitting Comments

    Comments are invited on the proposed changes to the 2015 Research 
Criteria.
    Please note that, during the rulemaking process resulting in the 
HHS final rule published elsewhere in this issue of the Federal 
Register, HHS received and considered public comments regarding whether 
HOPE Act kidney and liver transplants from donors with HIV should 
continue to be required to be conducted in accordance with the 2015 
Research Criteria. After consideration of public comments received, the 
Secretary determined that participation in clinical research will no 
longer be a requirement for HOPE Act kidney and liver transplants from 
donors with HIV.
    Further, in making the determination regarding HOPE Act kidney and 
liver transplants, the Secretary expressed the view in the notice of 
proposed rulemaking published on September 12, 2024, 89 FR 74174, that 
the current research and IRB requirements should be maintained for HOPE 
Act transplants of all other organs, considering the lack of data on 
outcomes for HOPE Act organ transplants other than kidney or liver 
transplants. This decision was affirmed in the HHS final rule published 
elsewhere in this issue of the Federal Register.
    Because the Secretary's determination regarding HOPE Act kidney and 
liver transplants, and the Secretary's decision that other HOPE Act 
organ transplants should remain subject to the Research Criteria, 
resulted from full notice and comment rulemaking procedures, NIH views 
comments concerning the Secretary's determination or decision to be 
outside the scope of this solicitation and such comments will not be 
considered. Specifically, related comments will not be considered with 
respect to these proposed changes to the 2015 Research Criteria: (1) 
eliminating the requirement that transplants involving kidneys and 
livers from donors with HIV comply with the NIH Research Criteria; (2) 
retaining the requirement that transplants involving all other organs 
(other than kidneys and livers) from donors with HIV comply with the 
NIH Research Criteria; and (3) removal of criteria specific to the 
transplantation of kidneys and livers.
    Do not include personal information in submitted comments that you 
do not want to be publicly disclosed.

III. Proposed Revision to the 2015 Research Criteria

    The proposed revision to the 2015 Research Criteria is as follows:
Proposed 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
Proposed Revised Hope Act Safeguards and Research Criteria
Table 1. Revised Final Human Immunodeficiency Virus (HIV) Organ 
Policy Equity (HOPE) Act Safeguards and Research Criteria for 
Transplantation of Organs 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.
------------------------------------------------------------------------


                               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 the time of
                                     publication of this research
                                     criteria document.
------------------------------------------------------------------------

    The 2015 Research Criteria are outlined 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 
proposed new HOPE Act Research Criteria in each category

[[Page 93620]]

and compares them to the 2015 NIH Research Criteria.

   Table 1--Proposed Revised Human Immunodeficiency Virus (HIV) Organ
      Policy Equity (HOPE) Act Safeguards and Research Criteria for
           Transplantation of Organs From Donors With HIV \1\
------------------------------------------------------------------------
                                                      Proposed revised
                                                     criteria (No longer
          Category              Previous criteria    pertains to kidney
                                                          and liver
                                                      transplants \5\)
------------------------------------------------------------------------
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.*
                              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.

[[Page 93621]]

 
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
                              Progression to         liver donation from
                               hepatic               a living donor with
                               insufficiency in      HIV no longer falls
                               liver donors.         under the Research
                                                     Criteria except
                                                     that these data
                                                     elements apply to
                                                     simultaneous
                                                     multiple organ
                                                     transplants.
                              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.

[[Page 93622]]

 
                              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.
                              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 proposed revisions in each category of the 
Research Criteria is provided below.
---------------------------------------------------------------------------

    \5\ 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.
---------------------------------------------------------------------------

Donor Eligibility
    The only change proposed by NIH to this category applies to all 
deceased donors with HIV. NIH proposes removing 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 NIH research criteria, NIH 
proposes removing 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 NIH 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 proposes removing 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, NIH proposes that the deceased 
donor eligibility criteria apply. If another type of organ is donated 
by a living donor with HIV, NIH proposes that the deceased donor 
eligibility criteria apply.
Recipient Eligibility
    The only change proposed in this category concerns CD4+ T-cell 
counts. The 2015 NIH 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, NIH proposes no minimum threshold CD4+ T-cell 
counts for other organs when all other eligibility criteria are met.
Transplant Hospital
    NIH proposes several changes to this category. The requirement for 
prior experience with transplantation of organs from donors without HIV 
in recipients with HIV. The 2015 NIH Research Criteria required 
experience with five transplants over the four preceding years 
involving organs from donors without HIV transplanted into recipients 
with HIV. NIH proposes removing 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 proposes that 
all patients with transplants involving donors with HIV be managed by 
multidisciplinary teams before, during, and after transplantation. NIH 
proposes specific members of this multidisciplinary team.
    NIH proposes removing the requirement that each living donor with 
HIV and each transplant recipient with HIV be provided with an HIV-
independent advocate. NIH proposes instead 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 proposed change to the 2015 Research 
Criteria will not alter that.

[[Page 93623]]

Organ Procurement Organization (OPO) Responsibilities
    NIH does not propose changes to this category.
Prevention of Inadvertent Transmission of HIV
    NIH does not propose changes to this category.
Required Outcome Measures and Data Elements
    The 2015 Research Criteria referenced required outcome measures. 
NIH proposes using the more precise ``Required Data Elements and 
Outcome Measures.'' NIH notes that data on these existing and proposed 
outcome measures is collected by the OPTN as specified by the 
Secretary. NIH does not intend to propose data collection requirements 
beyond those collected by the OPTN.
    Waitlist Candidates: NIH proposes adding several data elements for 
waitlist candidates. NIH proposes adding cytomegalovirus (CMV 
immunoglobulin G [IgG]) as a required outcome measure for co-infection. 
NIH also proposes adding 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 proposes adding additional elements 
related to the 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 proposes 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 NIH Research Criteria included as required 
outcome measures progression to renal insufficiency in kidney living 
donors. 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 proposes adding several additional data 
elements and outcome measures to those included for transplant 
recipients in the 2015 NIH Research Criteria. NIH proposes adding 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 proposed as a requirement of the Research Criteria, NIH 
proposes to provide 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/index.html) 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: November 21, 2024.
Lawrence A. Tabak,
Principal Deputy Director, National Institutes of Health.
[FR Doc. 2024-27733 Filed 11-26-24; 8:45 am]
BILLING CODE 4140-01-P`