[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