Notice2024-31265
Final Revised Human Immunodeficiency Virus (HIV) Organ Policy Equity Act Safeguards and Research Criteria for Transplantation of Organs From Donors With HIV
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Published
December 30, 2024
Issuing agencies
Health and Human Services DepartmentNational Institutes of Health
Abstract
Kidney and liver transplants from donors with HIV no longer require institutional review board (IRB)-approved research protocols or compliance with HHS research criteria per a November 27, 2024, final rule. Through this notice, the U.S. Department of Health and Human Services (HHS) announces the publication of this accompanying Final Revised Safeguards and Research Criteria for Transplantation of Organs from Donors with HIV to apply to non-kidney and non-liver organs from donors with HIV for transplantation in recipients with HIV. Under the HOPE Act, these transplants must still occur under an IRB-approved research protocol that is compliant with federal regulations governing human subjects' research. The goal of this research is to increase knowledge about the safety, efficacy, and effectiveness of transplants other than liver and kidney, from donors with HIV, thereby expanding access to organs for patients with HIV in need of transplants. HHS published Draft Revised Safeguards and Research Criteria on December 12, 2024. A summary of the public comments and HHS' responses follows. As explained below, NIH adopts revised research criteria as proposed except that NIH removed residual stigmatizing language from the title of the Research Criteria.
Full Text
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[Federal Register Volume 89, Number 249 (Monday, December 30, 2024)]
[Notices]
[Pages 106542-106548]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2024-31265]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Final Revised Human Immunodeficiency Virus (HIV) Organ Policy
Equity Act Safeguards and Research Criteria for Transplantation of
Organs From Donors With HIV
AGENCY: National Institutes of Health, Department of Health and Human
Services.
ACTION: Final notice.
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SUMMARY: Kidney and liver transplants from donors with HIV no longer
require institutional review board (IRB)-approved research protocols or
compliance with HHS research criteria per a November 27, 2024, final
rule. Through this notice, the U.S. Department of Health and Human
Services (HHS) announces the publication of this accompanying Final
Revised Safeguards and Research Criteria for Transplantation of Organs
from Donors with HIV to apply to non-kidney and non-liver organs from
donors with HIV for transplantation in recipients with HIV. Under the
HOPE Act, these transplants must still occur under an IRB-approved
research protocol that is compliant with federal regulations governing
human subjects' research. The goal of this research is to increase
knowledge about the safety, efficacy, and effectiveness of transplants
[[Page 106543]]
other than liver and kidney, from donors with HIV, thereby expanding
access to organs for patients with HIV in need of transplants. HHS
published Draft Revised Safeguards and Research Criteria on December
12, 2024. A summary of the public comments and HHS' responses follows.
As explained below, NIH adopts revised research criteria as proposed
except that NIH removed residual stigmatizing language from the title
of the Research Criteria.
FOR FURTHER INFORMATION CONTACT: Dr. Jonah Odim, Chief Clinical
Transplantation Section, Transplantation Branch, 5601 Fishers Lane,
Room 6B21, MSC 9827, Rockville, MD 20892-9827; by email at
<a href="/cdn-cgi/l/email-protection#80efe4e9edeac0eee9e1e9e4aeeee9e8aee7eff6"><span class="__cf_email__" data-cfemail="cfa0aba6a2a58fa1a6aea6abe1a1a6a7e1a8a0b9">[email protected]</span></a>; by telephone at (301) 828-7220.
SUPPLEMENTARY INFORMATION:
Background
A. HHS Oversight of Organ Allocation and Transplantation
HHS is responsible for overseeing the operation of the nation's
OPTN, including assisting in the equitable allocation of donor organs
for transplantation. 42 U.S.C. 274(b)(2)(D). The OPTN is a network of
transplant centers, organ procurement organizations, and other
providers who work collectively to develop, implement, and monitor
organ allocation policy and performance of the organ transplant system.
The OPTN is also charged with developing policies on many subjects
related to organ donation and transplantation, which include
establishing standards of quality pertaining to organs procured for use
in transplantation. 42 U.S.C. 274(b)(2)(E).
B. HOPE Act Requirements and Implementation
The enactment of the HOPE Act in 2013, Public Law 113-51,
eliminated the prohibition in the United States on transplantation of
organs from persons with HIV, allowing transplantation of these organs
if certain requirements are satisfied. Under the HOPE Act, organs from
donors with HIV may be transplanted only in recipients living with HIV
prior to receiving such an organ. 42 U.S.C. 274(b)(3)(A). Further, the
HOPE Act requires that transplants of HIV-positive organs occur only in
recipients with HIV who are participating in institutional review board
(IRB)-approved research protocols that adhere to certain criteria,
standards, and regulations. 42 U.S.C. 274(b)(3)(B)(i). However, the
Secretary may lift the research and IRB requirements if the Secretary
has determined that participation in such clinical research, as a
requirement for such transplants, is no longer warranted. 42 U.S.C.
274(b)(3)(B)(ii).
The HOPE Act outlines the process by which the Secretary may make
such a determination under 42 U.S.C. 274(b)(3)(B)(ii). Specifically,
the Secretary must routinely review the results of scientific research,
in conjunction with the OPTN, to determine whether the results warrant
revision of the OPTN standards of quality regarding organs from donors
with HIV. If the Secretary determines that those standards of quality
should be revised, the Secretary must direct the OPTN to revise the
standards. 42 U.S.C. 274f-5(c)(2). The Secretary is also required to
revise the regulatory provision implementing the HOPE Act, 42 CFR
121.6, upon determining that revisions to the OPTN standards of quality
are warranted. 42 U.S.C. 274f-5(c)(3).
C. Research Criteria for HOPE Act Transplants
In 2015, NIH published proposed research criteria for HOPE Act
transplants in the Federal Register and solicited public comment. 80 FR
34912 (June 18, 2015). After consideration of public comments received,
NIH published the ``Final Human Immunodeficiency Virus (HIV) Organ
Policy Equity (HOPE) Act Safeguards and Research Criteria for
Transplantation of Organs Infected With HIV'' (``2015 Research
Criteria''). 80 FR 73785 (November 25, 2015). The goals of the 2015
Research Criteria were to ensure that research using organs from donors
with HIV was conducted under conditions protecting the safety of
research participants and the public and that the results of this
research provide a basis for evaluating the safety of transplants of
organs from donors with HIV in recipients with HIV. 80 FR 73785.
Introduction
The HOPE Act requires the Secretary of Health and Human Services
(the Secretary) to develop and publish criteria for research involving
transplantation of organs from donors with HIV to recipients with HIV.
In 2015, the National Institutes of Health (NIH), U.S. Department of
Health and Human Services (HHS) published the initial Research Criteria
applicable to such transplants, which was in effect for all transplants
involving organs from donors with HIV as authorized by the HOPE Act.
Through a final rule published in the Federal Register on November 27,
2024 (89 FR 93484), the Secretary determined that participation in
clinical research should no longer be a requirement for transplantation
of kidneys and livers from donors with HIV to recipients with HIV and
amended the HHS regulations governing the operation of the Organ
Procurement and Transplantation Network (OPTN) to reflect this
determination. As a result, HOPE Act transplants involving kidneys and
livers from donors with HIV no longer need to comply with the NIH
Research Criteria. Given this regulatory change, NIH proposed revised
Research Criteria and solicited public comments on such revisions by
publication in the Federal Register on November 27, 2024 (89 FR 93616).
NIH proposed deleting aspects of the Research Criteria that are
specific to kidney and liver transplantation. NIH made additional
proposed changes to the Research Criteria based on its review of
scientific evidence and in consideration of prior public feedback
concerning the criteria, including comments provided in the recent
rulemaking procedure that modified the OPTN regulations. There were 4
public comments to the Draft Revised HOPE Safeguards and Research
Criteria. After considering the public comments, NIH now finalizes the
Revised HOPE Safeguards and Research Criteria. As explained below, NIH
adopts revised research criteria as proposed except that NIH removed
residual stigmatizing language from the title of the 2015 Research
Criteria.
Overview of and Response to Comments
Recipient Eligibility Criteria
One commenter supported eliminating the organ-specific experience
criteria of 5 HIV D-/R+ transplants over 4 years. Per the commenter,
this benchmark was too high a bar for U.S. heart and lung transplant
programs to satisfy; thereby, prohibiting participation in HOPE Act
transplantation. This commenter proposed eliminating the recipient
eligibility criteria of an HIV viral load <50 copies/mL in deference to
investigator clinical judgement. NIH chose to maintain the undetectable
viral load threshold (<50 copies/mL) that aligns with strong expert
opinion from the Guidelines for the use of antiretroviral agents in
adults and adolescents with HIV: Transplantation in people with HIV
current as of 24 September 2024, <a href="https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/transplantation">https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/transplantation</a>. This criteria, which applies to transplants involving
donors with HIV, does not preclude transplant programs from
[[Page 106544]]
listing suitable recipients for organs from donors without HIV.
Removal of Clinical Research Criteria for Living Donors With HIV
One commenter raised concerns over removal of clinical research
criteria for living donors with HIV given needs for longer term outcome
data. As described above, the final rule issued by the Secretary has
removed the mandated IRB-approved research protocol requirements for
HOPE Act kidney and liver transplantation. Living heart and lung donors
with HIV are rare occurrences in today's transplant practice. In the
event of an intended living donation other than liver and kidney from a
person with HIV, we include protections for living donors in the
Revised Research Criteria. The revised criteria provide that for such
transplants, the deceased donor eligibility criteria will apply.
Further, the OPTN collects data on all living donors and transplants,
which allows for additional oversight.
Removal of Stigmatizing Language (e.g., Donors Infected With HIV)
One commenter requested the removal of residual stigmatizing
language from the title of the 2015 Research Criteria, which has been
modified in this final document.
Elimination of Mandatory Pre-Implantation Donor Biopsies
This commenter endorsed the elimination of mandatory pre-
implantation donor biopsies, since this is not routinely required for
solid organ transplants, and the trend towards standardizing the
evaluation of donors with HIV to that of donors without HIV.
A final commenter supported the proposed changes to Research
Criteria for HOPE Act kidney and liver transplants and applauded
measures taken to improve kidney transplant access for people with HIV.
Conclusion
HHS appreciates the time and effort responding to the Request for
Comments. The comments represented the efforts of truly dedicated
individuals and organizations in transplantation. The deliberations
over the last 3 years and the responses surrounding the NPRM and the
Draft Revised Research Criteria were helpful in completing the Final
Revised Human Immunodeficiency Virus (HIV) Organ Policy Equity (HOPE)
Act Safeguards and Research Criteria for Transplantation of Organs from
Donors with HIV.
Changes to the 2015 Research Criteria
NIH has made several changes to the 2015 Research Criteria to
reflect the Secretary's determination, published by regulation on
November 27, 2024 that HOPE Act kidney and liver transplants are no
longer required to be conducted as research subject to the 2015
Research Criteria, and to continue to further the goals shared in 2015
with respect to HOPE Act transplants of other organs from donors with
HIV that remain subject to the Research Criteria. NIH has removed the
requirements from the 2015 Research Criteria applicable to HOPE Act
kidney and liver transplants.
NIH has also made other changes to the 2015 NIH Research Criteria
for conducting HOPE Act transplants of organs other than kidneys and
livers (primarily heart and lung transplants) in IRB-approved research.
These changes are intended to accelerate research, ensure research
participant safety, and maintain stakeholder confidence in clinical
research conducted under the HOPE Act. Notable revisions include the
elimination of (i) the transplant program experience requirement of
five organ-specific transplants of organs from a donor without HIV in a
recipient with HIV conducted over 4 years; (ii) mandated pre-implant
biopsies; and iii) the requirement for HIV independent advocates for
living donors with HIV and recipients with HIV. Other organs (including
multi visceral organs such as small intestine, stomach, liver, pancreas
and colon) and multi organ transplants (e.g., heart-kidney) must comply
with the Revised Research Criteria for inclusion of any non-kidney or
non-liver organs from donors with HIV and subject to IRB approval.
The revisions to the 2015 Research Criteria are as follows:
Final Revised Human Immunodeficiency Virus (HIV) Organ Policy Equity
(HOPE) Act Safeguards and Research Criteria for Transplantation of
Organs From Donors With HIV
Table of Contents
Abbreviations
Definitions
Final Revised Hope Act Safeguards and Research Criteria
Table 1--Final Revised Human Immunodeficiency Virus (HIV) Organ
Policy Equity (Hope) Act Safeguards and Research Criteria for
Transplantation of Organs From Donors With HIV
References
Abbreviations
------------------------------------------------------------------------
------------------------------------------------------------------------
AIDS....................... Acquired Immunodeficiency Syndrome.
ART........................ Antiretroviral Therapy.
CD4........................ Cluster of differentiation 4.
D-......................... Donor Human Immunodeficiency Virus
negative.
D+......................... Donor Human Immunodeficiency Virus
positive.
HBV........................ Hepatitis B virus.
HCT/Ps..................... Human Cells, Tissues, and Cellular and
Tissue-Based Products (HCT/Ps).
HCV........................ Hepatitis C virus.
HIV........................ Human Immunodeficiency Virus.
HIV-....................... Human Immunodeficiency Virus negative
(using serology and/or nucleic acid
testing using FDA-licensed, approved or
cleared devices).
HIV+....................... Human Immunodeficiency Virus positive
(using serology and/or nucleic acid
testing using FDA-licensed, approved or
cleared devices).
HOPE Act................... HIV Organ Policy Equity Act.
HRSA....................... Health Resources and Services
Administration.
IRB........................ Institutional review board.
NIH........................ National Institutes of Health.
NPRM....................... Notice of proposed rule making.
OI......................... Opportunistic infection.
OPO........................ Organ procurement organization.
PML........................ Progressive multifocal leukoencephalopathy.
R-......................... Recipient HIV negative.
R+......................... Recipient HIV positive.
RNA........................ Ribonucleic acid.
SOPs....................... Standard operating procedures.
------------------------------------------------------------------------
[[Page 106545]]
Definitions
------------------------------------------------------------------------
------------------------------------------------------------------------
Antiretroviral therapy (ART) When an HIV strain develops drug
resistance. resistance and/or genetic mutations
associated with drug resistance.
HIV superinfection................ Systemic HIV superinfection is
defined as the detection of HIV
viral sequences that
phylogenetically cluster with the
donor's viral population at two or
more time points in circulating
blood cells, plasma, or recipient
tissues other than the allograft.
Suppressed viral load............. HIV RNA below 50 copies per mL with
current technology at time of
publication of this research
criteria document.
------------------------------------------------------------------------
The NIH Research Criteria are set forth in six broad categories
(Donor Eligibility, Recipient Eligibility, Transplant Hospital
Criteria, Organ Procurement Organization (OPO) Responsibilities,
Prevention of Inadvertent Transmission of HIV, and Study Design/
Required Data Elements and Outcome Measures). Table 1 summarizes the
Final Revised HOPE Act Research Criteria in each category and compares
them to the 2015 Research Criteria.
---------------------------------------------------------------------------
\1\ Consistent with the final rule amending the OPTN
regulations, transplants using kidneys and livers from donors with
HIV no longer need to comply with the HOPE Act Research Criteria.
When multiple organs from donors with HIV are implanted
simultaneously (e.g., dual heart-kidney or dual lung-kidney), the
Research Criteria apply to such multiple organ transplants if the
transplant of any of the organs are subject to the revised Research
Criteria. For example, while a kidney transplant from a donor with
HIV no longer is required to be conducted in accordance with the
Research Criteria, a dual heart-kidney or dual lung-kidney
transplant with organs from donors with HIV is required to be
conducted in accordance with the Research Criteria and in accordance
with an IRB-approved research protocol. A dual liver-kidney
transplant with from donors with HIV is not required to be conducted
in accordance with the Research Criteria, as neither liver
transplants nor kidney transplants from donors with HIV are required
to be conducted as research.
Table 1--Final Revised Human Immunodeficiency Virus (HIV) Organ Policy
Equity (HOPE) Act Safeguards and Research Criteria for Transplantation
of Organs From Donors With HIV \1\
------------------------------------------------------------------------
Revised criteria [No
longer pertains to
Category Previous criteria kidney and liver
transplants \1\]
------------------------------------------------------------------------
Donor Eligibility:
All deceased donors with No evidence of No evidence of
HIV. invasive invasive
opportunistic opportunistic
complications of complications of
HIV infection. HIV infection.
Pre-implant donor There is no
organ biopsy. requirement for a
pre-implantation
biopsy.*
Viral load: no Viral load: no
requirement. requirement.
Deceased donor with The study team must The study team must
known history of HIV describe the describe the
and prior anticipated post- anticipated post-
antiretroviral therapy transplant transplant
(ART). antiretroviral antiretroviral
regimen(s) to be regimen(s) to be
prescribed for the prescribed for the
recipient and recipient and
justify its justify its
conclusion that the conclusion that the
regimen will be regimen will be
safe, tolerable, safe, tolerable,
and effective. and effective.
Living donor with HIV... Well-controlled HIV Thoracic Organs
infection defined Exception: The
as: living donor
<bullet> 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
<bullet> HIV-1 transplant or
ribonucleic acid ``domino'' heart
(RNA) <50 copies/mL. transplant. In such
<bullet> No evidence circumstances, the
of invasive deceased donor
opportunistic eligibility
complications of criteria should be
HIV infection. followed.
Pre-implant donor Other Organs: If a
organ biopsy.. living donor with
HIV donates another
type or organ
(other than kidney
and liver), the
deceased donor
eligibility
criteria should be
followed.*
Recipient Eligibility....... CD4+ T-cell count CD4+ T-cell count:
>=200/[micro]L no minimum
(kidney). threshold when all
CD4+ T-cell count other recipient
>=100 [micro]L eligibility
(liver) within 16 criteria are met.*
weeks prior to
transplant and no
history of
opportunistic
infection (OI); or
>=200 [micro]L if
history of OI is
present..
HIV-1 RNA <50 copies/ HIV-1 RNA <50 copies/
mL and on a stable mL and on a stable
antiretroviral antiretroviral
regimen. regimen.
No evidence of No evidence of
active active
opportunistic opportunistic
complications of complications of
HIV infection. HIV infection.
No history of No history of
primary central primary central
nervous system nervous system
(CNS) lymphoma or (CNS) lymphoma or
progressive progressive
multifocal multifocal
leukoencephalopathy leukoencephalopathy
(PML). (PML).
Transplant Hospital Criteria Transplant hospital Transplant hospital
with established with established
program for care of program for care of
subjects with HIV. patients with HIV.
HIV program HIV program
expertise on the expertise on the
transplant team. transplant team.
Organ-specific There is no longer a
experience with center specific
transplants of case experience
organs from donors requirement with
without HIV to transplants of
recipients with HIV organs from donors
(5 D-/R+ transplant without HIV to
cases over 4 years). recipients with
HIV.* Transplant
patients with
organs from donors
with HIV must be
managed with a
multidisciplinary
team before,
during, and after
transplant. The
multidisciplinary
team must include
transplant
surgeons,
physicians, HIV
specialists,
nurses, social
workers, and
pharmacists capable
of therapeutic drug
monitoring to
minimize drug-drug
interactions.
Standard operating Standard operating
procedures (SOPs) procedures (SOPs)
and training for and training for
the organ the organ
procurement, procurement,
implanting/ implanting/
operative, and operative, and
postoperative care postoperative care
teams for handling teams for handling
subjects with HIV, HIV-infected
and organs and subjects with HIV,
tissues from and organs and
individuals with tissues from
HIV. individuals with
HIV.
IRB-approved IRB-approved
research protocol research protocol
for transplantation for transplantation
of organs from of organs from
donors with HIV in donors with HIV in
recipients with HIV. recipients with HIV
for the applicable
organs.*
[[Page 106546]]
Institutional Institutional
biohazard plan biohazard plan
outlining measures outlining measures
to prevent and to prevent and
manage inadvertent manage inadvertent
exposure to and/or exposure to and/or
transmission of HIV. transmission of
HIV.
Provide each living There is no longer a
donor with HIV and requirement to
recipient with HIV provide an HIV
with an independent
``independent advocate beyond
advocate''. standard site
practices.*
Policies and SOPs Policies and SOPs
governing the governing the
necessary necessary
knowledge, knowledge,
experience, skills, experience, skills,
and training for and training for
independent independent
advocates. advocates.
OPO Responsibilities........ SOPs and staff SOPs and staff
training procedures training procedures
for working with for working with
deceased donors deceased donors
with HIV and their with HIV and their
families in families in
pertinent history pertinent history
taking; medical taking; medical
chart abstraction; chart abstraction;
the consent the consent
process; and process; and
handling blood, handling blood,
tissues, organs, tissues, organs,
and biospecimens. and biospecimens.
Biohazard plan to Biohazard plan to
prevent and manage prevent and manage
HIV exposure and/or HIV exposure and/or
transmission. transmission.
Prevention of Inadvertent Each participating Each participating
Transmission of HIV. Transplant Program Transplant Program
and OPO shall and OPO shall
develop an develop an
institutional institutional
biohazard plan for biohazard plan for
handling organs handling organs
from HIV-positive from HIV-positive
donors that is donors that is
designed to prevent designed to prevent
and/or manage and/or manage
inadvertent inadvertent
transmission or transmission or
exposure to HIV. exposure to HIV.
Procedures must be Procedures must be
in place to ensure in place to ensure
that human cells, that human cells,
tissues, and tissues, and
cellular and tissue- cellular and tissue-
based products (HCT/ based products (HCT/
Ps) are not Ps) are not
recovered from recovered from
donors with HIV for donors with HIV for
implantation, implantation,
transplantation, transplantation,
infusion, or infusion, or
transfer into a transfer into a
human recipient; human recipient;
however, HCT/Ps however, HCT/Ps
from a donor from a donor
determined to be determined to be
ineligible may be ineligible may be
made available for made available for
nonclinical nonclinical
purposes. purposes.
Required Data Elements and
Outcome Measures **
Wait List Candidates.... HIV status.......... HIV status.
CD4+ T-cell counts.. CD4+ T-cell counts.
Co-infection Co-infection:
(hepatitis C virus <bullet> Hepatitis C
[HCV], hepatitis B (HCV RNA).
virus [HBV]). <bullet> Hepatitis B
(HBV
deoxyribonucleic
acid, HBV
antibody).
<bullet>
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.*
<bullet>
Duration.
<bullet> Warm and
cold ischemia
time.
Normothermic
regional
perfusion.*
<bullet>
Duration.
<bullet> Warm and
cold ischemia
time.
Living Donors........... Progression to renal These data elements
insufficiency in no longer apply
kidney donors. since kidney or
liver donation from
a living donor with
HIV no longer falls
under the Research
Criteria except
that these data
elements apply to
simultaneous
multiple organ
transplants.
Progression to
hepatic
insufficiency in
liver donors.
Change in ART Change in ART
regimen as a result regimen as a result
of organ of organ
dysfunction. dysfunction.
Progression to Progression to AIDS.
acquired
immunodeficiency
syndrome (AIDS).
Failure to suppress Failure to suppress
viral replication viral replication
(persistent HIV (persistent HIV
viremia). viremia).
Death............... Death.
Transplant Recipients... Rejection rate Rejection rate
(annual up to 5 (annual through 5
years). years).
Progression to AIDS. Progression to AIDS.
New OI.............. New OI.
Failure to suppress Failure to suppress
viral replication viral replication
(persistent HIV (persistent HIV
viremia). viremia).
HIV-associated organ HIV-associated organ
failure. failure.
Malignancy.......... Malignancy.
Graft failure....... Graft failure.
[[Page 106547]]
Mismatched ART Mismatched ART
resistance versus resistance versus
donor. donor.
Death............... Death.
Type of rejection
(antibody mediated
versus cellular
rejection).*
Chronic heart
allograft
vasculopathy.*
Chronic lung
allograft
dysfunction.*
Hospitalized
infections.*
Estimated glomerular
filtration rate.*
HIV superinfection.*
Re-transplantation.*
Simultaneous
multiple organ
transplants.
------------------------------------------------------------------------
* Denotes a revision of the 2015 Research Criteria.
** The previous category of outcome measures (from the original 2015
Research Criteria) is modified to also include data elements.
A summary of the revisions in each category of the Research
Criteria is provided below as compared with the 2015 Research Criteria.
Donor Eligibility
The only change to this category applies to all deceased donors
with HIV. NIH has removed the requirement for a pre-implantation donor
organ biopsy. Although pre-implantation biopsies for kidneys and livers
have occurred regularly, pre-implant donor heart and lung biopsies are
not routinely performed. Likewise, donor biopsies for other organs are
not routine. Given that kidney and liver transplants are no longer
subject to the Research Criteria, NIH has removed the requirement for
pre-implantation biopsies. Any pre-implant biopsies obtained, as part
of future IRB-approved research protocols, should be stored in
accordance with local institutional requirements and the federal
regulations applicable to slides, tissues and blocks, if applicable. 42
CFR 493.1105 (<a href="https://www.ecfr.gov/current/title-42/chapter-IV/subchapter-G/part-493/subpart-J/section-493.1105">https://www.ecfr.gov/current/title-42/chapter-IV/subchapter-G/part-493/subpart-J/section-493.1105</a>).
With respect to living donors with HIV, the 2015 Research Criteria
defined a well-controlled HIV infection and required pre-implant donor
organ biopsies. The last living lobar lung transplant procedure in the
U.S. was performed in 2013. NIH has removed this element as not
relevant for heart and lung transplantation except in the rare
instances of living donor lung transplant or ``domino'' heart
transplants. In such circumstances, the deceased donor eligibility
criteria apply. If another type of organ is donated by a living donor
with HIV, the deceased donor eligibility criteria apply.
Recipient Eligibility
The only change in this category concerns CD4+ T-cell counts. The
2015 Research Criteria imposed requirements with respect to the CD4+ T-
cell counts specific to livers and kidneys. Given that kidney and liver
transplants are no longer required to comply with the Research
Criteria, there is no minimum threshold CD4+ T-cell counts for other
organs when all other eligibility criteria are met.
Transplant Hospital
NIH made several changes to this category. The requirement for
prior experience with transplantation of organs from donors without HIV
in recipients with HIV. The 2015 Research Criteria required experience
with five transplants over the four preceding years involving organs
from donors without HIV transplanted into recipients with HIV. NIH has
removed this requirement, which was perceived by many as burdensome and
a barrier to entry to transplant hospitals wishing to perform HOPE Act
transplants. To maximize favorable outcomes and effectively prevent and
manage adverse events, NIH has specified that all patients with
transplants involving donors with HIV be managed by multidisciplinary
teams before, during, and after transplantation. NIH outlines specific
members of this multidisciplinary team.
NIH has removed the requirement that each living donor with HIV and
each transplant recipient with HIV be provided with an HIV independent
advocate. NIH advises that standard site practices apply. Based on a
decade of HOPE Act clinical experience, stakeholder surveys have
indicated that a requirement for an independent advocate is widely
perceived as a redundant layer of consent and a potential barrier for
some HIV patients who would otherwise benefit from an HIV donor
transplant. The NIH notes that per current OPTN policy and guidance,
all living donors, including those with HIV, have an independent
advocate. NIH's change to the 2015 Research Criteria will not alter
that.
Organ Procurement Organization (OPO) Responsibilities
NIH did not make any changes to this category.
Prevention of Inadvertent Transmission of HIV
NIH did not make any changes to this category.
Required Outcome Measures and Data Elements
The 2015 Research Criteria referenced required outcome measures.
NIH is using the more precise ``Required Data Elements and Outcome
Measures.'' NIH notes that data on these existing and new outcome
measures is collected by the OPTN as specified by the Secretary. NIH
does not intend to incorporate data collection requirements beyond
those collected by the OPTN.
Waitlist Candidates: NIH has added several data elements for
waitlist candidates. NIH has added cytomegalovirus (CMV immunoglobulin
G [IgG]) as a required outcome measure for co-infection. NIH also
included the following additional data elements and outcome measures:
renal dysfunction, liver dysfunction, indication for transplant, use of
mechanical circulatory devices, and use of extracorporeal membrane
oxygenation, intra-aortic balloon pump, and ventricular assist device.
Donors (All): First, NIH included additional elements related to
type of deceased donation: after brain death (DBD) or after circulatory
death (DCD) given the increasing use of the latter technique in the
U.S. In addition, NIH has added the following data elements for all
donors (if applicable): ex-vivo perfusion and normothermic regional
perfusion including durations of warm and cold ischemia.
Living Donors: The 2015 Research Criteria included as required
outcome measures progression to renal insufficiency in kidney living
donors.
[[Page 106548]]
Because kidney and liver transplants are no longer subject to the
Research Criteria, NIH plans to retain these outcomes only where
applicable (e.g., for deceased donor heart-living donor kidney
transplants, deceased donor heart-living donor liver transplants, and
for other organs subject to the Research Criteria).
Transplant Recipients: NIH has added several additional data
elements and outcome measures to those included for transplant
recipients in the 2015 Research Criteria. NIH has added the following
outcome measures: type of rejection (antibody mediated versus cellular
rejection), chronic allograft vasculopathy (heart), chronic lung
allograft dysfunction (lung), hospital infections, estimated glomerular
filtration rate (heart and lung), HIV superinfection, graft failure
(heart and lung), re-transplantation, and simultaneous multiple organ
transplants.
While not included as a requirement of the Research Criteria, NIH
has included the following recommendation regarding patient management:
NIH recommends that transplant programs and healthcare providers
follow current and updated practice management guidelines. For specific
guidance, transplant programs and healthcare providers should consult
vaccination guidance (<a href="https://www.cdc.gov/acip-recs/hcp/vaccine-specific/index.html">https://www.cdc.gov/acip-recs/hcp/vaccine-specific/index.html</a>) and expert guidance for the management of patients
with HIV pre-, during-, and post-transplant summarized in:
Transplantation in people with HIV (<a href="https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new">https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new</a>).
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. <a href="https://doi.org/10.1016/j.healun.2019.09.011">https://doi.org/10.1016/j.healun.2019.09.011</a>.
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. <a href="https://doi.org/10.1128/cmr.00111-22">https://doi.org/10.1128/cmr.00111-22</a>.
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. <a href="https://doi.org/10.1097/QAI.0000000000002647">https://doi.org/10.1097/QAI.0000000000002647</a>.
Dated: December 20, 2024.
Lawrence A. Tabak,
Principal Deputy Director, National Institutes of Health.
[FR Doc. 2024-31265 Filed 12-27-24; 8:45 am]
BILLING CODE 4140-01-P
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