Rule2024-27410
Organ Procurement and Transplantation: Implementation of the HIV Organ Policy Equity (HOPE) Act
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Published
November 27, 2024
Effective
November 27, 2024
Issuing agencies
Health and Human Services Department
Abstract
The Department of Health and Human Services (HHS) amends the regulations implementing the National Organ Transplant Act of 1984, as amended (NOTA), to remove clinical research and institutional review board (IRB) requirements ("research and IRB requirements") for transplantation of kidneys and livers from donors with human immunodeficiency virus (HIV) to recipients with HIV. As allowed by the HIV Organ Policy Equity (HOPE) Act, the Secretary of HHS determines that participation in such clinical research should no longer be a requirement for transplantation of kidneys and livers from donors with HIV to recipients with HIV. This final rule serves as publication of the Secretary's determination and amends the regulations to reflect this determination. This final rule also serves as publication of the Secretary's direction to the Organ Procurement and Transplantation Network (OPTN) to adopt and use standards of quality with respect to kidneys and livers from donors with HIV to ensure that HOPE Act kidney and liver transplants are subject to OPTN policies that are consistent with NOTA, and in a way that ensures the revised requirements for transplantation of such organs will not reduce the safety of organ transplantation.
Full Text
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<title>Federal Register, Volume 89 Issue 229 (Wednesday, November 27, 2024)</title>
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[Federal Register Volume 89, Number 229 (Wednesday, November 27, 2024)]
[Rules and Regulations]
[Pages 93484-93498]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2024-27410]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
42 CFR Part 121
RIN 0937-AA13
Organ Procurement and Transplantation: Implementation of the HIV
Organ Policy Equity (HOPE) Act
AGENCY: Office of the Assistant Secretary for Health (OASH) and Health
Resources and Services Administration (HRSA), Department of Health and
Human Services (HHS).
ACTION: Final rule.
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SUMMARY: The Department of Health and Human Services (HHS) amends the
regulations implementing the National Organ Transplant Act of 1984, as
amended (NOTA), to remove clinical research and institutional review
board (IRB) requirements (``research and IRB requirements'') for
transplantation of kidneys and livers from donors with human
immunodeficiency virus (HIV) to recipients with HIV. As allowed by the
HIV Organ Policy Equity (HOPE) Act, the Secretary of HHS determines
that participation in such clinical research should no longer be a
requirement for transplantation of kidneys and livers from donors with
HIV to recipients with HIV. This final rule serves as publication of
the
[[Page 93485]]
Secretary's determination and amends the regulations to reflect this
determination. This final rule also serves as publication of the
Secretary's direction to the Organ Procurement and Transplantation
Network (OPTN) to adopt and use standards of quality with respect to
kidneys and livers from donors with HIV to ensure that HOPE Act kidney
and liver transplants are subject to OPTN policies that are consistent
with NOTA, and in a way that ensures the revised requirements for
transplantation of such organs will not reduce the safety of organ
transplantation.
DATES: This rule is effective November 27, 2024.
FOR FURTHER INFORMATION CONTACT: Frank Holloman, Director, Division of
Transplantation, Health Systems Bureau, HRSA, 5600 Fishers Lane, Room
08W63, Rockville, MD 20857; by email at <a href="/cdn-cgi/l/email-protection#02666d6c63766b6d6c426a7071632c656d74"><span class="__cf_email__" data-cfemail="f3979c9d92879a9c9db39b818092dd949c85">[email protected]</span></a>; or by
telephone (301) 443-7577.
SUPPLEMENTARY INFORMATION:
I. Public Participation
On September 12, 2024, HHS published a notice of proposed
rulemaking (NPRM) in the Federal Register (89 FR 74174) proposing both
that the Secretary of HHS determine that participation in clinical
research should no longer be required for transplantation of kidneys
and livers from donors with HIV to recipients with HIV, and that the
HHS regulations at 42 CFR part 121 implementing the HOPE Act be amended
consistent with this proposed determination. The NPRM provided for a
30-day comment period, and HHS received 56 comments raising a variety
of issues. HHS has carefully considered all comments in developing this
rule, as outlined in section III, below, and presents a summary of all
significant comments and Departmental responses.
II. Background
A. HHS Oversight of Organ Allocation and Transplantation
Within HHS, HRSA 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 allocation of
organs is guided by the OPTN in accordance with NOTA and with the HHS
regulations governing the operation of the OPTN in 42 CFR part 121. The
OPTN is also charged with developing policies on many subjects related
to organ donation, procurement, 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, amended
NOTA to eliminate 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 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).
HRSA published a final rule implementing the HOPE Act on May 8,
2015. 80 FR 26464.\1\ The 2015 rule amended 42 CFR 121.6 to permit
transplants of organs from donors with HIV in accordance with the HOPE
Act requirements.
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\1\ Federal Register. Organ Procurement and Transplantation:
Implementation of the HIV Organ Policy Equity (HOPE) Act. 80 FR
26464 (May 8, 2015). <a href="https://www.federalregister.gov/documents/2015/05/08/2015-11048/organ-procurement-and-transplantation-implementation-of-the-hiv-organ-policy-equity-act">https://www.federalregister.gov/documents/2015/05/08/2015-11048/organ-procurement-and-transplantation-implementation-of-the-hiv-organ-policy-equity-act</a>.
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The HOPE Act also directs the Secretary to develop and publish
criteria for the conduct of research relating to transplantation of
organs from donors with HIV into persons who are living with HIV before
receiving an HIV-positive organ. 42 U.S.C. 274f-5(a). Subsequent to
publication of the 2015 rule implementing the HOPE Act, the National
Institutes of Health (NIH) published the Final Human Immunodeficiency
Virus (HIV) Organ Policy Equity (HOPE) Act Safeguards and Research
Criteria for Transplantation of Organs Infected With HIV, on November
25, 2015. 80 FR 73785.\2\
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\2\ Federal Register. Final Human Immunodeficiency Virus (HIV)
Organ Policy Equity (HOPE) Act Safeguards and Research Criteria for
Transplantation of Organs Infected With HIV. 80 FR 73785 (Nov. 25,
2015). <a href="https://www.federalregister.gov/documents/2015/11/25/2015-30172/final-human-immunodeficiency-virus-hiv-organ-policy-equity-hope-act-safeguards-and-research-criteria">https://www.federalregister.gov/documents/2015/11/25/2015-30172/final-human-immunodeficiency-virus-hiv-organ-policy-equity-hope-act-safeguards-and-research-criteria</a>.
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In general, the NIH Research Criteria include safeguards designed
to protect both donors and recipients, as well as healthcare providers
at Organ Procurement Organizations (OPOs) and transplant centers.
Specifically, and in addition to the requirements in established OPTN
transplant policies, donors with HIV must not have evidence of
opportunistic infections and recipients must have a stable CD4+ T-cell
count and established HIV suppression and control on effective
antiretroviral therapy (ART). The study team must describe the
anticipated effective HIV treatment plan and ART regimen for patients
receiving an organ with a potentially different HIV strain.
Antiretroviral drugs suppress viral replication; however, HIV may
develop resistance to a specific drug necessitating a different
medication regimen to maintain effectiveness. Transplant hospitals
conducting HOPE Act operations are required to have expertise in
transplants provided to recipients with HIV. OPOs are required to have
procedures in place to address working with families of deceased donors
who lived with HIV and a biohazard plan to address viral exposure and
potential transmission. Finally, the Research Criteria establish
uniform outcome measures that must be incorporated in the research
design so that data on HOPE Act transplants can be analyzed
consistently and data collection is harmonized to inform future
implementation of the HOPE Act.
Publication of both the final rule implementing the HOPE Act and
the NIH Research Criteria necessitated that the OPTN update its
standards of quality for HIV-positive organ transplants and coordinate
related OPTN policies. On November 21, 2015, the OPTN published an open
variance (an experimental policy that tests
[[Page 93486]]
methods of improving organ allocation) providing standards for
transplant hospitals conducting HOPE Act transplants.\3\ The OPTN
expanded the variance in 2019 to include all solid organs,\4\ and
extended the variance through January 2026, to provide for the
gathering of data and subsequent evaluation of the outcomes of HOPE Act
transplants.\5\
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\3\ Organ Procurement and Transplantation Network. Policy
Notice: Modifications to the Open Variance for the Recovery and
Transplantation of Organs from HIV Positive Donors. 2016 Sep 1:
<a href="https://optn.transplant.hrsa.gov/media/1872/dtac_policynotice_hope_201606.pdf">https://optn.transplant.hrsa.gov/media/1872/dtac_policynotice_hope_201606.pdf</a>.
\4\ Organ Procurement and Transplantation Network. Policy
Notice: Modify HOPE Act Variance to Include Other Organs. 2019 Jun
10: <a href="https://optn.transplant.hrsa.gov/media/3000/dtac_policynotice_201906.pdf">https://optn.transplant.hrsa.gov/media/3000/dtac_policynotice_201906.pdf</a>.
\5\ Organ Procurement and Transplantation Network. Policy
Notice: Extend HIV Organ Policy Equity (HOPE) Act Variance. 2021 Dec
6: <a href="https://optn.transplant.hrsa.gov/media/t1sdej22/policy-notice_dtac_hope_variance.pdf">https://optn.transplant.hrsa.gov/media/t1sdej22/policy-notice_dtac_hope_variance.pdf</a>.
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C. Review of Research Results
The Secretary, in conjunction with the OPTN, reviewed 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 allowed 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 should be
conducted outside of a research setting.
1. OPTN Review and Recommendations
In 2018, the OPTN initiated a review of research results and data
relevant to HOPE Act transplants, forming a working group for this
purpose.\6\ The OPTN's assessment as to whether revision is warranted
for the OPTN standards of quality applicable to HOPE Act transplants
was based primarily on (1) the review of studies demonstrating the
safety and outcomes of organ transplantation in recipients with HIV and
(2) a recognition that the removal of the general research and IRB
requirements for HOPE Act transplants could expand access to organ
transplantation for all patients regardless of their HIV status. In
this context, safety is measured by accidental or inadvertent
transmission of HIV in the performance of HOPE Act transplants. (Of
note, there were no recorded accidental or inadvertent transmission
events in the data reviewed by the OPTN.) Outcomes are determined
primarily by transplant recipient or graft survival, compared to non-
HOPE Act transplants or transplant recipients without HIV. Measures
(e.g., CD4+ T-cell counts, ART resistance, and detectable HIV viral
loads) or variables such as opportunistic infections, HIV
superinfection, malignancy, rejection, or graft failure may also factor
into comparative outcomes in the short and long term.
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\6\ Organ Procurement and Transplantation Network. Public
Comment Proposal: Modify the HOPE Act Variance to Include Other
Organs. 2019 Jan 22: <a href="https://optn.transplant.hrsa.gov/media/2800/dtac_publiccomment_20190122.pdf">https://optn.transplant.hrsa.gov/media/2800/dtac_publiccomment_20190122.pdf</a>.
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The OPTN used three primary sources of data to assess HOPE Act
transplants, each of which contributed to the recommendation the OPTN
provided to the Secretary: (1) the research results of two pilot
studies evaluating HOPE Act kidney transplants and liver transplants,
and the progress of two ongoing NIH-funded clinical trials evaluating
HOPE Act kidney transplants and liver transplants, (2) the research
results of an older clinical trial analyzing safety and efficacy of
kidney transplants in a small cohort of transplant recipients with HIV,
and (3) OPTN data on the outcomes of all HOPE Act transplants.
Pilot Studies
A multicenter pilot study was launched in 2016 to determine safety
and efficacy of HOPE Act kidney transplants. The HOPE In Action
Consortium of 14 transplant centers conducting HOPE Act kidney
transplants found no major differences between HOPE Act transplants of
a kidney from a donor with HIV to a recipient with HIV and non-HOPE Act
kidney transplants from a donor without HIV to a recipient with HIV.\7\
Rates of opportunistic infections and infections requiring
hospitalization post-transplant did not differ significantly across the
study arms. Rejection was common for the study participants in the
first year after transplant, occurring in 50 percent of recipients who
received a kidney from a donor with HIV and 29 percent of recipients
who received a kidney from a donor without HIV, but this result was not
statistically significant. The insignificance of the result is due, in
part, to the relatively small sample size. This finding is consistent
with the earlier clinical trial of kidney transplantation in recipients
with HIV, discussed in the next subsection of this preamble, which also
found higher rejection rates in HIV allografts. The pilot study
investigators noted that despite rejection rates, 1-year renal function
was excellent for both study populations. Limitations of the pilot
study include study size (75 transplants), which investigators
attributed to the lower number of HOPE Act transplants conducted than
the projected potential. In general, the study authors concluded that
there is a survival benefit of transplantation for kidneys from donors
with HIV to recipients with HIV, and that the availability of HOPE Act
kidney transplants has the potential to mitigate disparities for a
vulnerable population that faces lower access to transplant and higher
waitlist mortality. The investigators further concluded that the
observed trend toward higher rejection, albeit not statistically
significant, for transplanted organs from donors with HIV merited
further investigation.
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\7\ Durand CM, Zhang W, Brown DM, Yu S, Desai N, Redd AD,
Bagnasco SM, Naqvi FF, Seaman S, Doby BL, Ostrander D, Bowring MG,
Eby Y, Fernandez RE, Friedman-Moraco R, Turgeon N, Stock P, Chin-
Hong P, Mehta S, Stosor V, Small CB, Gupta G, Mehta SA, Wolfe CR,
Husson J, Gilbert A, Cooper M, Adebiyi O, Agarwal A, Muller E, Quinn
TC, Odim J, Huprikar S, Florman S, Massie AB, Tobian AAR, Segev DL;
HOPE in Action Investigators. A prospective multicenter pilot study
of HIV-positive deceased donor to HIV-positive recipient kidney
transplantation: HOPE in action. Am J Transplant. 2021
May;21(5):1754-1764.
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A separate pilot study conducted by HOPE In Action Consortium
participants compared HOPE Act transplants of a liver from a donor with
HIV to a recipient with HIV and non-HOPE Act liver transplants from a
donor without HIV to a recipient with HIV, and found that there were no
differences in one-year graft survival, rejections, HIV breakthrough or
severe adverse events. While the recipients of HOPE Act liver
transplants presented with more opportunistic infections, infectious
hospitalizations, and cancer, compared to non-HOPE Act liver
transplants, the investigators determined that these findings warrant
further investigation and perhaps consideration of additional donor and
recipient infection and malignancy monitoring. In general, the
investigators concluded that the transplant outcomes were more
favorable compared to historical data on liver transplantation in
recipients with HIV, who are known to experience higher rates of
opportunistic infections and other complications. In addition, it was
noted that co-infections are more common among both donors and
recipients with HIV and confound the results. (Results of non-HOPE Act
transplants have confirmed that recipients with both HIV and a co-
infection have lower survival rates. Therefore, the presence of co-
infections could independently impact survival and other variables
measured by studies on HOPE Act transplants.)
[[Page 93487]]
This pilot study was the first multicenter prospective study reporting
results of U.S. transplants of livers from donors with HIV to
recipients with HIV and comparing outcomes according to donor HIV
status in order to assess attributable risk. The investigators
recognized as a limitation that the pilot study was relatively small
(45 transplants), and noted that increases among HOPE Act liver
transplant recipients in mortality, cytomegalovirus (CMV) viremia,
infectious hospitalizations, and cancer, were observed. However, they
note that these results should be considered in light of the relatively
high rate of mortality for recipients awaiting liver transplant. For
these patients, the benefit of undergoing a HOPE Act liver transplant
may outweigh the risks of living with HIV and end stage liver
disease.\8\
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\8\ Durand CM, Florman S, Motter JD, Brown D, Ostrander D, Yu S,
Liang T, Werbel WA, Cameron A, Ottmann S, Hamilton JP, Redd AD,
Bowring MG, Eby Y, Fernandez RE, Doby B, Labo N, Whitby D, Miley W,
Friedman-Moraco R, Turgeon N, Price JC, Chin-Hong P, Stock P, Stosor
V, Kirchner VA, Pruett T, Wojciechowski D, Elias N, Wolfe C, Quinn
TC, Odim J, Morsheimer M, Mehta SA, Rana MM, Huprikar S, Massie A,
Tobian AAR, Segev DL; HOPE in Action Investigators. HOPE in action:
A prospective multicenter pilot study of liver transplantation from
donors with HIV to recipients with HIV. Am J Transplant. 2022
Mar;22(3):853-864.
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Ongoing Clinical Trials
The OPTN further considered the progress of an NIH-funded study on
HOPE Act kidney transplants that was ongoing at the time of the OPTN's
analysis. The NIH-funded U01 HOPE Act kidney transplant clinical trial
was designed to analyze rejection and long-term outcomes of kidney
transplantation for recipients with HIV. While the study was
subsequently expanded, at the time of the OPTN's consideration the
study was designed to compare outcomes of 100 HOPE Act kidney
transplant recipients to 100 kidney transplant recipients with HIV who
received an HIV-negative organ at 15 transplant centers, adding to the
cohort accrued from the pilot studies discussed in the immediately
preceding section of this preamble.\9\ The results from this clinical
trial were published in October 2024 and are described in section 3,
``Additional Research Results Published Subsequent to Issuance of the
NPRM,'' below. Of note, these investigators were awarded an expansion
grant to evaluate longer-term outcomes in HOPE Act kidney transplants.
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\9\ National Institutes of Health RePORT. Kidney Transplantation
from Donors with HIV: Impact on Rejection and Long-term Outcomes.
Project No. 5U01AI177211-02. Accessed 21 May 2024. <a href="https://reporter.nih.gov/search/kcWJ0GeT8kigjO2_LU8R2g/project-details/10848468">https://reporter.nih.gov/search/kcWJ0GeT8kigjO2_LU8R2g/project-details/10848468</a>.
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Similarly, the OPTN considered the progress of an ongoing U01 HOPE
Act liver transplant clinical trial designed to compare outcomes
between HOPE Act transplants and non-HOPE Act transplants of livers
from donors without HIV. The study has enrolled 40 individuals in each
group over 3 years at 16 transplant centers,\10\ reaching target
enrollment, and now is in the phase of patient follow-up. The final
results are not yet published.
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\10\ National Institutes of Health RePORT. Hope In Action: A
Clinical Trial of HIV-to-HIV Liver Transplantation. Project No.
5U01AI138897-05. Accessed 21 May 2024. <a href="https://reporter.nih.gov/project-details/10459319">https://reporter.nih.gov/project-details/10459319</a>.
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Other Research Results
Prior to the initiation of the pilot studies and clinical trials
discussed previously, a clinical trial examined outcomes of 150 kidney
transplants in recipients with HIV conducted between November 2003 and
June 2009. The investigators found both recipient and graft survival
rates were high with no important increases in complications associated
with HIV.\11\ As noted in the description of the findings of the HOPE
Act kidney transplant pilot study described in the immediately
preceding subsection of this preamble, the investigators observed what
they described as ``unexpectedly higher'' rejection rates in the
transplant recipients with HIV participating in the study, compared
with kidney transplant recipients who are not living with HIV. This
higher rejection rate was blunted in transplant recipients that
received anti-T-cell antibody medication at the time of
transplantation. Studies of non-HOPE Act transplants have confirmed
that such immunosuppressive regimens can reduce the risk of rejection
for kidney transplant recipients with HIV.\12\
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\11\ Stock PG, Barin B, Murphy B, Hanto D, Diego JM, Light J,
Davis C, Blumberg E, Simon D, Subramanian A, Millis JM, Lyon GM,
Brayman K, Slakey D, Shapiro R, Melancon J, Jacobson JM, Stosor V,
Olson JL, Stablein DM, Roland ME. Outcomes of kidney transplantation
in HIV-infected recipients. N Engl J Med. 2010 Nov 18;363(21):2004-
14.
\12\ Locke JE, James NT, Mannon RB, Mehta SG, Pappas PG, Baddley
JW, Desai NM, Montgomery RA, Segev DL. Immunosuppression Regimen and
the Risk of Acute Rejection in HIV-Infected Kidney Transplant
Recipients. Transplantation. 2014 Feb 27;97(4):p 446-450.
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OPTN Data--HOPE Act Transplant Outcomes
Data from HOPE Act transplants is compiled by the OPTN on a
quarterly basis, including waitlist registrations and counts of HOPE
Act transplants, and is routinely reviewed. Prior to issuing its
recommendation to the Secretary, the OPTN reviewed data on over 300
patients included in the HOPE Act research variance for which no case
was halted, paused, or substantially amended to address safety
concerns.
OPTN Recommendations
Based on the assessment of the above-described research results and
data, in 2021 the OPTN recommended to the Secretary that the research
and IRB requirements of the HOPE Act be removed for all organs.\13\ The
OPTN specifically noted that in its review of the data safety
monitoring review board (DSMB) reports from five years of HOPE Act
transplants, with over 300 persons with HIV receiving HOPE Act
transplants, no DSMB identified patient safety concerns in HOPE Act
research. Further, there have been no reports made to the OPTN of
safety issues regarding HOPE Act transplants among OPO, hospital, or
transplant center personnel or in patients, in donor hospitals, or
transplant hospitals. The OPTN noted that it was the opinion of the
OPTN Safety Review Group that the research and IRB requirements for
HOPE Act transplants present a barrier to fully realizing the potential
of organ transplantation from donors with HIV to recipients with HIV,
as the research and IRB requirements limit access to such
transplants.<SUP>14 15</SUP>
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\13\ Cooper M. ``OPTN Letter to Secretary Becerra on the HOPE
Act.'' 2021 Oct 29. <a href="https://optn.transplant.hrsa.gov/media/ueyjdfnd/hope-act-letter.pdf">https://optn.transplant.hrsa.gov/media/ueyjdfnd/hope-act-letter.pdf</a>.
\14\ McCauley J. ``Fifty Sixth ACBTSA Meeting, Written Public
Comment--November 17, 2022 Meeting.'' 2022 Nov 8. <a href="https://optn.transplant.hrsa.gov/media/hwgncda2/optn-executive-committee_acbtsa-letter.pdf">https://optn.transplant.hrsa.gov/media/hwgncda2/optn-executive-committee_acbtsa-letter.pdf</a>.
\15\ Chandran S, Stock PG, Roll GR. Expanding Access to Organ
Transplant for People Living With HIV: Can Policy Catch Up to
Outcomes Data? Transplantation. 2024 Apr 1;108(4):874-883.
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2. Additional Research Results Published Subsequent to the OPTN
Assessment
Prior to publication of the NPRM, the Secretary further considered
additional research published providing more evidence for the safety of
organ transplantation from donors with HIV to recipients with HIV. In
general, this research demonstrates that the safety and outcomes of
kidney and liver HOPE Act transplants are well established, with over
517 HOPE Act kidney and liver transplants conducted to date.
One prospective study published in 2022, examined 92 HOPE Act
donors contributing 177 organs, which included 131 kidneys and 46
livers, to understand the characteristics of donors with HIV in terms
of clinical,
[[Page 93488]]
immunologic, and virologic profiles to ensure the safety of
transplantation. Of these donors, 58 were donors with HIV and 34 were
donors without HIV. For those donors with known HIV infection, 90
percent received ART treatment. The study concluded that although drug
resistant mutations (DRMs) were common, DRMs that could compromise the
effectiveness of certain ART were rare, reassuring the safety of using
organs from donors with HIV in recipients with HIV. Further, the study
also found that there were no major differences in comorbidities
between recipient groups that received an organ from a donor with HIV
compared to those that received an organ from a donor without HIV.\16\
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\16\ Werbel WA, Brown DM, Kusemiju OT, Doby BL, Seaman SM, Redd
AD, Eby Y, Fernandez RE, Desai NM, Miller J, Bismut GA, Kirby CS,
Schmidt HA, Clarke WA, Seisa M, Petropoulos CJ, Quinn TC, Florman
SS, Huprikar S, Rana MM, Friedman-Moraco RJ, Mehta AK, Stock PG,
Price JC, Stosor V, Mehta SG, Gilbert AJ, Elias N, Morris MI, Mehta
SA, Small CB, Haidar G, Malinis M, Husson JS, Pereira MR, Gupta G,
Hand J, Kirchner VA, Agarwal A, Aslam S, Blumberg EA, Wolfe CR, Myer
K, Wood RP, Neidlinger N, Strell S, Shuck M, Wilkins H, Wadsworth M,
Motter JD, Odim J, Segev DL, Durand CM, Tobian AAR; HOPE in Action
Investigators. National Landscape of Human Immunodeficiency Virus-
Positive Deceased Organ Donors in the United States. Clin Infect
Dis. 2022 Jun 10;74(11):2010-2019.
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In a March 2024 analysis of the impact of the HOPE Act on access to
kidney transplantation for recipients with HIV, the authors found 70
percent of HOPE Act recipients received a kidney transplant during the
4.5 year study period versus 43 percent of non-HOPE Act transplant
candidates at the same center.\17\ Furthermore, those who received
transplants in HOPE Act trials had shorter estimated wait times (median
10.3 months versus 60.8 months), and after adjusting for relevant
allocation factors including time on dialysis, kidney transplantation
was 3.3-fold higher for those who received an organ from a donor with
HIV.\18\ These findings suggest that the availability of kidneys from
donors with HIV increases access to transplantation among people with
HIV. Given that people with HIV who are living with end stage renal
disease (ESRD) have higher mortality than people with ESRD who are not
also living with HIV,\19\ in HHS's view, this data illustrates the
benefit of HOPE Act kidney transplants for this vulnerable population.
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\17\ Motter JD, Hussain S, Brown DM, Florman S, Rana MM,
Friedman-Moraco R, Gilbert AJ, Stock P, Mehta S, Mehta SA, Stosor V,
Elias N, Pereira MR, Haidar G, Malinis M, Morris MI, Hand J, Aslam
S, Schaenman JM, Baddley J, Small CB, Wojciechowski D, Santos CAQ,
Blumberg EA, Odim J, Apewokin SK, Giorgakis E, Bowring MG, Werbel
WA, Desai NM, Tobian AAR, Segev DL, Massie AB, Durand CM; HOPE in
Action Investigators. Wait Time Advantage for Transplant Candidates
With HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act.
Transplantation. 2024 Mar 1;108(3):759-767.
\18\ Motter JD, et al, on behalf of the HOPE in Action
Investigators. Wait Time Advantage for Transplant Candidates With
HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act.
Transplantation. 2024 Mar 1;108(3):759-767.
\19\ Motter JD, et al., on behalf of the HOPE in Action
Investigators. Wait Time Advantage for Transplant Candidates With
HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act.
Transplantation. 2024 Mar 1;108(3):759-767.
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The HOPE in Action Consortium also has published information on the
positive outcomes of living HOPE Act kidney donors. In a case series of
three transplants, investigators reported that two of the three donors
developed adverse events, but findings suggested these were medically
managed and that HIV RNA copies and CD4+ T-cell counts were stable at
two to four years post-transplant.\20\
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\20\ Durand CM, et al., on behalf of the HOPE in Action
Investigators. Living Kidney Donors with HIV: Experience and
Outcomes from a Case Series by the HOPE in Action Consortium. The
Lancet Regional Health Americas. 2023 Jul;24:100553.
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There is significantly less data on non-kidney and non-liver HOPE
Act transplants. Since 2019, when the OPTN's HOPE Act policy was
expanded to include all solid organs, only three heart transplant
programs have received approval to perform HOPE Act transplants. To
date, just three heart transplants have been conducted, including one
heart-kidney transplant.<SUP>21 22</SUP> No HOPE Act transplants have
been recorded among recipients in need of other organs. The lack of
data makes it difficult to assess the safety and outcomes of HOPE Act
transplants other than kidney and liver HOPE Act transplants.
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\21\ Montefiore News Releases. World's First HIV-Positive to
HIV-Positive Heart Transplant Performed at Montefiore Health System.
2022 Jul 22. <a href="https://www.montefiore.org/body.cfm?id=1738&action=detail&ref=2194">https://www.montefiore.org/body.cfm?id=1738&action=detail&ref=2194</a>.
\22\ Hemmige V, Saeed O, Puius YA, Azzi Y, Colovai A, Borgi J,
Goldstein DJ, Rahmanian M, Carlese A, Jorde UP, Patel S. HIV D+/R+
heart/kidney transplantation: First case report. J Heart Lung
Transplant. 2023 Mar;42(3):406-408.
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3. Additional Research Results Published Subsequent to Issuance of the
NPRM
Since publication of the NPRM, results from a new, groundbreaking
study were published in October 2024.\23\ In the largest prospective,
observational, multicenter study to date, researchers compared
transplantation of kidneys at 26 U.S. centers from deceased donors with
HIV and donors without HIV to recipients with HIV. The study enrolled
408 transplantation candidates, of whom 198 received a kidney from a
deceased donor; 99 received a kidney from a donor with HIV and 99 from
a donor without HIV. This study was larger than the HOPE Act pilot
study, described above, and was designed to assess whether kidney
transplantation from donors with HIV to recipients with HIV would be
noninferior to transplantation from donors without HIV. The study
further assessed safety and post-transplantation complications.
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\23\ C.M. Durand, A. Massie, S. Florman, T. Liang, M.M. Rana, R.
Friedman-Moraco, A. Gilbert, P. Stock, S.A. Mehta, S. Mehta, V.
Stosor, M.R. Pereira, M.I. Morris, J. Hand, S. Aslam, M. Malinis, G.
Haidar, C.B. Small, C.A.Q. Santos, J. Schaenman, J. Baddley, D.
Wojciechowski, E.A. Blumberg, K. Ranganna, O. Adebiyi, N. Elias,
J.A. Castillo-Lugo, E. Giorgakis, S. Apewokin, D. Brown, D.
Ostrander, Y. Eby, N. Desai, F. Naqvi, S. Bagnasco, N. Watson, E.
Brittain, J. Odim, A.D. Redd, A.A.R. Tobian, and D.L. Segev, for the
HOPE in Action Investigators. Safety of Kidney Transplantation from
Donors with HIV. New England Journal of Medicine. 2024 Oct 17;
391(15): 1390-1401.
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The primary outcome assessed was a safety outcome (a composite of
death from any cause, graft loss, serious adverse event, HIV
breakthrough infection, persistent failure of HIV treatment, or
opportunistic infection) for noninferiority (margin for the upper bound
of the 95% confidence interval, 3.00). Researchers found an adjusted
hazard ratio of 1.00 for the primary composite outcome, demonstrating
noninferiority of kidney transplantation from donors with HIV as
compared to kidney transplantation from donors without HIV.
Secondary outcomes included overall survival, survival without
graft loss, rejection, infection, cancer, and HIV superinfection. The
following secondary outcomes were similar whether the donor had HIV or
not: overall survival at 1 year (94% vs. 95%) and 3 years (85% vs.
87%), survival without graft loss at 1 year (93% vs. 90%) and 3 years
(84% vs. 81%), and rejection at 1 year (13% vs. 21%) and 3 years (21%
vs. 24%).
The incidence of serious adverse events, infections, and cancer was
similar in all groups studied. Of note, the incidence of HIV
breakthrough infection was approximately three times higher among HOPE
Act transplants (incidence rate ratio, 3.14; 95% CI, 1.02 to 9.63),
which the researchers attributed to non-adherence to antiretroviral
therapy. In all participants with HIV breakthrough infection, viral
suppression was regained. A single case of potential HIV superinfection
or dual infection occurred among the 58 recipients in this group,
without HIV breakthrough infection or clinical consequences.
[[Page 93489]]
Among the acknowledged limitations of this study are the lack of
true randomization, which the authors note was not possible due to the
U.S. national organ allocation process. The authors further note that
study participants were equally eligible for a kidney from a donor with
or a donor without HIV, and that study group assignment was determined
according to whichever organ was available first. The study group whose
donors did not have HIV served as a control group and included 27
donors who were treated as having HIV during allocation but did not; in
the authors' estimation, recipients of kidneys from these donors
represent an ideal counterfactual control group. Immunosuppression and
prophylaxis were heterogeneous; however, these factors were balanced
between the two groups and reflect real-world practice, which the
authors assert increases the generalizability of the study results.
This study is an important addition to the evidence base for HOPE
Act kidney transplants in that the finding that kidney transplantation
from donors with HIV was noninferior to kidney transplantation from
donors without HIV with respect to the primary safety outcome, and that
the incidence of serious adverse events, infections, surgical or
vascular complications, and cancer was similar in the two groups,
supporting the safety of HOPE Act kidney transplants.
4. HHS Advisory Committee on Blood and Tissue Safety and Availability
Recommendations
The Secretary also considered the HHS Advisory Committee on Blood
and Tissue Safety and Availability (ACBTSA) recommendation that the
Secretary eliminate research and IRB requirements for all HOPE Act
transplants. The ACBTSA working group developing this recommendation
considered the OPTN recommendation and the results of relevant
scientific research. While the ACBTSA working group proposed that the
full committee recommend that the Secretary eliminate research and IRB
requirements for all HOPE Act transplants, the working group expressed
concern about the elimination of research and IRB requirements for non-
kidney and non-liver HOPE Act transplants,\24\ and whether there was
sufficient data collected on other organs to justify a full adoption of
the OPTN's recommendation.
---------------------------------------------------------------------------
\24\ HHS Advisory Committee on Blood and Tissue Safety and
Availability. 2022. Fifty-Sixth ACBTSA Meeting November 17, 2022--
Meeting Summary. <a href="https://www.hhs.gov/oidp/advisory-committee/blood-tissue-safety-availability/meeting-summary/2022-11-17/index.html">https://www.hhs.gov/oidp/advisory-committee/blood-tissue-safety-availability/meeting-summary/2022-11-17/index.html</a>.
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The ACBTSA subsequently recommended that the Secretary act to lift
the statutory research and IRB requirements for all HOPE Act
transplants and at the same time recommended that the Secretary direct
the OPTN to adopt, for HOPE Act transplants of organs other than
kidneys and livers, organ-specific policies imposing additional
requirements for the conduct of these transplants, including collecting
safety and outcomes data for transplant candidates and recipients of
such transplants through an IRB-approved research protocol.
These recommendations were later approved by 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.
Upon review of the OPTN, ACBTSA and BOTSEC recommendations, and in
consideration of the results of relevant scientific research, the
Secretary proposed to determine that the research and IRB requirements
for kidney and liver HOPE Act transplants are no longer warranted. The
NPRM incorporated this approach, publishing the Secretary's proposed
determination for comment, and proposing regulatory changes to exempt
HOPE Act kidney and liver transplants from research and IRB
requirements. In an effort to avoid the use of stigmatizing language,
the NPRM further proposed wording changes to references to persons,
donors, and recipients with HIV, and organs from individuals with HIV.
III. Discussion of Public Comment
HHS received 56 comments from individuals and organizations
involved in healthcare, organ transplantation, HIV advocacy, health
equity, LGTBQIA+ health, and HOPE Act clinical research. The comments
received expressed overwhelming support for the finalization of this
rule. A total of 55 of the 56 commenters expressed support for the
proposed rule. One commenter did not support the proposed rule.
Additional consideration was given to comments that were expressed by
multiple individuals and entities. HHS has considered all of the
comments, and, in response to comments regarding the use of non-
stigmatizing language, made changes to the final rule as suggested by
commenters.
Themes identified in many comments include that the proposed rule,
if finalized, could reduce morbidity and mortality for people with HIV,
reduce barriers to organ transplantation, increase organ utilization,
reduce wait times for people on organ transplant wait lists, and reduce
stigma and discrimination associated with HIV. One commenter indicated
that, given that only 31 of the 250 transplant centers in the U.S.
currently participate in HOPE Act clinical trials, access to these
vital transplants is geographically limited: the proposed rule would
encourage more transplant centers to offer HOPE Act transplants,
enabling more equitable access to life-saving care for people with HIV
across the country and helping to generate additional clinical data to
enhance understanding and inform best practices in transplant care for
people with HIV. In addition, numerous commenters noted that research
has sufficiently demonstrated that HOPE Act kidney and liver
transplants are both safe and effective.
The NPRM specifically invited public comment on the future
Secretarial direction to the OPTN to revise the standards of quality
concerning kidneys and livers from donors with HIV. Some commenters
provided specific suggestions for the Secretary's direction, and other
comments received appear relevant to HHS's consideration as to the
content of the direction to the OPTN. These comments are noted below in
both the subheading discussing the comments specifically provided on
the content of the direction to the OPTN, and the subheadings relating
to the subject matter of the comment. HHS has considered these comments
in the development of the Secretary's direction to the OPTN, which is
provided in section V, ``Implementation Considerations,'' below.
Multiple commenters also provided specific suggestions for the
content of the revised NIH Research Criteria, and other comments
received appear relevant to the content of the Research Criteria. These
comments are noted below in both the subheading discussing the comments
specifically provided on the Research Criteria, as well as in the
subheadings relating to the subject matter of the comment when the
commenter did not specifically reference the Research Criteria. All
comments relating to the content of the revised Research Criteria were
provided to NIH for consideration in the development of the revised
Research Criteria.
Detailed descriptions of comments on specific aspects of the NPRM
preamble and the proposed regulation, and HHS's responses to these
comments, are provided below.
[[Page 93490]]
Removal of Research and IRB Requirements for All Organs
Several commenters suggested that the Secretary should consider in
this rule, or in a future rulemaking, the removal of research and IRB
requirements for all HOPE Act organ transplants instead of removing
research and IRB requirements only for kidney and liver transplants.
Some of these commenters referenced the October 2021 letter from the
OPTN to the Secretary providing that the OPTN had not identified any
patient safety concerns involving HOPE Act transplants and that no
research protocols applicable to HOPE Act transplants had been stopped,
paused, or substantially altered due to patient safety concerns.\25\
Many of these comments suggested that the available data was sufficient
to prove the safety and efficacy of HOPE Act transplantation for all
organ transplants, not only kidney and liver transplants. Others
suggested that HHS should continue supporting research on HOPE Act
transplants with the goal of generating sufficient evidence to make the
case for a future Secretarial determination and rulemaking process that
would remove the research and IRB requirements for all HOPE Act
transplants.
---------------------------------------------------------------------------
\25\ Cooper M. ``OPTN Letter to Secretary Becerra on the HOPE
Act.'' 2021 Oct 29. <a href="https://optn.transplant.hrsa.gov/media/ueyjdfnd/hope-act-letter.pdf">https://optn.transplant.hrsa.gov/media/ueyjdfnd/hope-act-letter.pdf</a>.
---------------------------------------------------------------------------
HHS response: In the process leading up to the development of the
NPRM, the Secretary considered whether to eliminate research and IRB
requirements for all HOPE Act transplants. As a part of this process,
the Secretary considered the October 2021 communication from the OPTN
referenced by commenters, recommendations of advisory bodies, and
research results and outcomes data on HOPE Act transplants. The vast
majority of this data was generated from kidney and liver transplants,
and, as discussed in the NPRM preamble, the Secretary notes the limited
evidence demonstrating safety and efficacy of non-kidney and non-liver
HOPE Act transplants. In order to lift the research and IRB
requirements for HOPE Act transplants, the HOPE Act requires that the
Secretary must determine that participation in clinical research is no
longer warranted. 42 U.S.C. 274(b)(3)(B)(ii). In the absence of
research results and robust outcomes data relevant to HOPE Act
transplants of organs other than kidneys and livers, the Secretary does
not have sufficient information about transplants of organs other than
kidneys and livers on which to base the statutorily required
determination. For this reason, the NPRM proposal to lift the research
and IRB requirements only for HOPE Act kidney and liver transplants is
incorporated in this final rule. As required by the HOPE Act, the
Secretary will periodically review the results of additional scientific
research relevant to transplants of organs other than kidneys and
livers, and will reevaluate in the future whether the evidence is
robust enough to demonstrate that other types of HOPE Act transplants
need not be conducted in the research context. HHS makes no changes to
the regulatory proposal in response to these comments.
Language Regarding HIV
Many commenters expressed support for the proposed revisions to the
regulatory language used when referencing people, donors, and
recipients with HIV. In general, commenters suggested that the proposed
changes are more respectful, reflect a person-centered approach, and
help to combat stigma associated with HIV. Others noted that these
wording changes help to create a more inclusive healthcare environment.
One commenter requested that the proposed modification to 42 CFR
121.6 regarding references to donor organs be changed from ``donor
organ(s) with HIV'' to ``organ(s) from donors with HIV.'' The commenter
stated that, in their view, the term ``organs from donors with HIV'' is
accurate and precise, stigma-reducing, and reflects a person-first
approach in describing these donated organs.
HHS response: HHS appreciates this feedback, and includes the
regulatory revisions in this final rule as proposed with regard to
references to people, donors, and recipients with HIV. Further, HHS
concurs with the suggested revision provided by the commenter with
respect to the references to donor organs, and has incorporated this
suggested revision and other similar revisions in the final rule at 42
CFR 121.6(b)(1)(ii)(B) introductory text, (b)(1)(ii)(B)(1) and (2), and
(b)(2).
Ongoing Data Monitoring
Multiple commenters expressed support for efforts to monitor
outcomes of HOPE Act transplants, both for patient safety and to
develop evidence for the safety and efficacy of HOPE Act transplants.
Commenters addressing patient safety indicated that while the
proposed rule may streamline the transplant process and increase the
availability of organs, patient safety must be the top priority and
rigorous safety standards must continue to apply. Several commenters
noted that areas needing further attention, such as monitoring for
rejection, malignancy, and infection, do not overshadow the overall
favorable outcomes for HOPE Act kidney and liver transplants.
Commenters emphasized the importance of continued monitoring of
outcomes for these transplants by the OPTN, and that transparency and
public communication of these outcomes are critical to maintaining
trust and ensuring the ongoing success of HOPE Act transplant programs.
Commenters indicated that application of the NIH Research Criteria has
provided essential protections with regard to outcomes monitoring for
HOPE Act kidney and liver transplants, and urged continued monitoring
of HOPE Act transplants to ensure these protections are maintained.
Other commenters expressed that data monitoring could help HOPE Act
transplant recipients and HOPE Act living donors who may need to be
monitored for the development of chronic or end-stage conditions. For
example, one commenter noted that living kidney donors ``are already at
higher risk of kidney disease and will now only have one kidney.''
Commenters addressing evidence development noted that monitoring
and evaluation of HOPE Act transplants may help develop evidence that
will inform future policy, including a potential future implementation
of the HOPE Act to remove research and IRB requirements for all HOPE
Act organ transplants.
Several commenters indicated that current data monitoring
requirements applicable to all organ transplants are sufficient. One
commenter indicated that there is no reason to continue monitoring HOPE
Act kidney and liver transplant outcomes above and beyond the baseline
safety and outcomes monitoring for all organ transplants in the United
States. One commenter indicated that the OPTN structure and outcome
data collected are sufficient in their current state to provide
oversight for all organs. Another commenter indicated comfort with
appropriate oversight and data management by the organizations
designated to oversee transplant services on a national level, which
could include comprehensive reporting systems to track outcomes and
address any issues promptly. The commenter further expressed an
expectation that this information be made available to the public is a
transparent manner.
HHS response: HHS notes that the final rule does not affect
existing data
[[Page 93491]]
monitoring or evaluation requirements for HOPE Act transplants, as
these are determined by OPTN policy and the NIH Research Criteria. HHS
agrees that patient safety remains a paramount concern and that
appropriate safety standards apply to protect organ donors and
transplant recipients. Further, HHS expects to utilize data on HOPE Act
transplant outcomes in its ongoing evaluation of the HOPE Act. These
comments were provided to the NIH working group for consideration in
the development of revisions to the Research Criteria. Further, HHS
considered these comments in developing the Secretary's direction to
the OPTN to revise the OPTN standards of quality embodied in OPTN
policy regarding organs from donors with HIV. HHS makes no changes to
the regulatory proposal in response to these comments.
Standards for Transplant Centers Performing HOPE Act Transplants
Several commenters provided suggestions for transplant centers that
are seeking to participate in HOPE Act transplants. One commenter
requested that HHS evaluate all outstanding requests by transplant
centers to participate in HOPE Act transplants, and approve qualifying
transplant centers as soon as possible to both expand access to care
and to generate additional data on the HOPE Act transplants they
perform. The commenter further requested that HHS explore providing
grants designed to build the capacity at transplant centers such that
more transplant centers will be able to meet the minimum requirements
necessary to become HOPE Act transplant centers.
HHS response: Thank you for these suggestions. While no changes
have been made to the regulatory proposal in response to these
comments, HHS will consider these suggestions in the Department's
ongoing approach to implementation of the HOPE Act.
Informed Consent and Autonomy of Transplant Recipients
Some commenters expressed the desire that, if HHS finalizes the
proposed rule, that HHS take steps to prioritize ethical considerations
relevant to the autonomy of donors and recipients. In particular,
commenters asked that transplant centers maintain meaningful processes
to provide patients with the opportunity to provide informed consent,
and that transplant candidates with HIV retain the option to elect a
non-HOPE Act transplant instead of a HOPE Act transplant.
HHS response: This rule does not affect existing OPTN policies that
require that informed consent is obtained from all transplant
candidates, including HOPE Act transplant candidates,\26\ or the
informed consent policies or practices at hospitals providing clinical
care to potential organ donors, OPOs, or individual transplant centers.
HHS supports retaining the existing approach in OPTN policy that
requires informed consent.
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\26\ Organ Procurement and Transplantation Network. OPTN
Policies. Updated October 31, 2024. <a href="https://optn.transplant.hrsa.gov/media/eavh5bf3/optn_policies.pdf">https://optn.transplant.hrsa.gov/media/eavh5bf3/optn_policies.pdf</a>.
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Further, existing OPTN policies do not prohibit transplant
candidates eligible for a HOPE Act transplant to choose a non-HOPE Act
transplant.\27\ There are no revisions made in this rule that would
force a transplant candidate to receive an organ from a donor with HIV.
HHS supports retaining the existing approach in OPTN policy that
permits transplant candidates eligible for a HOPE Act kidney or liver
transplant to choose a non-HOPE Act kidney or liver transplant.
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\27\ Organ Procurement and Transplantation Network. OPTN
Policies. Updated October 31, 2024. <a href="https://optn.transplant.hrsa.gov/media/eavh5bf3/optn_policies.pdf">https://optn.transplant.hrsa.gov/media/eavh5bf3/optn_policies.pdf</a>.
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HHS considered these comments in developing the Secretary's
direction to the OPTN to revise the OPTN standards of quality embodied
in OPTN policy regarding organs from donors with HIV, as provided below
in this preamble in the discussion of implementation considerations.
HHS makes no changes to the regulatory proposal in response to these
comments.
Education
Commenters expressed the desire for additional educational efforts
regarding HOPE Act transplantation. Some commenters suggested that HRSA
collaborate with the OPTN and work with OPOs to ensure that transplant
centers are making compassionate efforts to seek authorization from
potential kidney donors with HIV. Commenters further suggested that
HRSA partner with the Centers for Medicare & Medicaid Services (CMS) to
ensure that donor hospitals recognize every opportunity for organ
donation for patients with an HIV-positive diagnosis and make referrals
to the local OPO for an organ donation evaluation as mandated by the
CMS Conditions of Participation. Other commenters asked for educational
efforts aimed at people with HIV, healthcare professionals, students of
health sciences, transplant centers, OPOs, and the public at large to
increase awareness of the HOPE Act and opportunities to elect organ
donation regardless of HIV status.
HHS response: HHS is supportive of any and all efforts to increase
awareness and education about HOPE Act transplants, opportunities for
persons with HIV to participate as organ donors, and transplant
candidates with HIV to receive a HOPE Act transplant. While HHS is not
making any revisions to the regulatory proposal in response to these
comments, HHS will consider additional educational efforts along the
lines of those suggested by the commenters.
NIH Research Criteria
Several commenters provided specific suggestions for the content
and development of the revised NIH Research Criteria:
<bullet> Commenters 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 requirement is
not necessary for organs from donors with HIV to be used safely.
<bullet> Commenters suggested that each transplant team should
include infectious disease specialists with expertise in HIV care.
<bullet> One commenter requested the elimination of the biopsy
requirement.
<bullet> One commenter noted that, in revising the Research
Criteria, NIH should both 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.
<bullet> One commenter requested that NIH include people with HIV,
HIV researchers, physicians, and healthcare providers in the process of
developing revised Research Criteria, and indicated that these
individuals can provide invaluable insights that can only come from
lived experience.
HHS response: HHS appreciates these suggestions, and agrees that
these comments are relevant to the content of the NIH Research
Criteria. These comments were provided to the NIH working group for
consideration in the development of revisions to the Research Criteria.
HHS makes no changes to the regulatory proposal in response to these
comments.
Secretarial Direction to the OPTN
While multiple commenters provided suggestions that appear relevant
to the Secretary's future direction to the OPTN to revise the standards
of quality concerning kidneys and livers from donors with HIV, only a
few commenters specifically referenced the
[[Page 93492]]
content of the Secretarial direction and provided recommendations. One
commenter indicated that they defer to health care professionals as to
the content of such direction, and further urged HHS to make sure that
the final OPTN policies do not create additional barriers or lead to
unintended consequences that make it more difficult for individuals to
access these organs. One commenter requested that the direction to the
OPTN require intensive and multi-disciplinary counseling and
discussions to be conducted with the solid organ recipient, with
ongoing care before, during, and after the transplant, to ensure that
solid organ recipients understand the complexities of the transplant
procedure while also receiving the emotional and physical care they
need throughout the entirety of the process. The commenter further
noted the opportunity for the OPTN to define transplant program
collaboration on a more formal basis, recommending that the structure
of the transplant team include nephrologists and/or hepatologists,
infectious diseases experts, and transplant pharmacy members, and that
requirements be instituted for providing counseling or any specific
transplant training recommendations for infectious disease experts.
The commenters who provided views and suggestions that are relevant
to the Secretary's direction to the OPTN, while not specifically
referencing the content of the Secretary's direction, generally
indicated that the current requirements applicable to all organ
transplants are sufficient to appropriately ensure the safety of HOPE
Act kidney and liver transplants conducted outside of the research
context. One commenter indicated that there is no reason to impose
special monitoring requirements for HOPE Act kidney and liver
transplant outcomes, as appropriately protective standards are already
included in the baseline safety and outcomes monitoring for all organ
transplants in the United States. One commenter indicated that the OPTN
structure and outcome data collected are sufficient in their current
state to provide appropriate oversight for all organ transplants,
regardless of whether the transplant involves organs from donors with
HIV to recipients with HIV. Another commenter indicated comfort with
appropriate oversight and data management by the organizations
designated to oversee transplant services on a national level,
indicating that such oversight may include stringent medical protocols,
regular follow-ups, and comprehensive reporting systems to track
outcomes and address any issues promptly. The commenter further
expressed an expectation that safety and outcomes information be made
available to the public is a transparent manner.
One commenter noted that HHS stated in the NPRM that scientific
evidence demonstrates that transplants of kidneys and livers from
donors with HIV to recipients with HIV are safe and effective. Given
this view, the commenter opined that the current clinical standards of
care for non-HOPE Act organ transplants are sufficient to apply to
transplants of all kidneys and livers, of any HIV serostatus. The
commenter further expressed that additional scrutiny of transplants of
kidneys and livers from donors with HIV to recipients with HIV could be
viewed as discrimination against recipients with HIV who are willing to
accept offers of an organ from a donor with HIV, and infringes on
patient autonomy. The commenter noted that the OPTN already is
responsible for safety and outcomes monitoring for transplants that
involve donors or recipients with viruses other than HIV, including
cytomegalovirus, Epstein-Barr virus, hepatitis B and C viruses, and
severe acute respiratory syndrome coronavirus 2.
HHS response: HHS appreciates all of the comments and suggestions
regarding the content of the Secretary's direction to the OPTN. HHS has
carefully considered these comments in developing the Secretary's
direction to the OPTN to revise the OPTN standards of quality embodied
in OPTN policy regarding organs from donors with HIV. As discussed
below in section V, ``Implementation Considerations,'' through
publication of this final rule, the Secretary directs the OPTN to adopt
and use standards of quality with respect to kidneys and livers from
donors with HIV to ensure that HOPE Act kidney and liver transplants
are subject to OPTN policies that, from the OPTN's expertise, will not
reduce the safety of HOPE Act kidney and liver transplants, provide
appropriate oversight for these transplants, and require sufficient
data collection and outcomes monitoring.
Health Equity and Patient Experience
Many comments positively noted the health equity component of the
proposed rule and the potential impact to populations that are
disproportionately impacted by HIV and end-stage chronic diseases.
Several commenters requested that HHS consider the insights and
experiences of HOPE Act patients in this and future rulemaking efforts.
HHS response: We agree. HHS supports efforts to better address
health equity in organ transplantation and believes this rule will help
to increase access to care among populations that are disadvantaged.
HHS also is supportive of efforts to incorporate patient experience
into policy, and we have received, and considered, comments from HOPE
Act patients during this rulemaking process, including a comment from a
self-identified living donor of a kidney used in a HOPE Act transplant.
HHS makes no changes to the regulatory proposal in response to these
comments.
Approach to Patient Care
Several commenters suggested changes to clinical care standards for
HOPE Act transplant patients. One commenter requested that the
Department encourage transplant centers to incorporate syndemic care
approaches to address the complex needs of people with HIV. Syndemic
care aims to provide more holistic service delivery to prevention and
care, including by addressing the social determinants of health that
allow for health conditions to cluster and interact. Several commenters
requested that additional safety protocols be developed for transplant
centers, such as post-operative care guidelines for HOPE Act transplant
recipients.
HHS response: HHS is supportive of efforts to incorporate syndemic
care approaches within the organ transplantation domain. Regarding the
establishment of additional safety protocols for transplant centers,
currently safety protocols beyond those included in the NIH Research
Criteria are determined by individual transplant centers. These
comments were provided to the NIH working group for consideration in
the development of revisions to the Research Criteria. Further, HHS
considered these comments in developing the Secretary's direction to
the OPTN to revise the OPTN standards of quality embodied in OPTN
policy regarding organs from donors with HIV, as provided below in the
discussion of implementation considerations. HHS makes no changes to
the regulatory proposal in response to these comments.
Addressing Diverse Needs
Several commenters requested that HHS consider the unique
challenges of patients who are Black, Indigenous, and people of color
and patients living in rural areas. A commenter indicated that post-
transplant care is essential for
[[Page 93493]]
positive patient outcomes and factors such as implicit bias in medical
settings, socioeconomic disparities, and geographic limitations
frequently hinder equitable access to post-transplant care, especially
for people experiencing both geographic isolation and medical racism.
Long travel distances to transplant centers and lacking local
healthcare options can impede consistent follow-up care and medication
compliance.
HHS response: HHS is supportive of efforts to improve health equity
in organ transplantation and believes this rule will contribute to
improving access to care for patients who are Black, Indigenous, and
people of color and patients living in rural areas by allowing HOPE Act
kidney and liver transplants to be conducted at any transplant center
in the United States. HHS makes no changes to the regulatory proposal
in response to this comment.
Standards for Transplant Candidates
One commenter noted his opposition to lengthy sobriety requirements
for liver transplant candidates.
HHS response: Currently, sobriety requirements for transplant
candidates are determined by individual transplant centers. This
comment was provided to the NIH working group for consideration in the
development of revisions to the Research Criteria. Further, HHS
considered this comment in developing the Secretary's direction to the
OPTN to revise the OPTN standards of quality embodied in OPTN policy
regarding organs from donors with HIV, as provided below in this
preamble in the discussion of implementation considerations. HHS makes
no changes to the regulatory proposal in response to this comment.
Future Research on HOPE Act Transplants
Multiple commenters expressed support for additional research
evaluating the safety and efficacy of HOPE Act transplants. One
commenter suggested that the experience of HOPE Act transplant patients
should help inform the direction of future research on HOPE Act
transplants.
HHS response: HHS is supportive of additional research evaluating
the safety and efficacy of HOPE Act transplants, and considering
patient experiences in informing the direction of future research.
While no changes are made to the regulatory proposal in response to
these comments, HHS will consider these comments in further efforts to
implement the HOPE Act.
Beyond Scope
Some commenters provided comments or made suggestions that are
beyond the scope of the proposed rule.
One commenter requested that HHS establish a program to provide
technical assistance to state, local, and tribal health departments
with the goal of adopting policies to prevent health information from
being used in a criminal, civil, or immigration legal proceeding.
One commenter noted that none of the other comments provided on the
NPRM highlight that there will be a conflict between a majority of
expressly prohibitive or potentially permissive State laws and
expressly permissive Federal law when this proposed rule is finalized.
The commenter indicated that State laws that are silent on or
prohibitive of organ transplantation between people diagnosed with HIV
can and do preclude performance of HOPE Act transplants within a given
jurisdiction regardless of permissive Federal laws, and despite
Congress and Federal regulators having the authority to preempt state
and local health laws.
Multiple commenters noted that State criminal laws that prohibit
persons with HIV for donating or attempting to donate organs, blood,
tissue, and other bodily fluids are a legal barrier to implementation
of the HOPE Act.
HHS response: As these comments are not within the scope of the
proposed rule, these comments have not altered HHS's proposed approach
to lifting the research and IRB requirements for HOPE Act kidney and
liver transplants.
Opposition
One commenter opposed the proposed rule, suggesting that organs
from donors with HIV are not the same as organs from donors without
HIV, and expressing concern regarding the transmission of HIV through
organ transplantation to recipients without HIV.
HHS response: HHS notes that there have been no reported cases of
inadvertent HIV transmission resulting from HOPE Act transplants.
Further, under the requirements of the HOPE Act, transplantation of
organs from donors with HIV to recipients without HIV is prohibited.
HHS makes no changes to the regulatory proposal in response to this
comment.
IV. Secretarial Determination
The Secretary has reviewed the recommendations of the OPTN, the
ACBTSA, and the BOTSEC on implementation of the HOPE Act, the results
of research on HOPE Act transplants conducted to date as well as
results of other relevant research on organ transplants in recipients
with HIV, and public comment received on the NPRM. Pursuant to his
authority under the HOPE Act, 42 U.S.C. 274(b)(3)(B)(ii), and
consistent with the implementing regulations at 42 CFR 121.6, the
Secretary determines that participation in clinical research, and
therefore adherence to research and IRB requirements, as a requirement
for transplants of kidneys and livers from persons with HIV, is no
longer warranted. Through publication of this final rule, the Secretary
is lifting the statutory research and IRB requirements for such
transplants.
HHS anticipates that the Secretary's determination and publication
of this final rule will increase access to kidney and liver transplants
by allowing more transplant centers to perform HOPE Act kidney and
liver transplants. Currently, only a limited number of centers can
perform HOPE Act transplants, because there are specific requirements
stipulated by the NIH Research Criteria for such transplant centers.
These requirements include expertise in HIV infection management,
minimum organ-specific transplant team experience of five transplants
of organs from donors without HIV to recipients with HIV over four
years and an independent advocate for both recipients with HIV and
prospective living donors with HIV. The requirements for centers
conducting HOPE Act transplants have been subject to critique and have
been viewed by some as a barrier to participation in HOPE Act
transplant programs, which may impact equity and access to organ
transplantation throughout the United States.\28\ By eliminating the
requirement that HOPE Act kidney and liver transplants are conducted in
the research context, HHS expects that a larger number of transplant
centers will be able to conduct such transplants. This rule will enable
more transplant centers to transplant kidneys and livers donated by
both living and deceased donors with HIV, in recipients with HIV,
thereby expanding opportunities for people with HIV and end-stage
diseases.
---------------------------------------------------------------------------
\28\ Bowring, M.G., Ruck, J.M., Bryski, M.G., Werbel, W.,
Tobian, A.A.R., Massie, A.B., Segev, D.L., & Durand, C.M. (2023).
Impact of expanding HOPE Act experience criteria on program
eligibility for transplantation from donors with human
immunodeficiency virus to recipients with human immunodeficiency
virus. American Journal of Transplantation, 23(6), 860-864.
---------------------------------------------------------------------------
Further, HHS expects this rule will expand access to organ
transplantation for all patients, regardless of their HIV status. When
eligible for transplant, a
[[Page 93494]]
person with HIV is added to the waiting list. That patient may elect to
receive an organ from a donor with HIV, as a HOPE Act transplant,
should it become available, or may choose to wait for an organ from a
donor who did not have HIV. If the patient with HIV chooses the HOPE
Act transplant, this will allow another patient on the waiting list to
receive the next available organ from a donor who does not have HIV,
which would reduce the time spent waiting for a transplant. Of note,
patients who do not have HIV will not be offered an organ from a donor
who has HIV, as such transplants are not allowed under Federal law.
As of February 16, 2024, more than 103,000 men, women, and children
were on the national organ transplant waiting list.\29\ Every 10
minutes another person is added to the waiting list, and nearly 20
people die every day while waiting for a transplant.\30\ HHS expects
that the Secretary's determination and publication of this rule will
improve access to kidney and liver transplants both by increasing the
number of kidneys and livers available for transplant, and by allowing
more transplant centers to perform HOPE Act kidney and liver
transplants. This anticipated positive result is consistent with the
Department's commitment to reducing the number of persons on the organ
transplant waiting list.
V. Implementation Considerations
A. NIH Research Criteria
The HOPE Act provides the Secretary with the discretion to
determine what research criteria should apply to HOPE Act transplants.
42 U.S.C. 274f-5(a). NIH, in consultation with HRSA and the OPTN, and
including the input of other relevant Federal stakeholders, formed a
working group to develop revised NIH Research Criteria. The NIH
Research Criteria, as originally drafted, include a strong focus on
HOPE Act kidney and liver transplants, as these are the most common
types of HOPE Act transplants: as this rule removes HOPE Act kidney and
liver transplants from the research context, it is necessary that the
revised NIH Research Criteria appropriately address non-kidney and non-
liver HOPE Act transplantation.
Further, HHS recognizes the revised NIH Research Criteria should
reflect advances in research in the time since HOPE Act transplants
began, including the current needs of various entities involved in non-
kidney and non-liver HOPE Act transplants in consideration of input
from transplant centers, transplant surgeons, OPOs, HIV clinicians,
donors, recipients, HIV advocates, the OPTN, and individuals affected
by the HOPE Act.
HHS has considered the comments submitted in response to the NPRM
that are relevant to the revised NIH Research Criteria, as summarized
in the discussion of public comment in section III, supra. These
comments have been provided to NIH for consideration in developing the
revised NIH Research Criteria. HHS will publish updated Research
Criteria in the Federal Register for public comment.
B. Secretary's Direction To Revise OPTN Policies
As part of the implementation of the Secretary's determination that
participation in clinical research as a requirement for transplants of
kidneys and livers from persons with HIV is no longer warranted, the
Secretary must direct the OPTN to update its policies to clarify that
HOPE Act kidney and liver transplants may be conducted in a way
consistent with the statutory requirements at 42 U.S.C. 274, and that
ensures the revisions to the policies will not reduce the safety of
organ transplantation. 42 U.S.C. 274f-5(c)(2); 42 CFR 121.6(b)(3).
In the NPRM preceding publication of this final rule, HHS
specifically sought public comment on the nature and content of the
Secretary's direction to the OPTN, including the level of specificity
in the direction and the extent of the OPTN's discretion in developing
the revised policies; what factors should be considered in assessing
whether the revised policies are consistent with 42 U.S.C. 274; and
what factors should be considered in assessing whether the revisions to
the OPTN policies will not reduce the safety of organ transplantation.
HHS further welcomed comment on any other aspects relating to the
Secretary's direction to the OPTN to revise its standards of quality as
required by the HOPE Act.
As described in the discussion of public comment in section III,
supra, HHS received multiple comments relating to HHS's consideration
as to the direction to the OPTN. The vast majority of commenters agreed
that scientific evidence clearly demonstrates that HOPE Act kidney and
liver transplants are safe and effective. Many of those commenters
indicated that the current requirements applicable to all organ
transplants are sufficient to appropriately ensure the continued safety
of HOPE Act kidney and liver transplants conducted outside of the
research context. HHS has carefully considered all comments received in
the development of the Secretary's direction to the OPTN.
Through publication of this final rule, the Secretary directs the
OPTN to adopt and use standards of quality with respect to kidneys and
livers from donors with HIV to ensure that HOPE Act kidney and liver
transplants are subject to OPTN policies that are consistent with 42
U.S.C. 274, and from the OPTN's expertise, will not reduce the safety
of HOPE Act kidney and liver transplants, provide appropriate oversight
for these transplants, and require sufficient data collection and
outcomes monitoring.
In consideration of the public comments received, HHS notes that it
may be appropriate for the OPTN to determine that current OPTN policies
that are generally applicable to kidney and liver transplants provide
appropriate safety and oversight standards for HOPE Act kidney and
liver transplants. Alternatively, the OPTN may choose to revise OPTN
policies to provide additional standards for HOPE Act kidney and liver
transplants.
This rule provides the Secretary's determination that that
participation in clinical research as a requirement for transplants of
kidneys and livers from persons with HIV is no longer warranted;
revises 42 CFR 121.6 to reflect the removal of the statutory research
and IRB requirements for HOPE Act kidney and liver transplants; and
directs the OPTN to revise its standards of quality with respect to
kidneys and livers from donors with HIV consistent with 42 U.S.C. 274
and in a way that ensures the changes will not reduce the safety of
organ transplantation policies as required by the HOPE Act. The final
implementation step is for the OPTN to adopt and use standards of
quality as directed by the Secretary to reflect that HOPE Act kidney
and liver transplants no longer are subject to research and IRB
requirements.
As was stated in the NPRM, HHS expects that the OPTN will solicit
public comment on a proposed revision to relevant OPTN policies, and
update the OPTN policies containing standards of quality with respect
to kidneys and livers from donors with HIV, within 15 months from the
publication of this final rule. As publication of this final rule has
obviated current OPTN policies requiring HOPE Act kidney and liver
transplants to be conducted in accordance with research and IRB
requirements, HHS encourages the OPTN to act expeditiously to revise
these policies. This will allow transplant centers that had not
[[Page 93495]]
previously been performing HOPE Act kidney and liver transplants in the
research context to begin performing HOPE Act kidney and liver
transplants in accordance with the revised OPTN policies.
VI. Final Rule Requirements
A. Removal of Research and IRB Requirements for HOPE Act Kidney and
Liver Transplants
Consistent with the Secretary's determination under the HOPE Act,
this rule revises 42 CFR 121.6 to reflect the removal of the statutory
research and IRB requirements for kidney and liver HOPE Act
transplants. Section 121.6(b)(1)(ii)(B) provides that participation in
clinical research is no longer warranted for the following categories
of transplants:
<bullet> Transplant of a kidney from a donor with HIV; and
<bullet> Transplant of a liver from a donor with HIV.
In implementation, this means that HOPE Act kidney and liver
transplants will no longer be required to be conducted as research, and
instead will be conducted in accordance with OPTN policies applicable
to HOPE Act kidney and liver transplants. As noted above, the OPTN may
decide that OPTN policies that generally apply to kidney and liver
transplants are appropriate to apply to HOPE Act kidney and liver
transplants, or may create different policies for HOPE Act kidney and
liver transplants.
B. Revised Terminology: Persons With HIV
HHS is aware that previous language used in enacting and
implementing the HOPE Act contained vocabulary and phrases that some
people find stigmatizing--namely, references to ``infected with HIV''
when the regulatory language encompasses both living and deceased
donors with HIV, or recipients with HIV. For the references to both
living and deceased donors with HIV, HHS revises all current references
in 42 CFR 121.6(b) from ``individuals infected with human
immunodeficiency virus (HIV)'' and ``individuals infected with HIV'' to
``donors with HIV'' or, when discussing organs donated, ``organs from
donors with HIV'' and specifically ``kidneys from donors with HIV'' and
``livers from donors with HIV.'' Further, HHS revises the current
reference in 42 CFR 121.6(b)(1)(i) describing the allowable recipients
of HOPE Act transplants from individuals who are ``infected with HIV
before receiving such organ(s)'' to instead refer to individuals who
are ``living with HIV before receiving such organ(s).'' This is
consistent with the Centers for Disease Control and Prevention's (CDC)
Stigma Language Guide.\31\ These changed regulatory references are to
avoid stigmatizing language, and do not change the groups of people
referenced in 42 CFR 121.6.
---------------------------------------------------------------------------
\31\ Centers for Disease Control and Prevention. Let's Stop HIV
Together: Stigma Language Guide. <a href="https://www.cdc.gov/stophivtogether/hiv-stigma/ways-to-stop.html">https://www.cdc.gov/stophivtogether/hiv-stigma/ways-to-stop.html</a>. Accessed 2/23/2024.
---------------------------------------------------------------------------
VII. Effective Date
HHS finds that there is good cause for this rule to be effective
upon publication in accordance with 5 U.S.C. 553(d)(3) of the
Administrative Procedure Act and 5 U.S.C. 808(2) of the Congressional
Review Act.
The waiting list for kidney transplant in the U.S. currently
exceeds 88,700 candidates.\32\ The 2022 OPTN/U.S. Scientific Registry
of Transplant Recipients (SRTR) Annual Data Report indicated that over
the course of a year more than 4,400 adults died while waiting for a
kidney transplant, and an additional 4,500 persons were removed from
the waiting list because they became too sick to receive a
transplant.\33\ Most transplant candidates wait years for a kidney
transplant, often requiring dialysis or other interventions.
---------------------------------------------------------------------------
\32\ Organ Procurement and Transplantation Network. Dashboard
and metrics. <a href="https://insights.unos.org/OPTN-metrics/">https://insights.unos.org/OPTN-metrics/</a>. Accessed Feb
2024.
\33\ Organ Procurement and Transplantation Network (OPTN)/
Scientific Registry of Transplant Recipients (SRTR). 2022. ``Annual
Data Report.'' Accessed November 2024. <a href="https://srtr.transplant.hrsa.gov/ADR/Chapter?name=Liver&year=2022">https://srtr.transplant.hrsa.gov/ADR/Chapter?name=Liver&year=2022</a>.
---------------------------------------------------------------------------
In addition, thousands of Americans suffer from conditions
requiring liver transplant. As of November 8, 2024, 13,170 candidates
were added to the waiting list in 2024.\34\ In 2022, more than 1,031
liver patients died while awaiting transplant, according to the OPTN/
SRTR Annual Data Report.\35\
---------------------------------------------------------------------------
\34\ Organ Procurement and Transplantation Network. Dashboard
and metrics. <a href="https://optn.transplant.hrsa.gov/data/dashboards-metrics/">https://optn.transplant.hrsa.gov/data/dashboards-metrics/</a>. Accessed November 2024.
\35\ Organ Procurement and Transplantation Network (OPTN)/
Scientific Registry of Transplant Recipients (SRTR). 2021. ``Annual
Data Report.'' Accessed February 2024. <a href="https://srtr.transplant.hrsa.gov/annual_reports/2021_ADR_Preview.aspx">https://srtr.transplant.hrsa.gov/annual_reports/2021_ADR_Preview.aspx</a>.
---------------------------------------------------------------------------
HHS expects that this final rule will have the effect of decreasing
the time all candidates for kidney and liver transplants spend on the
waiting list, regardless of their HIV status. As described in section
IV, above, a transplant candidate with HIV may choose to receive a HOPE
Act kidney or liver transplant if an organ from a donor with HIV
becomes available, or may choose to wait for an organ from a donor
without HIV. Research has demonstrated that candidates with HIV who
accept a HOPE Act kidney transplant spend significantly less time
awaiting transplant than candidates on the waiting list for an kidney
from a donor without HIV. A 2023 study found that median wait time for
a HOPE Act kidney transplant was 10.8 months compared to 60.8 months--a
3.3-fold higher rate of transplant compared to non-HOPE Act
transplants.\36\ When candidates with HIV choose a HOPE Act transplant,
this data suggests that this will decrease the time they spent on the
waiting list. Additionally, this will have the effect of allowing a
candidate further down the waiting list to receive the next available
organ from a donor who does not have HIV, both reducing the time that
candidate spends waiting for a transplant and decreasing the time all
other candidates spend on the waiting list.
---------------------------------------------------------------------------
\36\ Motter JD, et al; HOPE in Action Investigators. Wait Time
Advantage for Transplant Candidates With HIV Who Accept Kidneys From
Donors With HIV Under the HOPE Act. Transplantation. 2024 Mar
1;108(3):759-767.
---------------------------------------------------------------------------
Moreover, HHS expects that this final rule also will increase
access to organ transplantation. Thirty-one transplant centers are
qualified to perform HOPE Act kidney and liver transplants as research
in conformance with the requirements of the NIH Research Criteria,
while 250 transplant centers operate nationwide. As, pursuant to this
rule, HOPE Act kidney and liver transplants no longer need to be
conducted as research, it can be reasonably expected that more
transplant centers than in the past will be able to offer HOPE Act
kidney and liver transplants to appropriate candidates on the
transplant center's waiting list. It also is reasonable to expect that
if a greater number of transplant centers will be able to offer HOPE
Act transplants, this will allow more candidates with HIV on the
waiting list to receive HOPE Act kidney and liver transplants.
Lastly, HHS believes that a delayed effective date is unnecessary
to afford affected parties a reasonable time to adjust practices in
accordance with this rule. From the economic analysis of impacts,
provided below in section IX, this final rule will have a minimal
direct impact on affected entities with regard to preparing for
implementation. The direct effect of this final rule on transplant
centers is considered to be limited to the time spent by transplant
centers to read and understand the final rule, educate their staff on
the content of this final rule, and review and update
[[Page 93496]]
internal policies. This rule does not impose obligations on transplant
centers, and rather increases available flexibilities in that
transplant centers are no longer required to conduct HOPE Act kidney
and liver transplants in the research context. Further, as described
above in section V(B), the final implementation step for HOPE Act
kidney and liver transplants to begin occurring outside of the research
context is for the OPTN to revise its policies to reflect that HOPE Act
kidney and liver transplants no longer are subject to research and IRB
requirements. HHS is encouraging the OPTN to act expeditiously to
revise these policies, and it is likely that transplant centers will
educate their staff and review and update internal policies relevant to
the content of this final rule after the OPTN has published its revised
policies for HOPE Act kidney and liver transplants. Transplant centers
do not have any obligations stemming from this rule until the OPTN
revises its policies. In light of this context, a delayed effective
date for this rule is unnecessary for implementation purposes.
Given that, and the expected positive effects on time candidates
spend on the waiting list and the increase in access to HOPE Act
transplants resulting from this rule, pursuant to 5 U.S.C. 553(d)(3)
and 5 U.S.C. 808(2) HHS finds that there is good cause for this rule to
be effective upon publication.
VIII. Paperwork Reduction Act of 1995
This rule does not impose any additional information collection
burden under the Paperwork Reduction Act and does not contain any
information collection requirements beyond those already imposed by
current regulations, which have been approved by the Office of
Management and Budget (OMB). The current data collection requirements
in the OPTN final rule approved by OMB under the Paperwork Reduction
Act of 1995 are assigned control numbers OMB No. 0915-0157 (for organ
donors, candidates, and recipients) and OMB No. 0915-0184 (for OPTN
membership application data).
IX. Final Economic Analysis of Impacts
We have examined the impacts of the final rule under Executive
Order 12866, Executive Order 13563, Executive Order 14094, the
Regulatory Flexibility Act (5 U.S.C. 601-612), the Congressional Review
Act (5 U.S.C. 801, Pub. L. 104-121), and the Unfunded Mandates Reform
Act of 1995 (Pub. L. 104-4).
Executive Orders 12866, 13563, and 14094 direct us to assess all
benefits, costs, and transfers of available regulatory alternatives
and, when regulation is necessary, to select regulatory approaches that
maximize net benefits (including potential economic, environmental,
public health and safety, and other advantages; distributive impacts;
and equity). Rules are ``significant'' under Executive Order 12866,
section 3(f)(1) (as amended by Executive Order 14094), if they have an
annual effect on the economy of $200 million or more (adjusted every 3
years by the Administrator of the Office of Information and Regulatory
Affairs (OIRA) for changes in gross domestic product); or adversely
affect in a material way the economy, a sector of the economy,
productivity, competition, jobs, the environment, public health or
safety, or State, local, territorial, or tribal governments or
communities. The regulatory impact analysis indicates, and OIRA has
determined, that the final rule is a significant regulatory action
under Executive Order 12866, section 3(f)(1), and that it meets the
criteria set forth in 5 U.S.C. 804(2) under the Congressional Review
Act.
The Regulatory Flexibility Act (RFA) requires agencies to consider
the impact of their regulatory proposals on small entities. Because the
impacts on kidney and liver transplants are small relative to the
number of transplants performed annually, and because the economic
impacts on affected small entities are small relative to the average
payroll of firms in the smallest enterprise size category, HHS
certifies that the final rule will not have a significant economic
impact on a substantial number of small entities.
The Unfunded Mandates Reform Act of 1995 (UMRA) generally requires
that each agency conduct a cost-benefit analysis; identify and consider
a reasonable number of regulatory alternatives; and select the least
costly, most cost-effective, or least burdensome alternative that
achieves the objectives of the final rule before promulgating any
proposed or final rule that includes a Federal mandate that may result
in expenditures of more than $100 million (adjusted for inflation) in
at least one year by State, local, and tribal governments, in the
aggregate, or by the private sector. Each agency issuing a final rule
with relevant effects over that threshold must also seek input from
State, local, and tribal governments. The current threshold after
adjustment for inflation using the Implicit Price Deflator for the
Gross Domestic Product is $183 million, reported in 2023 dollars. The
final rule will not result in an unfunded mandate in any year that
meets or exceeds this amount.
The final rule removes the current research and IRB requirements
for the transplantation of kidneys and livers from donors with HIV. We
have assessed the likely impacts of the final rule, and report in the
regulatory impact analysis (RIA) several sources of monetized,
quantified, and unquantified benefits, costs, or transfers. Most of the
monetized or quantified impacts relate to the incremental increases in
the number of kidney and liver transplants that will be performed
annually as a result of the final rule.
We report monetized benefits from increases in life expectancy for
both kidney and liver transplant recipients; and for kidney transplant
recipients, we also report monetized benefits from quality-of-life
improvements and time savings from fewer kidney dialysis visits. We
also anticipate quality-of-life improvements for liver transplant
recipients, and quantify the number of people affected who might
experience those benefits. We also identify several sources of
unquantified benefits, which could potentially be quantified through
additional research or data, including time savings for caregivers, and
cost savings for transplant centers from removing the research and
institutional review board requirements. We also identify difficult-to-
quantify benefits associated with revising vocabulary and phrases that
some people find stigmatizing through adoption of language that is
intended be respectful of people living with HIV, and living and
deceased donors with HIV. These changes may result in people living
with HIV experiencing more inclusive interactions when accessing
healthcare, generating additional benefits beyond the increases in life
expectancy and improvements in quality of life from improved access to
liver and kidney transplantation.
We report monetized costs from increases in medical expenditures
associated with organ transplantation; for kidney transplants, we
report net costs that account for reductions in medical expenditures
associated with kidney dialysis. We report this shift in expenditures
from kidney dialysis to kidney transplantation as a monetized transfer.
We also monetize the opportunity costs of the time spent by transplant
centers reading and understanding the final rule, reviewing policies
and procedures, and training staff.
Table 1 summarizes our estimates of the benefits, costs, and
transfers of the final rule, annualizing impacts over a 10-year
analytic time horizon covering 2025 through 2034 using a 2 percent real
discount rate, and reporting all
[[Page 93497]]
monetary estimates in constant 2023 dollars. Annualized benefits range
from $381 million to $858 million, with a primary estimate of $612
million; costs range from $73 million to $92 million, with a primary
estimate of $83 million; and transfers range from $24 million to $37
million, with a primary estimate of $30 million. Table 1 also reports
our estimates of the annualized net benefits of the final rule, which
range from $301 million to $772 million, with a primary estimate of
$530 million. The RIA concludes that the monetized net benefits,
combined with the quantified, but non-monetized, and unquantified
impacts, indicate that the final rule is highly likely to generate net
benefits to society. This finding is further supported through
additional quantitative assessments of uncertainty and sensitivity
analyses contained in the RIA. The full RIA is available in the docket
for this final rule at <a href="https://www.regulations.gov/docket/HRSA-2024-0001/document">https://www.regulations.gov/docket/HRSA-2024-0001/document</a>.
Table 1--Summary of Impacts of the Final Rule
[Millions of constant 2023 dollars]
--------------------------------------------------------------------------------------------------------------------------------------------------------
Primary Low High Discount Time
Category estimate estimate estimate Dollar year or unit rate (%) horizon Notes
--------------------------------------------------------------------------------------------------------------------------------------------------------
BENEFITS
--------------------------------------------------------------------------------------------------------------------------------------------------------
Annualized monetized benefits...... $612 $381 $858 2023....................... 2 2025-2034 Increased life
expectancy for organ
transplant
recipients; improved
quality of life for
kidney transplant
recipients; time
savings from fewer
kidney dialysis
visits.
Annualized quantified, but non- 72 64 81 People affected............ 2 2025-2034 Improved quality of
monetized, benefits. life for liver
transplant
recipients.
Unquantified benefits.............. ........... ........... ........... ........................... ........... 2025-2034 Time savings for
caregivers; cost
savings for
transplant centers
from removing the
research and
institutional review
board requirements;
difficult-to-
quantify benefits
associated with
stigma-reducing
terminology.
--------------------------------------------------------------------------------------------------------------------------------------------------------
COSTS
--------------------------------------------------------------------------------------------------------------------------------------------------------
Annualized monetized costs......... 83 73 92 2023....................... 2 2025-2034 Medical expenditures
associated with
transplantation;
time spent by
transplant centers
to read and
understand the final
rule, review
policies and
procedures, and
train staff.
--------------------------------------------------------------------------------------------------------------------------------------------------------
TRANSFERS
--------------------------------------------------------------------------------------------------------------------------------------------------------
Annualized monetized transfers..... 30 24 37 2023....................... 2 2025-2034 Shift in expenditures
from kidney dialysis
to kidney
transplantation.
--------------------------------------------------------------------------------------------------------------------------------------------------------
NET BENEFITS
--------------------------------------------------------------------------------------------------------------------------------------------------------
Annualized monetized net benefits.. 530 301 772 2023....................... 2 2025-2034
--------------------------------------------------------------------------------------------------------------------------------------------------------
Note: primary, low, and high estimates correspond to the mean, 5th percentile, and 95th percentile of the outcomes of a Monte Carlo simulation.
List of Subjects in 42 CFR Part 121
Health care, Hospitals, Organ transplantation, Reporting and
recordkeeping requirements, Transplant centers.
Accordingly, by the authority vested in me as the Secretary of
Health and Human Services, and for the reasons set forth in the
preamble, 42 CFR part 121 is amended as follows:
PART 121--ORGAN PROCUREMENT AND TRANSPLANTATION NETWORK
0
1. The authority citation for part 121 continues to read as follows:
Authority: Sections 215, 371-377, and 377E of the PHS Act (42
U.S.C. 216, 273-274d, 274f-5); sections 1102, 1106, 1138 and 1871 of
the Social Security Act (42 U.S.C. 1302, 1306, 1320b-8, and 1395hh);
section 301 of the National Organ Transplant Act, as amended (42
U.S.C. 274e); and E.O. 13879, 84 FR 33817.
0
2. In Sec. 121.6, revise paragraph (b) to read as follows:
Sec. 121.6 Organ procurement.
* * * * *
(b) HIV. (1) Organs from donors with human immunodeficiency virus
(HIV) may be transplanted only into individuals who--
(i) Are living with HIV before receiving such organ(s); and
(ii)(A) Are participating in clinical research approved by an
institutional review board, as defined in 45 CFR part 46, under the
research criteria published by the Secretary under subsection (a) of
section 377E of the Public Health Service Act, as amended; or
(B) The Secretary has published, through appropriate procedures, a
determination under section 377E(c) of the Public Health Service Act,
as amended, that participation in such clinical research, as a
requirement for transplantation of organs from donors with HIV, is no
longer warranted. The Secretary has determined that participation in
such clinical research is no longer warranted for the following
categories of transplants:
(1) Transplant of a kidney from a donor with HIV; and
(2) Transplant of a liver from a donor with HIV.
(2) Except as provided in paragraph (b)(3) of this section, the
OPTN shall adopt and use standards of quality with respect to organs
from donors with HIV to the extent the Secretary determines necessary
to allow the conduct of research in accordance with the criteria
described in paragraph (b)(1)(ii)(A) of this section.
[[Page 93498]]
(3) If the Secretary has determined under paragraph (b)(1)(ii)(B)
of this section that participation in clinical research is no longer
warranted as a requirement for transplantation of organs from donors
with HIV, the OPTN shall adopt and use standards of quality with
respect to organs from donors with HIV as directed by the Secretary,
consistent with 42 U.S.C. 274, and in a way that ensures the changes
will not reduce the safety of organ transplantation.
* * * * *
Dated: November 19, 2024.
Xavier Becerra,
Secretary.
[FR Doc. 2024-27410 Filed 11-26-24; 8:45 am]
BILLING CODE 4150-41-P
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