HHS Proposed Rule: HIV Organ Transplant Policy Equity Act Implementation

Content

ACTION:

Notice of proposed rulemaking.

SUMMARY:

The Department of Health and Human Services (HHS) proposes to amend 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 kidney 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 proposes to determine that participation
in such clinical research should no longer be a requirement for transplantation of HIV positive kidneys and livers from donors
with HIV to recipients with HIV. This proposed rule serves as publication of the Secretary's proposed determination and proposes
to amend the regulations to reflect this determination. Consistent with NOTA and current regulatory requirements, the Secretary's
proposed determination and the proposed corresponding regulatory revision, if finalized, will necessitate that the Organ Procurement
and Transplantation Network (OPTN) adopt and use standards of quality concerning kidneys and livers from donors with HIV,
as

     directed by the Secretary, 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:

Comments on this notice of proposed rulemaking should be received no later than October 15, 2024.

ADDRESSES:

You may send comments, identified by Document ID HRSA-2024-0001, to the Federal eRulemaking Portal: https://www.regulations.gov. For detailed instructions on sending comments and additional information on the rulemaking process, see the “Public Participation”
heading of the
SUPPLEMENTARY INFORMATION
section of this document.

In accordance with 5 U.S.C. 553(b)(4), a summary of this rulemaking may be found in the docket for this rulemaking at www.regulations.gov [Document ID HRSA-2024-0001].

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 donation@hrsa.gov; or by telephone (301) 443-7577.

SUPPLEMENTARY INFORMATION:

I. Public Participation

All interested parties are invited to participate in this rulemaking by submitting written comments and supportive data that
should be considered. HHS also invites comments that relate to the economic, legal, environmental, or federalism effects that
might result from this proposed rule. Comments that will provide the most assistance to HHS in finalizing the rule will reference
a specific portion of the proposed rule, explain the reason for any recommended change, and include data, information, or
authority that supports such recommended change.

Instructions: If you submit a comment, you must include the agency name and the Document ID HRSA-2024-0001 for this rulemaking. Regardless
of the method used for submitting comments or material, all submissions will be posted, without change, to the Federal eRulemaking
Portal at https://www.regulations.gov, and will include any personal information you provide. Therefore, submitting this information makes it public. You may wish
to consider limiting the amount of personal information that you provide in any voluntary public comment submission you make
to HHS. HHS may withhold information provided in comments from public viewing that it determines may impact the privacy of
an individual or is offensive. For additional information, please read the Privacy Act notice that is available via the link
in the footer of https://www.regulations.gov.

Docket: For access to the docket and to read background documents or comments received, go to https://regulations.gov, referencing Document ID HRSA-2024-0001. You may also sign up for email alerts on the online docket to be notified when comments
are posted or a final rule is published.

II. Background and Purpose

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 Code of Federal Regulations (CFR) part 121.
The OPTN is also charged with developing policies on many subjects related to organ donation and transplantation, which include
establishing standards of quality pertaining to organs procured for use in transplantation. 42 U.S.C. 274(b)(2)(E). In addition
to ensuring the efficient and effective allocation of donor organs through the OPTN, HHS supports efforts to increase the
number of transplants performed in the United States.

B. HOPE Act Requirements and Implementation

In 1988, NOTA was amended to prohibit the transplantation of organs from donors with HIV, referring to HIV as the etiologic
agent for acquired immunodeficiency virus or AIDS. Until 1997, a total of 32 kidney transplants were performed in recipients
with HIV, all with organs from donors without HIV. (1) Advances in antiretroviral therapies (ART) have now made it possible for individuals with HIV to live longer and with fewer
complications from the virus. Following the success of pioneering transplants occurring outside the United States of organs
from donors with HIV to recipients with HIV, (2) interest in developing specialized HIV transplant programs grew domestically. (3)

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 clinical 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. (4) The 2015 rule amended 42 CFR 121.6 to permit transplants of organs from donors with HIV in accordance with the HOPE Act requirements.

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, 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. [(5)]() The NIH Research Criteria were developed by an HHS working group of entities involved in organ transplantation, with input
  from multiple stakeholders.

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 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. (6) 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 methods of improving organ allocation) providing standards
for transplant hospitals conducting HOPE Act transplants. (7) The OPTN expanded the variance in 2019 to include all solid organs, (8) and extended the variance through January 2026, to provide for the gathering of data and subsequent evaluation of the outcomes
of HOPE Act transplants. (9)

C. Review of Research Results

As stated above, the HOPE Act requires that the Secretary, in conjunction with the OPTN, periodically review the results of
scientific research to determine whether the results warrant revision to the OPTN standards of quality with respect to organs
from donors with HIV and the safety of transplanting an organ from a donor with a particular strain of HIV into a recipient
with a different strain of HIV. 42 U.S.C. 274f-5(c)(1). This review allows the Secretary to determine if the safety and efficacy
of HOPE Act transplants are comparable to non-HOPE Act transplants and, if warranted, to further determine whether such transplants
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. (10) 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.

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 NIH-funded 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 funded by NIH 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 which participated in the pilot
study found that there were 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. (11) While donors with HIV were more likely to have co-infections, the study found that these were manageable in the larger clinical
context. 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 found to be statistically significant. The insignificance of the result is due, in part, to the relatively small sample
  size. In addition, the investigators indicated that this result could be due to chance. 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 that rejection of such transplants is common. 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 raises concerns that merited further investigation.

A separate pilot study funded by NIH and 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.) 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
the observed increases among HOPE Act liver transplant recipients in mortality, cytomegalovirus (CMV) viremia, infectious
hospitalizations, and cancer. 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. (12)

Ongoing Clinical Trials

Two NIH-funded studies on kidney and liver HOPE Act transplants are ongoing. The NIH-funded U01 HOPE Act kidney transplant
clinical trial is designed to analyze rejection and long-term outcomes of kidney transplantation for recipients with HIV.
The study will 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. (13) Similarly, the U01 HOPE Act liver transplant clinical trial is 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. (14)

Both U01 clinical trials have reached their target enrollments and now in phases of final data analysis (kidney) and patient
follow-up (liver). The final results are not yet published.

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. (15) 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. (16)

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. (17) 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. (18 19)

2. Additional Research Results Published Subsequent to the OPTN Assessment

Following the OPTN's review of research results and data relevant to HOPE Act transplants and its recommendation to the Secretary,
additional research has since been published providing more evidence for the safety of organ transplantation from donors with
HIV to recipients with HIV. In general, safety and outcomes of kidney and liver HOPE Act transplants is well established with
over 468 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, 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
donor organs with HIV in recipients with HIV. Further, the study also found that there were no major differences 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. (20)

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. (21) 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. (22) 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 ESRD have higher mortality than people with ESRD who are not also
living with HIV, (23) in HHS's view, this data illustrates the benefit of HOPE Act kidneys transplants for this vulnerable population.

In addition to providing important evidence for the survival benefit of organ transplantation for recipients with HIV, the
HOPE in Action Consortium has also published 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. (24)

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 one heart transplant has been conducted (dual organ: heart-kidney). (25 26) No HOPE Act transplants have been recorded among recipients in need of organs such as a lung, pancreas, islet, or intestine.
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.

3. HHS Advisory Committee on Blood and Tissue Safety and Availability Recommendations

Following the OPTN recommendation to the Secretary in 2021, the HHS Advisory Committee on Blood and Tissue Safety and Availability
(ACBTSA) formed a Working Group to evaluate the recommendation from the OPTN. After analyzing the OPTN recommendation, and
receiving presentations on data on HOPE Act kidney and liver transplants, and relevant research results on heart transplants
and lung transplants in recipients with HIV, the ACBTSA HOPE Act working group recommended to the full committee that the
Secretary

  eliminate research and IRB requirements for all HOPE Act transplants. However, the working group expressed concern about the
  elimination of research and IRB requirements for non-kidney and non-liver HOPE Act transplants, [(27)]() and whether there was sufficient data collected on other organs to justify a full adoption the OPTN's recommendation.

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.

4. HHS Secretary: Review

Upon review of the OPTN, ACBTSA and BOTSEC recommendations, and in consideration of the results of relevant scientific research,
the Secretary believes that the research and IRB requirements for kidney and liver HOPE Act transplants are no longer warranted.

The Secretary has been informed by the research results described in this preamble from pilot studies, clinical trials, and
case reports, as well as OPTN outcomes data on all HOPE Act transplants and additional data. Studies of kidney and liver HOPE
Act transplants have demonstrated survival benefit for transplant recipients with HIV, compared to non-HOPE Act transplants,
with few adverse consequences. (28 29 30) Additionally, the OPTN's letter to the Secretary noted that in five years of HOPE Act transplants with over 300 HOPE Act transplant
recipients with HIV, no patient safety concerns were identified, and no HOPE Act research has been halted, paused, or substantially
amended to address recipient safety concerns. (31)

The outcomes of HOPE Act transplants are considered in light of the limitations of organ transplantation generally: that too
few organs are available for the thousands of patients awaiting transplants. The pretransplant mortality rate for adults awaiting
a kidney transplant varies substantially across the country. The average is 5.4 deaths per 100 person years, but it is reported
to be as high as 7.5 deaths per 100 person years as of the most recent OPTN/SRTR Annual Data Report. (32) This results in most transplant candidates waiting years for a kidney transplant, often requiring dialysis or other interventions.

It is well established that pretransplant kidney mortality rates among candidates with HIV are higher than those without HIV.
In one study analyzing survival benefit of HIV-positive kidney transplantation (i.e., non-HOPE Act transplants), mortality rates among transplant candidates with HIV after one year were 8.7 deaths per 100 person
years compared to just 3.1 deaths per 100 person years among those that received a kidney transplant. (33) Therefore, it is hypothesized that reduction in waitlist times may indeed result in lower mortality for transplant candidates
with HIV and end-stage diseases.

Research has demonstrated that recipients with HIV may reduce the time on the kidney waitlist significantly if they are willing
to accept a HOPE Act transplant. As previously mentioned, one 2023 study found that median wait time for a HOPE Act transplant
was 10.8 months compared to 60.8 months—a 3.3-fold higher rate of kidney transplant compared to non-HOPE Act transplants. (34)

Significant progress has been made in the reduction of pretransplant mortality for liver transplant candidates over the past
decade. Rates have declined from a high of 17.9 deaths per 100 person years in 2014 to 12.3 deaths per 100 person years in
2022. (35) Like kidney transplant, research has also demonstrated the survival benefit of organ transplantation for those with HIV and
end-stage liver disease when compared to transplant candidates without HIV. (36)

It is also hypothesized that the expansion of kidney and liver HOPE Act transplantation will also help to reduce stigma and
health disparities associated with HIV. Stigma and physician reluctance to counsel potential transplant candidates with HIV
on the benefits of organ transplantation may contribute to the lower than projected counts of HOPE Act transplants to date. (37)

The Secretary also believes that the current research and IRB requirements should be maintained for HOPE Act transplants of
all other organs, in light of the lack of data on outcomes for HOPE Act organ transplants other than kidney or liver transplants.
At the time the ACBTSA developed its recommendations, no HOPE Act transplants outside of kidneys, livers, and one dual heart-kidney
transplant had been performed, and data on heart, lung, pancreas, islet, intestine, or other organ transplants from donors
with HIV to recipients with HIV that were conducted outside the U.S. is limited.

The HOPE Act requires that, for the statutory research and IRB requirements to be lifted for HOPE Act transplants, the Secretary
must determine that participation in such clinical research, as a requirement for these transplants, 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.

The Secretary acknowledges that the OPTN has argued that any research and IRB requirements serve as a barrier to access for
HOPE Act transplant candidates and may perpetuate inequities in HOPE Act transplant programs. (38) We believe, however, that the proposed rule balances the need to ensure the safety of HOPE Act transplants while removing
research and IRB requirements for HOPE Act kidney and liver transplants in transplant programs that are well established and
have demonstrated both efficacy and safety.

D. Diversity, Equity, Inclusion: Effects on Individuals in Need of Transplant

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 as a barrier to participation
in HOPE Act transplant programs, which may impact equity and access to organ transplantation throughout the United States. (39) By eliminating the requirement that HOPE Act kidney and liver transplants are conducted in the research context, it is anticipated
that a larger number of transplant centers will be able to conduct such transplants. This proposal 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.

Other factors, such as systemic racism, perpetuate long-standing inequalities and inequities in health care access including
organ transplantation. People who identify as Black or African American are four times more likely to develop ESRD compared
to non-Hispanic White people but are less likely to receive a kidney transplant. (40 41) These outcomes are not explained by individual characteristics alone, suggesting that other factors, such as lower socioeconomic
status and poor clinical communication, contribute to this inequity. (42 43)

Separate from organ transplantation, HIV disproportionately affects people of some racial and ethnic groups in the United
States, such as Black or African American and Hispanic or Latino populations. Prevalence rates suggest these communities have
higher rates of HIV compared to White populations. For example, according to the Centers for Disease Control and Prevention's
(CDC) HIV Surveillance Supplemental Report, 2023, people who identified as Black or African American represented 12.4 percent
of the population but 40.2 percent of those with diagnosed HIV in 2021. (44) In addition, people identified as Hispanic or Latino represent 17.6 percent of the population but make up 23.8 percent of
people with diagnosed HIV. (45) Incidence rates also confirm that new infections disproportionately affect Black or African Americans (40 percent of new infections),
and Hispanic or Latinos (29 percent of new infections), suggesting that prevention efforts are not adequately reaching these
populations. (46) Higher prevalence and incidence rates among communities over-represented in the HIV epidemic suggest that these communities
would also benefit from expanded access to HOPE Act transplants. In fact, in one 2019 study of HOPE Act deceased-donor characteristics,
investigators found a higher proportion of people who identify as Black or African American (72 percent) among HOPE Act kidney
transplant recipients than the percent of Black or African Americans in the general population. Among recipient characteristics
of HOPE Act liver transplant recipients in the same study, 23 percent identified as Black or African American. (47)

In addition to racial and ethnic diversity, gay, bisexual, and other men who have sex with men (MSM) are the most affected
group of people with HIV, accounting for 66 percent of new infections in 2021 even though they only compose 2 percent of the
population. (48 49) Lastly, people who identify as transgender represent 2 percent of all new HIV diagnoses, exceeding the proportion of people
who identify as transgender in the general population. (50)

In light of all of these considerations, HHS expects that this proposed rule, if finalized, will assist in improving access
to kidney and liver transplants for recipients with HIV. This anticipated positive result is consistent with the Department's
commitment to diversity, equity, and inclusion.

Further, this proposed rule to remove research and IRB requirements for kidney and liver HOPE Act transplants would, if finalized,
expand access to organ transplantation for all patients, regardless of their HIV status. When eligible for transplant, a 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. (51) Every 10 minutes another person is added to the waiting list, and nearly 20 people die every day while waiting for a transplant. (52) The current approach to acquiring organs for transplantation relies on the altruism of donors and their families.

According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), more than 1 in 7 adults in the
U.S. are affected by kidney disease. (53) Of those, more than 800,000 Americans are living with end-stage renal disease (ESRD), a condition that often requires renal
dialysis or kidney transplant. (54) Kidney transplants in 2023 set a new record, offering 27,332 ESRD patients and their families a life-changing organ. (55) Despite upward trends in the number of kidney transplants conducted year over year, tens of thousands of Americans remain
on the waiting list, which currently exceeds 88,700 candidates. (56) 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. (57) Furthermore, at least 562,000 Americans endure renal dialysis each year, often while awaiting a kidney transplant. (58)

In addition, thousands of Americans suffer from conditions requiring liver transplant. In 2023, more than 10,660 liver transplants
were carried out with organs from both living and deceased donors, setting an all-time record. (59) As of February 16, 2024, 9,882 candidates remain on the waiting list, but additional registrations are expected throughout
the year. (60) In 2021, more than 1,100 liver patients died while awaiting transplant, according to the OPTN/SRTR Annual Data Report. (61)

As such, HHS believes regulatory changes designed to increase the number of organs available for donation, such as those proposed
in this rule, could mitigate these outcomes. HHS is committed to reducing the number of persons on the organ transplant waiting
list by increasing the number of organs made available for transplantation.

E. Implementation Considerations

1. 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). If this proposed rule is finalized, HHS anticipates that NIH will, in consultation with HRSA and the
OPTN, and including the input of other relevant Federal stakeholders, revise and publish updated Research Criteria in the

  Federal Register
  for public comment later this year. The 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 the current Research Criteria will no
  longer be applicable to HOPE Act kidney and liver transplants once the Secretary's determination is implemented, much of the
  current criteria will no longer be relevant.

Further, HHS recognizes it will be appropriate to update the NIH Research Criteria to reflect advances in research in the
time since HOPE Act transplants began. The research criteria should reflect the current needs of various entities involved
in 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.

2. Secretarial Direction To Revise OPTN Policies

Should this proposed rule be finalized, 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). Through this NPRM, HHS specifically seeks 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 welcomes 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.

HHS expects that the OPTN would 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 a final rule.

F. Secretarial Determination

The Secretary has reviewed the recommendations of the OPTN, the ACBTSA, and the BOTSEC on implementation of the HOPE Act,
and 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. 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 proposes to determine 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 this rulemaking, the Secretary proposes to lift the statutory research and IRB requirements
  for such transplants.

Through this NPRM, HHS specifically seeks public comment on the Secretary's proposed determination that participation in clinical
research, and application of the statutory research and IRB requirements, as a requirement for transplants of kidneys and
livers from persons with HIV, is no longer warranted.

III. Discussion of the Proposed Rule

A. Removal of Research and IRB Requirements for HOPE Act Kidney and Liver Transplants

Consistent with the Secretary's proposed determination under the HOPE Act, this proposed rule, if finalized, will revise § 121.6
of the HHS regulations governing the OPTN to reflect the removal of the statutory research and IRB requirements for kidney
and liver HOPE Act transplants.

HHS proposes to revise § 121.6(b)(1)(ii)(B) to reflect the Secretary's proposed determination that participation in clinical
research is no longer warranted for the following categories of transplants:

(1) Transplant of a donor kidney with HIV; and

(2) Transplant of a donor liver with HIV.

In implementation, this proposal, if approved, would mean that HOPE Act kidney and liver transplants will no longer be conducted
as research, and instead will be conducted in accordance with newly adopted OPTN policies regarding kidneys and livers from
donors with HIV.

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 proposes
to revise all current references in § 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, “donor organs with HIV.” Further, HHS proposes
to revise the current reference in § 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. (62)

HHS is proposing these new regulatory references to “donors with HIV” and “living with HIV” with the intent to be respectful,
and not to change the group of people referenced in the current § 121.6.

V. Explanation of the 30-Day Public Comment Period

HHS is publishing this proposed rule with a 30-day public comment period, as multiple opportunities for public input on the
matters addressed through this rulemaking already have been provided. HHS has been collecting public commentary on the HOPE
Act since the OPTN provided its HOPE Act recommendations to Secretary Becerra in October 2021. ACBTSA heard a summary of the
OPTN's consideration of the HOPE Act soon after its December 1, 2021 public meeting. Following this presentation, ACBTSA formed
a working group to develop a recommendation regarding the HOPE Act. During the ACBTSA's November 17, 2022 public meeting,
ACBTSA received written public comment on its proposed recommendations to the Secretary regarding removing the research and
IRB requirements for kidney and liver HOPE Act transplantations. (63)

HHS has actively engaged transplant surgeons, researchers, advocates, donors, and recipients involved in organ transplantation
in the course of drafting a recommendation to the Secretary. The Department has reviewed dozens of comments received in response
to discussions held by the ACBTSA, the BOTSEC and the Presidential Advisory Council on HIV/AIDS (PACHA). (64 65) The Department understands that there is widespread support for the proposed recommendation including the endorsement of at
least 35 non-governmental organizations involved in HIV advocacy, organizations representing entities involved in organ transplantation,
associations representing transplant surgeons, nephrologists, HIV clinicians, epidemiologists, and many more individuals.

Given the multiple committees and policy mechanisms employed for discussion of potential changes to requirements for HOPE
Act transplants, previous efforts to gather public commentary and the considerable public health impact this proposed policy
may have on those in need of organ transplantation, HHS believes the 30-day public comment period is sufficient and most expedient.

VI. Paperwork Reduction Act of 1995

This proposed rule, if finalized, would 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. The current data collection requirements in the OPTN final rule
approved by the 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).

VII. Preliminary Economic Analysis of Impacts

We have examined the impacts of the proposed 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. This analysis indicates that
  this proposed rule is a significant regulatory action under Executive Order 12866 section 3(f)(1).

The Regulatory Flexibility Act requires us to analyze regulatory options that would minimize any significant impact of a rule
on small entities. Because the impacts are small relative to the number of organ transplants performed annually, and because
the costs are small relative to the average payroll of firms in the smallest enterprise size category, we propose to certify
that the proposed 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 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, or by the private sector. Each agency must also seek input from State, local, and Tribal governments. (66) The current threshold after adjustment for inflation using the Implicit Price Deflator for the Gross Domestic Product is $183
million, reported in 2023 dollars. This proposed rule, if finalized, would not result in an unfunded mandate in any year that
meets or exceeds this amount.

This proposed rule would, if finalized, remove the current research and institutional review board (IRB) requirements for
transplants of human immunodeficiency virus (HIV)-positive kidneys and livers. This would result in impacts related to changes
in the number of kidney and liver transplants performed annually. We monetize benefits associated with increases in life expectancy
for organ transplant recipients and, for kidney transplant recipients, benefits associated with improved quality of life and
time savings from fewer kidney dialysis visits. We monetize costs from medical expenditures associated with organ transplantation;
for kidney transplants, we report impacts that are net of medical expenditures associated with kidney dialysis. We also monetize
costs associated with organ transplant centers reading and understanding the rule, reviewing policies and procedures, and
training staff. We report the shift in expenditures associated with kidney dialysis to expenditures associated with kidney
transplantation separately as transfers. We estimate that the annualized benefits over a 10-year time horizon covering 2025
through 2034 would range from $561 million to $1.26 billion at a 2 percent discount rate, with a primary estimate of $900
million. The annualized costs would range from $134 million to $174 million, with a primary estimate of $154 million. The
annualized transfers would range from $24 million to $39 million, with a primary estimate of $31 million.

| Category | Primary
estimate | Low
estimate | High
estimate | Dollar year
or unit | Discount
rate(%) | Time
horizon | Notes |
| --- | --- | --- | --- | --- | --- | --- | --- |
| BENEFITS: | | | | | | | |
| Annualized monetized benefits | $900 | $561 | $1,261 | 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-monetized, benefits | 147 | 129 | 166 | People affected | 2 | 2025-2034 | Improved quality of life for liver transplant recipients. |
| Unquantified benefits | | | | | | 2025-2034 | Time savings for caregivers; cost savings related to removing the research and institutional review board requirements. |
| COSTS: | | | | | | | |
| Annualized monetized costs | $154 | $134 | $174 | 2023 | 2 | 2025-2034 | Net costs associated with organ transplants; costs associated with organ transplant centers reading and understanding the
rule, reviewing policies and procedures, and training staff. |
| TRANSFERS: | | | | | | | |
| Annualized monetized transfers | $31 | $24 | $39 | 2023 | 2 | 2025-2034 | Shift in expenditures associated with kidney dialysis to expenditures associated with kidney transplantation. |
| NET BENEFITS: | | | | | | | |
| Annualized monetized net benefits | $746 | $412 | $1,101 | 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. | | | | | | | |
We have developed a comprehensive preliminary economic analysis of impacts that assesses the impacts of the proposed rule,
which is available in the docket for this proposed rule Document ID HRSA-2024-0001.

List of Subjects in 42 CFR Part 121

Health care, Hospitals, Transplant centers, Organ transplantation, Reporting and recordkeeping requirements.

Dated: September 6, 2024. Xavier Becerra, Secretary. 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 proposed to be amended as follows:

PART 121—ORGAN PROCUREMENT AND TRANSPLANTATION NETWORK

1. The authority citation for part 121 continues to read as follows:

Authority:

Sections 215, 371-77, 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.

1. In § 121.6, revise paragraph (b) to read as follows:

§ 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 transplants of donor organs 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 donor kidney with HIV; and

(2) Transplant of a donor liver 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 donor organs 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.

(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 transplants of donor organs with HIV, the OPTN shall adopt and use standards of
quality with respect to donor organs 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.

---

[FR Doc. 2024-20643 Filed 9-11-24; 8:45 am] BILLING CODE 4150-28-P

Footnotes

(1) Werbel WA, Durand CM. Solid Organ Transplantation in HIV-Infected Recipients: History, Progress, and Frontiers. Curr HIV/AIDS
Rep. 2019 Jun;16(3):191-203.

(2) Muller E, Barday Z, Mendelson M, Kahn D. HIV-Positive to HIV-Positive Kidney Transplantation—Results at 3 to 5 Years. New
England Journal of Medicine. 2015 Feb 12;372(7):613-620.

(3) Botha J, Fabian J, Etheredge H, Conradie F, Tiemessen CT. HIV and Solid Organ Transplantation: Where Are we Now. Curr HIV/AIDS
Rep. 2019 Oct;16(5):404-413.

(4) Federal Register
. Organ Procurement and Transplantation: Implementation of the HIV Organ Policy Equity (HOPE) Act. 2015 May:80 FR 26464. https://www.federalregister.gov/documents/2015/05/08/2015-11048/organ-procurement-and-transplantation-implementation-of-the-hiv-organ-policy-equity-act.

(5) Federal Register
. Final Human Immunodeficiency Virus (HIV) Organ Policy Equity (HOPE) Act Safeguards and Research Criteria for Transplantation
of Organs Infected With HIV. 2015 Nov:80 FR 73785. https://www.federalregister.gov/documents/2015/11/25/2015-30172/final-human-immunodeficiency-virus-hiv-organ-policy-equity-hope-act-safeguards-and-research-criteria.

(6) HIV.gov. Opportunistic Infections: HIV Treatment Overview. https://www.hiv.gov/hiv-basics/staying-in-hiv-care/other-related-health-issues/opportunistic-infections. Accessed Apr 2024.

(7) 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: https://optn.transplant.hrsa.gov/media/1872/dtac_policynotice_hope_201606.pdf.

(8) Organ Procurement and Transplantation Network. Policy Notice: Modify HOPE Act Variance to Include Other Organs. 2019 Jun
10: https://optn.transplant.hrsa.gov/media/3000/dtac_policynotice_201906.pdf.

(9) Organ Procurement and Transplantation Network. Policy Notice: Extend HIV Organ Policy Equity (HOPE) Act Variance. 2021 Dec
6: https://optn.transplant.hrsa.gov/media/t1sdej22/policy-notice_dtac_hope_variance.pdf.

(10) Organ Procurement and Transplantation Network. Public Comment Proposal: Modify the HOPE Act Variance to Include Other Organs.
2019 Jan 22: https://optn.transplant.hrsa.gov/media/2800/dtac_publiccomment_20190122.pdf.

(11) 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.

(12) 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.

(13) 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. https://reporter.nih.gov/search/kcWJ0GeT8kigjO2_LU8R2g/project-details/10848468.

(14) 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. https://reporter.nih.gov/project-details/10459319.

(15) 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.

(16) 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.

(17) Cooper M. “OPTN Letter to Secretary Becerra on the HOPE Act.” 2021 Oct 29. https://optn.transplant.hrsa.gov/media/ueyjdfnd/hope-act-letter.pdf.

(18) McCauley J. “Fifty Sixth ACBTSA Meeting, Written Public Comment—November 17, 2022 Meeting.” 2022 Nov 8. https://optn.transplant.hrsa.gov/media/hwgncda2/optn-executive-committee_acbtsa-letter.pdf.

(19) 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.

(20) 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.

(21) 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.

(22) 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.

(23) Ibid.

(24) 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.

(25) Montefiore News Releases. World's First HIV-Positive to HIV-Positive Heart Transplant Performed at Montefiore Health System.
2022 Jul 22. https://www.montefiore.org/body.cfm?id=1738&action=detail&ref=2194

(26) 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.

(27) HHS Advisory Committee on Blood and Tissue Safety and Availability. 2022. Fifty-Sixth ACBTSA Meeting November 17, 2022—Meeting
Summary. https://www.hhs.gov/oidp/advisory-committee/blood-tissue-safety-availability/meeting-summary/2022-11-17/index.html.

(28) Durand CM, et al; 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.

(29) Durand CM, et al; 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.

(30) 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.

(31) Cooper M. “OPTN Letter to Secretary Becerra on the HOPE Act.” 2021 Oct 29. https://optn.transplant.hrsa.gov/media/ueyjdfnd/hope-act-letter.pdf.

(32) Organ Procurement and Transplantation Network (OPTN)/Scientific Registry of Transplant Recipients (SRTR). 2022. “Annual Data
Report: Kidney.” Accessed May 2024. https://srtr.transplant.hrsa.gov/annual_reports/2022/Kidney.aspx.

(33) Locke JE, Gustafson S, Mehta S, Reed RD, Shelton B, MacLennan PA, Durand C, Snyder J, Salkowski N, Massie A, Sawinski D,
Segev DL. Survival Benefit of Kidney Transplantation in HIV-infected Patients. Ann Surg. 2017 Mar;265(3):604-608.

(34) 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.

(35) Organ Procurement and Transplantation Network (OPTN)/Scientific Registry of Transplant Recipients (SRTR). 2022. “Annual Data
Report: Liver.” Accessed May 2024. https://srtr.transplant.hrsa.gov/annual_reports/2022/Liver.aspx.

(36) Ragni MV, Eghtesad B, Schlesinger KW, Dvorchik I, Fung JJ. Pretransplant survival is shorter in HIV-positive than HIV-negative
subjects with end-stage liver disease. Liver Transpl. 2005 Nov;11(11):1425-30.

(37) Klitenic SB, Levan ML, Van Pilsum Rasmussen SE, Durand CM. Science Over Stigma: Lessons and Future Direction of HIV-to-HIV
Transplantation. Curr Transplant Rep. 2021;8(4):314-323.

(38) McCauley J. “Fifty Sixth ACBTSA Meeting, Written Public Comment—November 17, 2022 Meeting.” 2022 Nov 8. https://optn.transplant.hrsa.gov/media/hwgncda2/optn-executive-committee_acbtsa-letter.pdf.

(39) 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.

(40) National Institute of Diabetes and Digestive and Kidney Diseases. n.d. Kidney Disease Statistics for the United States. Accessed
February 2024. https://www.niddk.nih.gov/health-information/health-statistics/kidney-disease.

(41) U.S. Department of Health and Human Services. Office of Minority Health: Organ Donation and African Americans. https://minorityhealth.hhs.gov/organ-donation-and-african-americans. Accessed 2/27/2024.

(42) El-Khoury B, Yang TC. Reviewing Racial Disparities in Living Donor Kidney Transplantation: a Socioecological Approach. J
Racial Ethn Health Disparities. 2023 Mar 29:1-10.

(43) Siminoff LA, Burant CJ, Ibrahim SA. Racial disparities in preferences and perceptions regarding organ donation. J Gen Intern
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(44) Centers for Disease Control and Prevention. Estimated HIV incidence and prevalence in the United States, 2017-2021. HIV Surveillance
Supplemental Report, 2023; 28 (No.3). https://www.cdc.gov/hiv/library/reports/hiv-surveillance.html. Published May 2023.

(45) Ibid.

(46) Centers for Disease Control and Prevention. Estimated HIV incidence and prevalence in the United States, 2017-2021. HIV Surveillance
Supplemental Report, 2023; 28 (No.3). https://www.cdc.gov/hiv/library/reports/hiv-surveillance.html. Published May 2023.

(47) Wilk AR, Hunter RA, McBride MA, Klassen DK. National landscape of HIV+ to HIV+ kidney and liver transplantation in the United
States. American Journal of Transplantation 2019;19(9):2594-2605.

(48) Centers for Disease Control and Prevention. Surveillance Supplemental Report, 2023, 2003 May;28(No.3). https://www.cdc.gov/hiv/library/reports/hiv-surveillance.html.

(49) Purcell DW, Johnson CH, Lansky A, et al. Estimating the population size of men who have sex with men in the United States
to obtain HIV and syphilis rates. Open AIDS J 2012; 6:98-107.

(50) Centers for Disease Control and Prevention. HIV Surveillance Report, 2021; vol. 34. https://www.cdc.gov/hiv/library/reports/hiv-surveillance.html. Published May 2023.

(51) Organ Procurement and Transplantation Network. 2024. Dashboard and metrics. Accessed February 2024. https://insights.unos.org/OPTN-metrics/.

(52) Health Resources and Services Administration. Organ Donation Statistics. Accessed February 2024. https://www.organdonor.gov/learn/organ-donation-statistics.

(53) National Institute of Diabetes and Digestive and Kidney Diseases. n.d. Kidney Disease Statistics for the United States. Accessed
February 2024. https://www.niddk.nih.gov/health-information/health-statistics/kidney-disease.

(54) National Institute of Diabetes and Digestive and Kidney Diseases. n.d. Kidney Disease Statistics for the United States. Accessed
Feb 2024. https://www.niddk.nih.gov/health-information/health-statistics/kidney-disease.

(55) Ibid.

(56) Organ Procurement and Transplantation Network. Dashboard and metrics. https://insights.unos.org/OPTN-metrics/. Accessed Feb 2024.

(57) Organ Procurement and Transplantation Network (OPTN)/Scientific Registry of Transplant Recipients (SRTR). 2021. “Annual Data
Report.” Accessed Feb 2024. https://srtr.transplant.hrsa.gov/annual_reports/2021_ADR_Preview.aspx.

(58) National Institute of Diabetes and Digestive and Kidney Diseases. n.d. Kidney Disease Statistics for the United States. Accessed
Feb 2024. https://www.niddk.nih.gov/health-information/health-statistics/kidney-disease.

(59) United Network for Organ Sharing (UNOS). February 14, 2024. A decade of record increases in liver transplant. Accessed Feb
2024. https://unos.org/news/in-focus/a-decade-of-record-increases-in-liver-transplant/.

(60) Organ Procurement and Transplantation Network. Dashboard and metrics. https://insights.unos.org/OPTN-metrics/. Accessed Feb 2024.

(61) Organ Procurement and Transplantation Network (OPTN)/Scientific Registry of Transplant Recipients (SRTR). 2021. “Annual Data
Report.” Accessed February 2024. https://srtr.transplant.hrsa.gov/annual_reports/2021_ADR_Preview.aspx.

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

(63) HHS Advisory Committee on Blood and Tissue Safety and Availability. 2022. Fifty-Sixth ACBTSA Meeting November 17, 2022—Meeting
Summary.

(64) 79th Presidential Advisory Council on HIV/AIDS (PACHA) Full Council Meeting |12.06.23 | Part 4. Uploaded by U.S. Department
of Health and Human Services. 2023 Dec 14. https://www.youtube.com/watch?v=oHM3ygWpMek.

(65) HHS Presidential Advisory Council on HIV/AIDS (PACHA). Seventy-Ninth PACHA Meeting December 6, 2023—Meeting Summary. 2023
Dec 6. https://files.hiv.gov/s3fs-public/2024-03/PACHA-Dec-2023-meeting-summary-final.pdf.

(66) U.S. Office of Management and Budget, Office of Information and Regulatory Affairs. “2018, 2019, and 2020 Report to Congress
on the Benefits and Costs of Federal Regulations and Agency Compliance with the Unfunded Mandates Reform Act.” https://www.whitehouse.gov/wp-content/uploads/2021/01/2018_2019_2020-OMB-Cost-Benefit-Report.pdf.

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