Organ Procurement and Transplantation: Implementation of the HIV Organ Policy Equity (HOPE) Act

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.

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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. 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, interest in developing specialized HIV transplant programs grew domestically.

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. 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. 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. 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. The OPTN expanded the variance in 2019 to include all solid organs, and extended the variance through January 2026, to provide for the gathering of data and subsequent evaluation of the outcomes of HOPE Act transplants.

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. 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. 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.

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. 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.

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. 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.

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. 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.

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.

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. 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. 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, 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.

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). 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, 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. 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.

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. 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. 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.

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. 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.

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.

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. 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. 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. 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.

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. 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. 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. 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.

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. 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.

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. Every 10 minutes another person is added to the waiting list, and nearly 20 people die every day while waiting for a transplant. 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. 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. Kidney transplants in 2023 set a new record, offering 27,332 ESRD patients and their families a life-changing organ. 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. 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. Furthermore, at least 562,000 Americans endure renal dialysis each year, often while awaiting a kidney transplant.

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. As of February 16, 2024, 9,882 candidates remain on the waiting list, but additional registrations are expected throughout the year. In 2021, more than 1,100 liver patients died while awaiting transplant, according to the OPTN/SRTR Annual Data Report.

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.

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.

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). 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. 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.