[Federal Register Volume 84, Number 166 (Tuesday, August 27, 2019)]
[Notices]
[Pages 44904-44907]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-17759]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


Request for Information: Regarding Revisions to the PHS Guideline 
for Reducing Human Immunodeficiency Virus (HIV), Hepatitis B Virus 
(HBV), and Hepatitis C Virus (HCV) Through Organ Transplantation

AGENCY: Office of Infectious Disease and HIV/AIDS Policy, Office of the 
Assistant Secretary for Health, Office of the Secretary, Department of 
Health and Human Services.

ACTION: Request for information; notice.

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SUMMARY: The Office of the Assistant Secretary for Health in the 
Department of Health and Human Services (HHS) seeks public comment 
regarding proposed revisions to the 2013 PHS Guideline for Reducing 
Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and 
Hepatitis C Virus (HCV) Through Organ Transplantation.

DATES: To be assured consideration, comments must be received at the 
address provided below no later than 5:00 p.m. ET on September 26, 
2019.

ADDRESSES: Electronic responses are strongly preferred and may be 
addressed to [email protected]. Written responses should be addressed to: 
U.S. Department of Health and Human Services, Mary E. Switzer Building, 
330 C Street SW, Room L001, Washington, DC 20024 Attn: ACBTSA--RFI.

FOR FURTHER INFORMATION CONTACT: Mr. James Berger, Designated Federal 
Official, Office of Infectious Disease and HIV/AIDS Policy, (202) 795-
7608.

SUPPLEMENTARY INFORMATION: 

I. Background

    Since implementation of the Guideline in 2014,\1\ the organ 
donation and transplantation community monitored the impact of the 
recommendations on provider and patient perceptions, organ utilization, 
and clinical outcomes. HHS conducted analyses to inform efforts to 
revise the Guideline recommendations. In April 2019, the Assistant 
Secretary for Health of the Department of Health and Human Services 
(HHS) received input from the Advisory Committee on Blood and Tissue 
Safety and Availability (ACBTSA) regarding revisions to the Guideline 
recommendations to reflect recent epidemiologic trends in clinical 
characteristics of deceased organ donors and scientific advances and 
improvements in testing for and treatment of HIV, HBV, and HCV 
infections.
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    \1\ Seem DL, Lee I, Umscheid CA, Kuehnert MJ. PHS guideline for 
reducing human immunodeficiency virus, hepatitis B virus, and 
hepatitis C virus transmission through organ transplantation. Public 
health reports (Washington, DC: 1974). 2013;128(4):247-343.
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    HHS is asking respondents to review the proposed revisions to the 
current Guideline and provide assessments on updating the Guideline, 
whether these changes are achievable in the clinical setting, or if 
there are potential barriers to implementation. In addition, impact on 
organ allocation and utilization should be considered. Other comments 
pertinent to these proposed revisions are welcome.
    Since the emergence of the human immunodeficiency virus (HIV) 
epidemic, the U.S. Public Health Service (PHS) has made recommendations 
to reduce the risk of HIV transmission associated with organ 
transplantation.2 3 Historically, recommendations included 
identifying risk factors among organ donors associated with HIV 
infection to minimize risk of potential transmission to recipients. 
Recommendations also included laboratory screening of donors using 
anti-HIV antibody testing, with additional testing recommendations 
added as technologies such as nucleic acid testing (NAT) were 
developed. In 2013, based on donor-derived transmission events and 
reports of poor recipient outcome from hepatitis B (HBV) and C (HCV) 
transmission, the PHS released a revised guideline. The 2013 Guideline 
added organ donor screening recommendations for HBV (hepatitis B 
surface antigen (HBsAg) and total antibody to hepatitis B core antigen 
(anti-HBc)) and HCV (antibody to hepatitis C (anti-HCV) and NAT), in 
addition to HIV, to reduce the risk of unintended transmission through 
transplantation. This revised Guideline was enhanced by recommending 
specific recipient informed consent and post-transplant recipient 
monitoring for evidence of possible disease transmission.
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    \2\ CDC. Guidelines for preventing transmission of human 
immunodeficiency virus through transplantation of human tissue and 
organs. Centers for Disease Control and Prevention. MMWR 
Recommendations and reports: Morbidity and mortality weekly report 
Recommendations and reports/Centers for Disease Control. 1994;43(RR-
8):1-17.
    \3\ CDC. Testing donors of organs, tissues, and semen for 
antibody to human T-lymphotropic virus type III/lymphadenopathy-
associated virus. MMWR Morbidity and mortality weekly report. 
1985;34(20):294.
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    Per the 1994 guideline, donors with risk factors for HIV infection 
and transmission to recipients were designated ``Centers for Disease 
Control and Prevention (CDC) High Risk'' donors. The 2013 Guideline 
changed this terminology to ``Increased Risk Donor (IRD)'' and 
recommended HCV nucleic acid testing (NAT) for all donors and HIV NAT 
or p24 antigen testing for IRD. For living donors, testing was 
recommended to be performed as close as possible to the date of the 
organ recovery but at least within 28 days prior to surgery. For 
deceased donors, specimens for testing were to be obtained before 
procurement but with no specific recommendation on the timing of 
collection relative to organ recovery. The term ``Increased Risk'' was 
adopted over ``High Risk'' to convey the continued but small 
possibility of donor-derived disease transmission from donors with risk 
factors, even with use of the more sensitive NAT screening tests.
    The 2013 Guideline specifically outlines 12 medical or social 
history criteria resulting in IRD designation if these risk factors 
occurred within the 12 months prior to organ recovery. The 12 criteria 
are:
    1. Sex with a person known or suspected to have HIV, HBV, or HCV 
infection.

[[Page 44905]]

    2. Men who have had sex with men (MSM).
    3. Women who have had sex with a man with a history of MSM 
behavior.
    4. Sex in Sex with a person who had sex in exchange for money or 
drugs.
    5. Sex with a person that has injected drugs by intravenous, 
intramuscular, or subcutaneous route.
    6. Injecting drugs by intravenous, intramuscular, or subcutaneous 
route for nonmedical reasons.
    7. Incarceration for >72 consecutive hours.
    8. Syphilis, gonorrhea, chlamydia, or genital ulcers.
    9. Child (age <=18 months) born to a mother known to be infected 
with, or at increased risk for HIV, HBV, or HCV.
    10. Child breastfed within the preceding 12 months by mother known 
to be infected with, or at increased risk for HIV infection.
    11. Hemodialysis (only increased risk for HCV).
    Deceased donors for whom medical or social history are unavailable 
at the time of organ recovery are designated IRD. Donors are also 
designated as IRD if the organ-donation serum specimen used for HIV, 
HBV, or HCV testing meets criteria for hemodilution due to the donor 
receiving crystalloid or colloid infusion prior to specimen collection, 
based on hemodilution calculations described in FDA guidance (https://www.fda.gov/media/73072/download). The 2013 recommendations were not 
intended to restrict transplantation (or exclude specific donors) but 
to facilitate appropriate donor laboratory screening, enhance informed 
decision making by recipients and families, and ensure prompt 
recognition and treatment of donor-derived disease transmission events.
    The following issues regarding the perceived impact of the 2013 
Guideline on organ utilization and allocation, clinical decision-
making, and recipient outcomes have been reported in the scientific 
literature or communicated directly to relevant federal agencies, 
including CDC and the Health Resources and Services Administration 
(HRSA):
    1. As a result of the national substance abuse and overdose 
epidemic, an increasingly larger number and proportion of organ donors 
are designated as IRD. These donors are often younger and have better 
organ quality compared with non-IRD standard risk donors (SRD).
    2. Organs from IRD are underutilized compared with organs from SRD.
    3. The ``IRD'' label may discourage organ acceptance and 
utilization by transplant physicians and transplant candidates:
    a. The label may result in a perception that the risk is higher 
than the true risk for disease transmission and resultant morbidity and 
mortality of using these organs.
    b. The label may convey a perception that IRD organs are of poorer 
quality despite scientific evidence that demonstrates these donors are 
often younger and have higher-quality organs.
    c. Due to misperceptions related to disease transmission risk or 
organ quality, candidates may opt to decline an IRD organ offer and 
choose to wait for another organ, resulting in preventable morbidity 
and mortality had they accepted receipt of the IRD organ.
    4. Not all criteria for current IRD designation are actually 
associated with a significant risk of HIV, HBV, and HCV infection and/
or transmission and some of the criteria should be removed.
    5. The 2013 Guideline recommendation designates donors as IRD if 
risk factors occur within 12 months prior to donation. Because organ 
procurement organizations (OPOs) have universally implemented screening 
of organ donors for HIV, HBV, and HCV by NAT, the 12 month timeframe 
should be shortened.
    6. Because all organ donors are universally screened by NAT and the 
risk of unexpected donor-derived disease transmissions has decreased, 
donor risk designation and informed consent requirements should be 
modified.
    7. Because the number of organ donors with risk factors has 
increased and effective suppression of HIV and HBV and a cure of HCV 
infection are available, all recipients should be screened for HIV, 
HBV, and HCV post-transplant, including recipients of organs from 
donors without recognized risk factors due to inherent uncertainty of 
questionnaire responses provided by donor next of kin.
    HHS conducted additional data analyses in order to better 
understand the impact of the PHS Guideline recommendations on organ 
utilization, allocation, and recipient outcomes. The following analytic 
activities were undertaken by HHS with associated findings summarized:
    1. A descriptive analysis of Organ Procurement and Transplantation 
Network (OPTN) data to calculate the total numbers and proportions of 
organ donors classified as IRD by year (since 2010) and further 
stratify by viral bloodborne pathogen screening results was conducted. 
This analysis found that the percentage of adult donors classified as 
IRD has increased from 9.3% (2010) to 26.2% (2017), with higher 
percentages in some geographic regions. The percentage of deceased 
donors with drug intoxication as the mechanism of death increased from 
4.3% (2010) to 12.6% (2016); approximately 60% of these donors have a 
history of nonmedical injection drug use (IDU). Additionally, the 
number of HCV-infected donors identified via NAT has increased among 
IRD since 2014.
    2. A descriptive analysis was performed of all CDC-led outbreak 
investigations (2014-2017) of donor-derived HBV/HCV transmissions, 
including a summary of clinical outcomes and antiviral treatment of 
infected recipients. CDC investigated 9 potentially donor-derived 
transmission events of HCV, involving 31 HCV-negative recipients, of 
whom 20 developed HCV infection. During this period, CDC also 
investigated 7 potentially donor-derived transmission events of HBV, 
involving 15 HBV-negative recipients, of whom 7 developed HBV 
infection. No recipient died of either HCV- or HBV-related 
complications. In these cases, identification of organ donors with risk 
factors for viral bloodborne pathogen infection and IRD designation led 
to early diagnosis and treatment of recipient infection, which possibly 
averted graft failure or death.
    3. Logistic regression analyses were conducted of national OPTN 
donor and recipient data to quantify the impact of IRD designation on 
organ utilization and thereby determine whether or not IRD designation 
was associated with organ underutilization, and if so, then to what 
extent. After adjusting for variables that may have impacted organ 
acceptance decisions (including donor HBV/HCV serostatus), there was no 
observed underutilization of livers or hearts from IRD donors. IRD 
designation appeared to be associated with underutilization of adult 
kidneys but the magnitude was smaller than previous estimates and this 
association appeared attributable to low use by a subset of transplant 
centers, rather than broad underutilization by all U.S. transplant 
programs.
    4. Mathematical modeling was performed using Monte Carlo simulation 
to estimate the current probability of undetected HIV, HBV, or HCV 
infection in an IRD donor for whom all recommended NAT testing was 
negative. These analyses were conducted to identify a shorter, but safe 
timeline during which risk behaviors result in IRD designation. The 
probability of undetected infection in donors with high-risk behaviors 
30 days after the most recent potential risk

[[Page 44906]]

behavior was <1/1,000,000 for HIV and HCV and near 1/1,000,000 for HBV. 
The time period during which high risk behaviors lead to donor 
classification as increased risk can be safely reduced from 12 months 
to a shorter interval. HHS conducted an assessment of the current 
criteria that result in IRD designation to determine which criteria 
have been previously implicated in a donor-derived transmission of HIV, 
HBV, or HCV and are therefore associated with significant 
epidemiological risk of transmission. Criteria that were not previously 
implicated in cases of transmissions from IRD-designated organs 
included being a women who had sex with a man with a history of same-
sex sexual contact or having been newly diagnosed or have been treated 
for syphilis, gonorrhea, chlamydia, or genital ulcers, and 
hemodialysis.
    In April 2019, HHS convened the Advisory Committee on Blood and 
Tissue Safety and Availability (ACBTSA) to receive expert input on 
whether, and if so, how, the current PHS Guideline recommendations 
should be revised (https://www.hhs.gov/oidp/advisory-committee/blood-tissue-safety-availability/meetings/2019-04-15/index.html). 
Additionally, HHS solicited input from this committee on specific 
changes to current recommendations. The committee voted in favor of the 
following recommendations:
    1. Continued recognition and designation of a category of potential 
organ donors with an augmented chance of transmission of HIV, HBV, and 
HCV.
    2. Screen all organ donors for HIV, HBV, and HCV using NAT in 
addition to serology.
    3. Shorten the current 12-month risk factor timeframe to 3 months.
    4. Test all recipients, regardless of donor risk profile, for HIV, 
HBV, and HCV using NAT between 2 and 4 weeks after transplantation. 
Repeat testing, particularly for HBV, to be considered in future 
discussions.
    5. Change the current ``increased risk donor'' terminology to 
reduce cognitive bias and improve decision making among clinicians and 
patients.
    6. Remove the following as medical/social criteria:
    a. Women who have had sex with a man with a history of same-sex 
sexual contact;
    b. Newly diagnosed or have been treated for syphilis, gonorrhea, 
chlamydia, or genital ulcers;
    c. Hemodialysis;
    d. Hemodiluted blood specimen used for infectious disease testing;
    e. Child (age <=18 months) born to a mother at increased risk for 
HIV, HBV, or HCV;
    f. Child breastfed within the preceding 12 months by mother at 
increased risk for HIV infection.
    7. Continue the following criteria that would result in augmented 
donor risk designation: Sex with a person known or suspected to be HIV, 
HBV, or HCV infected; Man who has sex with men; Sex in exchange for 
money/drugs; Sex with a person who had sex in exchange for money/drugs; 
Non-medical injection of drugs; Sex with person who has engaged in non-
medical drug injection; Incarceration for >72 hours; Unknown medical/
social history; Child born to a mother with HIV.
    8. Support the development and use of tools and processes to 
educate transplant providers and enhance the process of transplant 
candidate counseling in order to enhance organ utilization.

II. Potential Revisions to the 2013 Guideline

    HHS has reviewed the ACBTSA recommendations and other available 
information and is considering the following revisions to current 
recommendations in the 2013 Guideline:
    1. Test all organ donors for HIV, HBV, and HCV using serological 
tests (including total antibody to hepatitis B core antigen [total 
anti-HBc], hepatitis B surface antigen [HBsAg], and hepatitis C 
antibody [anti-HCV]) and NAT.
    a. For living potential donors, testing should continue to be 
performed as close as possible to the surgery, but at least within the 
7-day time period prior to organ recovery.
    b. For deceased donors, the donor specimen should be collected 
within 72 hours prior to organ recovery with results of these screening 
tests available at the time of organ recovery. If the donor sample used 
for testing was collected more than 24 hours prior to organ recovery, 
an additional donor specimen should be collected in the immediate 24 
hours prior to organ recovery and tested for HIV, HBV, and HCV by NAT. 
Results of these screening tests should be made available as soon as 
possible, even if these results might not be available at the time of 
organ recovery.
    2. Regardless of donor risk profile for HIV, HBV, or HCV, 
transplant programs should test all organ recipients:
    a. Before transplantation for HIV, HBV, and HCV using NAT and 
serologic tests including total anti-HBc, HBsAg, anti-HCV, and 
hepatitis B surface antibody (anti-HBs);
    b. At 4-6 weeks following transplantation for HIV, HBV, and HCV 
(with NAT); and
    c. At 12 months following transplantation for HBV (with NAT).
    3. OPOs should ascertain whether any of the following medical or 
social risk criteria were present in potential organ donors within 30 
days prior to organ recovery:
    a. Sex with a person known/suspected to be HIV, HBV, or HCV 
infected
    b. Being a man who has had sex with another man
    c. Sex in exchange for money/drugs
    d. Non-medical drug injection
    e. Sex with a person with history of non-medical drug injection
    f. Incarceration for >72 consecutive hours
    g. Child breastfed by a mother with HIV
    h. Child born to a mother with HIV, HBV, or HCV

    OPOs should identify donors for whom medical and social history is 
unknown at the time of organ recovery, which is also considered a risk 
criterion.
    4. When donors with >=1 of the criteria as specified under #3 are 
identified, OPO's should communicate this information to the 
appropriate transplant centers. Transplant centers should discuss this 
information with transplant candidates and families as part of 
transplantation-related informed consent discussions. Transplant 
centers should make efforts to contextualize these discussions and 
should include the following:
    a. The risk of undetected HIV, HBV, or HCV infection is very low
    b. Recipients are universally tested for HIV, HBV, and HCV after 
transplantation and should transmission occur, effective therapies are 
available
    c. Recipients may have a higher chance of survival by accepting 
organs from donors with risk factors for HIV, HBV, and HCV compared 
with waiting for an organ from a donor without recognized risk factors
    5. Remove any specific label (e.g., ``increased risk donor'') to 
describe donors with risk factors for undetected HIV, HBV, or HCV 
infection, with inclusion of additional strategies to enhance recipient 
safety.
    6. No requirement for specific informed consent with recipients who 
are considering acceptance of these organs, though recipients would 
still be informed of certain donor risk factors.
    7. All organ transplant candidates should be vaccinated for HBV per 
previous recommendations (https://doi.org/10.1111/ctr.13563).
    8. HHS proposes no additional substantive changes to the following 
sections of the 2013 PHS Guideline:

[[Page 44907]]

    a. Collection and/or storage of donor and recipient specimens
    b. Tracking and reporting of HIV, HBV, and HCV infection in donors 
or recipients
    HHS recognizes that the elimination of a specific label, (e.g., 
``increased risk donor'') to designate a separate group of organ donors 
with specific characteristics associated with a relatively small 
increased risk of donor-derived transmission of HIV, HBV, or HCV is a 
change to one of the ACBTSA recommendations for Guideline revision. HHS 
also acknowledges the diversity of opinions expressed during the 
deliberations of this committee regarding whether or not to continue to 
use any label to designate this group of organ donors. HHS has 
evaluated the potential advantages and disadvantages of using such a 
label for a specific subset of all organ donors and proposes the 
approach outlined above for several reasons:
    1. Designating a subset of organ donors does not necessarily 
prevent or reduce the risk of transmission of disease (HIV, HBV, or 
HCV).
    2. Next-of-kin interviews used to identify risk factors may be 
unreliable.
    3. For transplant candidates with end-stage organ disease, the risk 
of severe morbidity or mortality associated with HIV, HBV, or HCV 
transmission as a result of accepting an IRD organ is less than the 
risk of mortality while remaining on the wait list for another organ 
offer.
    4. The risk of morbidity or mortality from HIV, HBV, or HCV 
transmission from an IRD organ is less than other risks of organ 
transplant-related complications, including organ rejection, and 
infections resulting from immune suppression.
    5. Use of a label to specify an organ donor group with small risk 
of disease transmission (e.g., HIV, HBV, HCV) can detract from the 
recognition of other known clinical attributes in some donors that can 
place recipients at even greater risk for morbidity and mortality.
    We seek informed feedback regarding this proposed approach to 
revising the recommendations in the 2013 Guideline, including the 
feasibility of the recommended timing of testing for living and 
deceased donors.

    Dated: August 8, 2019.
Tammy R. Beckham,
Director, Office of Infectious Disease and HIV/AIDS Policy.
[FR Doc. 2019-17759 Filed 8-26-19; 8:45 am]
 BILLING CODE 4150-28-P