[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