Recommendations

The guideline recommendations are categorized into the following six topic areas:

• Risk assessment of living and deceased donors
• Living and deceased solid organ donor testing
• Transplant candidate informed consent
• Recipient testing and vaccination
• Collection and storage of donor and recipient specimens
• Tracking and reporting of donor-derived disease transmission events

Steps of the organ transplantation process related to the recommendations (Box), differences between the 2013 and 2020 recommendations (Table 2), and donor and recipient testing recommendations by type of assay and timing of testing (Table 3) are summarized. All 2013 and 2020 recommendations are listed in detail (Supplementary Appendix 2; https://stacks.cdc.gov/view/cdc/88644).

Recommendations in this guideline are included in the bulleted lists that follow. The lists are followed by the rationale for new or modified recommendations. Certain recommendations remain unchanged from the 2013 PHS guideline except for minor wording changes or reorganization (Supplementary Appendix 2;https://stacks.cdc.gov/view/cdc/88644). No further rationale is included here for these recommendations.

Risk Assessment of Living and Deceased Donors

• All living potential donors and persons contacted about deceased donors (e.g., next of kin, life partner, cohabitant, caretaker, friend, or primary treating physician) should be informed of the donor evaluation process, including the review of medical and social history, physical examination, and laboratory tests to identify the presence of infectious agents or medical conditions that could be transmitted by organ transplantation.
• OPOs should ascertain, confidentially, whether any of the following criteria that would put organ recipients at risk for acquiring HIV, HBV, and HCV infections were applicable to potential organ donors within 30 days before organ procurement:
  • Sex (i.e., any method of sexual contact, including vaginal, anal, and oral) with a person known or suspected to have HIV, HBV, or HCV infection
  • Man who has had sex with another man
  • Sex in exchange for money or drugs
  • Sex with a person who had sex in exchange for money or drugs
  • Drug injection for nonmedical reasons
  • Sex with a person who injected drugs for nonmedical reasons
  • Incarceration (confinement in jail, prison, or juvenile correction facility) for ≥72 consecutive hours
  • Child breastfed by a mother with HIV infection
  • Child born to a mother with HIV, HBV, or HCV infection
  • Unknown medical or social history
• Living potential donors who have past or ongoing risk for acquiring HIV, HBV, or HCV infection should receive individualized counseling on specific strategies to prevent exposure to these viruses during the period before surgery.
• Remove any specific term (e.g., “increased risk donor”) to describe donors with risk factors for acute HIV, HBV, or HCV infection.

Donors who meet one or more of the listed criteria might be at risk for having an acute HIV, HBV, or HCV infection ^[1]. Because donors are universally screened for HIV, HBV, and HCV infections by NAT ^[28], the risk for undetected infection is very low but persists because of the window period, the time during which a donor can be infected but the virus is not yet detectable ^[35]. NAT window periods have been estimated to be an average of 11–13 days for HIV, 20–22 days for HBV, and 3–5 days for HCV ^[28,52,53]. The estimated risk for undetected infection is fewer than one per 1 million donors for HIV after 14 days, for HBV after 35 days, and for HCV after 7 days from the time of most recent potential exposure to the day of a negative NAT for donors with risk behaviors ^[35]. Even when assuming the unlikely scenario that a donor was infected with a single virion, the risk for undetected infection by NAT would be fewer than one per 1 million donors 21 days after infection with HIV, 71 days after infection with HBV, and 12 days after infection with HCV.

The 2013 PHS guideline recommendations were largely based on evidence gathered from nontransplant populations or expert opinion regarding the risk for HIV, HBV, and HCV infections among solid organ donors ^[1]. The criteria included in this recommendation are supported by studies conducted specifically to answer questions related to this guideline and a review of cases adjudicated by the OPTN ad hoc Disease Transmission Advisory Committee during 2008–2018 for which donor-derived HBV or HCV transmission was deemed proven or probable (Table 1). No organ donor–derived HIV transmissions have been reported in the United States from deceased donors since 2007 ^[11] and from living donors since 2009 ^[12].

Among the 14 donor risk criteria included in the 2013 PHS guideline (applicable for the 12 months before organ procurement), eight were repeatedly reported as donor criteria associated with donor-derived disease transmission events from reports to the OPTN ad hoc Disease Transmission Advisory Committee, including 1) sex with a person known or suspected to have HIV, HBV, or HCV infection; 2) man who has had sex with another man; 3) sex in exchange for money or drugs; 4) sex with a person who has had sex in exchange for money or drugs; 5) drug injection for nonmedical reasons; 6) sex with a person who injected drugs for nonmedical reasons; 7) incarceration for ≥72 consecutive hours; and 8) unknown medical or social history (Table 1). Four risk criteria had not been associated with a donor-derived transmission event, including 1) woman who has had sex with a man who has had sex with another man; 2) child born to a mother known to be infected with or at increased risk for infection with HIV, HBV, or HCV; 3) child breastfed by a mother known to be infected with or at increased risk for HIV infection; and 4) person with a history of hemodialysis (Table 1). In addition, two risk criteria (newly diagnosed or treated syphilis, gonorrhea, chlamydia, or genital ulcers and hemodiluted blood specimen used for infectious disease testing) were each reported only once (Table 1) ^[10].

Although OPTN does not routinely collect data on specific criteria resulting in IRD designations, a recent analysis was conducted to determine the criteria resulting in IRD designation among a random sample of IRDs during 2018 ^[45]. Among 179 IRDs with only one risk factor resulting in designation, 12% had received outpatient hemodialysis, 12% were designated IRDs because of hemodilution of the specimen used for infectious disease testing, and 6% had a recent diagnosis of an STD or recent treatment for an STD ^[45]. In addition, no donors were designated as IRDs because they were a woman who had had sex with a man who had had sex with another man or because they were a child breastfed by a mother with or at risk for HIV; only 0.6% were designated an IRD because they were a child born to a mother infected with or at increased risk for infection with HIV, HBV, or HCV ^[45].

Outbreaks of HCV infection have been reported in hemodialysis settings, prompting recommendations for routine screening of maintenance hemodialysis patients to detect incident cases ^[54]. Although outpatient hemodialysis is a risk factor for HCV infection, the incidence among U.S. dialysis recipients has steadily decreased since 1996 ^[50], and strategies to prevent and interrupt health care transmission have been adopted nationally ^[55].

Hemodilution of donor specimens used for infectious disease testing was associated with a donor-derived transmission of HIV in 1986 ^[10]. Although OPOs should continue to attempt to obtain nonhemodiluted specimens for infectious disease testing, hemodilution likely has a minimal impact on HIV, HBV, and HCV NAT results because of the high sensitivity and low limit of detection of these tests ^[43].

The risk for HIV acquisition has been reported to be higher among those with a diagnosis of syphilis and to a lesser extent among those with gonorrhea, chlamydia, and herpes simplex virus ^[56–59]. However, HIV transmission from a donor with or who has been treated for syphilis, gonorrhea, chlamydia, or genital ulcers has never been reported. Although rare in the United States, perinatal transmission of HIV, HBV, and HCV continues to occur ^[60–62]. Therefore, although donor-derived HIV, HBV, or HCV transmission from a pediatric donor has not been previously reported, the recommendation is to determine whether a potential pediatric donor is a child who has been born to a mother infected with HIV, HBV, or HCV or has been breastfed by a mother infected with HIV.

Organs from IRDs might be underused compared with organs from standard risk donors ^{[18,21,22,63]}. Declining an IRD organ has been associated with poorer outcomes among transplant candidates, including higher mortality or receiving organs of lower overall quality, compared with accepting an IRD organ ^{[22,23,26,64–67]}. Use of IRD organs is an important strategy to increase the availability of organs, particularly as the proportion of donors with risk factors for HIV, HBV, or HCV infections continues to increase ^[28].

Living and Deceased Solid Organ Donor Testing

• Test all potential organ donors for HIV, HBV, and HCV infections using serologic tests (including anti-HIV antibody, total anti-HBc, HBsAg, and anti-HCV) in addition to NAT for all three viruses, regardless of the risk criteria identified during screening using assays licensed, approved, or cleared by the Food and Drug Administration (FDA) for donor screening.
  • For living potential donors, testing should continue to be performed as close as possible to the surgery but at least within the 28 days before organ procurement.
  • For deceased potential donors, the donor specimen should be collected within 96 hours before organ procurement, with results of these screening tests available at the time of organ procurement.

Because next-of-kin interviews used to identify risk factors might be unreliable ^[34], the 2013 PHS guideline recommended HCV NAT for all donors and HIV NAT or p24 antigen testing for IRDs ^[1]. NAT has a shorter window period compared with serology or antigen testing, and all organ donors are screened for HIV, HBV, and HCV infections using NAT ^[28]. Donor-derived HCV transmission events associated with acute, window-period donor infection have been reported, primarily among donors who injected drugs for nonmedical reasons ^[34]. Investigation of these transmission events has revealed that the initial donor screening NAT can have false-negative results, and subsequent HCV NAT testing of a donor sample collected on the day of organ procurement can identify donor infection. Potential organ donors known to be infected with HIV, HBV, or HCV do not need to be retested for the virus with which they are infected. For example, a potential organ donor already known to be infected with HCV should be tested for HIV and HBV infections but not HCV.

Transplant Candidate Informed Consent

• An informed consent process discussion between the transplant candidate or medical decision-maker and the listing clinician should be initiated before placing a patient on a transplant waiting list. This discussion should include opportunities to address concerns related to the risk for HIV, HBV, or HCV transmission via organ transplantation.
• When donors with one or more of the risk criteria specified under Risk Assessment of Living and Deceased Donors are identified, OPOs should communicate this information to the appropriate transplant centers. Transplant centers should include this information in informed consent discussions with transplant candidates or their medical decision-makers. No separate, specific informed consent is recommended. Transplant centers should make efforts to contextualize these discussions and should include the following:
  • The risk for undetected HIV, HBV, or HCV infection is very low but not zero ^[34,35].
  • Recipients will be tested for HIV, HBV, and HCV infections after transplantation and should transmission occur, effective therapies are available ^[31–33].
  • Transplant candidates might have a higher chance of survival by accepting organs from donors with risk factors for HIV, HBV, and HCV infections compared with waiting for an organ from a donor without recognized risk factors ^[22,23].
• If before transplantation or repair of a transplanted organ the transplant center team knows or anticipates that stored blood vessel conduits (from a donor who is different from the donor of the primary organ being transplanted or repaired) may be used, and the blood vessel donor meets risk criteria listed under Risk Assessment of Living and Deceased Donors, then the transplant center team should include this risk information in the informed consent discussion.

Recipient Testing and Vaccination

• Regardless of a donor’s risk profile for HIV, HBV, or HCV infections, transplant programs should test all organ recipients using assays licensed, approved, or cleared by FDA for diagnosis.
  • Before transplantation, HIV testing should be performed using a CDC-recommended laboratory HIV testing algorithm ^[68] ; hepatitis B testing should be performed using total anti-HBc, HBsAg, and hepatitis B surface antibody (anti-HBs); and hepatitis C testing should be performed using anti-HCV antibody and HCV NAT. Blood samples should be obtained from the transplant candidate during hospital admission for the organ transplant before implantation of the organ. Results of transplant candidate testing do not have to be available at the time of transplantation.
  • At 4–6 weeks after transplantation, transplant centers should test recipients for HIV, HBV, and HCV infections using NAT.
  • Clinicians caring for liver recipients should maintain heightened awareness of the potential for delayed appearance of HBV infection and consider additional testing using HBV NAT at 1 year.
  • Recipients who develop signs or symptoms of liver injury (e.g., jaundice or elevated liver function tests) after transplantation should be tested for viral hepatitis, even if previous hepatitis B or hepatitis C testing was negative.
• All organ transplant candidates should be vaccinated against HBV infection.

All recipients should be screened for HIV, HBV, and HCV infections after transplantation because next-of-kin interviews do not accurately identify all donors with risk factors ^[34] and effective treatment with viral suppression of HIV and HBV infections and curative treatment of HCV infection are available ^[31],[33]. Early identification of donor-derived infections and implementation of medical therapies are likely to reduce the risk for graft failure and death ^[31],[34]. Testing 4–6 weeks posttransplant is recommended because earlier testing might result in a false-negative result because of the test window period. Pretransplant testing is recommended to determine whether any recipient HIV, HBV, or HCV infection existed before transplantation. Organ recipients known to be infected with HIV, HBV, or HCV do not need to be retested immediately before transplantation or 4–6 weeks after transplantation for the virus with which they are infected. For example, a transplant candidate already known to be infected with HCV should be tested for HIV and HBV but not HCV.

Use of organs from donors who are positive for anti-HCV or HCV RNA ^[69,70] and organs from donors with risk factors for viral hepatitis is increasing ^[19,28], and clinicians caring for transplant recipients should maintain awareness for atypical, late clinical presentations of HBV infection. Late development of posttransplant HBV infection can occur through reactivation of covalently closed circular DNA (cccDNA) sequestered in hepatocytes after primary infection in the donor, even when resolved ^[71]. Reactivation of resolved donor HBV infection in total anti-HBc positive, HBsAg-negative liver transplants can occur many months posttransplant ^[72]. Resolved or inactive HBV infection might reactivate in the context of recipient immune suppression ^[71] or rarely with direct acting antiviral therapy for hepatitis C with risk for liver decompensation ^[73]. In 2019, CDC investigated 13 cases of HBV infection in liver recipients associated with donors who had a positive urine drug screen or a history of drug injection for nonmedical reasons or both; all 13 donors were positive for anti-HCV positive and negative for HBV DNA and total anti-HBc. Although rare, seronegative (total anti-HBc negative) occult HBV infection is known to occur ^[74]. Posttransplant exposure to bloodborne pathogens through behavioral risks or health care–associated infection also might occur.

As part of the strategy to eliminate HBV transmission in the United States, the Advisory Committee on Immunization Practices (ACIP) has recommended hepatitis B vaccination for adults at risk for HBV infection since 1982, for all infants since 1991, and for children aged ≤18 years since 1999 ^[62,75]. The Infectious Diseases Society of America (IDSA) and the American Society of Transplantation (AST) recommend that all anti-HBs–negative (<10 mIU/mL) solid organ transplant candidates should receive hepatitis B vaccination ^[76,77]. AST recommends that hepatitis B vaccination should begin as early as possible, and accelerated schedules may be given ^[62] but might be less immunogenic ^[77]. AST also recommends checking postvaccination titers approximately 4 weeks after the last dose of vaccine. IDSA recommends that if postvaccination titers are insufficient (<10 mIU/mL), a second complete series should be administered ^[76]. In addition, ACIP and IDSA recommend that patients aged ≥20 years and on hemodialysis should receive a high-dose 40 ^μg hepatitis B vaccine series ^[62,76]. Completion of a vaccine series might not be possible when organ transplantation is emergently needed (e.g., acute liver failure).

Collection and Storage of Donor and Recipient Specimens

• OPOs and living donor recovery centers should archive donor blood specimens for at least 10 years. These specimens should be collected within 24 hours before organ procurement. Two blood specimens should be collected for archiving: an ethylenediaminetetraacetic acid (EDTA) plasma specimen or serum specimen for serologic assays and a separate EDTA plasma specimen for NAT. If only feasible to collect one specimen, a plasma specimen collected in EDTA, rather than a serum specimen, is optimal.
• For deceased donors, living donors, transplant candidates, and recipients, two blood specimens should be collected when HIV, HBV, or HCV infection testing is planned: an EDTA plasma specimen or serum specimen for serologic assays and a separate EDTA plasma specimen for NAT.
• All stored blood vessel conduits from a donor found to be infected with HIV, HBV, or HCV should be quarantined immediately and not released for clinical use unless the HIV-, HBV-, or HCV-infected vessel conduits are needed for the initial transplant procedure in the recipient. After completing the initial transplant procedure, any remaining vessel conduits should be disposed of in accordance with hospital policy to prevent inadvertent release from quarantine and unintentional use in other patients.

The recommendations for Collection and Storage of Donor and Recipient Specimens have not been changed from the 2013 PHS guideline, with the exception that this guideline includes a recommendation on the timing of blood donor specimen collection. The remaining recommendations in this section have been reorganized to increase clarity (Supplementary Appendix 2; https://stacks.cdc.gov/view/cdc/88644">https://stacks.cdc.gov/view/cdc/88644).

Tracking and Reporting of Donor-Derived Disease Transmission Events

• When an OPO, living donor recovery center, or transplant center receives information, including before organ recovery, that 1) an organ or blood vessel conduit donor meets one or more of the criteria as specified under Risk Assessment of Living and Deceased Donors; 2) the donor is infected with HIV, HBV, or HCV; or 3) an organ recipient infection with HIV, HBV, or HCV is suspected to be donor derived, they should contact other organizations involved with organs or tissue procured from the donor, including 1) OPTN, 2) the OPO or living donor recovery center, 3) transplant centers, and 4) any institutions considering tissue and eye recovery. Living donors who test positive for HIV, HBV, or HCV infections should be notified of the results.
• An OPO, living donor recovery center, or transplant center also should notify the appropriate public health authorities if the deceased donor, living donor, or transplant recipient is infected with HIV, HBV, or HCV.
• OPOs, in coordination with OPTN, should have a system in place allowing tracking between a common deceased donor and 1) recovered organs, 2) recovered associated blood vessel conduits, and 3) recovered tissues and eyes to facilitate notification when a donor-derived disease transmission is suspected. This system should include accurate records of the distribution and disposition of each organ and initial distribution of associated blood vessel conduits, along with procedures to facilitate the timely notification of transplant centers and tissue and eye recovery establishments when a donor-derived disease transmission is suspected. To facilitate notification by OPO, transplant centers should keep accurate records of all organs and associated blood vessel conduits received and the disposition of each.

The recommendations for Tracking and Reporting of Donor-Derived Disease Transmission Events have not been changed from the 2013 PHS guideline. They have only been reorganized to increase clarity (Supplementary Appendix 2; https://stacks.cdc.gov/view/cdc/88644).

Additional Considerations for Donors with Laboratory Evidence of HIV, HBV, or HCV Infection

The recommendations described in this guideline are applicable when donors do not have laboratory evidence of HIV, HBV, or HCV infection. For transplant candidates who are considering organs from HBV- or HCV-infected donors, transplant centers should obtain specific informed consent that includes discussion of the risks related to disease transmission. When organs from HIV-infected donors are used, OPOs and transplant centers should refer to the regulatory framework resulting from enactment of the HIV Organ Policy Equity (HOPE) Act ^[78].

Historically, HCV transmission through organ transplantation has been associated with poor clinical outcomes ^[11,13,14]. DAA therapy is now available and can cure HCV infection ^[32]. Use of organs from HCV-viremic donors appears to be increasing ^[79]. Early evidence suggests that DAA prophylaxis or treatment of HCV-negative recipients of organs from HCV-viremic donors is safe and effective with high rates of sustained virologic response ^[80–82]. Use of organs from HCV-viremic donors could increase the supply of available organs ^[83]. Despite evidence of safety and efficacy, some reports suggest complications associated with the transplantation of HCV-infected donor organs into uninfected recipients, including graft rejection, delayed graft function, and BK virus and cytomegalovirus viremia ^[84–87]. Furthermore, insurance payer-related delays for DAA therapy also have been reported ^[88]. Transplant centers that offer or will offer transplantation of organs from HCV-viremic donors to HCV-negative recipients should address the following considerations in their planning and practices. These considerations are distinct from the recommendations for transplanting organs from donors without laboratory evidence of HIV, HBV, or HCV infection and are not be required to be incorporated into OPTN policy:

• Transplant centers should develop and maintain a plan for education and informed consent of HCV-negative transplant candidates who are considering an organ from an HCV-viremic donor.
• Transplant centers should ensure development of a testing and treatment protocol for their transplant program for HCV-negative transplant candidates who receive an organ from an HCV-viremic donor.
• Transplant centers should ensure payment- and reimbursement-related barriers will not result in a delay of HCV diagnosis or treatment of recipients who receive organs from HCV-viremic donors.
• Clinicians caring for recipients of organs from donors with HCV infection or recent drug injection for nonmedical reasons should maintain awareness of multiple rapidly changing infectious disease risks associated with drug injection for nonmedical reasons, including but not limited to hepatitis A virus ^[89], HBV, HCV ^[90], HIV ^[91], and bacterial and fungal infections ^[92], and monitor organ recipients accordingly.
• In accordance with state requirements for reporting notifiable infectious diseases, if an organ recipient becomes newly infected with HCV, the transplant center should notify public health authorities in the recipient’s residence jurisdiction.