Summary and Introduction

The recommendations in this report supersede the U.S Public Health Service (PHS) guideline recommendations for reducing transmission of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) through organ transplantation (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 Rep 2013;128:247–343), hereafter referred to as the 2013 PHS guideline. PHS evaluated and revised the 2013 PHS guideline because of several advances in solid organ transplantation, including universal implementation of nucleic acid testing of solid organ donors for HIV, HBV, and HCV; improved understanding of risk factors for undetected organ donor infection with these viruses; and the availability of highly effective treatments for infection with these viruses. PHS solicited feedback from its relevant agencies, subject-matter experts, additional stakeholders, and the public to develop revised guideline recommendations for identification of risk factors for these infections among solid organ donors, implementation of laboratory screening of solid organ donors, and monitoring of solid organ transplant recipients. Recommendations that have changed since the 2013 PHS guideline include updated criteria for identifying donors at risk for undetected donor HIV, HBV, or HCV infection; the removal of any specific term to characterize donors with HIV, HBV, or HCV infection risk factors; universal organ donor HIV, HBV, and HCV nucleic acid testing; and universal posttransplant monitoring of transplant recipients for HIV, HBV, and HCV infections. The recommendations are to be used by organ procurement organization and transplant programs and are intended to apply only to solid organ donors and recipients and not to donors or recipients of other medical products of human origin (e.g., blood products, tissues, corneas, and breast milk). The recommendations pertain to transplantation of solid organs procured from donors without laboratory evidence of HIV, HBV, or HCV infection. Additional considerations when transplanting solid organs procured from donors with laboratory evidence of HCV infection are included but are not required to be incorporated into Organ Procurement and Transplantation Network policy. Transplant centers that transplant organs from HCV-positive donors should develop protocols for obtaining informed consent, testing and treating recipients for HCV, ensuring reimbursement, and reporting new infections to public health authorities.

Introduction

Background

Since the emergence of human immunodeficiency virus (HIV) in the United States, the U.S. Public Health Service (PHS) has made recommendations to minimize the risk for potential HIV transmission to organ transplant recipients ^[1–4]. After the recognition that HIV can be transmitted through blood transfusion ^[5,6], in 1985, PHS recommended laboratory screening of organ donors using anti-HIV antibody testing ^[3]. In addition, PHS recommended assessment of HIV risk through medical record review and ascertainment of medical and social risk factors through interview of living donors ^[4]. Subsequent investigations reported 53 organ and tissue transplant-associated HIV transmissions before the implementation of donor anti-HIV antibody testing ^[7]. During 1987–1992, transmission of HIV to seven organ recipients was reported from donors who tested negative for HIV antibody at the time of organ donation ^[8–10]. In 1991, a PHS work group was formed, and in 1994, PHS published comprehensive recommendations intended to prevent HIV transmission through organ transplantation ^[2]. These recommendations included universal donor anti-HIV antibody screening, standard ascertainment of risk factors for or clinical evidence of HIV infection among organ donors, and measures to enhance detection, reporting, and tracking of HIV infection among transplant recipients ^[2]. Donors were considered to be at high risk for HIV acquisition on the basis of the report of specific high-risk behaviors within either the previous 12 months (for high-risk sex or exposure to HIV-infected blood) or 5 years (for a man who has had sex with another man, drug injection for nonmedical reasons, or sex in exchange for money or drugs) before organ procurement. Even if anti-HIV antibody testing was negative, persons at high risk for infection were to be excluded from organ donation unless the benefits of transplantation outweighed the risk for disease transmission ^[2].

Despite these recommendations, HIV transmissions continued to occur, although rare, through organ transplantation ^[11,12]. In addition, transmission of hepatitis B virus (HBV) and hepatitis C virus (HCV) through solid organ transplantation was associated with poor recipient outcomes ^[11,13–16]. In 2013, on the basis of donor-derived disease transmission events, improved epidemiologic understanding of risk factors, and availability of nucleic acid testing (NAT) for screening organ donors, PHS published a revised guideline ^[1]. The 2013 PHS guideline recommended screening all donors for HIV infection using antibodies to HIV-1/2 (anti-HIV-1/2) or HIV antigen/antibody (Ag/Ab) combination assay, for HBV infection using hepatitis B surface antigen (HBsAg) and total antibody to hepatitis B core antigen (anti-HBc), and for HCV infection using antibody to HCV (anti-HCV) and NAT to reduce the risk for unintended transmission through transplantation. Implementation of the 2013 PHS guideline also resulted in a change of the term referring to donors with risk factors for HIV, HBV, or HCV infection from “high risk donor” (used after implementation of the 1994 guideline) to the term “increased risk donor” (IRD). “Increased risk” replaced “high risk” to convey the continued but small possibility of donor-derived disease transmission from donors with risk factors. The 2013 PHS guideline identified 12 medical or social history criteria resulting in an IRD designation if these risk factors were applicable within the 12 months before organ procurement. In addition, if the medical or social history of the deceased donor was unavailable at the time of organ procurement or the organ donor’s serum specimen used for HIV, HBV, or HCV testing was hemodiluted, the donor was designated as an IRD ^[1,17]. When donors were classified as IRDs, the 2013 PHS guideline recommended additional donor screening by HIV NAT or HIV Ag/Ab combination testing, obtaining specific informed consent from the organ transplant candidate regarding the risk for potential disease transmission, and testing of organ recipients before and after transplant to monitor for HIV, HBV, and HCV transmission. For living donors, testing was recommended to be performed as close as possible to the date of the organ procurement but at least within 28 days before surgery. For deceased donors, the 2013 PHS guideline recommended obtaining specimens for testing before procurement but did not include a recommendation on the timing of specimen testing relative to organ procurement. The 2013 PHS guideline recommendations were not intended to restrict transplantation or exclude specific donors but rather to facilitate appropriate donor laboratory screening, enhance informed decision-making by transplant candidates and families, and ensure prompt recognition and treatment of donor-derived infections.

Several studies have reported underuse of organs from donors designated as high risk or increased risk ^[18–21]. However, these studies have methodological limitations, including limited risk adjustment models (e.g., not controlling for donor HCV serology results) ^[18,22] and older study time frames before the implementation of donor NAT testing and increased availability of hepatitis C treatment ^[18,21]. Organ transplant candidates who are on the waiting list are at high risk for death, and those who decline IRD organs have higher rates of death and graft failure than patients who accept IRD organs ^[22],23,24]. Because IRDs often are younger and have fewer comorbid conditions, they might have higher organ quality than standard risk donors ^{[20,22,23,25]}. Several factors might be associated with a recipient or transplant program declining an IRD organ. The “increased risk donor” terminology might result in patient or provider apprehension regarding organ quality or the risk for disease transmission ^[26,27]. Potential underuse of IRD organs is concerning because a growing number and proportion of organ donors are designated as IRDs as a result of the national opioid epidemic ^[19,28].

During 2018–2019, members of the transplant community communicated directly to relevant federal agencies, including CDC and the Health Resources and Services Administration, regarding the perceived impact of the 2013 PHS guideline on organ use and allocation and clinical decision-making ^[29,30]. These issues included the following:

• Certain criteria for current IRD designation are not actually associated with a significant risk for HIV, HBV, and HCV infections or transmission and should be removed ^[30].
• The 2013 PHS guideline designates donors as IRDs if risk factors occur within 12 months before organ procurement. Because organ procurement organizations (OPOs) have universally implemented screening of organ donors for HIV, HBV, and HCV infections by NAT since 2017, the 12-month time frame should be shortened ^[29,30].
• All recipients should be screened for HIV, HBV, and HCV infections after transplantation, including recipients of organs from donors without recognized risk factors, because the number and proportion of organ donors with risk factors have increased ^[28], effective suppression of HIV and hepatitis B and a cure for HCV infection are available to recipients should they become infected ^[31–33], and questionnaire responses provided by donors’ next of kin regarding risk factors can be inaccurate ^[34].

To address these issues and further assess the impact of the 2013 PHS guideline recommendations on organ use, allocation, and recipient outcomes, CDC conducted additional analyses ^[28,34–36]. One study determined that the percentage of adult donors classified as an IRD increased from 9.3% in 2010 to 26.2% in 2017 ^[28]. Among IRDs, 16% had detectable HCV RNA in the blood, compared with 1% among donors without increased risk ^[28]. Despite universal adoption of donor HIV, HBV, and HCV testing and NAT, transmission of HBV and HCV from IRDs to recipients continues ^[34]. However, early testing of recipients after transplant, as recommended in the 2013 PHS guideline, has led to early diagnosis and treatment of recipient infection, which possibly averted graft failure or death ^[34]. IRD designation appeared to be associated with underuse of adult kidneys, although the magnitude was smaller than previous estimates ^[36]. This association appeared to be attributable to underuse by a subset of transplant centers rather than broad underuse by all U.S. transplant programs ^[36]. IRD designation also was associated with minimal underuse of adult lungs and pediatric hearts but was not associated with significant underuse of other organs ^[36]. Finally, CDC determined that the risk for undetected infection in donors with high-risk behaviors screened by NAT 30 days after the most recent potential risk behavior was fewer than one per 1 million for HIV and hepatitis C and close to one per 1 million for hepatitis B ^[35].

Rationale and Scope

Federal regulation and oversight of solid organ transplantation is authorized by the National Organ Transplant Act (NOTA), which was initially approved in 1984 and subsequently amended ^[37]. NOTA established the Organ Procurement and Transplantation Network (OPTN). OPTN oversees organ transplantation in the United States and develops national organ transplant policies ^[37]. Oversight of OPTN was delegated to the Health Resources and Services Administration. A final rule established a regulatory framework for the structure and operations of OPTN and required that policies must be consistent with CDC recommendations for organ donor testing and recipient monitoring intended to prevent infectious disease transmission ^[38]. Consistent with OPTN policies, OPOs and transplant centers report all suspected or confirmed donor-derived infections or malignancies to OPTN ^[39],[40]. OPTN’s ad hoc Disease Transmission Advisory Committee reviews all reports to determine whether transmission has occurred from donors to recipients and whether additional risk mitigation interventions are necessary to prevent future transmission ^[39],[40].

As additional epidemiologic information has become available and as scientific advancements have been introduced related to testing and treatment, PHS has periodically revised recommendations intended to reduce the risk for HIV, HBV, and HCV transmission through organ transplantation ^{[1–4],[10],[41]}. In response to feedback from the transplant community ^[29],[30]; universal adoption of donor HIV, HBV, and HCV NAT screening ^[28]; and availability of highly effective therapies for these three viral diseases ^[31]–[33], PHS has revised recommendations previously included in the 2013 PHS guideline to reflect recent, organ transplant-specific evidence and to increase the use of organs while continuing to maintain transplant recipient safety. This 2020 guideline supersedes the 2013 PHS “Guideline for Reducing Human Immunodeficiency Virus, Hepatitis B Virus, and Hepatitis C Virus Transmission Through Organ Transplantation.”

The recommendations in this guideline are intended to apply only to solid organ donors and recipients and not to donors or recipients of other medical products of human origin (e.g., blood products, tissues, corneas, and breast milk). The recommendations apply to OPOs, transplant centers, and other transplant recipient health care providers. The recommendations pertain to use of solid organs procured from donors without laboratory evidence of HIV, HBV, or HCV infection. Additional considerations when using solid organs procured from donors with laboratory evidence of HIV, HBV, or HCV infection are included. As a result of the opioid epidemic, an increasing number of deceased donors have detectable HCV RNA ^[19],[28]. To safely increase the availability of organs by using organs from HCV-viremic donors, considerations for transplantations in HCV-negative recipients with organs from HCV-viremic donors are included. These considerations are not PHS recommendations and were not included in the 2013 PHS guideline.