1

PHS GUIDELINE FOR REDUCING TRANSMISSION OF HUMAN 

IMMUNODEFICIENCY VIRUS (HIV), HEPATITIS B VIRUS (HBV),

AND HEPATITIS C VIRUS (HCV) THROUGH SOLID ORGAN 

TRANSPLANTATION

Debbie L Seem, RN, MPH 1, Ingi Lee, MD, MSCE 2, Craig A Umscheid, MD, MSCE 2, and 

Matthew J Kuehnert, MD 1

1 Division of Healthcare Quality Promotion

Centers for Disease Control and Prevention

Atlanta, GA

2 Center for Evidence-based Practice

University of Pennsylvania Health System

Philadelphia, PA

 

Disclaimer: This information is distributed solely for the purpose of pre-dissemination peer review 

under applicable information quality guidelines. It has not been formally disseminated by the 

Centers for Disease Control and Prevention. It does not represent and should not be construed to 

represent any agency determination or policy.
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Acknowledgement

We would like to recognize Jonathan R. Treadwell, Ph.D., Senior Research Analyst, and 

Meredith Noble, M.S., Senior Research Analyst, from the Evidence-based Practice Center, ECRI 

Institute, Plymouth Meeting, PA, who authored Solid Organ Transplantation and the Probability 

of Transmitting HIV, HBV, or HCV: A Systematic Review to Support an Evidence-based 

Guideline, referred to as the Evidence Report in this guideline. 

The Expert Panel and Review Committee contributed throughout the guideline development 

process and provided in-depth review of the key evidence search questions, bibliography 

resulting from the literature review, and draft evidence report. Further input was sought from 

subject matter experts to address specific issues in development of the guideline; in particular, 

we express our thanks to Scott Halpern, MD, PhD, MBE, Michael G Ison, MD, MS, and Jutta 

Preiksaitis, MD, for writing the original drafts of the Expert Opinion summaries.

The opinions of individual members of the Expert Panel or Review Committee might not be 

reflected in all the recommendations herein, as the guideline represents the position of the Public 

Health Service agencies, and is not a consensus document.

Expert Panel

Branson, Bernard, MD

Associate Director for Laboratory 

Diagnostics, Office of the Director, Division 

of HIV/AIDS Prevention, NCHHSTP;

Centers for Disease Control and Prevention

Grohskopf, Lisa A, MD, MPH

Medical Officer, Epidemiology Branch, 

Division of HIV/AIDS Prevention, 

NCHHSTP; Centers for Disease Control and 

Prevention

Holmberg, Scott, MD, MPH 

Chief, Epidemiology and Surveillance 

Branch, Division of Viral Hepatitis, 

NCHHSTP; Centers for Disease Control and 

Prevention

Thompson, Nicola D, PhD, MS

Epidemiologist, Epidemiology and 

Surveillance Branch, Division of Viral 

Hepatitis, NCHHSTP; Centers for Disease 

Control and Prevention

Review Committee

Bridges, Nancy D, MD

Chief, Transplantation Immunobiology 

Branch; National Institute of Allergy and 

Infectious Diseases; National Institutes of 

Health

DeMaria, Alfred, Jr, MD

Medical Director, Bureau of Infectious 

Disease Prevention, Response and Services;

State Epidemiologist; Massachusetts 

Department of Public Health; Council of 

States and Territorial Epidemiologists 

Representative

Durbin, Richard C, MBA

Director, Division of Transplantation,

Healthcare Systems Bureau; Health 

Resources and Services Administration
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Review Committee cont.

Fishman, Jay A, MD

Associate Director, MGH Transplantation 

Center; Director, Transplant Infectious 

Disease and Compromised Host Program; 

Massachusetts General Hospital; Professor 

of Medicine, Harvard Medical School

Holmberg, Jerry A, PhD

Senior Advisor for Blood Policy, Office of 

the Secretary, Office of the Assistant 

Secretary for Health; U.S. Department of 

Health and Human Services

St. Martin, Laura, MD, MPH

Medical Officer, Division of Human 

Tissues; Food and Drug Administration

Tritz, Karen L, MSW

Technical Director, Division of Continuing 

Care Providers Survey and Certification 

Group; Centers for Medicare and Medicaid 

Services

Ziermann, Rainer, PhD

Senior Director, Clinical Research

Roche Molecular Systems 
4

Disclosure of Financial Interests and Relationships

We requested guideline authors and Expert Panel members to report conflicts of interest. The authors DLS, IL, 

CAU and MJK report no actual or potential conflicts of interest. IL and CAU received funding from CDC to 

support the guideline development process. No Expert Panel members reported conflicts of interest.
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Table of Contents

Abbreviations...................................................................................................................................6

I. Executive Summary.............................................................................................................8

II. Summary of Recommendations.........................................................................................11

III. Recommendations for Further Research............................................................................18

IV. Scope and Purpose .............................................................................................................20

V. Background........................................................................................................................22

VI. Methods .............................................................................................................................26

VII. Evidence Review ...............................................................................................................38

Expert Opinion Summaries.........................................................................85

VIII. Appendices.........................................................................................................................91

References....................................................................................................................................146
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Abbreviations

ALT Alanine aminotransferase

Anti-HBs Antibody to hepatitis B surface antigen 

Anti-HBc Antibody to hepatitis B core antigen 

Anti-HCV Antibody to hepatitis C virus

Anti-HIV Antibodies to human immunodeficiency virus, types I and II

CDC Centers for Disease Control and Prevention

CSW Commercial sex worker

DNA Deoxyribonucleic acid

EDTA Ethylenediaminetetraacetic acid

EIA Enzyme immunoassay

ELISA Enzyme-linked immunoassay

FDA Food and Drug Administration

GRADE Grading of Recommendations Assessment, Development, and Evaluation

HAART Highly active anti-retroviral therapy

HBIG Hepatitis B immune globulin

HBsAg Hepatitis B surface antigen

HBV Hepatitis B virus

HCV Hepatitis C virus

HHS U.S. Department of Health and Human Services

HIV Human immunodeficiency virus

HMO Health maintenance organization

HRSA Health Resources and Services Administration

HSV Herpes simplex virus

IDU Injection drug use

IVDU Intravenous drug use

IgG anti-HBc Immunoglobulin G antibodies to hepatitis B core antigen

IgM anti-HBc Immunoglobulin M antibodies to hepatitis B core antigen

IRD Increased risk donor

IVDU Intravenous drug use

MSM Men who have sex with men

NAT Nucleic acid test
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NHANES National Health and Nutrition Examination Survey

OPO Organ procurement organization

OPTN Organ Procurement and Transplantation Network

PCR Polymerase chain reaction

PHS Public Health Service

PPV Positive predictive value

RCT Randomized controlled trial

RIBA Recombinant immunoblot assay

RNA Ribonucleic acid

RT-PCR Reverse transcriptase polymerase chain reaction

SOT Solid organ transplantation

SRTR Scientific Registry of Transplant Recipients

STD Sexually transmitted disease

UNOS United Network for Organ Sharing

QALYs Quality of life years
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I. Executive Summary

This guideline supplants the 1994 Public Health Service (PHS) Guidelines for Preventing Transmission of HIV 

through Transplantation of Human Tissue and Organs.

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The most significant changes involve:

● expanding the guideline to include hepatitis B virus (HBV) and hepatitis C virus (HCV), in addition to 

human immunodeficiency virus (HIV); 

● utilizing factors known to be associated with increased likelihood of HIV, HBV or HCV to identify 

potential donors at increased risk for transmitting infection;

● distinguishing between expected and unexpected transmission of HBV and HCV in goals for prevention;

and

● limiting the focus to solid organ transplants and vessel conduits recovered for organ transplant purposes. 

As with the 1994 guideline, the recommendations address adult and pediatric donors who are living or 

deceased, as well as transplant candidates and recipients. 

Transmission of HIV, HBV and HCV through organ transplantation is a critical patient safety and public health 

issue. Such events can result in serious illness and death in organ recipients who are immunosuppressed, 

particularly when transmission is unexpected. In this situation, the recipient can unintentionally infect others,

creating the need for infection control response in both the healthcare and community settings. Unexpected 

transmission of HIV, HBV and HCV from infected donors has been reported in heart, liver, kidney and 

pancreas recipients.2-11 However, intentional transplantation of organs from HBV- and HCV- infected donors is 

accepted medical practice in narrowly specified situations. These organs are typically offered to recipients 

known also to be infected with the same pathogen, or in rare circumstances, to uninfected recipients in cases of 

urgent medical need where benefit is deemed to outweigh risks. In these situations, prophylaxis or treatment 

with immunizations, anti-virals and/or immunoglobulin is offered, if appropriate, to prevent transmission or 

reduce the disease severity. Although there may be a potential benefit of transplanting organs from HIVinfected donors into HIV-infected recipients, Organ Procurement and Transplantation Network (OPTN) policy, 

as required by the HHS Final Rule [42 CFR Part 121], prohibits the knowing acquisition and transplantation of 

organs infected with HIV.

The purpose of this document is to provide guidance to organ procurement organizations (OPOs); transplant

centers, including physicians, nurses, administrators, and clinical coordinators; laboratory personnel responsible 

for testing and storing donor and recipient specimens; and persons responsible for developing, implementing, 

and evaluating infection prevention and control programs for OPOs and transplant centers. In constructing this 

guideline, the PHS sought assistance from public and private health professionals and representatives of 

transplantation, organ recovery, public health and other organizations. 

This guideline is based on a targeted systematic review of the best available evidence, with explicit links 

between the evidence and recommendations. To accomplish this, we used an adapted GRADE approach for 

evaluating quality of evidence and determining strength of recommendations. The methodology, structure, and 

components of this guideline are approved by the Centers for Disease Control and Prevention (CDC). A more 

detailed description of our approach is available in the Methods section.

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To evaluate the evidence on reducing transmission of HIV, HBV and HCV, we examined data addressing 10 

key questions within five major topic areas (Table 1). A sixth topic area includes questions addressed by Expert 

Opinion (EO). We drew upon experts to draft summaries related to these questions anticipating that a 

systematic review of the literature would produce insufficient evidence-based data. The summaries were written 

and edited by the guideline authors.
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Table 1. Questions for Systematic Review

Major topic area of the guideline Question for Systematic Review

I. Probability of transmission of HIV, 

HBV, or HCV through solid organ 

transplantation (SOT)

1. What are the prevalence and incidence rates of HIV, HBV, 

and HCV among potential solid organ donors?

2. What are the rates of transmission to recipients from donors 

infected with HIV, HBV, or HCV? Do the rates vary by the 

organ transplanted or when the donor was infected?

II. Methodology to better estimate 

donor infection with HIV, HBV, or 

HCV

3. What behavioral risk factors are associated with an 

increased probability of infection with HIV, HBV, or HCV? 

What is the prevalence of these characteristics among 

potential solid organ donors? 

4. What nonbehavioral factors are associated with an increased 

probability of infection with HIV, HBV, or HCV? What is 

the prevalence of these factors among potential solid organ 

donors? 

5. What are the test characteristics of the screening methods 

available to detect HIV, HBV, and HCV in potential solid 

organ donors? Do test characteristics differ in particular 

populations and with donor clinical status (i.e., donation 

after brain death versus donation after cardiac death OR 

adult vs. pediatric donors)?

III. Donor interventions to decrease 

transmission of HIV, HBV, or HCV 

from infected donors

6. Which donor interventions reduce the probability of 

pathogen transmission from an organ donor infected with 

HIV, HBV, or HCV to a previously uninfected recipient?

IV. Potential risks and benefits of 

transplanting, or not transplanting, 

solid organs from donors positive 

for HIV, HBV, or HCV

7. How do the clinical outcomes of recipients of organs from 

donors infected with HIV, HBV, or HCV compare to those 

who remain on the transplant list?

V. Potential risks and benefits of 

transplanting, or not transplanting, 

organs from donors with risk 

factors for HIV, HBV, or HCV

8. How do the clinical outcomes of transplant recipients who 

receive organs from donors with behavioral or 

nonbehavioral risk factors compare to those who remain on 

the transplant list?

9. What is the impact of excluding potential solid organ donors 

with behavioral or nonbehavioral risk factors on the organ 

donor pool?

10. What is the impact of false positive tests on the organ donor 

pool?
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Major topic area of the guideline Question for Systematic Review

VI. Approaches to informing recipients 

about the risks of HIV, HBV, and 

HCV transmission and evaluation

for possible exposure posttransplantation

Note: The related three questions were 

not part of the systematic literature 

review.

EO1. How and when should informed consent be obtained from 

potential recipients to help them consider the risks (i.e., 

probability of acquiring the disease and consequences of 

disease acquisition) of donor-derived HIV, HBV, and HCV?

EO2. When should testing of a transplant recipient be done to 

detect HIV, HBV, and HCV transmission from the donor?

EO3. How should donor and recipient specimens be collected 

and stored for potential investigation of donor-derived HIV, 

HBV, and HCV infection?

Evidence addressing the key questions was used to formulate recommendations and is available in the Evidence 

Review in the body of the guideline and the GRADE Tables in the appendices. Evidence-based 

recommendations were cross-checked with those from previously published guidelines identified in an initial 

systematic search.

The guideline authors used the narrative evidence summaries to develop guideline recommendations. If 

weighing the critical outcomes for a given intervention or question resulted in a net benefit or a net harm, then a 

Category I Recommendation was formulated to recommend strongly for or against the given intervention 

respectively. If weighing the critical outcomes for a given intervention or question resulted in a tradeoff 

between benefits and harms, then a Category II Recommendation was formulated to recommend that providers 

or institutions consider the intervention when deemed appropriate.

Levels A and B represent the quality of the evidence underlying the recommendation, with A representing high 

to moderate quality evidence and B representing low to very low-quality evidence. Level IC represents required 

practices, regardless of the quality of evidence.

Expert Opinion. Recommendations from the Expert Opinion are linked to key questions. These 

recommendations were agreed upon by expert consensus and are designated either IB if they represent a strong 

recommendation based on accepted practices or IIB if they are a weak recommendation.

Recommendations from previous guidelines or reports for topics not directly addressed by our systematic 

review of the evidence were included in our Summary of Recommendations if they were deemed critical to the 

target users of this guideline. Unlike recommendations informed by our systematic review, these 

recommendations will not be linked to a key question and were listed as Category I recommendations as the 

critical outcome for each intervention was determined to result in a net benefit.

The Summary of Recommendations is organized as follows: 1) Donor risk assessment; 2) Donor screening; 3) 

HBV-infected donors and transplantation; 4) HCV-infected donors and transplantation; 5) Recipient informed 

consent; 6) Recipient testing; 7) Donor and recipient specimen collection and storage; and 8) Tracking and 

reporting of HIV, HBV, and HCV.

Areas in need of further research identified during the evidence review are outlined in the Recommendations for 

Further Research. This section includes guidance for specific methodological approaches that should be used in 

future studies, such as the use of clinically relevant outcome measures. 

Readers who wish to examine the primary evidence underlying the recommendations are referred to the 

Evidence Review in the body of the guideline, GRADE Tables (from the Evidence Report) in the Appendices, 
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and the Evidence Report accessible at http://www.regulations.gov. The Evidence Review includes narrative 

summaries of the data presented in the Evidence Report. In the Evidence Report, the Evidence Tables include 

all study-level data used in the guideline, and the GRADE Tables assess the overall quality of evidence for each 

question. Finally, the Evidence Report presents a clearly delineated search strategy that will be used for periodic 

updates to ensure that the guideline remains a timely resource as new information becomes available. 

II. Summary of Recommendations

Table 2. Categorization Scheme for Recommendations 

Category IA Strong recommendation supported by high to moderate quality evidence 

suggesting net clinical benefits or harms.

Category IB Strong recommendation supported by low to very low quality evidence 

suggesting net clinical benefits or harms.

Category IC Strong recommendation required by state or federal regulation, regardless 

of the quality of evidence.

Category IIA Weak recommendation supported by high to moderate quality evidence 

suggesting a trade-off between clinical benefits and harms.

Category IIB Weak recommendation supported by low to very low quality evidence 

suggesting a trade-off between clinical benefits and harms.

No recommendation Unresolved issue for which there is any quality evidence with uncertain 

trade-offs between clinical benefits and harms.

Category I: Recommendations not linked to a key question and no systematic review of the literature 

performed, but the critical outcome was determined to result in a net benefit.

If a recommendation was based on evidence for one of the 10 key questions, the key question was referenced

(e.g., Question 3); the Evidence Review for the key questions starts on page 38. If a recommendation was based 

on evidence for one of the three Expert Opinion questions, the Expert Opinion question was referenced (e.g., 

Expert Opinion – Question 1); the Expert Opinion summaries start on page 85. Additional information on 

categorizing the recommendation can be found under Formulating Recommendations starting on page 35.

It is important to clarify that when recovered or transplanted organs are referred to in the following 

recommendations, associated vessels are also implied since these vessel conduits may be transplanted with the 

recovered donor organ or with a recipient of an organ from a different donor.

Donor Risk Assessment

1. All prospective living donors and individuals interviewed about deceased potential organ donors (i.e., next 

of kin, life partners, cohabitants, friends, healthcare provider) should be informed of the general nature of 

the donor evaluation process, including the review of medical and behavioral history, physical examination, 

and blood tests to identify the presence of infectious agents or medical conditions that could be transmitted 

by organ transplantation. (Category I)
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2. To ascertain whether potential organ donors are average risk or at increased risk for having HIV, HBV, or 

HCV, prospective living donors and next-of-kin, as well as individuals familiar with deceased donors (i.e., 

life partners, cohabitants, friends, healthcare provider), should be interviewed in a confidential and sensitive 

manner about behaviors that may have increased the potential donor‟s probability of HIV, HBV or HCV 

infection. (Refer to Table 3 for risk factors) (Category IB) (Questions 3/4A)

3. For prospective living donors with a history of behaviors associated with an increased risk of acquiring 

HIV, HBV or HCV identified during evaluation, individualized counseling and a detailed discussion of 

specific strategies to prevent exposure to these viruses should occur; however, in most circumstances a 

discussion of strategies to avoid these behaviors should be provided. (Refer to Table 3 for risk factors) 

(Category 1)

4. For potential pediatric donors for whom maternal transmission of HIV, HBV or HCV infection is a 

consideration, the mother and, if possible, the father should be interviewed about behaviors that may have 

placed them at risk for acquiring an infection that could have been transmitted to their child. (Category I)

5. Children with any risk factors associated with increased probability of HIV, HBV or HCV should be 

identified as having an increased probability of HIV, HBV or HCV infection. (Category IB) (Questions 

3/4B)

6. Children ≤ 2 years of age born to mothers with HIV, HBV, or HCV infection or mothers who meet the 

behavioral or nonbehavioral criteria for increased probability of infection (regardless of their HIV, HBV or 

HCV status) should also be identified as having an increased probability of HIV, HBV or HCV infection. 

(Category IB) (Questions 3/4C)

7. Massive blood loss and intravascular volume replacement by infusion of crystalloid and colloid solution and 

transfusion of blood products can cause plasma dilution and result in unreliable test results for transmissible 

infections. Donors should be considered at increased risk for harboring HIV, HBV and HCV when donor 

samples are determined to be diluted by an accepted plasma dilution algorithm and calculation method, such 

as provided by FDA,13 designed to evaluate volumes administered in the 48 hours before specimen 

collection, even when no risk factors are identified. (Category IB) (Expert Opinion - Question 3D)

Donor Screening 

In recommendations 3, 4 and 5 under Donor Screening, “the most sensitive test available” may include fourth 

generation antigen/antibody tests, as these tests become available and are FDA-licensed or approved for use in 

the United States. We include the above language in the recommendations should these types of tests be 

licensed or approved in the future.

1. Screening tests for HBV [i.e., hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen

(anti-HBc)], HCV (i.e., anti-HCV), and HIV (i.e., anti-HIV 1/2) should be performed on all potential organ 

donors (living or deceased). (Category I) (Question 5A)

2. All prospective living donors should have serologic screening for HIV, HBV and HCV and NAT screening

for HIV and HCV as close to the time of organ recovery as feasible, but no longer than 7 days pre-recovery. 

Test results should be obtained before organ recovery occurs, if feasible. (Category I) 

3. Deceased potential organ donors also should be screened for HIV using NAT or the most sensitive test 

available regardless of risk of having HIV and regardless of time relative to procurement (i.e., Donor 
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specimens should be obtained before procurement; however, NAT results should be obtained either before, 

if timing allows, or after procurement). (Category IB) (Question 3A)

4. Deceased potential organ donors also should be screened for HCV using NAT or the most sensitive test 

available regardless of risk of having HCV and regardless of time relative to procurement (i.e., Donor 

specimens should be obtained before procurement; however, NAT results should be obtained either before, 

if timing allows, or after procurement). (Category IB) (Question 1B)

5. Deceased potential organ donors reported to have behavioral or nonbehavioral factors during the previous 

12 months identifying them as being at increased risk for having HBV also should be screened with HBV 

NAT or the most sensitive test available, in addition to routine serologic testing and regardless of time 

relative to procurement (i.e., Donor specimens should be obtained before procurement; however, NAT 

results should be obtained either before, if timing allows, or after procurement). (Refer to Table 3 for risk 

factors) (Category IB) (Question 3B)

6. When a deceased potential organ donor‟s behavioral/medical history questionnaire cannot be obtained or 

behavioral and nonbehavioral risk factors cannot be determined, donor NAT screening or the most sensitive 

test available for HBV should be performed. (Category IB) (Questions 3/4D).

Table 3. Factors identified in the literature to be associated with increased likelihood of 

recent HIV, HBV or HCV infection (See Appendix I for more detailed information)

● Sexual Contact

■ Persons who have had sex with ≥2 partners in the preceding 12 months

■ Persons who have had sex with a person known or suspected to have HIV, HBV or 

HCV infection in the preceding 12 months

■ Men who have had sex with another man (MSM) in the preceding 12 months

■ Women who have had sex with a man with a history of MSM behavior in the 

preceding 12 months

■ Persons who have had sex in exchange for money or drugs in the preceding 12 

months

■ Persons who have had sex with a person who had sex in exchange for money or 

drugs in the preceding 12 months

■ Persons who have had sex with a person who injected drugs by intravenous, 

intramuscular, or subcutaneous route for non-medical reasons in the preceding 12 

months

● Birth to a mother infected with HIV, HBV or HCV (for infants ≤2 years of age)

● Persons who have injected drugs by intravenous, intramuscular, or subcutaneous route for 

non-medical reasons in the preceding 12 months

● Intra-nasal use of an illicit drug (e.g., cocaine, heroin) in the preceding 12 months

● Inmate of a correctional facility (e.g., jail, prison, juvenile detention) >3 consecutive days 

in the preceding 12 months

● Persons who have, or have been treated for, syphilis, gonorrhea, or genital ulcers in the 

preceding 12 months

● Persons who have been on hemodialysis in the preceding 12 months (for HCV only)

● Persons who have immigrated to the United States in the preceding 12 months from a 

country of intermediate or high hepatitis B prevalence (for HBV only)
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7. Only FDA licensed-screening tests or approved-diagnostic tests should be used to test blood samples from 

living or deceased organ donors for HIV, HBV or HCV. (Category I) 

8. Since rates of infection transmission and recipient outcomes vary by organ, organ donor screening for 

deceased donors should still be done even if results cannot be obtained before the organ is transplanted, in 

order to guide recipient management post-transplantation. Specifically, screening results for HIV, HBV or 

HCV may be reported following organ transplantation in situations of life-threatening illness where benefits 

of transplantation outweigh potential risks of infection transmission. (Category IB) (Question 7J)

9. All donor (living or deceased) screening tests, including diagnostic and confirmatory (if required), for HIV, 

HBV and HCV should be performed as described in the package insert. Testing by the conventional 

algorithm should be performed as early as possible, even if it follows the procurement of the organs. 

(Category I)

HBV-Infected Donors and Transplantation

For a non-liver allograft, a presumed HBV-infected donor is defined as being positive for HBsAg, IgM antiHBc and/or HBV NAT. For a liver allograft donor, being positive for IgG anti-HBc is also included. 

A presumed HBV-infected transplant candidate is defined as being positive for HBsAg, IgM anti-HBc, and/or 

HBV NAT. A candidate who is IgG anti-HBc-positive only could be a chronic carrier with HBsAg at an 

undetectable level or could have cleared the virus.

1. Transplantation of a liver allograft from an HBV-infected donor into an HBV-infected transplant candidate 

may be considered when risk-benefit is considered favorable by the patient and transplant center. 

(Category IIB) (Question 7A)

2. Transplantation of a liver allograft from an HBV-infected donor into an HBV-uninfected transplant 

candidate should be avoided unless the risk to the recipient of not performing the transplant is elevated and 

deemed to be greater than the risk of disease development. Should liver transplantation occur, strategies to 

further minimize this risk should be considered (e.g., HBV vaccination of the transplant candidate; hepatitis 

B immune globulin, and anti-viral therapy). (Category IB) (Question 7B).

3. Transplantation of a non-hepatic organ from an HBV-infected donor into an HBV-uninfected transplant 

candidate may be considered when risk-benefit is considered favorable by the patient and transplant center. 

(Category IIB) (Question 7C)

4. When allografts from HBV-infected donors are utilized, transplant centers should obtain informed consent 

from the patient regarding the probability of HBV transmission and implement strategies to further 

minimize the consequences of acquiring an HBV infection, as appropriate (e.g., HBV vaccination of the 

transplant candidate if anti-HBs negative; hepatitis B immune globulin, and anti-viral therapy). (Category 

IB) (Question 7D)

5. The use of a non-hepatic organ from an IgG anti-HBc positive only donor may be considered for 

transplantation, as a positive IgG anti-HBc with negative HBsAg and negative anti-HBs is of unclear 

clinical significance; the probability of HBV transmission to the uninfected recipient is likely low; and 

graft/patient survival post-transplantation is unknown. Strategies to further minimize this risk should be 

considered (e.g., HBV vaccination of the transplant candidate if anti-HBs negative; hepatitis B immune 

globulin, and anti-viral therapy). (Category IIB) (Question 7E)
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6. Testing with HBV NAT and ascertainment of IgM and IgG anti-HBc status should be considered for total 

anti-HBc positive only donors to better evaluate the HBV risk in the recipient post-transplantation. 

(Category IIB) (Question 7F)

HCV-Infected Donors and Transplantation

A presumed HCV-infected donor or candidate is defined as being positive for anti-HCV and/or HCV NAT. 

1. Transplantation of an organ from an HCV-infected donor into an HCV-infected transplant candidate may be 

considered given that the risk-benefit appears favorable, as patient and graft survival appear to be similar to 

receiving an organ from an HCV-uninfected donor. (Category IIB) (Question 7G)

2. Transplantation of an organ from an HCV-infected donor into an HCV-uninfected transplant candidate 

should not be performed unless the risk to the recipient of not performing the transplant* is elevated and 

deemed to be greater than the probability of HCV transmission and risk of disease development. (Category 

IB) (Question 7H) *Life-threatening illness requiring transplantation when no other organs are available and no 

other lifesaving therapies exist.

3. When organs from HCV-infected donors are utilized, transplant centers should obtain informed consent 

from the patient regarding the probability of HCV transmission and implement strategies to detect new 

infection quickly by post-transplant recipient testing using HCV NAT at minimum and also evaluating for 

the use of anti-viral therapy. (Category IB) (Question 7I)

Recipient Informed Consent

1. A shared decision-making process between the prospective recipient and the listing clinician should start at 

the time the patient is placed on the transplant waitlist. Patients should be counseled to consider potential 

risks of both accepting and rejecting specific types of organs from donors known to be infected with HBV 

or HCV; or donors at increased risk for HBV, HCV, or HIV infection. (Category IB) (Expert Opinion –

Question 1A)

2. Patients should be allowed opportunities to discuss with clinicians issues related to organ and associated risk 

acceptance at any time while on the waiting list. (Category IB) (Expert Opinion - Question 1C)

3. At the time of the organ offer, the transplant center team primarily responsible for the patient‟s care should 

have a discussion with the prospective recipient that includes more specific information regarding the 

probability that this specific donor may transmit HIV, HBV, or HCV based on the donor history and blood 

test results available at that time to enable the potential recipient to understand the risk. Since vessel 

conduits may be transplanted from a different organ donor than the primary organ transplant, with different 

associated donor risks, an additional informed consent discussion by the transplant center team may need to 

take place separately for the vessel conduit. (Category IB) (Expert Opinion – Question 1D)

4. Transplant candidates should be informed that although all donors are screened for HIV, HBV, and HCV, 

there are limits to screening and no screening question or laboratory screening test can completely eliminate 

the risk for transmitting these infections. (Category IB) (Expert Opinion – Question 1E)
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Recipient Testing

1. Transplant candidates, for whom follow-up testing is planned post-transplant, should have a serologic 

assessment of their HIV, HBV, and HCV status at the time that they are admitted to the hospital to undergo 

the organ transplant but prior to implantation of the organ. (Category IB) (Expert Opinion - Question 2A)

2. Post-transplant testing should be done for HIV, HBV, and HCV, unless infection has been documented pretransplant, for all recipients of organs from living or deceased donors specifically when 1) recognized risk 

factors place them at increased probability of acquiring donor-derived HIV, HBV or HCV; 2) the donor 

screening specimens are hemodiluted; 3) a donor medical or social history is unavailable; or 4) the donor 

screening assay is repeatedly reactive. (Category IB) (Expert Opinion - Question 2B)

3. Where the donor (living or deceased) was infected with HBV or HCV, post-transplant recipient testing

should be done, unless recipient infection has been documented pre-transplant. (Category IB) (Expert 

Opinion - Question 2C)

4. Recipient testing should be conducted for HBV, with respect to Expert Opinion 2B and 2C

recommendations, at a minimum of 3 times at intervals of 1, 3 and 12 months post-transplant and include 

screening for anti-HBs, anti-HBc, and HBsAg (unless known through prior testing to be infected pretransplant). (Category IB) (Expert Opinion - Question 2D)

5. Recipient testing should be conducted for HIV with respect to Expert Opinion 2B and 2C recommendations, 

at a minimum of 2 times at intervals of 1and 3 months post-transplant and include anti-HIV-1 and 2 and 

HIV NAT or testing of equivalent sensitivity (unless known through prior testing to be infected pretransplant). NAT or testing of equivalent sensitivity is important for HIV detection as infected recipients 

may remain seronegative due to immunosuppression. (Category IB) (Expert Opinion - Question 2E)

6. Recipient testing should be conducted for HCV with respect to Expert Opinion 2B and 2C 

recommendations, at a minimum of 2 times at intervals of 1and 3 months post-transplant and include HCV 

antibody and HCV NAT or testing of equivalent sensitivity (unless known through prior testing to be 

infected pre-transplant). NAT or testing of equivalent sensitivity is important for HCV detection as infected 

recipients may remain seronegative due to immunosuppression. (Category IB) (Expert Opinion - Question 

2F)

Donor and Recipient Specimen Collection and Storage 

1. For initial deceased donor screening, consider collecting a separate ethylenediaminetetraacetic acid (EDTA)

plasma specimens for NAT rather than using serum samples for serologic assays. When an alternate 

specimen is not available and a previously assayed serum is used for NAT, documentation should be

provided. (If only one specimen tube is feasible, all FDA licensed-screening tests and/or FDA-approved 

tests are licensed for use with serum or EDTA plasma specimens.) (Category IIB) (Expert Opinion -

Question 3B)

2. For archival blood specimens, consider collecting two separate samples from all donors (living and 

deceased) and those recipients who receive organs from donors at increased risk for HIV, HBV, or HCV to 

reduce the possibility of specimen cross-contamination. Ideally, one sample from each individual of 10 ml 

in a serum separator tube would be collected and processed to create 5 ml aliquots of serum for serologic 

testing. A second plasma sample of 3-5 ml collected in EDTA would be processed to create 1 ml aliquots 

for NAT. Smaller samples would be collected from pediatric donors and from pediatric recipients prior to 
17

implantation of the organ. Samples should be stored for at least 10 years. (If only one specimen tube is 

feasible, all FDA licensed-screening tests and/or FDA-approved tests are labeled for use with serum or 

EDTA plasma specimens.) (Category IIB) (Expert Opinion - Question 3A)

3. When storage capacity exists and specimen volume permits, separating EDTA plasma samples that might be 

used for future NAT into multiple aliquots should be considered prior to long term storage as repeated 

freeze-thaw cycles can cause moderate reduction in viral nucleic acid levels, with plasma samples 

maintained at approximately minus 70oC. (Category IIB) (Expert Opinion - Question 3C)

4. Storage of archival serum or plasma specimens for serology testing should be according to the test 

manufacturer‟s package insert. (Most manufacturers recommend long-term storage at -20°C or colder.) 

(Category I)

5. Archival blood samples from prospective living donors should be drawn no longer than 7 days before organ 

recovery and stored for at least 10 years. (Category I)

6. Infusion of crystalloid and colloid solutions and transfusion of blood products can result in false negative 

results for transmissible infections. Therefore, efforts should be made by the OPO to collect a qualified 

specimen; that is, a specimen that is deemed acceptable for testing according to an accepted plasma dilution 

algorithm and calculation method, such as provided by FDA.

13 (Category I)

7. All stored blood vessels from a donor found to be HIV, HBV, or HCV infected should be retrieved and 

quarantined immediately and either used only for research purposes or destroyed. (Category I) 

Tracking and Reporting of HIV, HBV, and HCV

1. When reviewing medical records, OPO findings consistent with HIV, HBV, or HCV (e.g., mention of a 

positive test and/or risk factors for infection) in the deceased potential donor should be reported to the 

transplant center receiving the organ offer. (Category IB) (Question 4A)

2. Any documentation of new infection in a recipient must be reported to the OPTN as required by policy and 

to appropriate local and state health departments as required by local and state law. (Category IC) (Expert 

Opinion - Question 2H)

3. Data on the results of pre- and post-transplant bloodborne pathogen infection assessments in recipients 

should be collected nationally and analyzed on a regular basis to inform policy decisions and future 

screening recommendations. Nationally aggregated data on donor-derived infections should be disseminated 

to allow the transplant community to have access to the data. (Category IB) (Expert Opinion - Question 

2G)

4. Each institution involved in the procurement or storage of donor organs or blood vessels should have a graft 

identification system that allows for tracking of organs and associated blood vessels from the donor source 

to the recipient institution and vice versa. Furthermore, each OPO should have mechanisms in place to 

facilitate the communication between institutions for the purposes of tracking organs and blood vessels to 

recipients who should be notified if HIV, HBV, or HCV transmission from donor source material is 

suspected or confirmed. OPOs should keep accurate records of the distribution of each organ and associated 

vessels. (Category I)
18

5. The transplantation center should keep accurate records of all organs and blood vessels received and the 

disposition of each. Records of transplanted organs and blood vessels and stored blood vessels should be 

maintained in a place where this information is easily accessible. Recorded information should include the 

organ type and blood vessels; donor identification number; name of OPO supplying the organ and blood 

vessels; recipient-identifying information; and date of transplantation to the recipient or discard date. 

(Category I)

6. If a transplant recipient is found to be newly infected with HIV, HBV, or HCV post-transplant, the 

transplant center should, consistent with state law, immediately notify the state health department and the 

OPO from which the organ recovery originated. (Category IC)

7. Upon being notified that an organ recipient infected with HIV, HBV or HCV is suspected of being donor 

derived, the OPO should notify the OPTN and public health authorities where the affected donor organs 

were recovered; the transplant center should notify the public health authorities that have jurisdiction where 

the affected recipient was transplanted. The procuring OPO, in collaboration with the state or local health 

department and with assistance from CDC, is responsible for determining as soon as possible whether the 

donor was infected. The investigation should include assessment of the HIV, HBV or HCV infection status 

of all recipients of those organs and tissues and performance of laboratory screening of any stored donor 

material. (Category IC)

8. When HIV, HBV, or HCV infection is suspected or confirmed to be donor-derived, the OPO should notify 

all transplant centers caring for recipients of that donor‟s organs and vessels, and institutions that recovered 

tissues from the donor. (Category I) 

9. Results of HIV, HBV and HCV screening tests for organ donors should be handled confidentially, in 

accordance with general medical practices and applicable federal and state statutes, regulations, and 

guidelines. (Category IC)

10. Prospective living donors should be notified if they are found through the screening process to be HIV, 

HBV or HCV infected. (Category I)

11. Confirmed positive HIV, HBV or HCV test results in a prospective organ donor should be reported to state 

health agencies by the OPO in accordance with state and local health department notification policies. 

(Category IC)

12. Because of the possibility of sexual or parenteral transmission of infection, the spouse or known sex 

partners of deceased donors with HIV, HBV or HCV should be notified of their partner‟s infection status in 

accordance with state law. Prior to notification of these persons, transplant and procurement organizations 

should be aware of their state and local health department notification policies. (Category IC) 

III. Recommendations for Further Research

The systematic review uncovered numerous gaps in the literature affecting the ability to adequately address 

many of the ten key questions reviewed for this guideline. Additionally, many of the studies were not of 

sufficient quality to allow firm conclusions regarding certain interventions. In order to address identified gaps, 

future studies should include the following to maximize impact:

1. Primary analytic research methods
19

2. Adjustment for confounders

3. Statistical power to detect significant differences

4. Clinically relevant outcomes

5. Controls in both clinical and laboratory settings

The following are specific areas recommended for further research. Some of the recommendations are also 

listed as “no recommendation/unresolved issue” in the Evidence Review.

1. Estimate the incidence and prevalence of HIV, HBV and HCV among deceased potential organ donors 

in the United States.

2. The risk-benefit of transplanting organs from HIV-infected donors into HIV-infected recipients, given 

the need for transplants in HIV-infected recipients and improved outcomes with the availability of 

highly active anti-retroviral therapy (HAART). However, prior to any research, legal analysis of the 

National Organ Transplant Act of 1984 [42 USC Sec. 273] and the HHS Final Rule [42 CFR Part 121] 

may be required, which obligate the OPTN to adopt standards that prevent recovery of organs from 

HIV-positive donors that result in a potential HIV transmission.

3. Identify behavioral and non-behavioral risk factors associated with increased incidence and prevalence 

of HIV, HBV, and HCV specifically among the potential organ donor population, including pediatric 

donors.

4. Develop and implement a validated uniform donor infection risk assessment questionnaire.

5. Assess the validity of screening test results for HIV, HBV and HCV in relevant populations. This is also 

needed to enable the calculation of useful statistics including predictive values, likelihood ratios, and 

post-test probabilities of these tests among potential organ donors.

6. Evaluate fourth generation HIV and HCV antibody/antigen assays in transplant recipients and deceased 

organ donors for approval as licensed screening tests.

7. Assess interventions (e.g., pathogen reduction methods) to reduce or eliminate the viral burden of HIV, 

HBV, and HCV in donors or donor organs before or after recovery, but prior to transplantation.

8. Evaluate outcomes of patients receiving HBV- or HCV-positive organs versus remaining on the 

transplant list, with statistical adjustment for relevant baseline characteristics and consideration of 

prophylaxis post-transplant and patient race and ethnicity. More comprehensive analyses of competing 

risks would help inform critical decision making.

9. Evaluate transplant candidate and recipient outcomes if organ donors with behavioral or nonbehavioral 

risk factors were excluded from donating. This process may also require comparing incidence of 

infection among population subsets within risk factors.

10. To better quantify risk based on behavior in a given donor, transplant centers may consider using a 

relative or comparative risk-based quantitative process, such as a donor risk index, to allow the 

transplant center and patient to assess a donor based on level of risk for transmitting HIV, HBV, or 

HCV. However, since data may be lacking for calculation of precise quantitative values, risk 

assessments in this guideline are qualitative, i.e., a donor is categorized at increased risk or not at 

increased risk

11. Evaluate the rate of false positive immunoassay and NAT results for HIV, HBV and HCV among 

potential organ donors and the percentage of cases where donors are declined due to such results 

stratified by organ type.

12. Develop standardized algorithms for real-time discrimination of initially reactive organ donor NAT 

results to separate true versus false positive results.

13. Identify the limits of acceptable plasma dilution. Plasma dilution algorithms and calculation methods are 

not standardized for organ donors and the limits of acceptable plasma dilution have not been validated 

across HIV, HBV and HCV serological assays used for organ donors. In addition, evaluate the effect of
20

analyte movement from the vascular compartment during and immediately following introduction of 

crystalloids or colloids to the vascular system. 

14. For transplant candidates who are HBV-uninfected and receive a non-hepatic organ from an HBV 

infected donor who is anti-HBc positive only, evaluate transmission rates where IgM and IgG testing is 

performed and various prophylaxis measures, including vaccination, are used in order to improve 

knowledge on best practices to minimize transmission risk.

IV. Scope and Purpose

This guideline supplants the 1994 PHS Guidelines for Preventing Transmission of HIV through Transplantation 

of Human Tissue and Organs.

1

The revised guideline includes specific recommendations for implementation. 

Recommendations for further research are also included to address the knowledge gaps in HIV, HBV and HCV 

transmission prevention, detection, and management identified during the literature review and through expert 

opinion.

The major changes to the guideline are:

● Addition of HBV and HCV, in addition to HIV.

● Utilizing the factors known to be associated with increased likelihood of recent HIV, HBV or HCV to 

identify potential donors at increased risk for transmitting infection versus exclusionary criteria for 

donation.

● Focusing on solid organs from deceased and living donors since the Food and Drug Administration 13 has 

since implemented more comprehensive regulations of tissues and semen donors.

● Distinguishing between expected and unexpected transmission of HBV and HCV.

In the future this guideline may apply to vascularized composite allotransplantation (the transplantation of 

multiple tissues as one unit, such as a limb or face) depending on regulatory decision making concerning the 

definition of an organ.

This document is intended for use by OPO staff; transplant staff including physicians, nurses, administrators, 

and clinical coordinators; and laboratory staff responsible for testing and storing donor and recipient specimens; 

and persons responsible for developing, implementing, and evaluating infection prevention and control 

programs for organ procurement organizations and transplant centers.

To evaluate the evidence on reducing transmission of HIV, HBV and HCV, we examined data addressing ten 

key questions within five major topic areas. A sixth topic area includes questions addressed by Expert Opinion 

(EO). We drew upon experts to draft summaries related to these questions anticipating that a systematic review 

of the literature would produce insufficient evidence-based data. The summaries were written and edited by the 

guideline authors.

Table 1. Questions for Systematic Review

Major topic area of the guideline Question for Systematic Review

I. Probability of transmission of HIV, 

HBV, or HCV through solid organ 

transplantation (SOT)

1. What are the prevalence and incidence rates of HIV, HBV, 

and HCV among potential solid organ donors?

2. What are the rates of transmission to recipients from donors 

infected with HIV, HBV, or HCV? Do the rates vary by the 

organ transplanted or when the donor was infected?
21

Major topic area of the guideline Question for Systematic Review

II. Methodology to better estimate 

donor infection with HIV, HBV, or 

HCV

3. What behavioral risk factors are associated with an 

increased probability of infection with HIV, HBV, or HCV? 

What is the prevalence of these characteristics among 

potential solid organ donors? 

4. What nonbehavioral factors are associated with an increased 

probability of infection with HIV, HBV, or HCV? What is 

the prevalence of these factors among potential solid organ 

donors? 

5. What are the test characteristics of the screening methods 

available to detect HIV, HBV, and HCV in potential solid 

organ donors? Do test characteristics differ in particular 

populations and with donor clinical status (i.e., donation 

after brain death versus donation after cardiac death OR 

adult vs. pediatric donors)?

III. Donor interventions to decrease 

transmission of HIV, HBV, or HCV 

from infected donors

6. Which donor interventions reduce the probability of 

pathogen transmission from an organ donor infected with 

HIV, HBV, or HCV to a previously uninfected recipient?

IV. Potential risks and benefits of 

transplanting, or not transplanting, 

solid organs from donors positive 

for HIV, HBV, or HCV

7. How do the clinical outcomes of recipients of organs from 

donors infected with HIV, HBV, or HCV compare to those 

who remain on the transplant list?

V. Potential risks and benefits of 

transplanting, or not transplanting, 

organs from donors with risk 

factors for HIV, HBV, or HCV

8. How do the clinical outcomes of transplant recipients who 

receive organs from donors with behavioral or 

nonbehavioral risk factors compare to those who remain on 

the transplant list?

9. What is the impact of excluding potential solid organ donors 

with behavioral or nonbehavioral risk factors on the organ 

donor pool?

10. What is the impact of false positive tests on the organ donor 

pool?

VI. Approaches to informing recipients 

about the risks of HIV, HBV, and 

HCV transmission and evaluation

for possible exposure posttransplantation

Note: The related three questions were 

not part of the systematic literature 

review.

EO1. How and when should informed consent be obtained from 

potential recipients to help them consider the risks (i.e., 

probability of acquiring the disease and consequences of 

disease acquisition) of donor-derived HIV, HBV, and HCV?

EO2. When should testing of a transplant recipient be done to 

detect HIV, HBV, and HCV transmission from the donor?

EO3. How should donor and recipient specimens be collected 

and stored for potential investigation of donor-derived HIV, 

HBV, and HCV infection?
22

V. Background

Federal Oversight of Organ Recovery and Transplantation

Several federal agencies either regulate or oversee procurement and transplantation of organs. These activities 

range from the publication of PHS guidelines that address the transmission of communicable diseases through 

transplantation to regulatory requirements. The Health Resources and Services Administration (HRSA)

provides oversight of solid organ transplantation through the OPTN, established by Congress under the National 

Organ Transplant Act of 1984. Public Health Service Act 42 CFR. Part 121, requires the OPTN be

administrated by a private, non-profit entity; through a contract overseen by HRSA, the United Network for 

Organ Sharing is the entity that operates the OPTN. The Centers for Medicare and Medicaid Services

establishes performance standards and conducts surveys of transplant centers [42 CFR Parts 405, 482, 488, and 

498] and OPOs [42 CFR Parts 413, 441, 486 and 498] to determine certification or recertification. Currently, 

there are 58 OPOs and 253 organ transplant centers in the United States.

HIV, HBV, HCV and Organ Transplantation

Transplantation of solid organs, including kidney, heart, liver, lung, pancreas, and intestine, to patients with end 

stage organ disease is performed to improve their survival and functional capacity. Organs can be donated by 

living or deceased donors with a majority of organs recovered from heart beating, deceased donors. 

Transplantation rates differ by organ. Kidney transplantation occurs most often followed by liver, heart, lung, 

kidney-pancreas, intestine, and heart-lung. On average, three organs are recovered from each deceased donor. In 

2010, 28,662 patients on the United Network for Organ Sharing (UNOS) transplant waitlist received organ 

transplants from 7,943 deceased donors and 6,564 living donors in the United States.

14

There is currently a significant discrepancy between the number of candidates on the transplant list and the 

limited number of organs available with thousands of patients on the waitlist dying annually. To narrow this gap 

and given the urgency of organ transplantation, attempts have been made to increase the organ donor pool by 

including expanded criteria donors; and donors who may either be at increased probability of harboring 

transmissible infections including HIV, HBV, or HCV.

Donor-Derived Infections

In a study of 13,667 potential organ donors evaluated January 2004 to mid-2008 by 17 OPOs, the prevalence of 

HIV and HCV in normal-risk donors was 0.10% and 3.45%, respectively; the prevalence of HIV and HCV 

among potential donors identified by OPOs as “high risk” was 0.50% and 18.20%, respectively. The 17 OPOs 

recover more than half of the organ donors in the United States. Blood screening tests that produce nucleic acid 

test (NAT)-positive, antibody-negative serologic results are indicative of recent, or incident, infections. 

Applying a model based on known prevalence, the estimated incidence of undetected viremia for normal-risk 

potential donors was 1 in 50,000 for HIV and 1 in 5,000 for HCV. For high-risk potential donors, the incidence 

of undetected viremia was 1 in 11,000 for HIV and 1 in 1,000 for HCV.

15 In a 2008 survey of the 58 OPOs, 

approximately one-half performed HIV and HCV NAT for all donors and one-fourth performed HBV NAT.

16

In 2005, the Organ Procurement and Transplantation Network (OPTN) policy required OPOs and transplant 

centers to report suspected, unexpected donor-derived infections to UNOS. The results from 2005-2007 are 

available, although underreporting may have resulted in an underestimation of the true incidence. Of 80 

potential donor-derived disease transmissions reported to UNOS, 30 cases were confirmed. HIV, HBV and 

HCV were among the top five most reported suspected donor-derived transmissions, although further testing of 

stored donor specimens were negative using NAT in most cases.17
23

Expected versus Unexpected Donor-Derived Infection

Donor-derived infections are differentiated into expected vs. unexpected transmission. Expected transmission is 

a common occurrence in organ transplantation. Given the large disparity between the need and availability of 

solid organs and that certain organ transplants are life saving, it has become acceptable medical practice that 

certain infections may be transmitted in organ transplantation. When routine screening tests detect the infection 

in the donor, OPTN policy requires potential recipients to be informed of the risk prior to transplantation.

18

Preventive strategies are offered, if available, to the recipient post-transplantation. In contrast, unexpected 

transmission occurs when the pathogen was not detected prior to transplantation, with or without screening for 

the infectious disease.

Expected HBV and HCV Donor-Derived Infection

Transplantation of organs from HBV- and HCV-infected donors is accepted medical practice. These organs are 

typically offered to recipients known also to be infected with the same pathogen, or in rare circumstances, to 

uninfected recipients in cases of urgent medical need where benefit is deemed to outweigh risks. In these 

situations, prophylaxis or treatment with immunizations, anti-virals and/or immunoglobulin is offered if 

appropriate to prevent transmission or reduce the disease severity. Post-transplant recipient testing is also 

critical. 

Unexpected HIV, HBV and HCV Donor-Derived Infection

Reports of unexpected HIV, HBV and HCV transmission have occurred when screening could not identify 

donor infection. Most commonly, this happens when a donor becomes infected with the virus close to the time 

of organ donation. There is an initial period of time after exposure, called the eclipse phase, during which viral 

replication occurs in target cells.

19,20 The primary site for HIV is the CD4+ lymphocytes located in gutassociated lymph nodes.

21 Hepatitis virus replication is mainly confined to hepatocytes in the liver. During this

eclipse phase, plasma viremia is not detectable nor thought to be transmitted through blood transfusion; 

however, the virus can be transmitted through infected organs. At the end of the eclipse phase, low 

concentrations of virus begin to circulate in the blood, but are not detectable by NAT until the ramp-up phase, 

identified as an exponential increase in virus.20 Viral production eventually plateaus and is followed by a 

decline due to the formation of antibodies, which may be days or weeks after commencement of the ramp-up 

phase.

22 In addition to the window period between exposure and the ability of certain assays to detect infection, 

false-negative test results can occur for other reasons (e.g., hemodilution of the donor sample from blood 

transfusions). 

The window period between viremia and detection of viral material or antibodies can vary depending on the 

particular virus, the sensitivity of the test used, and possibly the initial viral load at the time of inoculation. For 

individual donor NAT screening, HIV detection is estimated to be 5-6 days after the onset of viremia with a 

smaller window period of 3-5 days for HCV. Antibody detection of HIV is estimated to be 19-20 days after the 

onset of viremia for HIV and ranging from 58-65 days for HCV.19,22,23 For HBV, the window period for viral 

detection is much longer compared to HIV and HCV with estimates ranging from 20-25 days with individual 

donor NAT screening and 36-44 days to detection of HBsAg.22,24

In 1986, two transplant recipients acquired HIV from the same donor. The organ donor initially tested HIV 

antibody negative after receiving a large number of transfusions. However, a blood specimen collected two days 

later at the time of organ recovery tested HIV antibody positive.3In 2007, simultaneous transmission of HIV 

and HCV occurred in four organ recipients from the same donor who was identified as high risk due to a 

reported history of engaging in MSM behavior. Routine donor screening results were negative for HIV and 

HCV antibodies. Ten months after transplantation, a kidney recipient tested positive for HIV and HCV. 

Subsequently, the heart, liver and other kidney recipient tested positive for HIV and HCV, and an archived

donor specimen tested positive for HIV and HCV by NAT.11 In 2009, a liver transplant recipient who was
24

HCV-seronegative prior to surgery inadvertently received a stored vessel conduit from an HCV-seropositive

donor and tested HCV- positive post-transplant. The transplanted liver and vessel conduit were from two 

different donors. Transplant centers are allowed to store donor vessel conduits up 14 days after recovery for use 

in transplant patients experiencing surgical complications.

9

In 2009, a kidney recipient acquired HIV from a 

living donor transplant. The donor had a history of engaging in MSM behavior, but tested HIV-negative by EIA 

approximately 2 months before organ recovery. One year post-recovery, the donor tested HIV-positive. Stored

recipient specimens collected 11 days pre-transplant and 12 days post-transplant were tested by HIV NAT with 

the post-transplant specimen confirmed positive. A stored donor specimen collected 11 days pre-transplant was 

HIV NAT-positive.

10

Current Guidelines and Regulations

Several guidelines and regulations have been implemented to decrease the risk of unexpected donor-derived 

HIV, HBV, and HCV. The National Organ Transplant Act, passed by the US Congress in 1984, established the 

OPTN. The Health Resources and Services Administration (HRSA) of the U.S. Department of Health and 

Human Services (HHS) administers the OPTN contract to oversee solid organ transplantation in the United 

States, through a contract with UNOS. A total of 58 OPOs and approximately 252 transplant centers are 

members of the OPTN. As members of the OPTN, transplant centers and OPOs agree to comply with the HHS 

Final Rule and policies. 

Transplantation of Organs from HIV-, HBV-, HCV-Infected Donors

OPTN policy recommends that “organs from donors with a positive screening test or confirmed medical 

condition that may be transmittable, with the exception of HIV, may be transplanted at the discretion of the 

transplanting program with the informed consent of the recipient.”

18

Screening of Donors

OPTN policy lists the minimum procurements standards for an OPO in evaluating deceased donors, which 

includes obtaining a donor history, reviewing the medical chart, obtaining vital signs, performing a physical 

examination, and performing pertinent laboratory tests including FDA-licensed anti-HIV I/II and hepatitis 

serologic testing.

25 Currently, there are no OPTN policies that address screening of living donors. Instead, 

transplant programs that perform living donor transplants are required to develop protocols for medical 

evaluation of potential living donors to include screening for evidence of transmissible diseases. Approved 

guidance documents have been developed to aid this process.26 OPTN policy defines a potential donor as 

“increased risk”25 if he/she meets any of the exclusionary criteria in the 1994 PHS Guidelines for Preventing 

Transmission of HIV through Transplantation of Human Tissue and Organs.

In 1994, the PHS released Guidelines for Preventing Transmission of HIV through Transplantation of Human 

Tissue and Organs,

1 which included donor exclusionary criteria. Currently, potential blood and tissue donors 

who have risk factors for bloodborne pathogen infection, such as HIV, are excluded from donating, since the 

availability of blood and tissue exceeds supply. In contrast, organs may be considered life-saving and since 

demand far exceeds demand, “increased risk” donors are not excluded but can be accepted by transplant centers 

if patients are informed of the risks involved and consent.

18 Currently, OPTN-defined “increased risk” criteria, 

originally developed only for HIV, have been expanded by many OPOs to assess risk for other infections, 

including HBV and HCV. A recent OPO survey found that the percentage of recovered organ donors who were 

reported as having “increased risk” behaviors varied among these organizations from a range of 2.3% to 26.1% 

of annual donor volume.16

Screening of Recipients

Prior to transplantation, HIV, HBV and HCV screening is required by OPTN policy unless this practice violates 

specific laws or regulations.

18 Transplant centers may choose to evaluate candidates for additional infections to 
25

determine suitability for placement on the transplant waitlist. Candidates who test positive for HIV may be 

placed on the waitlist if judged to be medically appropriate by the transplant center.

Since donor-derived infections can result in substantial morbidity and mortality, particularly when there is a 

delay in diagnosis, the 1994 PHS Guidelines recommended recipients be tested for HIV immediately prior to 

transplantation and at 3 months post-transplant until the risk of HIV transmission from organ donors was 

clarified by future studies. However, testing recipients who receive organs from “increased risk” donors is not 

required by OPTN policy, and data have shown it is not standard practice.27 Benefits of routine testing in these 

situations include early identification of infection and treatment before signs and symptoms develop, as well as 

early notification of organ recipients from the same donor should the donor be a suspected source.

Reporting

In 2005, OPTN policy was revised to require OPOs and transplant centers to report potential donor-derived 

infections to the OPTN.18 When an organ recipient is suspected of having a donor-derived infection, UNOS and 

all institutions that recovered or transplanted organs from the donor are notified. In most instances an 

investigation ensues with testing of stored donor serum and recipient specimens in order to determine the 

infection source and provide information to facilitate medical treatment decisions. Current standards by the 

Association of Organ Procurement Organization (AOPO) require donor serum be maintained for 10 years 

following procurement of organs. HIV, HBV or HCV are nationally notifiable diseases and confirmed 

infections require notification to local or state health agencies, as stipulated. All cases are reviewed by the 

OPTN Ad Hoc Disease Transmission Advisory Committee (DTAC) to determine the likelihood of the donor 

being the source of infection.17

Available Screening Tests

OPTN policy requires deceased donor screening for anti-HIV, HBsAg, anti-HBc, and anti-HCV. An FDAlicensed screening test is required for anti-HIV. FDA-licensed, approved or cleared serological screening tests 

are required for HBV and HCV; however, an FDA-licensed, approved or cleared diagnostic test is permitted 

when an FDA screening test is unavailable.

25

The FDA has licensed several HIV, HBV, and HCV screening tests, including enzyme immunoassays (EIAs) 

that detect antibodies to the virus, antigen assays, and NAT. Each generation of serologic test has decreased the 

window period for detection of infection. The FDA determines if these assays can be used on either fresh or 

frozen samples of serum or plasma and if approved for use in living or cadaveric (post-asystole) donors. Blood 

samples are recovered pre-asystole from potential donors after they are pronounced dead by neurological 

criteria and also from donation after circulatory death donors pre-asystole. Fourth generation tests, which are

combined antibody-antigen tests, have recently been developed for HIV and HCV. The FDA-approved HIV 

antigen-antibody test can be used in blood donor screening under urgent circumstances when licensed tests are 

unavailable or impractical for the circumstances. The HCV fourth generation assay application for FDA 

licensure or approval for use in the United States has not occurred.

Although there are minimum standards on organ donor screening, actual screening protocols vary. The 

serologic tests used differ based on the OPO. In addition, the use of NAT for HIV, HBV and HCV screening 

varies significantly. NAT has received increased attention given the potential for false negative results during 

the window period before antibodies develop. However, there are also concerns with NAT including the lack of 

standardization in algorithms on an initial positive result; potential for false positive results if testing is not 

performed in a well-controlled lab or testing volume is low28; and feasibility/turn-around time. Approximately

50% of OPOs perform HIV and HCV NAT on all potential donors compared to 25% for HBV NAT. Of the 

OPOs that use NAT, 45% send the specimens to a different state where 24/7 NAT screening is available. Other 

OPOs reported using on-site locations, transplant center laboratories, and outside labs within the same state.16
26

VI. Methods

This guideline was based on a targeted systematic review of the best available evidence on preventing 

transmission of HIV, HBV, and HCV through solid organ transplantation. We used an adapted Grading of 

Recommendations Assessment, Development and Evaluation (GRADE) approach12,29-32 to provide explicit 

links between the available evidence and the resulting recommendations. Our guideline development process is 

outlined in Figure 1.

Figure 1. The Guideline Development Process

 

GUIDELINE SEARCH

DEVELOPMENT OF KEY QUESTIONS Review of relevant guidelines to inform key questions

LITERATURE SEARCH Databases identified; search strategy developed; references stored; duplicates resolved

ABSTRACT AND FULL-TEXT SCREENING To identify studies which were a) relevant to one or more key questions b) primary research, systematic review or meta-analysis and c) written in English

DATA EXTRACTION AND SYNTHESIS Data abstracted into evidence tables; individual study quality assessed

DRAFT RECOMMENDATIONS Grade of evidence base evaluated; narrative summaries drafted; recommendations drafted from summaries, and recommendation strength assigned FINALIZE RECOMMENDATIONS Recommendations finalized; guideline published
27

Development of the guideline involved participations of three groups. The Working Group included members 

of the CDC Office of Blood Organ and Other Tissue Safety in the Division of Healthcare Quality Promotion; 

Center for Evidence-based Practice at the University of Pennsylvania Health System; and the ECRI Institute 

Evidence-based Practice Center. The Working Group was accountable for all phases of guideline methodology, 

including development of key questions, the evidence report, and the guideline itself, as well as providing the 

Expert Panel and Review Committee with progress updates. The Expert Panel comprised individuals with 

subject matter expertise in HIV and hepatitis; assistance was sought from various members of the Expert Panel 

to address specific issues throughout development of the guideline. The Review Committee was formed to 

provide stakeholder input from a public health, regulatory, and transplantation infectious disease perspective for 

the topics addressed in the guideline, as well as contribution from manufacturers of infectious disease tests. 

Both the Expert Panel and Review Committee participated in regular progress updates via conference calls at 

key steps and provided review and feedback on the key questions, bibliography resulting from the literature 

review, evidence report and guideline.

Development of Key Questions

We first conducted an electronic search of the National Guideline Clearinghouse, MEDLINE, EMBASE, and 

the Cochrane Health Technology Assessment Database, and contacted experts to identify existing national and 

international guidelines and reviews relevant to HIV, HBV, and HCV transmission in solid organ 

transplantation. A preliminary list of key questions was developed from a review of the relevant guidelines and 

reviews identified in the search. Key questions were put in final form after vetting them with the Expert Panel 

and Review Committee. An analytic framework depicting the relationship among the key questions is included 

in Figure 2.
28

Figure 2.Analytic Framework

Literature Search

Following the development of the key questions, search terms were developed for identifying literature most 

relevant to those questions. For the purposes of quality assurance, we compared these terms to those used in 

relevant seminal studies and reviews. These search terms were then incorporated into search strategies for the 

relevant electronic databases. Searches were performed in MEDLINE, EMBASE, the Cochrane Library, 

DARE, HTA, NHS EED, and Healthcare Standards and last updated June 30, 2009. Resulting references were 

imported into a citation management database where duplicates were resolved. Mechanisms used to retrieve 

additional relevant information included review of bibliographies/reference lists from peer reviewed and gray 

literature (gray literature consists of reports, studies, articles, and monographs produced by federal and local 

government agencies, private organizations, educational facilities, consulting firms, and corporations; these 

documents do not appear in the peer-reviewed journal literature). The detailed search strategy used for 

identifying primary literature can be found in the evidence report Solid Organ Transplantation and the 

Probability of Transmitting HIV, HBV, or HCV: A Systematic Review to Support an Evidence-based Guideline.
29

Study Selection

Titles and abstracts from references were screened by a single reviewer (JT or MN from ECRI). Full text 

articles were retrieved if they were relevant to one or more key questions, and met inclusion criteria. These 

criteria included universal as well as question specific criteria. Universal criteria included studies that were 1) 

written in the English language, 2) peer-reviewed, full length publications with original data, and 3) included 

HIV, HBV, or HCV with determination of the infection based on laboratory test(s) rather than subjective 

estimates, physician interviews, or patient interviews. Additional criteria applied on a per-question basis are 

depicted in Table 4.

Multiple publications of the same study were treated as a single study rather than as multiple studies to avoid 

double-counting patients. Full-text articles were screened by two independent reviewers (JT and MN) and 

disagreements were resolved by discussion. The results of this process are depicted in Figure 3. To ensure that 

all relevant studies were captured in the search, the bibliography was vetted by the Expert Panel and Review 

Committee.

Table 4. Question-Specific Inclusion Criteria

Inclusion Criteria*

Questions for Systematic Review

1 2 3 4 5 6 7 8 9 10

Pertinent data on at least five people         

Data collected in U.S.A.    

Rates not restricted to actual donors 

At least one of four populations: 1) Potential organ donors; 2) organ donors 

with samples taken prior to 1992 that were retrospectively tested for HCV; 

3) potential tissue donors; or 4) the general population (for this last 

population, we included only the most up-to-date epidemiological 

estimates)



Regardless of exhibiting symptoms for HIV, HBV or HCV  

Donor seropositive pre-transplant   

Recipient seronegative pre-transplant 

Single type of organ, or separated data on different types of organs   

Waitlist control OR Control is recipients of organs from uninfected donors 

If pre-transplant infected recipients and pre-transplant uninfected recipients 

were included, the study must have reported separate outcome data on 

these two types of recipients.



Reported patient survival, graft survival, or quality of life.  

At least one of four populations, enrolling individuals of any age: 1) 

Potential organ donors; 2) potential tissue donors; 3) potential blood 

donors; or 4) a sample representative of the general population (i.e., 

population unselected for any particular demographic, occupational, or 

behavioral characteristics, or health status other than HCV, HBV, or HIV 

infection status)

 
30

Inclusion Criteria*

Questions for Systematic Review

1 2 3 4 5 6 7 8 9 10

A study of a specific demographic or socioeconomic subpopulation was 

included for HBV, but excluded for HIV and HCV.

 

A study of a specific subpopulation of patients who were all selected for 

having the same behavioral risk factor was excluded for all three 

pathogens.

 

Article must have been published in 1990 or later if pertinent to HIV or 

HCV, or 1966 or later if pertinent to HBV.

 

In order to identify risk factors for the pathogen, study must have enrolled 

people with the risk factor as well as people without the risk factor; 

similarly, the study must have enrolled people positive for the pathogen as 

well as people negative for the pathogen.

 

For identification of clinical signs and symptoms that may indicate infection, 

data may be from any country. For identification of co-morbidities or 

demographic factors that may be associated with infection, data must be 

from U.S only.



Reported at least one of the tests listed in Table 5. 

Reported at least one of the following:

● Sensitivity and specificity 

● Positive and negative predictive values (clinical populations only)

● Positive and negative likelihood ratios (clinical populations only)

● Sufficient data to calculate the above 

● Window period

● Turnaround time



Reported data on an individual test basis rather than multiple tests or 

algorithms.



Inactivation procedure performed before transplant on organs obtained 

from infected individuals.



Donor positive pre-transplant for behavioral risk factor or signs/symptoms 

risk factor or comorbidity risk factor.



Waitlist control OR Control is recipients of organs from donors without that 

risk factor.



Reported the number of organs that would not be included in the organ 

pool if donors with behavioral or nonbehavioral risk factors identified in 

questions 3 and 4 were excluded.



Reported the number of organs that would not be included in the organ 

pool if false positives were excluded.



*For each Question for Systematic Review, five universal criteria were also applied (see text above). A checkmark in a given column means that a 

study must have met that criterion in order to be included for the numbered Question for Systematic Review.

The specific tests of interest for Question 5 are listed in Table 5. For the systematic review of the literature, tests 

of interest included immunoassays and NAT currently used in the United States by OPOs; fourth-generation 

HIV and HCV antibody/antigen tests currently in use outside of the United States also were included. Other 

FDA- licensed assays not included in the literature review and identified as not routinely used by U.S. OPOs are 

indicated with an asterisk.
31

Table 5. Tests of Interest for Question 5

Virus Test Name Manufacturer Use

Tests Currently Available for Use by U.S. Organ Procurement Organizations

HIV

anti-HIV-1/2 (detects 

antibodies to HIV-1, HIV-2 

and if applicable HIV-1 

group 0)

Genetics System (GS) HIV-1/HIV-2 

Plus 0 EIA

Bio-Rad Laboratories FDA licensed for 

donor screening

HIVAB HIV-1/HIV-2 (rDNA) EIA Abbott Laboratories FDA licensed for 

donor screening

Abbott PRISM HIV 0 Plus* Abbott Laboratories FDA licensed for 

donor screening

HBV

HBsAg (detects Hepatitis B

surface antigen)

Abbott PRISM HBsAg Assay Abbott Laboratories FDA licensed for 

donor screening

Genetic Systems (GS) HBsAg EIA 3.0 Bio-Rad Laboratories FDA licensed for 

donor screening

Auszyme Monoclonal* Abbott Laboratories FDA licensed for 

donor screening

ADVIA Centaur HBsAg Assay Siemens Healthcare 

Diagnostics

FDA approved for 

diagnosis

AxSYM HBsAg Abbott Laboratories FDA approved for 

diagnosis

HBV

anti-HBs (detects 

antibodies to the surface 

antigen)

Ausab EIA Abbott Laboratories FDA licensed for 

donor screening

HBV

anti-HBc (detects 

antibodies to the core 

antigen)

Abbott PRISM HBcore Abbott Laboratories FDA licensed for 

donor screening

CORZYME Abbott Laboratories FDA licensed for 

donor screening

Ortho HBc ELISA Test System Ortho Clinical 

Diagnostics

FDA licensed for 

donor screening

ADVIA Centaur HBc Total Assay Siemens Healthcare 

Diagnostics

FDA approved for 

diagnosis

AxSYM Core 2.0 Abbott Laboratories FDA approved for 

diagnosis

HCV

anti-HCV (detects 

antibodies to HCV) 

Abbott HCV EIA 2.0 Abbott Laboratories FDA licensed for 

donor screening

ADVIA Centaur Anti-HCV Siemens Healthcare 

Diagnostics

FDA approved for 

diagnosis

AxSYM Anti-HCV Abbott Laboratories FDA approved for 

diagnosis

Ortho HCV Version 3.0 ELISA Test 

System

Ortho Clinical 

Diagnostics

FDA licensed for 

donor screening

Abbott PRISM HCV* Abbott Laboratories FDA licensed for 

donor screening

HIV-1, HCV and HBV NAT

(detects HIV-1 and HCV 

RNA and HBV DNA)

Procelix Ultrio* Gen-Probe, Inc. FDA licensed for 

donor screening

COBAS TaqScreen MPX Test* Roche Molecular 

Systems, Inc

FDA licensed for 

donor screening
32

Virus Test Name Manufacturer Use

HIV-1 and HCV NAT

(detects HIV-1 and HCV 

RNA)

ProCleix HIV-1/HCV Gen-Probe, Inc. FDA licensed for 

donor screening

HIV-1 NAT

(detects HIV-1 RNA)

COBAS AmpliScreen HIV-1 Test v. 1.5 Roche Molecular 

Systems, Inc

FDA licensed for 

donor screening

HCV NAT

(detects HCV RNA)

COBAS AmpliScreen HCV Test v. 2.0 Roche Molecular 

Systems, Inc

FDA licensed for 

donor screening

HBV NAT

(detects HBV DNA)

COBAS AmpliScreen HBV Test Roche Molecular 

Systems, Inc.

FDA licensed for 

donor screening

Fourth Generation Tests (currently not in use in U.S. Organ Procurement Organizations)

HIV

(detects HIV-1 p24 antigen 

and antibodies to HIV-1, 

groups M and O, and/or 

HIV-2)

ARCHITECT HIV Ag/Ab Combo Abbott Laboratories FDA licensed for 

diagnosis

AxSYM HIV Ag/Ab Combo Abbott Laboratories Not FDA licensed, 

approved or cleared

COBAS Core HIV Combi Roche Diagnostics Not FDA licensed, 

approved or cleared

Enzygnost HIV Integral II Siemens Healthcare 

Diagnostics

Not FDA licensed, 

approved or cleared

Genscreen Plus HIV Ag/Ab Combo Bio-Rad Laboratories Not FDA licensed, 

approved or cleared

Genscreen HIV Ultra Ag/Ab Assay Bio-Rad Laboratories Not FDA licensed, 

approved or cleared

Murex HIV Ag/Ab Combo Abbott Laboratories Not FDA licensed, 

approved or cleared

Modular E170 HIV Combi Roche Diagnostics Not FDA licensed, 

approved or cleared

VIDAS DUO ULTRA bioMerieux Clinical 

Diagnostics

Not FDA licensed, 

approved or cleared

VIDAS DUO QUICK bioMerieux Clinical 

Diagnostics

Not FDA licensed, 

approved or cleared

Vironostika HIV Uni-Form II Ag/Ab bioMerieux Clinical 

Diagnostics

Not FDA licensed, 

approved or cleared

HCV

anti-HCV (detects 

antibodies to HCV)

INNOTEST HCV Ab IV Innogenetics NV Not FDA licensed, 

approved or cleared

Murex 4.0 Abbott Laboratories Not FDA licensed, 

approved or cleared

HCV

(detects HCV antigen and 

antibodies to HCV

Monolisa HCV Ag/Ab Ultra Bio-Rad Laboratories Not FDA licensed, 

approved or cleared

EIA or ELISA– Enzyme-linked immunosorbent assay

NAT – Nucleic acid test

*FDA- licensed assays identified as not routinely used by U.S. OPOs and not included in the literature review
33

Figure 3. Study Flow Diagram

Data Extraction and Synthesis

For those studies meeting inclusion criteria, data were extracted by a single author (JT or MN from ECRI). 

Disagreements were resolved by the remaining authors. Data and analyses were extracted as originally 

presented in the included studies. For the purposes of our review, statistical significance was defined as p ≤ 

0.05.
34

Grading of Evidence

First, the quality of each study was assessed using the quality assessment criteria (adapted from existing 

methodology checklists) listed in Table 5 of the Evidence Report. Next, the quality of the evidence base was 

assessed using methods adapted from the GRADE Working Group. In summary, GRADE tables were 

developed for each of the interventions or questions addressed within the evidence tables. Included in the 

GRADE tables were the intervention of interest, any outcomes listed in the evidence tables that were judged to 

be clinically important, the quantity and type of evidence for each outcome, the relevant findings, and the 

GRADE of evidence for each outcome, as well as an overall GRADE of the evidence base for the given 

intervention or question. 

The initial GRADE of evidence for each outcome was deemed high if the evidence base included a randomized 

controlled trial (RCT) or a systematic review of RCTs, low if the evidence base included only observational 

studies, or very low if the evidence base consisted only of expert opinion or uncontrolled studies. The initial 

GRADE could then be modified by eight criteria. Criteria that can decrease the GRADE of an evidence base 

include shortcomings in quality, consistency, directness, or precision and publication bias (e.g., Was the funding 

for this study derived from a source that would not benefit financially from either data favorable to the test or 

data unfavorable to the test?). Criteria that can increase the GRADE include a large magnitude of effect, a doseresponse gradient, or inclusion of unmeasured confounders that would increase the magnitude of effect and are 

listed in Table 6. Studies equivalent to RCTs (e.g., a controlled study not requiring randomization, like a study 

in genetically identical mice) would also start out as high level evidence, but would often lose points for 

indirectness. For questions regarding prevalence, incidence or rates of transmission from donors to recipients, 

no randomized trials were necessary to address the questions. Therefore the starting evidence grade was High, 

and we applied the other components of the GRADE system as appropriate. 

Table 6: Rating the Quality of Evidence Using the GRADE Approach

Type of Initial Criteria to Decrease Criteria to Increase Overall Quality

Evidence Grade Grade Grade Grade

 

RCT → High

Observational → Low

study

Any other 

evidence → Very

(e.g., expert low

opinion)

Quality

Serious (-1 grade) or very 

serious (-2 grades) 

limitation to study quality

Inconsistency

Important inconsistency

(-1 grade)

Indirectness

Some (-1 grade) or major 

(-2 grades) uncertainty 

about directness

Imprecision

Imprecise or sparse data

(-1 grade)

Publication bias

High risk of bias (-1 grade)

Strong association

Strong (+1 grade) or 

very strong evidence 

of association

(+2 grades)

Dose-response

Evidence of a doseresponse gradient

(+1 grade)

Unmeasured 

Confounders

Inclusion of 

unmeasured 

confounders increases 

the magnitude of 

effect (+1 grade)

 High

 Moderate

 Low

 Very Low
35

After determining the GRADE of the evidence base for each outcome of a given intervention or question, we 

calculated the overall GRADE of the evidence base for that intervention or question. The overall GRADE was 

based on the GRADE category occurring most often for the outcomes deemed critical to making a 

recommendation; if more than one GRADE category occurred at the same counts, the overall GRADE was 

based on the lowest GRADE. For questions that had no outcomes that were deemed critical by the working 

group, no overall GRADE was assigned to the evidence. GRADE definitions are as follows in Table 7:

Table 7. Interpretation of GRADE Ratings

Quality Rating Interpretation

High Further research is very unlikely to change our confidence in the 

estimate of effect

Moderate Further research is likely to have an important impact on our confidence 

in the estimate of effect and may change the estimate

Low Further research is very likely to have an important impact on our 

confidence in the estimate of effect and is likely to change the estimate

Very Low Any estimate of effect is very uncertain

Note: These interpretations are from Box 2 of Guyatt et al. (2008).29

Formulating Recommendations

Narrative evidence summaries were then drafted by the guideline authors using the evidence and GRADE 

tables. One summary was written for each key question. The guideline authors used the narrative evidence 

summaries to develop guideline recommendations. In some instances, multiple recommendations emerged from 

a single narrative evidence summary. 

Factors determining the strength of a recommendation included:

1. the values and preferences we used to determine which outcomes were critical, 

2. the harms and benefits that emerged by weighing the critical outcomes, and 

3. the overall GRADE of the evidence base for the given intervention or question.

The new categorization scheme for recommendations is provided in Table 8.

31

If weighing the critical outcomes for a given intervention or question resulted in a net benefit or a net harm, 

then a Category I Recommendation was formulated to recommend strongly for or against the given intervention 

respectively. If weighing the critical outcomes for a given intervention or question resulted in a tradeoff 

between benefits and harms, then a Category II Recommendation was formulated to recommend that providers 

or institutions consider the intervention when deemed appropriate. If weighing the critical outcomes for a given 

intervention or question resulted in an uncertain tradeoff between benefits and harms, then a No 

Recommendation was formulated to reflect this uncertainty. 

Category I recommendations are defined as strong recommendations with the following implications:

1. For patients: Most people in the patient‟s situation would want the recommended course of action and only 

a small proportion would not; patient should request discussion if the intervention is not offered.
36

2. For clinicians: Most patients should receive the recommended course of action.

3. For policymakers: The recommendation may be adopted as policy or is current federal and/or state statutes, 

regulation, or standards.

Category II recommendations are defined as weak recommendations with the following implications:

1. For patients: Most people in the patient‟s situation would want the recommended course of action, but 

many would not.

2. For clinicians: Different choices will be appropriate for different patients and clinicians must help each 

patient to arrive at a management decision consistent with her or his values and preferences.

3. For policymakers: Policy making will require substantial debate and involvement of many stakeholders.

Levels A and B represent the quality of the evidence underlying the recommendation, with A representing high 

to moderate quality evidence and B representing low to very low-quality evidence. Level IC represents required 

practices, regardless of the quality of evidence.

Expert Opinion. Recommendations from the Expert Opinion are linked to key questions. These 

recommendations were agreed upon by expert consensus and are designated either IB if they represent a strong 

recommendation based on accepted practices or IIB if they are a weak recommendation.

Previous Guideline and Recommendations. Our evidence-based recommendations were cross-checked with 

those from guidelines identified in our original systematic search. We identified 15 recommendations from the 

1994 PHS Guidelines for Preventing Transmission of HIV through Transplantation of Human Tissue and 

Organs1for topics not directly addressed by our systematic review of the evidence and included these 

recommendations in our Summary of Recommendations as they were deemed critical to the target users of this 

guideline. The recommendations were revised to make applicable to current expected or actual practice. Three 

recommendations, in response to a 2009 HIV transmission from a living organ donor,

10 were deemed critical to 

the target users and included in the Summary of Recommendations for the same reason. Unlike 

recommendations informed by our literature search, these recommendations are not linked to a key question and

were listed as Category I recommendations as the critical outcome for each intervention was determined to

result in a net benefit.

It is important to note that the strength of a Category IA recommendation is equivalent to that of a Category IB 

or IC recommendation; it is only the quality of the evidence underlying the IA recommendation that makes it 

different from a IB or IC. For IB recommendations, although there may be low to very low-quality evidence 

directly supporting the benefits of the intervention, the theoretical benefits are clear, and the theoretical risks are 

marginal.

Table 8. Categorization Scheme for Recommendations 

Category IA Strong recommendation supported by high to moderate quality evidence 

suggesting net clinical benefits or harms.

Category IB Strong recommendation supported by low to very low quality evidence 

suggesting net clinical benefits or harms.

Category IC Strong recommendation required by state or federal regulation, regardless 

of quality of evidence.

Category IIA Weak recommendation supported by high to moderate quality evidence 

suggesting a trade-off between clinical benefits and harms.
37

Category IIB Weak recommendation supported by low to very low quality evidence 

suggesting a trade-off between clinical benefits and harms.

No 

recommendation

Unresolved issue for which there is any quality evidence with uncertain 

trade-offs between clinical benefits and harms.

The wording of each recommendation was carefully selected to reflect the recommendation's strength. We used 

the active voice when writing Category I recommendations - the strong recommendations. Phrases like “must”

"should" or "should not" and verbs without conditionals were used to convey certainty. We used a more passive

voice when writing Category II recommendations - the weak recommendations. Words like "consider” and 

phrases like "may be considered” or “should be considered” were chosen to reflect the lesser certainty of the 

Category II recommendations. Rather than a simple statement of fact, each recommendation is actionable, 

describing precisely a proposed action to take. All recommendations focus only on efficacy, effectiveness, and 

safety. Yet, the optimal use of these guidelines should include a consideration of the costs relevant to the local 

setting of guideline users.

The category "No recommendation/unresolved issue" was most commonly applied to situations in which either 

1) the overall quality of the evidence base for a given intervention was low to very low and there was no 

consensus on the benefit or risks of the intervention or 2) there was no published evidence on outcomes deemed 

critical to weighing the risks and benefits of a given intervention. If the latter was the case, those critical 

outcomes were noted at the end of the relevant evidence summary.

Tables and Figures in the Evidence Report

The Tables (in italics) and Figures (in italics) in this guideline are from the evidence report Solid Organ 

Transplantation and the Probability of Transmitting HIV, HBV, or HCV: A Systematic Review to Support an 

Evidence-based Guideline, except for Table 3. After a period of public comment for the guideline, the evidence 

report will be posted on the CDC website http://www.cdc.gov/transplantsafety.

Finalizing the Guideline

After a draft of the tables, narrative summaries, and recommendations was completed, the guideline authors

shared the draft guideline with the Expert Panel and Review Committee for an in-depth review. Revisions to the 

guideline were made based in part on feedback from members of the Expert Panel and Review Committee. The 

opinions of individual members of the Expert Panel or Review Committee were not fully reflected in this 

document as the guideline represents the position of the Public Health Service agencies, and is not a consensus 

document. The CDC then submitted the guideline for review and approval by HHS operating divisions. 

Following further revisions, the guideline was posted on the Federal Register for public comment. After a 

period of public comment, the guideline will be revised accordingly, and the final guideline will be published 

and posted on the CDC website http://www.cdc.gov/transplantsafety.

Updating the Guideline

Future revisions to this guideline will be dictated by new research and technological advancements for 

preventing transmission of HIV, HBV, and HCV through solid organ transplantation, and will occur at the 

request of the CDC. 
38

VII. Evidence Review

The tables listed in the Evidence Review correspond to tables in the Evidence Report accessible at 

http://www.regulations.gov.

TOPIC I: PROBABILITY OF TRANSMISSION OF HIV, HBV, OR HCV THROUGH SOLID ORGAN 

TRANSPLANTATION (Questions 1and 2)

Question 1. What are the prevalence and incidence rates of HIV, HBV, and HCV 

pathogens among potential solid organ donors?

For the three listed pathogens, the quality of evidence for U.S. incidence (the percentage of potential organ 

donors who newly acquire the pathogen) and prevalence (the percentage of potential organ donors at a given 

time who test positive for the pathogen) rates were reviewed. Due to the small amount of evidence on potential 

solid organ donors, the scope was expanded to include other possibly relevant populations. Ultimately, the 

search comprised potential deceased and living solid organ donors,5,33-44 potential tissue donors,45 and the U.S. 

general population.46-51 The U.S. general population studies did not indicate if cases included living organ or 

tissue donors. Testing methods and criteria varied among the included studies. Some studies reported hepatitis 

prevalence but did not differentiate HBV from HCV. Additionally, it is not clear if antibody tests were 

confirmed by a more specific method such as Western blot, recombinant immunoblot assay (RIBA) or NAT in 

most of these studies. These differences in donor populations and methods used to diagnose and report infection 

probably contributed to the range in reported incidence and prevalence rates.

Q1.A. HIV Prevalence and Incidence

There was low quality evidence from four studies that examined HIV prevalence and incidence among donors 

and the general population in the United States, and no studies providing data from 2000 or later for potential 

deceased or living organ donors. (Table 12) Of the four studies that provided “prevalence” data, two related to 

organ donation.(Table 7) In a 1995 study of potential living-related donors, 0% of 22 were HIV positive.34 In a 

1993 study of deceased potential organ donors, 2% of 94 were positive for HIV or syphilis; it was unclear if all 

potential donors had been tested for HIV.36 Among 10,910 potential tissue donors, the prevalence of confirmed 

HIV was 0.093%.45 (Table 9) HIV prevalence in a U.S. general population study was approximately 0.37%.52

(Table 11) The U.S. general population studies did not indicate if cases included living organ or tissue donors. 

Our search did not identify studies estimating “incidence” of HIV in organ donors. However, two U.S. studies 

looked at HIV incidence in the tissue donor and general population. The estimated incidence was 30.11 per 

100,000 person-years among potential tissue donors45 (Table 9) and 18.8 per 100,000 person-years among the 

U.S. general population.46,47 (Table 11)

Q1.B. HBV Prevalence and Incidence

Review of the available studies found low quality evidence estimating HBV prevalence and incidence in donors 

and the general population in the United States (Table 12) Five studies provided prevalence data.34-36,45,50

Among 446 potential organ donors, 4.9% were positive for HBV.35 The rate of viral hepatitis, type unspecified, 

was 5.3% in a study of 94 deceased potential donors; it was unclear if all potential donors had been tested for 

HBV in this study.

36 A second study of hepatitis, type unspecified, reported a prevalence of 18.2% among 

potential living-related organ donors.34 (Table 7) Among 10,901 potential tissue donors, the prevalence of 

confirmed HBV was 0.229%.45 (Table 9) The prevalence of HBV chronic infection in the U.S. general 

population, including incarcerated individuals, was 0.36%.50 (Table 11) Our search did not identify studies 

estimating incidence of HBV in organ donors. However, two U.S. studies looked at HBV incidence in tissue 
39

donors and the general population. The incidence of HBV was 18.325 per 100,000 person years for potential 

tissue donors45 (Table 9) and 14.4 per 100,000 person-years for the general population.48,49 (Table 11) 

Q1.C. HCV Prevalence and Incidence

We found low quality evidence from nine U.S. studies that estimated HCV prevalence and incidence in donors 

and the general population. (Table 12) Most of the prevalence data for organ donors was derived from donations 

that occurred before 1992. Among 55 potential living-related donors, the prevalence of HCV was 3.6%.33 A 

1993 study of 94 deceased potential donors identified 5.3% as having active hepatitis, type unspecified; it was

not clear if all 94 potential donors had been tested.36 Another study reported the prevalence of unspecified 

hepatitis at 18.2% among potential living-related donors.34 (Table 7) Of four retrospective studies of organ 

donation that occurred from 1986 to 1992, the combined estimate of HCV prevalence was 4.0%;37-44 three of 

the studies comprised deceased donors and the fourth did not report whether donors were deceased or living. 

(Table 8) The prevalence of HCV was 1.091% among 10,915 potential tissue donors.45 (Table 9) The 

prevalence of HCV chronic infection in the U.S. general population, excluding incarcerated individuals, was 

1.1%.51 (Table 11) Our search did not identify studies estimating “incidence” of HCV in organ donors. 

However, two U.S. studies looked at HCV incidence in tissue donors and the general population. The incidence 

of HCV was 12.380 per 100,000 person-years for potential tissue donors.45 (Table 9) and 5.7 per 100,000 

person-years for the general population.48,49 (Table 11) 

Question 2. What are the rates of transmission to recipients from donors infected with 

HIV, HBV, or HCV? Do the rates vary by the organ transplanted or when the donor was 

infected?

This question concerns the specific situation when the donor tests positive for a pathogen but the transplant 

candidate does not. No studies were identified that reported on HIV transmission results likely due to federal 

regulations that prohibit transplantation of organs from individuals known to be HIV-infected. However, a 

number of studies addressed HBV and HCV, where considerable variation in transmission rates was observed. 

This variation could have been influenced by numerous factors, including:

● the organ transplanted; 

● whether HBV prophylaxis was used in the case of an HBV-positive donor; 

● type of serologic testing used for detection; 

● the specific antibodies or antigens for which the donor was positive; 

● when the studies were performed, as earlier generations of HCV serological assays were less sensitive than 

the current generation;

● whether NAT screening, which would detect recent infection, was performed; and 

● the frequency and length of follow-up testing after transplantation.

Figures 4 through 10 provide data on some of these factors to aid interpretation of results.

We considered HBV transmission rates where the donor was anti-HBc positive with HBsAg status unknown to 

be the most critical (no studies were found that examined transmission rates from anti-HBc and HBsAg positive 

donors), except when the recipient tested anti-HBs positive. For HCV, positive anti-HCV results may reflect 

patients who had HCV in the past and cleared the infection. Therefore, we considered transmission rates where 

the donor was positive for HCV ribonucleic acid (RNA) to be most critical. The rows addressing these critical 

results for HBV and HCV are shaded in Table 21.

Q2.A. HBV transmission from liver transplantation

We found low quality evidence from 17 observational studies53-74 that examined the transmission rate of HBV 

from infected donors to uninfected recipients. (Table 21) Transmission rates were likely underreported in some 
40

studies as the use of prophylaxis can result in negative recipient testing despite transmission. Studies measured 

virus transmission in 14 different ways with results ranging from 0% to 94% (Table 14, Figures 4 and 5). This 

difference may be due to whether HBV prophylaxis was used, with the lowest rates found primarily in studies 

where all recipients received prophylaxis. There was also significant variation in the frequency of posttransplant screening and liver biopsy.71 Eight studies reported de novo HBV infection occurring in 72 recipients 

between 3 and 48 months post-transplant.

54,55,57-63,73,75 (Table 23) 

Q2.B. HBV transmission from kidney transplantation

This review found low quality evidence from 9 observational studies63,65,66,72,75-80 regarding estimated 

transmission rates of HBV from infected donors to uninfected recipients. (Table 21) Transmission rates were 

likely underreported in some of the studies as the use of prophylaxis can result in negative recipient testing 

despite transmission. Studies measured virus transmission in 13 different ways for transmission of HBV from 

kidney transplantation with results ranging from 0% to 13% (Table 15, Figures 6 and 7). Of the four critical 

transmission rates where the donor was anti-HBc positive with HBsAg status unknown, HBV was not detected.

None of these four studies reported whether prophylaxis was used. De novo HBV infection occurred in 0 

recipients between 3 and 12 months post-transplant.

75 (Table 23) 

Q2.C. HBV transmission from heart transplantation

We found very low quality evidence from 6 observational studies63,65,66,81-85 regarding transmission rates of 

HBV from infected donors to uninfected recipients. (Table 21) Transmission rates are likely underreported in 

some of the studies as the use of prophylaxis can result in negative recipient testing despite transmission. 

Studies measured virus transmission in nine different ways for transmission of HBV from heart transplantation 

with results ranging from 0% to 65% (Table 16, Figure 7). Of the two critical transmission rates where the 

donor was anti-HBc positive with HBsAg status unknown, the range was 18 to 65% when recipients were tested 

for anti-HBc63,82 and 0% to 4% when tested for HBsAg;63,81 none of these studies reported whether prophylaxis 

was used. Frequency of post-transplant screening varied in three studies that reported this.

81,83,84 Two studies 

reported de novo HBV infection occurring in 1 recipients between 6-10 hours and 10 months posttransplant.81,82 (Table 23) 

Q2.D. HBV transmission from lung transplantation

Review of the one study that met inclusion criteria found low quality evidence estimating HBV transmission 

from infected donors to uninfected recipients. (Table 21) The study measured virus transmission in two 

different ways; no recipients were reported as having a positive test (Table 17, Figure 7).86 All recipients 

received prophylaxis, which may result in negative recipient testing despite transmission. The study did not 

report on the frequency of post-transplant screening, and no de novo HBV post-transplant infections were 

reported. (Table 23) 

Q2.E. HCV transmission from liver transplantation

We found low quality evidence from two studies37,44,87 that looked at transmission rates of HCV from infected 

donors to uninfected recipients. (Table 21) Studies measured virus transmission in three different ways for 

transmission of HCV from liver transplantation with results ranging from 24% to 100%. (Table 18, Figure 8) 

HCV transmission was detected in 67% of recipients tested for anti-HCV and 100% of recipients tested for 

HCV-RNA in one study where transmission rates were considered critical. The frequency of performing posttransplant immunoassay testing varied considerably.

37,44,87 One study reported de novo HCV infection occurring 

in 48 recipients within 24 months.

37,44 (Table 23)

Q2.F. HCV transmission from kidney transplantation

There was very low quality evidence from 10 studies5,38-43,88-97 that examined transmission rates of HCV from 

infected donors to uninfected recipients. (Table 21) Studies measured virus transmission in eight different ways 
41

with results ranging from 0% to 100% (Table 19, Figure 9). Of the four critical transmission rates identified, the 

range was 0% to 35% when recipients were tested for anti-HCV,38,95,96 0% when tested for RIA, and 0% to 57% 

when tested for HCV-RNA. Four studies reported the frequency of post-transplant immunoassay testing which 

varied such that the data were not useful.

5,39-41,91,92,97 Five studies reported de novo HCV infection occurring in 

41 recipients between 10 and 60 months post-transplant.42,43,91-93,95-97 (Table 23) The quality of evidence was 

rated as very low. (Table 21)

Q2.G. HCV transmission from heart transplantation

Review of four observational studies98-103 found very low quality evidence regarding transmission rates of HCV 

from infected donors to uninfected recipients. (Table 21) Studies measured virus transmission in six different 

ways for transmission of HCV from heart transplantation with results ranging from 11% to 100%. (Table 20, 

Figure 10) Two critical transmission rates detected HCV transmission in 44% of recipients when tested for antiHCV and 100% when tested for HCV-RNA.56 One study reported regular monitoring without stating a 

frequency of post-transplant serology testing.56 One study reported de novo HCV infection occurring in 3 

recipients between 19 and 55 months post-transplant.102 (Table 23)

Questions 1 and 2 Recommendations

1.A. Further research is needed to estimate the incidence and prevalence of HIV, HBV and HCV 

among deceased potential organ donors in the U.S. (No Recommendation/unresolved issue)

(Question 1)

1.B. Deceased potential organ donors should be screened for HCV using NAT or the most sensitive 

test available regardless of risk of having HCV and regardless of time relative to procurement (i.e., 

Donor specimens should be obtained before procurement; however, NAT results should be obtained 

either before, if timing allows, or after procurement). (Category IB) (Question 1)
42

Figure 4. LIVER Transplantation: HBV Positivity in Recipients after the Use of Anti-HBc+ Donors

Note: This figure displays the reported rates of positivity among pre-transplant negative recipients after receiving organs from positive 

donors. The title of the figure indicates the relevant pathogen(s) and organ(s). The definitions of donor positivity appear on the left side 

of the figure, and the definitions of recipient post-transplant positivity appear on the right side of the figure. 

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Transmission rate (proportion)

DONOR

was:

RECIPIENT was 

post-transplant

positive for:

HBsAg

serum HBV

anti-HBc

anti-HBs

HBeAg

"Developed de

novo infection"

LIVER TRANSPLANT

anti-HBc+

- All recipients received prophylaxis, - Some recipients received prophylaxis,

- No recipients received prophylaxis, X - Study did not report whether prophylaxis was used
43

Figure-5. LIVER Transplantation: HBV Positivity in Recipients after the Use of Organs from 

Anti-HBc+ HBsAg- Donors

Note: This figure displays the reported rates of positivity among pre-transplant negative recipients after receiving organs from positive 

donors. The title of the figure indicates the relevant pathogen(s) and organ(s). The definitions of donor positivity appear on the left side 

of the figure, and the definitions of recipient post-transplant positivity appear on the right side of the figure. 

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Transmission rate (proportion)

HBsAg

serum HBV DNA

anti-HBc

anti-HBs

HBeAg

lymphocytes HBV DNA

liver HBV DNA

LIVER TRANSPLANT

anti-HBc+

HBsAgDONOR

was:

RECIPIENT was 

post-transplant

positive for:

- All recipients received prophylaxis, - Some recipients received prophylaxis,

- No recipients received prophylaxis, X - Study did not report whether prophylaxis was used
44

Figure 6. KIDNEY Transplantation: HBV Positivity in Recipients after the Use of Organs from Anti 

HBc+ Donors or Anti-HBc+ HbsAg- Donors

Note: This figure displays the reported rates of positivity among pre-transplant negative recipients after receiving organs from positive 

donors. The title of the figure indicates the relevant pathogen(s) and organ(s). The definitions of donor positivity appear on the left side 

of the figure, and the definitions of recipient post-transplant positivity appear on the right side of the figure. 

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Transmission rate (proportion)

HBsAg

serum HBV DNA

anti-HBc

anti-HBs

HBeAg

anti-HBc+

anti-HBc+

HBsAgHBsAg

anti-HBs

anti-HBc

KIDNEY TRANSPLANT

DONOR

was:

RECIPIENT was 

post-transplant

positive for:

- All recipients received prophylaxis, - Some recipients received prophylaxis,

- No recipients received prophylaxis, X - Study did not report whether prophylaxis was used
45

Figure 7. Kidney, Heart and Liver: HBV Positivity in Recipients after the Use of Organ Donors Positive 

for HBV

Note: This figure displays the reported rates of positivity among pre-transplant negative recipients after receiving organs from positive 

donors. The title of the figure indicates the relevant organ(s). The definitions of donor positivity appear on the left side of the figure, and 

the definitions of recipient post-transplant positivity appear on the right side of the figure. 

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Transmission rate (proportion)

HBsAg

serum HBV DNA

anti-HBc

anti-HBs or anti-HBc

KIDNEY TRANSPLANT

anti-HBc+

HBsAganti-HBc+

HBsAgserum HBV-

"HBV viremia"

LUNG TRANSPLANT

HEART TRANSPLANT

anti-HBc+

HBsAg

anti-HBs

anti-HBc

anti-HBc+, HBsAganti-HBs+

anti-HBc+

HBsAgserum HBVHBsAg

serum HBV DNA

lymphocyte HBV DNA

anti-HBc+

HBsAgHBsAg

anti-HBc

DONOR

was:

RECIPIENT was 

post-transplant

positive for:

anti-HBc+, HBsAgHBsAg

- All recipients received prophylaxis, - Some recipients received prophylaxis,

- No recipients received prophylaxis, X - Study did not report whether prophylaxis was used
46

Figure 8. LIVER transplantation: HCV Positivity in Recipients after the Use of Organs Donors Positive 

for HCV

Note: This figure displays the reported rates of positivity among pre-transplant negative recipients after receiving organs from positive 

donors. The title of the figure indicates the relevant organ(s). The definitions of donor positivity appear on the left side of the figure, and 

the definitions of recipient post-transplant positivity appear on the right side of the figure. Prophylaxis was not generally applicable to 

the HCV studies, therefore all studies are represented by X‟s.

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Transmission rate (proportion)

LIVER TRANSPLANT

anti-HCV+

anti-HCV+,

serum HCV+

anti-HCV

HCV-RNA

DONOR

was:

RECIPIENT was 

post-transplant

positive for:

anti-HCV

anti-HCV+,

serum HCV+

- All recipients received prophylaxis, - Some recipients received prophylaxis,

- No recipients received prophylaxis, X - Study did not report whether prophylaxis was used
47

Figure 9. KIDNEY Transplantation: HCV Positivity in Recipients after the Use of Organs from Donors 

Positive for HCV

Note: This figure displays the reported rates of positivity among pre-transplant negative recipients after receiving organs from positive 

donors. The title of the figure indicates the relevant organ(s). The definitions of donor positivity appear on the left side of the figure, and 

the definitions of recipient post-transplant positivity appear on the right side of the figure. 

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Transmission rate (proportion)

anti-HCV

HCV-RNA

Radio-immuno-assay

KIDNEY TRANSPLANT

anti-HCV+

anti-HCV+,

serum HCV+

anti-HCV

anti-HCV OR indeterminate

HCV-RNA

DONOR

was:

RECIPIENT was 

post-transplant

positive for:

anti-HCV+,

RIBA+

anti-HCV

HCV-RNA

- All recipients received prophylaxis, - Some recipients received prophylaxis,

- No recipients received prophylaxis, X - Study did not report whether prophylaxis was used
48

Figure 10. HEART Transplantation: HCV Positivity in Recipients after the Use of Organs from Donors 

Positive for HCV

Note: This figure displays the reported rates of positivity among pre-transplant negative recipients after receiving organs from positive 

donors. The title of the figure indicates the relevant organ(s). The definitions of donor positivity appear on the left side of the figure, and 

the definitions of recipient post-transplant positivity appear on the right side of the figure. Prophylaxis was not generally applicable to 

the HCV studies, therefore all studies are represented by X‟s.

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Transmission rate (proportion)

HEART TRANSPLANT

anti-HCV+

anti-HCV+,

serum HCV+

"detectable" anti-HCV

anti-HCV

HCV-RNA

liver HCV

"Any HCV infection"

anti-HCV

HCV-RNA

DONOR

was:

RECIPIENT was 

post-transplant

positive for:

- All recipients received prophylaxis, - Some recipients received prophylaxis,

- No recipients received prophylaxis, X - Study did not report whether prophylaxis was used
49

TOPIC II: METHODOLOGY TO BETTER ESTIMATE DONOR INFECTION WITH HIV, HBV, OR 

HCV (Questions 3, 4, 5)

Question 3. What behavioral risk factors are associated with an increased probability of 

infection with HIV, HBV, or HCV? What is the prevalence of these characteristics among 

potential solid organ donors?

The first half of the question attempts to identify behaviors that may put individuals at increased risk for HIV, 

HBV, or HCV, while the second half of the question addresses the frequency of those behaviors among 

potential solid organ donors. The following sections present all behaviors identified as exclusion criteria from 

the 1994 guideline, as well as additional behaviors identified from the literature but not included as exclusion 

criteria from the 1994 guideline. The prior guideline stated that “Regardless of their HIV antibody test results, 

persons who meet any of the criteria listed should be excluded from donation of organs or tissues unless the risk 

to the recipient of not performing the transplant is deemed to be greater than the risk of HIV transmission and 

disease.”:

● Men who have sex with men in the preceding 5 years;

● persons who report nonmedical intravenous, intramuscular, or subcutaneous injections of drugs in the 

preceding 5 years;

● persons with hemophilia or related clotting disorders who have received human-derived clotting factor 

concentrates;

● men and women who have engaged in sex in exchange for money or drugs in the preceding 5 years;

● persons who have had sex in the preceding 12 months with any person described in the above items or with 

a person known or suspected to have HIV infection;

● persons who have been exposed in the preceding 12 months to known or suspected HIV-infected blood 

through percutaneous inoculation or through contact with an open wound, nonintact skin, or mucous 

membrane;

● inmates of correctional systems;

● children meeting any of the exclusionary criteria listed above for adults;

● children born to mothers with HIV infection or mothers who meet the behavioral exclusionary for adult 

donors unless child> 18 months of age, who is born to mother with or at risk for HIV infection, has not been 

breast fed with the last 12 months, and HIV antibody tests, physical examination and review of medical 

records do not indicate evidence of HIV infection; and

● child≤ 18 months of age, who is born to a mother with or at risk for HIV infections or has been breast fed 

within the past 12 months

Given the paucity of data evaluating behavioral risk factors for HIV, HBV and HCV in potential organ donors, 

we also searched for studies meeting inclusion criteria in the following populations: general population (i.e.,

unselected for any particular demographic, occupational, or behavioral characteristics, or health status other 

than HCV, HBV, or HIV infection), tissue donors, and blood donors. After broadening the search, there were 

only a few articles meeting inclusion criteria that identified behavioral risk for HBV. Therefore, studies of 

demographic or socioeconomic subpopulations, such as college students or veterans admitted to a psychiatric 

inpatient ward were included for HBV. In addition, there was a lack of data for evaluating nonbehavioral risk 

factors in organ donors.

Based on the quality of evidence from the literature review, the association of behavioral and nonbehavioral 

factors with the risk of HIV, HBV or HCV was categorized as follows. Behavioral and nonbehavioral 

characteristics that were associated with HIV, HBV, or HCV and identified by “low,” “moderate,” or “high” 

quality evidence in the systematic review are reported in Table 9 of this document. Due to the lack of evidence 
50

in the literature meeting inclusion criteria identifying risk factors for incident infection, the potential risk factors 

identified from the literature review in Table 9 were modified by subject matter experts on HIV and hepatitis to 

create a revised list of risk factors for screening in Table 3 of this document. The revised list takes into 

consideration that 1) certain risk factors can be omitted because they are likely markers for other factors 

identified in the systematic review and 2) certain risk factors should be added because scientific evidence 

associating certain factors with the bloodborne pathogens exists, but may not have met the inclusion criteria of 

the systematic review or studies were of insufficient quality to draw conclusions.

Q3.A. HIV and Behavioral Risk Factors

Exclusionary Criteria from the 1994 Guideline

Q3.A.1 Men Who Have Sex with Men (MSM)

There was moderate quality evidence identifying MSM as a risk factor for HIV. (Table 36) The 1994 guideline 

excludes from becoming organ donors “Men who have had sex with another man in the preceding 5 years.” We 

identified zero studies that addressed this particular time frame. Two studies of the general population, one 

using National Health and Nutrition Examination Survey (NHANES) data104 and the other using New York 

City HANES data,

105 found a significantly higher rate of HIV for MSM in univariate analyses.105 Among 

infected males, 52%104 and 53.8%105 reported a history of MSM behavior. (Table 35) The prevalence of MSM,

reported as 3.7%104 and 9.3%105 of men in the general population studies, was rated as low quality evidence. 

(Table 37)

Q3.A.2. Injection Drug Use (IDU)

We found low quality evidence suggesting an association between IDU and HIV. (Table 36) The 1994 

guideline excludes from becoming organ donors “Persons who report nonmedical intravenous, intramuscular, or 

subcutaneous injection of drugs in the preceding 5 years.” We identified zero studies that investigated the risk 

of IDU within this particular time frame; most studies evaluated lifetime IDU. Studies typically did not 

distinguish between IDU and intravenous drug use (IVDU). Two studies of the general population, using 

NHANES and HANES data, found significant associations between IDU and HIV with large effect sizes in 

univariate analyses.104,105 (Table 35) A third study of patients at an urban medical care center did not find an 

association in univariate analysis.106 The prevalence of IDU, reported as 1.4%105 and 7.9%,

106 (Table 37) was 

rated as low quality evidence. (Table 38)

Q3.A.3. Sex Worker 

A single study found very low quality evidence which did not find an association between sex workers and 

HIV. (Table 36) The 1994 guideline excludes from becoming organ donors “Men and women who have 

engaged in sex in exchange for money or drugs in the preceding 5 years.” We did not find any literature that 

studied the association between this factor and HIV within this particular time frame. One corneal donor study 

involving a next-of-kin interview did not find any association between sex work and infection with HIV.107

(Table 35) One urban medical care center reported a 2.3% prevalence of exchanging sex for drugs or money,106

(Table 37) and this evidence was rated low quality. (Table 38)

Q3.A.4. High Risk Sex Partner

The 1994 guideline excludes from becoming organ donors persons who have had sex in the preceding 12 

months with any of the following persons: MSM, IDUs, sex workers, or persons known or suspected to have 

HIV infection. We did not identify any literature on infection risk in people with high-risk sex partners during 

the listed time frame.
51

Q3.A.4.a. Sex with Injection Drug User

Our search did not identify studies that examine the association between sex with an injection drug user and 

acquiring HIV.

Q3.A.4.b. Sex with a Sex Worker

No studies were identified that looked at the association between HIV and sex with a sex worker. One study in 

an urban medical care center reported 7.4% of patients had had sex with a sex worker106 (Table 37) and this 

evidence was rated low quality (Table 38).

Q3.A.4.c. Sex with People Known to be HIV Infected

There was low quality evidence associating having sex with someone who is HIV-positive and having HIV. 

(Table 36) One study of a general population found that the relationship between having a sex partner with HIV 

and acquiring HIV was significant with a large magnitude of effect in a univariate analysis.106 (Table 35) The 

study reported that 3.6% of participants indicated having sex with someone known to be infected with HIV.106

(Table 37), and this evidence was rated low quality. (Table 38)

Q3.A.4.d. Other High Risk Sex Partners

No studies were identified that met the inclusion criteria.

Q3.A.5. Inmates

A single study found very low quality evidence to suggest an association between being incarcerated and having 

HIV. (Table 36) The 1994 guideline excludes from becoming organ donors inmates of correctional systems. No 

studies that examined the association between “present” incarceration and infection were identified. However, 

one study examined and did not identify an association of lifetime history of incarceration as reported by nextof-kin with HIV infection in potential corneal donors.107 (Table 35) 

Q3.A.6. Risk Factors in Children

We identified no literature on any behavioral risk factors in children, or on the risk of infection from mothers 

who engage in those risk behaviors. While vertical transmission is generally recognized as a mode of hepatitis 

or HIV transmission, this body of literature lacks the evidence to assess the 1994 criteria as risk factors.

Additional Potential Behavioral Factors for HIV from 2009 Literature Search

Q3.A.7. Multiple Sex Partners

Review of the available studies reveals low quality evidence to suggest an association between having multiple 

sex partners and being at increased risk of HIV. (Table 36) Studies defined multiple partners using different 

thresholds. Having multiple partners, including heterosexual partners, was associated with HIV infection in one 

general population study of hospital inpatients and outpatients.

104 HANES data of New York City adults found

having multiple sex partners in the past year was not associated with HIV,105 nor was having at least 10 lifetime 

sex partners in the patient study,106 but having 50 or more lifetime sex partners was associated with HIV in an 

NHANES study.104 All of these analyses were univariate. (Table 35) In the studies, 3.5%104 and 6.6%105

reported having at least 50 lifetime sex partners; 74% reported having sex with at least two partners104 and with 

2-49 partners during their lifetime;105 whereas 22% reported having sex with multiple partners during the 

previous year.105 (Table 37) We found low quality evidence regarding the prevalence of individuals having at 

least 50 partners, whereas we found moderate quality evidence regarding prevalence estimates of having 

multiple sex partners, at least 2 sex partners, and between 2 and 49 partners. (Table 38)
52

Q3.A.8. Same Sex Partners

We found low quality evidence to suggest an association between having a same sex partner and acquiring HIV. 

(Table 36) A univariate association with a large magnitude of effect between having a same-sex partner and 

HIV, including both men and women was detected in a general population study.

106 (Table 35) The prevalence 

of same-sex partners was reported as 8.2%106 (Table 36), and this evidence was rated low quality. (Table 38)

Q3.A.9. Age at First Sexual Intercourse

There was low quality evidence to support younger age at first sexual intercourse as a risk factor for HIV 

infection. (Table 36) An NHANES study reported that first sexual intercourse at 18 years or younger was 

associated with HIV in univariate analysis with a large effect size.

104 (Table 35) The proportion of adults who 

reported having sex at age 18 or younger was 59%,

104 (Table 37) and this evidence was rated high quality. 

(Table 38)

Q3.A.10. Additional Various [Sexual] Associations

We report additional reported associations between sexual practices and infection identified in the literature but

did not assign GRADE ratings because these factors were reported by so few studies. Not using condoms was 

not associated with HIV infection in two general population studies.105,106 Anal-insertive sex that occurred at 

least six weeks ago, and anal-receptive sex at least six weeks ago among women and men was associated with 

HIV in a general population.106 Having vaginal sex was associated with a reduced risk in HIV compared with 

people who did not have vaginal sex (but may have been having anal sex) in the general population study.109

(Table 35)

Q3.A.11. Non-injection Substance

Q3.A.11.a. Other Illicit Drugs

We found low quality evidence associating use of cocaine or street drugs and HIV infection. (Table 36) HIV 

was associated with any prior cocaine or street drug use in univariate analysis using NHANES data104 and in 

multivariate analysis108 among members of the general population. (Table 35) The proportion of respondents 

who reported using street drugs/cocaine was 21%,

104 (Table 37) and this evidence was rated moderate quality 

due to indirectness. (Table 38)

Q3.A.11.b. Alcohol

There was very low quality evidence associating alcohol with an increased risk of HIV. (Table 36) HIV was 

associated with having an alcohol and/or (unspecified) drug problem among health maintenance organizations 

(HMO) enrollees,109 but not with alcohol use among potential corneal donors.107 Both of these analyses were 

univariate. (Table 35)

Q3.A.11.c. Tobacco

One study found was very low quality evidence which did not find an association between cigarette use and 

HIV (Table 36) among corneal donors.107 (Table 35)

Q3.A.12. Tattoos and Piercing

One study found very low quality evidence which did not find an association between tattoos, piercings, and 

acupuncture (as collectively analyzed as one outcome and reported by next-of-kin) in potential corneal donors. 

(Table 36).

107 (Table 35)

Q3.A.13. International Travel

One study revealed very low quality evidence that did not find an association between international travel and 

HIV (Table 36) among potential corneal donors.107 (Table 35)
53

Q3.B. HBV and Behavioral Risk Factors

Exclusionary Criteria from the 1994 Guideline

Q3.B.1. Men Who Have Sex with Men (MSM)

The review demonstrated moderate quality evidence to support an association between MSM behavior and 

HBV. (Table 36) The 1994 guideline excludes from becoming an organ donor “Men who have had sex with 

another man in the preceding 5 years.” We identified zero studies that addressed this particular time frame. Two 

studies found associations with HBV. One study compared the prevalence of HBV among MSM in a sample 

drawn from the general population (4.7% HBV positive) to those who self-report as not MSM (age-adjusted 

prevalence of HBV 5.7%) and found a significantly increased prevalence of HBV (age adjusted prevalence 

26.8%) among MSM.110 In a population of college students, HBV infection rates among MSM were compared 

to men who have never had sex and showed that the rate of HBV was higher among MSM in both univariate 

and multivariate analyses.111 For both studies, the magnitude of the effect was large. (Table 33)

Q3.B.2. Injection Drug Use (IDU)

There was low quality evidence to support IDU as a risk factor for HBV infection. Although all but one study 

found an association, not all of the studies found a large magnitude of effect. (Table 36) The 1994 guideline 

excludes from becoming an organ donor “Persons who report nonmedical intravenous, intramuscular, or 

subcutaneous injection of drugs in the preceding 5 years.” We identified zero studies that investigated the risk 

of IDU within the listed time frame; most studies associated lifetime IDU with infection. In general, studies did 

not distinguish between IDU and intravenous drug use IVDU. HBV was significantly associated with IDU in 

four studies,

111-114 and three of these studies had large effect sizes,111-113 with a point estimate OR of 2.0 or 

higher. One study comprised volunteers from the general population,

112 two comprised IVDU veterans in 

inpatient psychiatric hospitals,113,114 and one involved college students.111 Only two studies112,114 performed 

multivariate analyses. The fifth study did not find an elevated risk in an obstetric population.115 One study also 

considered steroid injection but did not find a significant relationship between injection steroid use and HBV 

infection.111 (Table 33) Prevalence of injection drug use reported in the general population study was 3.5%.112

(Table 37), and this evidence was rated low quality. (Table 38)

Q3.B.3. Sex Worker 

We found very low quality evidence relating sex work and HBV infection. (Table 36) The 1994 guideline 

excludes from becoming an organ donor “Men and women who have engaged in sex in exchange for money or 

drugs in the preceding 5 years.” We did not find any literature that studied the association between this factor 

and the given time frame. None of the three studies found an association between sex work (including sex 

bartering or sex for drugs) and HBV.107,113,114 A study of corneal donors did not find any association between 

sex work and infection with HBV in univariate analysis.107 Two studies of psychiatric inpatient veterans did not 

detect an association between sex bartering113 or unprotected sex for drugs114 with HBV infection in 

multivariate analyses. (Table 33)

Q3.B.4. High Risk Sex Partner

The 1994 guideline excluded persons who have had sex in the preceding 12 months with any of the following 

persons from becoming an organ donor: MSM, injection drug users, sex workers, or persons known or 

suspected to have HBV infection. We did not identify any literature on infection risk in people with high-risk 

sex partners during the listed time frame. However, having a high-risk or infected sex partner was associated 

with HBV in six of seven studies. 
54

Q3.B.4.a. Sex with Injection Drug User

Review of the available studies revealed very low quality evidence supporting an association between HBV 

infection and having sex with an injection drug user. (Table 36) Four studies examined sex with an injection 

drug user.

111-113,116 Sex with an injection drug user was significantly associated with HBV in the general 

population in multivariate analysis112 and in univariate analyses among college students111 but not among 

veterans admitted to the inpatient psychiatric ward.113 Sex or household contact with an injection drug user was 

associated with HBV infection in univariate but not multivariate analysis.116 (Table 33) In one study, 5% of the 

general population participants reported having sex with an injection drug user112 (Table 37), and this evidence 

was rated low quality. (Table 38)

Q3.B.4.b. Sex with a Sex Worker

A single study of psychiatric inpatient veterans found very low quality evidence which did not find an 

association between HBV and having sex with a sex worker (Table 36) in univariate analysis.113 (Table 33) 

Q3.B.4.c. Sex with People Known to be HBV Infected 

There was very low quality evidence to support having a sex partner with a known HBV infection as a risk 

factor for HBV. (Table 36) Sex with a partner with hepatitis was found to be a significant risk factor for HBV in 

college students111 but not in an obstetric population.115 Both of these analyses were univariate. (Table 33) 

Q3.B.4.d. Other High Risk Sex Partners

Additional high-risk sex partners not mentioned in the original guideline were reported by one study.116 HBV 

infection was not associated with sex with a blood transfusion recipient, with a health care worker, or a person 

with a foreign birth in an endemic area. This study was reported because it is germane to the larger issue of 

having high-risk sex partners. However, the quality of the evidence was not rated because this factor was 

reported by one study only. (Table 33) 

Q3.B.5. Inmates

We found very low quality evidence to suggest an association between being incarcerated and having HBV. 

(Table 36) The 1994 guideline excludes inmates of correctional systems from donating organs. There were no 

studies identified that examined the association between present incarceration and HBV. However, the search 

did identify studies that examined the association between recent or lifetime history of incarceration. A history 

of incarceration was associated with HBV in three of four studies.107,111,113,116 In the general population, 

imprisonment within the last six months was associated with recent HBV infection in univariate but not 

multivariate analysis.116 Incarceration was also significantly associated with HBV in univariate analysis among 

psychiatric inpatient veterans113 and among college students incarcerated for at least 24 hours.111 A history of 

incarceration as reported by next-of-kin was not associated with HBV in potential corneal donors.107 (Table 33)

Q3.B.6. Risk Factors in Children

We identified no literature on any behavioral risk factors in children, or on the risk of infection from mothers 

who engage in those risk behaviors. While vertical transmission is generally recognized as a mode of hepatitis 

or HIV transmission, this body of literature lacks the evidence to assess the 1994 criteria as risk factors.

Additional Potential Risk Factors for HBV from 2009 Literature Search

Q3.B.7. Multiple Sex Partners

Review of the outlined studies demonstrated moderate quality evidence to support having multiple sex partners 

as risk factor for HBV infection. The strength of this association was due to a positive dose response 

association. (Table 36) Having multiple partners, including heterosexual partners, was associated with increased 

risk of HBV infection in five studies.110-112,114,116 Studies defined multiple partners using different thresholds. In 
55

multivariate analyses, HBV infection was associated with sex with multiple partners in a general population112

and among psychiatric inpatient veterans,114 and with multiple partners within the last six months in a general 

population.116 In a sample of people representative of the general population, having ≥2-9, ≥10-14 or ≥50 

lifetime sex partners, compared to 0-1 lifetime partners, was associated with HBV in multivariate analysis. 

However, the prevalence of HBV in the general population was 4.7% compared to age-adjusted prevalence of 

4.4% of individuals having 2-9 lifetime sexual partners.110 Among college students, > 50 lifetime heterosexual 

partners and > 5 heterosexual partners in the preceding four months were both associated with HBV infection in 

univariate analyses.111 (Table 33) In one study, 26% of respondents reported having sex with multiple 

partners,112 (Table 37) and this evidence was rated moderate quality. (Table 38)

Q3.B.8. Same Sex Partners

Our search did not identify any studies that examined an association between same sex partners and HBV 

infection.

Q3.B.9. Age at First Sexual Intercourse

There was low quality evidence to suggest an association between age at first sexual intercourse and HBV 

infection. (Table 36) Age of 18 years or younger was not associated with HBV in a multivariate analysis of 

general population participants in an NHANES study.110 Age at first intercourse of 15 years or younger was 

associated with HBV infection among college students.111 (Table 33) 

Q3.B.10. Additional Various [Sexual] Associations

Our search did not find other studies regarding association between other sexual behaviors and an increased risk 

for HBV.

Q3.B.11. Non-injection Substance

Q3.B.11.a. Other Illicit Drugs

There was very low quality evidence associating non-injection illicit drug use with HBV. (Table 36) Two of 

five studies found an association with HBV and non-injection illicit drugs.107,110,111,113,114 An NHANES study of 

the general population found any prior cocaine use was associated with HBV in a multivariate analysis, but this 

study did not control for injection drug use, a major confounding variable.110 HBV infection was associated 

with intranasal drug use among the college students.124 However, HBV infection was not associated with 

inhaled or „snorted‟ drugs in psychiatric inpatient veterans.113,114 Illicit drug use was not associated with HBV in 

a corneal donor study.107 (Table 33)

Q3.B.11.b. Alcohol

There was very low quality evidence to suggest an association between alcohol use and HBV infection. (Table 

36) Alcohol use, as reported by next-of-kin, was not associated with HBV infection among potential corneal

donors in univariate analysis.107 HBV was not associated with alcohol use disorder among psychiatric inpatient 

veterans in multivariate analysis.114 (Table 33) 

Q3.B.11.c. Tobacco 

A single study found very low quality evidence to suggest an association between tobacco use and HBV. (Table 

36) No association was found between cigarette smoking and HBV among corneal donors.107

Q3.B.12. Tattoos and Piercing

We found low quality evidence that did not support having tattoos and piercings as a risk factor for HBV. 

(Table 36) Tattoos, piercing, and acupuncture (collectively analyzed as one outcome and reported by next-ofkin) were not associated with HBV in corneal donors.107 Tattoos were not associated with HBV infection 
56

among psychiatric inpatient veterans,113 women receiving prenatal care,115 or among college students,111 unless 

the college students were tattooed with reused non-autoclaved needles. Having a tattoo in the last six months 

was not associated with acute HBV infection.116 Piercings were not associated with HBV among psychiatric 

inpatient veterans,113 and body piercings were not associated with HBV among college students.111 Piercings 

within the last six months were not associated with acute HBV in the general population either.116 (Table 33)

Q3.B.13. International Travel

We found very low quality evidence which did not find an association between international travel and having 

HBV (Table 36) among potential corneal donors.107 (Table 33)

Q3.C. HCV and Behavioral Risk Factors

Exclusionary Criteria from the 1994 Guideline

Q3.C.1. Men Who Have Sex with Men (MSM)

There was very low quality evidence to support MSM behavior as a risk factor for HCV infection. (Table 36)

The 1994 guideline excludes from becoming an organ donor “Men who have had sex with another man in the 

preceding 5 years.” We identified zero studies that addressed this particular time frame. One study comprising 

blood donors found a significant association between HCV and MSM in univariate analysis; however, an 

increased prevalence was not found adjusting for confounding by IVDU.117 A general population study found 

no association in univariate analysis.118 (Table 68)

Q3.C.2. Injection Drug Use (IDU)

This review demonstrated moderate quality evidence to support IDU as a risk factor for HCV. There were 

consistently large effect sizes found in all studies except one study on steroid use. (Table 36) The 1994 

guideline excludes from becoming an organ donor “Persons who report nonmedical intravenous, intramuscular, 

or subcutaneous injection of drugs in the preceding 5 years.” We identified zero studies that investigated the 

risk of IDU within this time frame; most studies associated lifetime IDU with infection. In general, studies did 

not distinguish between IDU and IVDU. Three blood donor studies117,119,120 and four general population 

studies51,109,112,118 detected associations between IDU and HCV. (Table 68) One blood donor study found use 

within the last six months was associated with infection.119 One blood donor study also considered past steroid 

injection reported by three donors and did not find an increased risk; however, a trend was found toward higher 

infection rate longer than six months ago.119 Two blood donor studies and three general population 

studies51,112,118 performed multivariate analyses and determined IDU was an independent risk factor; the other 

studies performed univariate assessments only. Additionally, reporting living with an injection drug user was 

associated with HCV among blood donors, even when adjusted for confounding by IDU,117 as was living with 

an injection drug user in the last six months.119 A general population study reported that both being at a social 

gathering with injection drugs and witnessing the use of injection drugs were associated with HCV.121

Prevalence of injection drug use reported in the general population studies were 1.7%51 and 3.5%.112 (Table 37), 

and this evidence was rated low quality. The lower estimate was derived from NHANES51 data and the higher 

was drawn from patients and volunteers in urban areas.112

Q3.C.3. Sex Worker

We found low quality evidence to suggest an association between sex work and HCV. (Table 36) The 1994 

guideline excludes from becoming an organ donor “Men and women who have engaged in sex in exchange for 

money or drugs in the preceding 5 years.” We did not find any literature that studied the association between 

this factor and the given time frame. Sex work was significantly associated with HCV in multivariate-analysis

in a blood donor study117 and in univariate analyses in two general population studies.118,121 However, in one 

study, all women who reported sex work also reported IDU.118 One study of corneal donors did not find any 
57

association between sex work and infection with HCV.107 (Table 68) One urban medical care center study 

reported 2.3% of participants reported exchanging sex for money or drugs,

106 (Table 37) and this evidence was 

rated low quality. (Table 38)

Q3.C.4. High Risk Sex Partner

The 1994 guideline excludes from donating organs persons who have had sex in the preceding 12 months with 

any of the following persons: MSM, IDUs, sex workers, or persons known or suspected to have HCV infection. 

We did not identify any literature on infection risk in people with high-risk sex partners during the listed time 

frame. Having a high-risk or infected sex partner was associated with HCV in ten studies.

Q3.C.4.a. Sex with Injection Drug User

Review of the outlined studies found moderate quality evidence supporting having sex with an IDU as a risk 

factor for HCV. Studies consistently found an association with large magnitude of effect. (Table 36) Sex with 

an injection drug user or intravenous drug user was significantly associated with HCV in blood donors in 

univariate117 and multivariate analyses,119 and in the general population in univariate121 and multivariate 

analysis.112 (Table 68) In one study, 5% of patients reported having sex with an injection drug user,

112 (Table

37) and this evidence was rated low quality. (Table 38)

Q3.C.4.b. Sex with a Sex Worker

We found very low quality evidence to suggest an association between having sex with a sex worker and having 

HCV. (Table 36) Sex with a sex worker was associated with HCV among blood donors in univariate and 

multivariate analyses

117 in general population studies;118,121 however, the relationship was no longer significant 

in a multivariate analysis.118 (Table 68)

Q3.C.4.c. Sex with People Known be HCV Infected

We found low quality evidence to support having sex with people known to be HCV infected as a risk factor for 

HCV infection in (Table 36) two studies of blood donors, one with multivariate analysis117 and one with 

univariate analysis119 One study limited the behavior to the previous six months.119 (Table 68)

Q3.C.4.d. Other High Risk Sex Partners

Some miscellaneous types of high-risk sex partners pertinent to high-risk sex partners not mentioned in the 

original guideline were also reported, such as sexual promiscuity (defined as history of a sexually transmitted 

disease (STD) or at least five sex partners per year)120 and sex with a transfusion recipient117 in blood donors. 

We report these studies here because they are germane to the larger issue of having high-risk sex partners. 

However, no GRADE rating was given because these two studies reported on different factors. (Table 68)

Q3.C.5. Inmates

We found low quality evidence to support incarceration as a risk factor for HCV. The 1994 guideline excludes 

from becoming organ donors inmates of correctional systems. No studies that examined the association between 

present incarceration and infection were identified. However, the searches did identify studies that examined the 

association between recent or lifetime history of incarceration. A history of incarceration was associated with 

HCV in four of five studies.107,117,119-121 Incarceration was associated with HCV in three blood donor 

studies.117,119,120 One study found that incarceration for more than three days was an independent risk factor,117

while another study found no association once adjusted for confounding by IDU.120 In addition, having been 

arrested was associated with HCV infection in a univariate analysis of a general population sample.121 A history 

of incarceration as reported by next-of-kin was not associated with HCV infection in potential corneal

donors.107 (Table 68) 
58

Q3.C.6. Risk Factors in Children

We identified no literature on any behavioral risk factors in children, or on the risk of infection from mothers 

who engage in those risk behaviors. While vertical transmission is generally recognized as a mode of hepatitis 

or HIV transmission, this body of literature lacks the evidence to assess the 1994 criteria as risk factors.

Additional Potential Risk Factors for HCV from 2009 Literature Search

Q3.C.7. Multiple Sex Partners

Review of the outlined studies found moderate quality evidence confirming an association between HCV 

infection and having multiple sex partners. Studies demonstrated a positive dose-response association. (Table 

36) Having multiple partners (defined using different thresholds) was associated with increased risk of infection 

in six studies.51,109,112,117,119,121 Having at least 11 male sexual partners (compared to having zero sexual 

partners) was associated with HCV infection in multivariable analysis in female blood donors,117 whereas 

having the same number of lifetime female partners was not associated with HCV in men. Having two or more 

sexual partners, whether same sex or not, in the last six months was associated with an increased rate of HCV 

infection overall in a univariate analysis.119 A general population study did not find HCV was associated with 

having frequent sex partners109 multiple sex partners112 and at least 20 sexual partners in univariate anlaysis.51

Another general population study also reported greater numbers of sex partners associated with HCV infection 

in univariate analysis.121 One study noted the strong association between greater numbers of sex partners and 

IDU. Of the 18.5% of their patients who reported having at least 10 sex partners in their sample, 84% also 

reported IDU.118 (Table 68) In a study of the U.S. general population, 29% of survey respondents indicated 

having had at least 10 sex partners51 and 26% of volunteers from an urban area reported sex with multiple 

partners.112 (Table 37) There was moderate quality evidence regarding the prevalence of having multiple sex 

partners (number undefined) and having at least 2 sex partners. (Table 38)

Q3.C.8. Same Sex Partners

There was very low quality evidence to suggest an association between same sex partners and HCV. (Table 36) 

A study of female blood donors found an increased risk of HCV in females with same-sex partners in 

multivariate analysis.117 This risk was no longer significant when adjusted for confounding by IDU. Among 

outpatients, no association was found between having sex with a person of the same sex and HCV infection in 

univariate analysis.121 (Table 68)

Q3.C.9. Age at First Sexual Intercourse

We found low quality evidence associating younger age at first intercourse with HCV infection. This single 

study identified a dose-dependent relationship. (Table 36) In the general population, first sexual intercourse at 

age of 17 years or younger was associated with HCV in a univariate analysis. The study stratified age at first 

intercourse (i.e., age younger than 11, age 12-15, and age 16-17 years). The groups of people who were younger 

at the time of their first sexual intercourse had the highest risk of HCV.51 (Table 68) The proportion of adults 

who reported having sex at age 18 or younger was 58%51 (Table 37) and this evidence was rated moderate 

quality (Table 38)

Additional Various [Sexual] Associations

Unprotected sex was associated with HCV infection in a general population.109 However, we did not assign a 

GRADE rating because only one study reported this factor. (Table 68)
59

Q3.C.10. Non-injection Substance

Q3.C.10.a. Other Illicit Drugs

There was low quality evidence associating HCV with non-injection drug use. (Table 36) Seven of eight studies 

found an association with HCV and non-injection substances.51,107,109,117-121 Intranasal drugs were associated 

with HCV infection in blood donors,117,119,120 when adjusted for confounding by IDU or other factors in two 

studies.117,120 In a general population study, use of snorting or inhaling nonprescription drugs,121 inhaling 

cocaine,109 using intranasal cocaine,118 and use of non-injection drugs other than marijuana51 were all associated 

with increased prevalence of HCV. One of the studies using NHANES data found only a marginal independent 

association with HCV between non-injection drug use (except marijuana) compared to those who reported 

either no illicit drug or marijuana use,

51 while another study did not; however, cocaine use in the absence of 

IDU or tattoos was unusual in their sample.118 Being at a social gathering with cocaine was associated with 

HCV.121 And having friends who use street drugs was associated with an increased risk of HCV among blood 

donors.119 Illicit drug use was not associated with HCV in a corneal donor study.107 (Table 68) In the general 

population, 17% reported lifetime use of drugs other than marijuana51 (Table 37), and this evidence was rated 

moderate quality. (Table 38)

Q3.C.10.b. Alcohol

There was very low quality evidence to suggest a relationship between alcohol use and HCV. (Table 36) HCV 

was associated with heavy alcohol use in heart donors,122 and with having at least two units of alcohol per day 

among adults tested for HCV because of clinical suspicion.

118 However, HCV was not associated with alcohol 

use among corneal donors,107 having at least 5 alcoholic drinks weekly in patients,121 or alcoholism in HMO 

enrollees.109 All of these analyses were univariate. (Table 68) 

Q3.C.10.c. Tobacco

We found very low quality evidence associating tobacco use with HCV. (Table 36) We also found low quality 

evidence estimating the prevalence of tobacco use. (Table 38) A history of tobacco use was associated with 

HCV in heart donors,122 and cigarette smoking was associated with HCV in corneal donors 107 in univariate 

analyses. (Table 68) Among actual heart donors, 36% had a history of tobacco use122 (Table 37) and the 

evidence was rated low quality. (Table 38)

Q3.C.11. Tattoos and Piercing

Review of available studies found low quality evidence to associate tattoos and piercings with HCV. Tattoos 

were consistently associated with HCV in six of seven studies,107,109,117-121 whereas piercings were 

inconsistently associated with HCV (Table 36) in three of six studies.109,117-121 Three blood donor studies 

reported tattoos were associated with HCV in univariate analyses.117,119,120 One study focused on having had a 

tattoo within the last six months and the risk of acute HCV.119 When multivariate analyses were performed, 

tattoos were not significantly associated with infection in one study,

119 but remained an independent predictor in 

a second study, although the odds of infection were reduced once adjusted for confounding by IDU.117 Three 

general population studies109,118,121 also detected significant associations between tattoos and HCV. Only study 

of the three general population studies found that tattoos were an independent predictor.118 Adults were enrolled 

based upon clinical suspicion of hepatitis, and most reported that their tattoos had been applied by friends, 

fellow gang members, or fellow inmates. Among blood donors, HCV was not associated with body piercing in 

the last 6 months,119 but was associated with ear piercing among men,120 and pierced ears or body parts.117 Two 

general population studies did not find an association between body piercing and HCV.109,118 In two general 

population studies,118,121 only one found ear piercing in adult patients was associated with HCV in a univariate 

analysis.121 Tattoos, piercing, and acupuncture (as collectively analyzed as one outcome and reported by nextof-kin) were not associated with HCV in potential corneal donors.107 (Table 68) 
60

Q3.C.12. International Travel

We found low quality evidence that did not suggest an association between international travel and HCV 

infection. Among potential corneal donors, international travel was not associated with HCV.107 International 

travel within the last six months was not associated with acute HCV in a general population117 or among blood 

donors. Having ever lived outside the United States was not found to be significantly associated with HCV in a 

blood donor study.

117 (Table 68) 

Question 4. What nonbehavioral factors are associated with an increased probability of 

infection with HIV, HBV, or HCV? What is the prevalence of these factors among 

potential solid organ donors?

The primary intent of this question was to identify signs and symptoms of incident infections (i.e., recently 

acquired), but also include data on signs and symptoms of chronic infection, medical co-morbidities, 

socioeconomic information, and demographic factors. The second half of the question addresses the frequency 

of these nonbehavioral factors. Information regarding exclusionary factors listed in the 1994 guideline is 

presented first, and then information regarding additional factors for which at least two studies provided 

evidence regarding the same factor is presented.

Due to the lack of evidence in the literature meeting inclusion criteria identifying risk factors for incident 

infection, the potential risk factors identified from the literature review in Table 9 of this document were 

modified by subject matter experts on HIV and hepatitis to create a revised list of risk factors for screening in 

Table 3 of this document. The revised list takes into consideration that 1) certain risk factors can be omitted 

because they are likely markers for other factors identified in the systematic review and 2) certain risk factors 

should be added because scientific evidence associating certain factors with the bloodborne pathogens exists, 

but may not have met the inclusion criteria of the systematic review or studies were of insufficient quality to 

draw conclusions.

Q4.A. HIV and Nonbehavioral Risk Factors

Q4.A.1. People with Hemophilia or Related Clotting Disorder who Received Clotting Factor Blood Products

No studies were identified that met the inclusion criteria. The 1994 guideline excludes from donating “Persons 

with hemophilia or related clotting disorders who have received human-derived clotting factor concentrates.” 

Q4.A.2. Exposure to Infected or Suspected Infected Blood

No studies were identified that met the inclusion criteria. The 1994 guideline excludes from donating “Persons 

who have been exposed in the preceding 12 months to known or suspected HIV-infected blood through 

percutaneous inoculation or through contact with an open wound, nonintact skin, or mucous membrane.” 

Q4.A.3. Children

We did not identify any literature regarding the nonbehavioral risk factors listed above, in children, or in 

children of mothers who engage in those nonbehavioral risk factors. 

Q4.A.4. Signs and Symptoms

No studies were identified that met the inclusion criteria. An objective of this section was to identify 

nonbehavioral factors that could be predictive of infection, especially acute infection during the window period 

before tests could recognize the infection. 
61

Additional Risk Factors from 2009 Literature Search

Q4.A.5. Receipt of Blood Transfusion

No studies were identified that met the inclusion criteria.

Q4.A.6. Nonspecific Exposure

Q4.A.6.a. Accidental Needle Stick

A single study found very low quality evidence that did not find an association between accidental needle sticks 

and HIV infection. (Table 42) Data was collected from next-of-kin for potential corneal donors. The study did 

not identify if the needle stick occurred in an occupational or nonoccupational setting.

107 (Table 41) 

Q4.A.6.b. Hemodialysis

No studies were identified that met the inclusion criteria.

Q4.A.6.c. Surgery

A single study found very low quality evidence which did not find an association between having surgery and 

acquiring HIV. (Table 42) Data were collected from next-of-kin for potential corneal donors.107 (Table 41) 

Q4.A.6.d. Organ and Corneal Transplantation Recipients

No organ donor studies were identified that met the inclusion criteria. There was very low quality evidence 

which did not find an association between having a corneal transplant with HIV. (Table 42) Receipt of organ 

transplantation was not associated with a greater risk of HIV in a corneal donor study.107 (Table 41) 

Q4.A.6.e. Acupuncture

No studies were identified that met the inclusion criteria.

Q4.A.6.f. Dental Work

No studies were identified that met the inclusion criteria.

Q4.A.6.g. Blood Draws

There was very low quality evidence that did not find an association between having blood drawn and HIV. 

(Table 42) A corneal donor study did not find an association between blood drawn for HIV testing and HIV, 

based upon next of-kin interviews.107 (Table 41) 

Q4.A.6.h. Other Blood Exposure

No studies were identified that met the inclusion criteria.

Q4.A.6.i. Household Exposure

No studies were identified that met the inclusion criteria.
62

Q4.A.7. Other Infections

This review found low quality evidence associating HIV with having another infection. (Table 42) In general 

population studies, HIV infection was associated with a diagnosis of an STD in one study,106 herpes simplex 

virus-2 (HSV-2) in two studies with large effect sizes in univariate analyses,104,105 and syphilis or infections 

other than HIV in a fourth study in multivariate analysis.108 Rabies exposure was not associated with HIV in a 

corneal donor study.107 (Table 41) The prevalence of antibodies to HSV-2 was 28% in a general population 

study comprising New Yorkers.105 STD diagnoses were reported by 18% of patients in an urban medical care 

center.106 (Table 43) 

Q4.A.8. Demographic Factors

Q4.A.8.a. Sex

Three general population studies did not find an association between male sex and HIV, and the evidence was 

rated low quality.

105,106,123 (Table 41) 

Q4.A.8.b. Age or Year of Birth

We found very low quality evidence to suggest a relationship between age and having HIV. (Table 42) Studies 

assessed different age ranges, complicating comparison. One study found adults aged 18 to 30 had increased 

prevalence of HIV in a multivariate analysis.

123 Another study found higher prevalence of HIV in adults aged 

25 to 40 compared to younger people aged 15 to 24 years in univariate analysis with a large effect size,106 

109

and a third found increased prevalence among adults aged 35 to 44 years.108 (Table 41) 

Q4.A.8.c. Race or Ethnicity, and National Origin

We found very low quality evidence to suggest an association between race or ethnicity and HIV. (Table 42)

Two general population studies found a higher prevalence of HIV in Asians and Hispanic ethnicity compared to 

White race

105,106 and those who spoke Spanish compared to English in emergency room patients.123 in univariate 

analyses These same studies found increased prevalence of HIV with a large effect size among people of Black 

race105,106 but a third study in the general population did not.123 (Table 41) 

Q4.A.8.d. Occupation

No studies were identified that met the inclusion criteria.

Q4.A.8.e. Education

Neither of two general population studies found an association between having less than a high school 

education and having HIV.104,106 The evidence was rated very low quality. (Table 41) 

Q4.A.8.f. Economic Factors

There was very low quality evidence suggesting an association between economic factors and having HIV. 

(Table 42) Being homeless was independently associated with an increased prevalence of HIV in public 

hospital emergency room patients123 while having a poverty index of less than one was not associated with 

HIV.104 (Table 41) 

Q4.A.8.g. Health Insurance

Patients with no health insurance had higher prevalence of HIV in one study of hospital patients,106 but not in 

another such study.123 (Table 41) This evidence was rated as very low quality. (Table 42)
63

Q4.A.8.h. Marital Status

A single study found low quality evidence to suggest a relationship between marital status and having HIV. 

(Table 42) Being married or cohabitating was associated with a lower prevalence of HIV in the general 

population. 104 (Table 41) 

Q4.B. HBV and Nonbehavioral Risk Factors

Q4.B.1. People with Hemophilia or Related Clotting Disorder who Received Clotting Factor Blood Products

We identified zero studies that studied whether this factor was associated with an increased prevalence of 

infection. The 1994 guideline excludes from donating “Persons with hemophilia or related clotting disorders 

who have received human-derived clotting factor concentrates.” 

Q4.B.2. Exposure to Infected or Suspected Infected Blood

There was very low quality evidence supporting exposure to blood known or suspected to be HBV infected as a 

risk factor for HBV. (Table 42) The 1994 guideline excludes from donating “Persons who have been exposed in 

the preceding 12 months to known or suspected HIV-infected blood through percutaneous inoculation or 

through contact with an open wound, nonintact skin, or mucous membrane.” Among embalmers, no association 

was found between needle stick injury with exposure to HBV during embalming and HBV infection.124 (Table 

39) 

Q4.B.3. Children

We did not identify any literature regarding the nonbehavioral risk factors, listed above, in children, or in 

children of mothers who engage in those nonbehavioral risk factors risk factors. 

Q4.B.4. Signs and Symptoms

No studies were identified that met the inclusion criteria. An objective of this section was to identify 

nonbehavioral factors that could be predictive of infection, especially acute infection during the window period 

before tests could recognize the infection. 

Additional Risk Factors from 2009 Literature Search

Q4.B.5. Receipt of Blood Transfusion

There was very low quality evidence to support receipt of blood transfusions as a risk factor for HBV. (Table 

42) Although no studies reported on risk in people with clotting disorders or who have received clotting factor 

blood products, several investigated the risk of infection associated with blood transfusion. Blood transfusion 

was independently associated with HBV infection in a general population,112 as was blood transfusion before 

1991 among college students.111 Blood transfusion was not associated with HBV in a low prevalence obstetric 

patients study.115 Among volunteers from an urban area, 20% reported having ever had a blood transfusion.112

(Table 39) There was low quality evidence estimating the prevalence of receiving a blood transfusion. (Table 

44)

Q4.B.6. Nonspecific Exposure

Q4.B.6.a. Accidental Needle Stick

Review of the literature revealed very low quality evidence that did not suggest an association between 

accidental needle stick and acquiring HBV. (Table 42) In a general population study, needle stick injuries were 

actually associated with lower prevalence of HBV infection.112This may be because a substantial proportion of 

the enrollees were healthcare workers, and in that study healthcare workers had a lower prevalence of HBV than 
64

the group as a whole. According to data collected from next-of-kin, accidental needle sticks were not associated 

with HBV among potential corneal donors.107 (Table 39) 

Q4.B.6.b. Hemodialysis

We found moderate quality evidence suggesting hemodialysis as a risk factor for HBV. (Table 42)

Hemodialysis was associated with HBV among participants in a general population study112 and college 

students111 with large effect sizes in univariate analyses. (Table 39) 

Q4.B.6.c. Surgery

We found very low quality evidence which did not suggest an association between having had surgery and 

HBV. (Table 42) In the general population, surgery was associated with a slightly lower HBV prevalence in 

univariate analysis,112 and surgery during the last six months was not associated with acute HBV.116 Based upon 

next-of-kin data for potential corneal donors, no association was found between HBV and surgeries.107 (Table 

39)

Q4.B.6.d. Organ and Corneal Transplantation Recipients

No organ donor studies were identified that met the inclusion criteria. There was very low quality evidence 

associating having had a corneal transplant and HBV. (Table 42) Receipt of organ transplantation was not 

associated with a greater risk of HBV in a corneal donor study,107 or with HBV among psychiatric inpatient 

veterans.113 (Table 39) 

Q4.B.6.e. Acupuncture

There was low quality evidence which did not suggest a relationship between acupuncture and having HBV. 

(Table 42) Acupuncture during the last six months was not associated with an increased incidence of acute 

HBV in the general population,116 or an increased prevalence of HBV among psychiatric inpatient veterans.113

(Table 39) 

Q4.B.6.f. Dental Work

A single general population study found very low quality evidence which did not suggest an association 

between dental work within the last six months and HBV.116 (Tables 42 and 39)

Q4.B.6.g. Blood Draws

A single study found very low quality evidence which did not suggest an association between blood draws and 

having HBV. (Table 42) Blood draws are probably a proxy for other risk factors. A corneal donor study did not 

find an association between HIV testing and HBV based upon next-of-kin interviews.107 (Table 39) 

Q4.B.6.h. Other Blood Exposure

These factors here reported because of their relevance but did not rate the GRADE for these outcomes due to 

lack of replication of the factors. Neither bloody object contact113 nor combat exposure114 were associated with 

HBV among psychiatric inpatient veterans. 

Q4.B.6.i. Household Exposure

This review found very low quality evidence associating household exposure with someone with HBV and 

having HBV. (Table 42) Having household contact with someone with hepatitis was associated with HBV 

among college students,111 as was a family history of HBV among Asian Americans in multivariate analysis.125

However, having a household member with HBV was not associated with HBV in an obstetric population;115

nor was being the wife of a man with HBV among Korean American church goers.126 Sharing a razor or 

toothbrush with a household member was not associated with HBV in a general population study.116 (Table 39) 
65

Q4.B.7. Other Infections

We found low quality evidence to suggest an association between having HBV and exposure to, or having, 

other types of infection. (Table 42) Among college students, HBV infection was associated with having had a 

sexually transmitted disease (STD) in multivariate analysis.111 Rabies exposure was not associated with HBV in 

a corneal donor study.107 (Table 39) 

Q4.B.8. Demographic Factors

Q4.B.8.a Sex

We found very low quality evidence to suggest an association between sex and having HBV. (Table 42) Males 

had higher rates of HBV than females in studies of the general population,

112 Asian American population in 

multivariate analyses,125 and psychiatric inpatient veterans (of whom nearly all were male),113 but not in studies 

of Korean American church goers.127 Among college students, females had higher rates of HBV in multivariate 

analysis,111 Among children who had received a blood transfusion, rates were not significantly different 

between genders.128 (Table 39) 

Q4.B.8.b. Age or Year of Birth

There was very low quality evidence to suggest age as a risk factor for HBV. (Table 42) Studies assessed 

different age ranges, complicating comparison. One general population study found an increased risk of HBV in 

individuals >60 years of age in multivariate analysis.112 The remaining studies were in demographic or 

socioeconomic subpopulations. One study of college students found an association with increased mean age in 

multivariate analysis,111 while a study of psychiatric inpatient veterans did not.113 In univariate analyses, 

increased prevalence was associated with age over 35 years among embalmers in high-prevalence urban areas 

with a large effect size124 and “age younger than 20 years” among Korean-American church-goers,

126 but not 

age over 50 years among psychiatric inpatient veterans in multivariate analysis.114 In another study of KoreanAmerican church-goers, lower prevalence was found in people under 49 years.127 The last study comprising 

Asian Americans did not find any association between age and HBV.

125 (Table 39) 

Q4.B.8.c. Race or Ethnicity, and National Origin

This review found very low quality evidence to suggest a relationship between HBV and an individual‟s race, 

ethnicity or national origin. (Table 42) Regarding race or ethnicity, non-Hispanic Black race, compared with 

non-Hispanic White race, was associated with a higher prevalence of HBV in a general population,110 among 

college students111, and psychiatric inpatient veterans in multivariate analyses.

114 This association was not found 

in a study of psychiatric inpatient veterans.113 Being Mexican-American was not associated with a different 

prevalence of HBV than non-Hispanic White race in a multivariate analysis of a general population study.110

And in demographic or socioeconomic subpopulations, Hispanic ethnicity113 and Hispanic or Latino ethnicity111

were not associated with HBV infection. Additionally, White race or Hispanic ethnicity was associated with 

lower HBV prevalence in a general population study in multivariate analysis.112 Among college students, Asian 

students had higher rates of HBV.111 Regarding national origin, HBV was independently associated with being 

born in Southeast Asia or Africa in one general population study.

112 A special population study found children 

born in Korea had higher prevalence of HBV than children born in the United States.

126 Other special 

population studies did not find significantly different rates of Asian Americans born in East Asia (excluding 

China) or Southeast Asia or Pacific Islands compared to Asian Americans born in China.125 In a general 

population study, acute HBV was not associated with birth in an area with a high endemic rate of HBV or 

having a household contact with someone who was born in an endemic area.116 In multivariate analyses, a 

general population study110 and a study of Asian Americans study125 found that being born in the United States

was associated was lower prevalence of HBV; the relative odds of HBV comparing “other” national origins to 

the United States was 3.4. Among African American, Caucasian, Asian, and Hispanic children who received 

blood transfusions, the prevalence of HBV was not significantly different.116 (Table 39) 
66

Q4.B.8.d. Occupation

There was low quality evidence supporting an association between the type of occupation and having HBV. It is 

important to note that some of these studies included data on healthcare workers before 1992, when HBV 

vaccination requirements for healthcare workers took effect. A single study found very low quality evidence 

showing no association between military service and HBV. (Table 42) Being a healthcare worker with frequent 

blood exposure was associated with an increased prevalence of HBV in college students,111 but being a 

healthcare worker was not associated with HBV in general population studies110,112 or having been a healthcare 

worker in psychiatric inpatient veterans.113 Another general population study did not associate healthcare 

employment or household contact with someone who is a healthcare worker with HBV,116 and a special 

population study did not associate being a healthcare worker or the spouse of one with HBV.115 Being in the 

military also was not associated with HBV in a general population study.110 (Table 39) 

Q4.B.8.e. Education

There was very low quality evidence suggesting a relationship between education level and HBV status. (Table 

42) Compared to patients with some college education, those with less than a high school education had higher 

prevalence of HBV in multivariate analysis.110 A second study reported that students enrolled in 4-year colleges 

had lower rates of HBV than students enrolled in 2-year colleges in multivariate analysis.111 However, years of 

education was not associated with HBV among psychiatric inpatient veterans.113 (Table 39) 

Q4.B.8.f. Economic Factors

We found very low quality evidence which did not find an association between economic factors and HBV.

(Table 42) Being homeless was not associated with an increased risk of HBV among psychiatric inpatient 

veterans.113 Another special population study did not associate homelessness, institutionalization, or other nonindependent living arrangement with HBV.114 (Table 39) 

Q4.B.8.g. Health Insurance

No studies were identified that met the inclusion criteria.

Q4.B.8.h. Marital Status

We found low quality evidence to support marital status as a risk factor for HBV. (Table 42) A general 

population study reported that being divorced or single was associated with a higher prevalence of HBV than 

any other status in multivariate analysis.110 Being currently married was not associated with any difference in 

HBV prevalence than any other status among psychiatric inpatient veterans.114(Table 39) 

Q4.C. HCV and Nonbehavioral Risk Factors

Q4.C.1. People with Hemophilia or Related Clotting Disorder who Received Clotting Factor Blood Products

We identified zero studies that studied whether this factor was associated with an increased prevalence of 

infection. The 1994 guideline excludes from donating “Persons with hemophilia or related clotting disorders 

who have received human-derived clotting factor concentrates.” 

Q4.C.2. Exposure to Infected or Suspected Infected Blood

No studies were identified that met the inclusion criteria. The 1994 guideline excludes from donating “Persons 

who have been exposed in the preceding 12 months to known or suspected HIV-infected blood through 

percutaneous inoculation or through contact with an open wound, nonintact skin, or mucous membrane.” 

Q4.C.3. Children

We did not identify any literature regarding the nonbehavioral risk factors, listed above, in children, or in 

children of mothers who engage in those nonbehavioral risk factors risk factors. 
67

Q4.C.4. Signs and Symptoms

Review of the outlined studies found low quality evidence associating HCV with jaundice, alanine 

aminotransferase (ALT) reactivity, and elevated ALT with large effect sizes. There was very low quality 

evidence associating HCV with elevated liver enzyme and the effect size was not large. (Table 42) There was 

low quality evidence regarding the prevalence of sign and symptoms for HCV (Table 44) An objective of this 

section was to identify nonbehavioral factors that could be predictive of infection, especially acute infection 

during the window period before tests recognize the infection. Four studies were identified.51,109,119,121 In blood 

donors, ALT reactivity was significantly associated with infection with a large magnitude of effect.119 In a 

general population, serum ALT of >40 U/L was associated with HCV.51 Elevated liver enzymes were

significantly associated with HCV with a large effect size in adults, comprising individuals at risk for HCV and 

healthcare workers, enrolled in a HMO.109 In addition, jaundice was associated with HCV in adults in a general 

medical clinic with a large effect size.121 All four were univariate analyses. (Table 40) In one study, 9% of 

respondents had ALT levels >40 U/L.51 (Table 43) and evidence was rated low quality.

Additional Risk Factors from 2009 Literature Search

Q4.C.5. Receipt of Blood Transfusion

We found moderate quality evidence supporting an association between receiving blood transfusions and HCV 

with a large effect size. (Table 42) Although no studies reported on risk in people with clotting disorders or who 

have received clotting factor blood products, many did investigate the risk of infection associated with blood 

transfusion. All eight studies found some association with transfusion and HCV infection. Receiving a blood 

transfusion was independently associated with HCV in three blood donor studies (data collection occurring 

1994-96, 1991, and 1992-93)117,120,129 and three general population studies (data collection occurring 1999-

2002, 2000-2002, and 1992).

51,112,118 the remaining two general population study performed univariate 

analyses.109,121 In a study of blood donors, sex with a blood transfusion recipient was also associated with 

HCV.117 Additionally, a significant association was found between blood transfusion and HCV among donors 

who had never injected drugs. (Table 40) Among general population survey respondents, 6% aged 20 to 59 

years and 16% of those aged at least 60 years reported having a blood transfusion before 1992.51 Among 

volunteers from an urban area, 20% reported having ever had a blood transfusion.112 (Table 43) We found low 

quality evidence regarding estimates of the prevalence of having blood transfusions. (Table 44)

Q4.C.6. Nonspecific Exposure

Q4.C.6.a. Accidental Needle Stick

There was very low quality evidence supporting accidental needle stick as a risk factor for HCV. (Table 42) In a 

general population study, needle stick injuries were actually associated with lower prevalence of HCV 

infection.112 This may be because a substantial proportion of the enrollees were healthcare workers, and in that 

study healthcare workers had a lower prevalence of HCV and HBV than the group as a whole. Needle stick 

injuries among healthcare worker blood donors were not associated with HCV either.120 However, bloody 

needle stick injuries in a medical setting was independently associated with an increased prevalence of HCV.117

According to data collected from next-of-kin, accidental needle sticks were not associated HCV among 

potential corneal donors.107 (Table 40) 

Q4.C.6.b. Hemodialysis

There was low quality evidence which found an association between hemodialysis and HCV. (Table 42) In two 

general population studies, HCV infection was independently associated with hemodialysis112 and with “kidney 

dialysis” in univariate analysis with a large effect size.121 A third study involving adults with known HCV, risk 
68

factors for HCV, or planned hemodialysis did not find an association between hemodialysis and HCV in 

univariate analysis.118 (Table 40) 

Q4.C.6.c. Surgery

We found very low quality evidence supporting having had surgery with HCV infection. (Table 42) In a 

univariate analysis, being hospitalized was associated with HCV with a large effect size; however, having 

surgery or a medical procedure in the six months before blood donation was not associated with HCV.119

Having a history of surgery was not associated with HCV in general population studies.109,112 However, lifetime 

history of surgery or sutures was independently associated with elevated HCV prevalence in blood donors.117

Based upon next-of-kin data for potential corneal donors, no associations was found between HCV and 

surgeries.107 (Table 40) 

Q4.C.6.d. Organ and Corneal Transplantation Recipients

No organ donor studies were identified that met the inclusion criteria. A single study found very low quality 

evidence to suggest an association between having a corneal transplant and HCV. (Table 42) Receipt of organ 

transplantation was not associated with a greater risk of HCV in a corneal donor study.107 (Table 40) 

Q4.C.6.e. Acupuncture

There was low quality evidence which did not find an association between acupuncture and HCV (Table 42)

among blood donors,

120,129 or people in a general population study.118 (Table 40) 

Q4.C.6.f. Dental Work

There was low quality evidence which did not suggest an association between having dental work and HCV. 

(Table 42) Dental work was not associated with HCV among blood donors,117 nor was having dental work in 

the six months before blood donation.119 (Table 40) 

Q4.C.6.g. Blood Draws

We found very low quality evidence suggesting an association between having blood drawn and HCV infection. 

(Table 42) A general population study reported an association between having had a blood test for HBV and 

having an HCV infection in univariate analysis with a large effect size.121 In the same study, being a blood 

donor was associated with reduced risk of HCV, and having been rejected as a blood donor was associated with 

an increased risk of HCV, also with a large effect size.121 Based upon next-of-kin data for potential corneal

donors, no associations was found between HIV testing and HCV.107 (Table 40) 

Q4.C.6.h. Other Blood Exposure

These factors were reported because of their relevance but GRADE ratings were not done due to lack of 

replication of the factors. Having been stuck or cut with a bloody object was independently associated with 

HCV among blood donors.129 Among blood donors, blood exposure during fighting, by biting, at an accident 

site, or during a manicure in the last six months was associated with HCV in univariate analysis with a large 

effect size, but not during a haircut in the last six months.119 Contact with blood was not associated with HCV in 

members of a general population.118 (Table 40) 

Q4.C.6.i. Household Exposure

We found very low quality evidence to suggest a relationship between household exposure to HCV and having 

HCV. (Table 42) Among blood donors, living with someone with hepatitis or having a relative with hepatitis 

was not associated with HCV infection, but in multivariate analysis living with a transfusion recipient was.117

Additionally, sharing a toothbrush or razor with person(s) unspecified was associated with HCV among blood 

donors.117 In general population studies, having at least one family member treated for viral hepatitis was not 
69

associated with an increased risk of HCV in one study,109 but having at least one family member with HCV was 

associated with an increased risk in another study.121 (Table 40) 

Q4.C.7. Other Infections

We found low quality evidence to suggest an association between STD or other infections and having HCV.

(Table 42) We found moderate quality evidence estimating the prevalence of HSV-2 infection. (Table 44)

Among blood donors, HCV was significantly associated with history of STD,117,120 having a STD within six 

months of donating,119 and seropositivity for other reactive infectious diseases119,129 with two of the studies 

demonstrating an independent association.117,129 Among people from general populations, having past treatment 

for STDs was not associated with HCV,121 but having HSV infection was.51 HIV infection was not associated 

with HCV infection in univariate analysis of a general population.118 Rabies exposure was not associated with 

HCV in a corneal donor study.107 (Table 40) Antibodies to HSV-2 were detected in 19% of general nationwide 

population aged 18 to 49 years.51

Q4.C.8. Demographic Factors

Q5.C.8.a. Sex

We found very low quality evidence to suggest an association between gender and having HCV. (Table 42) 

Being male was independently associated with an increased risk of HCV among heart transplant donors122 and 

blood donors,129 but was not associated in two blood donor studies.119,120 In the general population, significantly 

higher proportions of males had HCV infection in four51,112,121,130 out of five studies.109 (Table 40) 

Q4.C.8.b. Age or Year of Birth

There was very low quality evidence associating age and HCV. (Table 42) Studies assessed different age 

ranges, complicating comparison. An organ donor study found that HCV infection was associated with older 

median age.122 One blood donor study associated HCV with older mean age,119 while the other did not.120 In 

general population studies, HCV was associated with increased mean age130 and decade of birth (with people 

born between 1940 and 1959 having the highest prevalence),121 but not age less than 50 years109 or age less than 

60 years.112 (Table 40) 

Q4.C.8.c. Race or Ethnicity, and National Origin

Review of the outlined studies found very low quality evidence associating HCV with an individual‟s race or 

ethnicity, as well as very low quality evidence associating HCV with national origin/birthplace and preferred 

language (Table 42) Among heart donors, ethnicity was not associated with HCV.122 Black race was associated 

with increased rates of HCV compared to White race in two blood donor studies,120,129 of which one was an 

independent finding.129 In general population studies, Black race or Hispanic ethnicity was independently 

associated with infection in one study;51 however, Black race or Hispanic ethnicity was not associated with 

infection in two other studies.121,130 Among blood donors, one study found that Hispanic ethnicity had a higher 

risk of HCV than White race in multivariate analysis,129 but another did not.119 Being Asian was associated with 

having a lower prevalence of HCV compared to White race among blood donors in multivariate analysis.129

One blood donor study did not associate foreign birth with HCV,119 but another did in multivariate analysis.129

A general population study found people born outside of the U.S. had a lower prevalence of HCV in 

multivariate analysis.51 Birth in Southeast Asia or Africa was not associated with an increased prevalence of 

HCV in another general population study.112 Another general population study found no association between 

HCV and U.S. citizenship.121 Among African American, Caucasian, Asian, and Hispanic children who received 

blood transfusions, the prevalence of HCV was not significantly different.112 (Table 40) 
70

Q4.C.8.d. Occupation

We found very low quality evidence to support an individual‟s type of occupation as being a risk factor for 

HCV. (Table 42) Among blood donors, occupational blood exposure was independently associated with HCV 

infection,117 but a medical or dental job or public safety job with frequent blood contact was not.119 In the 

general population, work contact with blood was not associated with increased HCV,109 and being a healthcare 

worker was associated with a lower rate of HCV. 112 In two general population studies, having served in the 

armed forces was not associated with HCV.51,109 A study of health clinic patients did associate having a job at a 

prison with having HCV.121 (Table 40) 

Q4.C.8.e. Education

There was very low quality evidence suggesting an association between level of education and HCV infection. 

(Table 42) Lower educational attainment was associated with HCV in blood donors119,120 with one study having 

a large effect size in univariate analysis.119 One general population study associated having fewer than 12 years 

of education with having HCV,51 but two others found no association between educational attainment and 

HCV.121,130 (Table 40)

Q4.C.8.f. Economic Factors

There was very low quality evidence associating economic factors and HCV. (Table 42) Ever having been 

homeless was associated with an increased risk of HCV in adults attending general medicine or hepatology 

clinics.121 Neither income nor living in poverty was associated with HCV.

51,121 (Table 40) 

Q4.C.8.g. Health Insurance

A single study found very low quality evidence to suggest an association between type of health coverage 

(Medicaid, Medicare, private, or self-pay) and having HCV (Table 42), with Medicaid patients having the 

highest prevalence of HCV.130 (Table 40) 

Q4.C.8.h. Marital Status

A single study found low quality evidence associating marital status and HCV. (Table 42) Being married was 

associated with a lower rate of HCV in one blood donor study.117 (Table 40)

Question 5. What are the test characteristics of the screening methods available to detect 

HIV, HBV, and HCV in potential solid organ donors? Do test characteristics differ in 

particular populations and with donor clinical status (i.e., donation after brain death 

versus donation after cardiac death OR adult versus pediatric donors)?

Numerous tests exist to detect HIV, HBV and/or HCV in potential donors, and this question concerns the 

accuracy, sensitivity, and specificity of those tests, as well as the length of the window period and the 

turnaround time to perform the tests. For the systematic review of the literature, tests of interest included

immunoassay tests and NAT currently used in the United States by OPOs, as well as fourth-generation HIV and 

HCV antibody/antigen tests currently in use outside of the United States. Other FDA licensed assays, such as 

the Abbott Prism HCV, Procleix Ultrio Assay and Abbott Prism HIV O Plus were not included for review as 

these assays are not routinely used by OPOs. The p24 antigen test for HIV was not included because it is no 

longer used by OPOs. Additionally, an HCV antigen assay used in Europe was not included because the assay 

was licensed subsequent to the guideline literature search.

Initial searches of bibliographic databases were for test instruments for HBV, HCV, or HIV. Once the list of 

included tests was generated, additional searches were performed specifically by each test‟s name. The focus of 
71

these searches was to identify peer-reviewed literature regarding window period, turnaround time, and test 

performance characteristics. Because this strategy did not identify information for all of the listed tests, we also 

searched other literature sources, including FDA product labeling information, package inserts, manufacturer‟s 

Web sites, and additional sources including the World Health Organization. FDA approval information was 

searched for all tests as well. We used these sources for information on turnaround time and window period but 

not other test characteristics (e.g., sensitivity and specificity), because these sources of information generally do 

not report sufficient information to enable assessment of the study design, quality, and other factors that impact 

the outcomes and the strength of the evidence. Where data from sources other than clinical literature were used 

for the other characteristics, the source is clearly noted in the Evidence Report extraction tables. 

The window period is particularly important in this context because a recently infected potential organ donor 

who is tested using immunoassays only would not be diagnosed prior to donation of solid organs. The 

information regarding window periods is derived from testing seroconversion panels (series of blood draws 

from patients who eventually become seropositive). A limitation of the panels is that the samples are not

typically collected daily but at irregular intervals. Furthermore, studies generally reported the difference in 

window period between two tests (e.g., Test 2 detected infection an average of # days later than Test 1). 

Therefore, information capturing absolute window periods was unavailable. Information on the time required to 

fully administer tests was sparse. Window period and turnaround time were not assessed using GRADE because 

information often came from sources other than peer-reviewed publications. No studies reported on positive 

predictive values (PPV) or likelihood ratios. There were no studies comparing test characteristics between 

different donor populations. Although a large number of peer-reviewed publications and pieces of gray 

literature were included, little (or no) data addressed each individual study of interest. None of the studies 

focused on pediatric use. 

Q5.A. HIV

Immunoassays and Nucleic acid tests (NAT) currently in use by U.S. OPOs

Q5.A.1 HIV 3rd generation immunoassays

We found low quality evidence addressing the sensitivity and specificity of third generation immunoassay tests. 

(Table 56) Test sensitivity and specificity were calculated in two analytic studies with a sensitivity of 99.4-

100% and specificity of 97.7- 99.7%.131,132 (Table 55) Seroconversion panels showed positive responses ranging 

from the same day to about 14 days sooner than Western blot.

131-134 (Tables 52 and 54). No data were found on 

the duration of time required for the test to be performed (turnaround time).

Q5.A.2. HIV NAT

We found low quality evidence regarding the sensitivity and specificity of NAT assays. (Table 56) Test 

sensitivity and specificity were calculated in analytic and clinical studies with a sensitivity range of 92.6-100% 

and a specificity range of 96.9-100%. These studies included individual and HIV/HCV combined assays.

132,135,136 (Table 55) NAT results were positive ranging from 2-24.5 days before antibody assays.135,137-141 NAT 

results were reactive from 0-28 days before antigen tests135,137,138,140,141 (Tables 52 and 54) One study reported a 

turnaround time of two hours for HIV alone testing,142 whereas another reported that an experienced operator 

required 6 hours to perform two HIV/HCV combined assays and 6.5 hours to perform three HIV/HCV 

combined assays.

137 (Tables 51 and 54)

Immunoassays currently not in use by U.S. OPOs

Q5.A.3. HIV 4th generation immunoassays
72

There was low to moderate quality evidence that examined the specificity and sensitivity accuracy of fourth 

generation EIA tests. (Table 56) Test sensitivity and specificity were calculated in five analytic and three 

clinical studies with a sensitivity of 100% 143-149 and a specificity range of 82.5-100%.143-145,147-152 (Table 55) 

Five studies reported differences in window period time from third generation antibody and polymerase chain 

reaction (PCR) assays using seroconversion panels. (Tables 52 and 54) Fourth generation assays were reactive 

ranging from 0- 6.15 days before third generation antibody assays.144,147-149,153,154 However, when compared 

with NAT, fourth generation assays were reactive ranging from 2.31-2.75 days after RT-PCR.

149,153 (Table 10) 

Turnaround time ranged from 26 minutes to 4 hours depending on the test brand. (Tables 51 and 54)

Q5.B. HBV

Immunoassays and Nucleic acid tests (NAT) currently in use by U.S. OPOs

Q5.B.1. HBsAg

This review found low to moderate quality evidence regarding the sensitivity and specificity accuracy of 

HBsAg assays. (Table 56) Test sensitivity and specificity were calculated in analytic and clinical studies with a 

sensitivity of 100% and a specificity of 97.9-99.4%.155,156 (Table 55) HBsAg detected reactive results 0-7 days 

earlier than unnamed licensed references.

157-159 (Tables 52 and 54) Two studies reported a turnaround time of 

29-30 minutes.63,146 (Tables 51 and 54)

Q5.B.2. Anti-HBs

Our search did not identify any studies examining anti-HBs sensitivity and specificity. In one study of 40 

seroconversion panels, the anti-HBs assay was reactive a median of 14-18 days after the NAT method.160 In 

another study, the window period for the HBsAg and anti-HBs assays were the same for 10 of 21 

seroconversion panels with anti-HBs reactivity occurring later for the remaining 11 panels.161 (Tables 52 and 

54) No studies reported on the turnaround time for performing the test.

Q5.B.3. Anti-HBc

Our search did not identify any studies examining anti-HBc sensitivity and specificity accuracy. In one study of 

7 seroconversion panels, the anti-HBc assay detected infection at the same time as an unnamed reference in 6 

panels and one day sooner in the seventh.162 Per product label, anti-HBc appears in the serum of patients 

infected with HBV one to four weeks after the appearance of HBsAg, at the onset of symptoms.163 (Tables 52 

and 54) No studies reported on turnaround time for performing the test. 

Q5.B.4. HBV NAT

We found very low quality evidence regarding the sensitivity and specificity of NAT assays. (Table 56) Test 

sensitivity and specificity were calculated in one clinical study with a sensitivity of 84.8% and specificity of 

100%.164 (Table 55) NAT assay were reactive 10 - 20 days before HBsAg.160,165 (Tables 52 and 54) No studies 

reported turnaround time for conducting the test.

Q5.C. HCV

Immunoassays and Nucleic acid tests (NAT) currently in use by U.S. OPOs

Q5.C.1. HCV 2nd or 3rd generation immunoassays

There was moderate quality evidence demonstrating the sensitivity and specificity of second and third 

generation immunoassays. (Table 56) Test sensitivity and specificity were calculated in clinical studies with test 

sensitivity of 73.2-100% and specificity of 92.7-99.9% in second generation assays166-168 and test sensitivity of 

100% and a specificity range of 94.4-99.9% in third generation assays.

169-172 (Table 55) Of 19 blood donors who 
73

were RNA-positive but initially negative by a second generation immunoassay, second generation assays were

positive a median of 34-63 days later.173. A third generation assay was positive a mean of 26-32 days before 

second generation assays.174,175 (Tables 52 and 54) No studies reported turnaround time for conducting the test.

Q5.C.2. HCV NAT

We found low quality evidence regarding the sensitivity and specificity of NAT assays (Table 56) Test 

sensitivity and specificity were calculated in analytical and clinical studies with a sensitivity of 99.3-99.6% and 

a specificity of 97.4-99.6%. These studies comprised individual and HIV/HCV combined assays.135,136,142

(Table 55) HCV NAT was reactive a mean of 32-85 days before third generation antibody assays;137,175,176, a 

mean of 113 days before a second generation assay;176 and a mean of 5 days before a 4th generation test.177

(Tables 52 and 54) One study reported a turnaround time of 2 hours to perform the test.142 (Tables 51 and 54)

Immunoassays currently not in use by U.S. OPOs

Q5.C.3. HCV 4th generation immunoassays

Our search did not identify any studies regarding the sensitivity and specificity of fourth generation 

immunoassays. A fourth generation assay was reactive a mean of 21.6-26 days before 3rd generation 

assays.

177,178 Fourth generation assays were reactive a mean of 4.8-30 days after NAT.178,179 (Tables 52 and 54) 

One study reported a turnaround time of 190 minutes to perform the test.179 (Tables 51 and 54)

Questions 3, 4, and 5 Recommendations

3/4.A. To ascertain whether potential organ donors are average risk or at increased risk for 

having HIV, HBV, or HCV, prospective living donors and next-of-kin, as well as individuals 

familiar with deceased donors (i.e., life partners, cohabitants, friends, healthcare provider),

should be interviewed in a confidential and sensitive manner about behaviors that may have 

increased the potential donor‟s probability of HIV, HBV or HCV infection. (Refer to Table 3 for 

risk factors) (Category IB) (Questions 3 and 4) 

3.A. Deceased potential organ donors also should be screened for HIV using NAT or the most 

sensitive test available regardless of risk of having HIV and regardless of time relative to 

procurement (i.e., Donor specimens should be obtained before procurement; however, NAT 

results should be obtained either before, if timing allows, or after procurement). (Category IB)

(Question 3)

3.B. Deceased potential organ donors reported to have behavioral or nonbehavioral factors 

during the previous 12 months identifying them as being at increased risk for having HBV also

should be screened with HBV NAT or the most sensitive test available, in addition to routine 

serologic testing and regardless of time relative to procurement (i.e., Donor specimens should be 

obtained before procurement; however, NAT results should be obtained either before, if timing

allows, or after procurement). (Refer to Table 3 for risk factors) (Category IB) (Question 3)

3/4.B. Children with any risk factors associated with increased probability of HIV, HBV or 

HCV should be identified as having an increased probability of HIV, HBV or HCV infection. 

(Category IB) (Questions 3 and 4)
74

3/ 4.C. Children ≤ 2 years of age born to mothers with HIV, HBV, or HCV infection or mothers 

who meet the behavioral or nonbehavioral criteria for increased probability of infection

(regardless of their HIV, HBV or HCV status) should also be identified as having an increased 

probability of HIV, HBV or HCV infection. (Category IB) (Questions 3 and 4)

4.A. When reviewing medical records, OPO findings consistent with HIV, HBV, or HCV (e.g., 

mention of a positive test and/or risk factors for infection) in the deceased potential donor should 

be reported to the transplant center receiving the organ offer. (Category 1B) (Question 4)

3 /4.D. When a deceased potential organ donor‟s behavioral/medical history questionnaire 

cannot be obtained or behavioral and nonbehaviroal risk factors cannot be determined, donor 

NAT screening or the most sensitive test available for HBV should be performed. (Category 

IB) (Questions 3 and 4)

5.A. Screening tests for HBV (i.e., HBsAg, anti-HBc), HCV (i.e., anti-HCV), and HIV (i.e., 

anti-HIV 1/2) should be performed on all potential organ donors (living or deceased). (Category 

I) (Question 5)

Table 9 lists the factors identified from the evidence in the literature review that were associated with an 

increased likelihood of HIV, HBV or HCV infection. Given the paucity of literature identifying risk factors for 

incident infection, the potential risk factors in Table 9 were reviewed with subjects matter experts on HIV and 

hepatitis to create a revised list of risk factors (Table 3) that would facilitate screening out incident (recent)

HIV, HBV, or HCV infections in potential organ donors. Table 3 supplants the identified factors in Table 9.

Table 9. Behavioral Characteristics Associated with HIV, HBV, or HCV Identified by Low to 

High Quality Evidence from the Systematic Review

HIV

● MSM

● IDU

● Non-injection illicit drug use

● Multiple sex partners

● Sex with partner known to be HIV infected

● Age ≤ 18 years at first sexual intercourse

HBV

● MSM

● IDU

● Multiple sex partners

HCV

● IDU

● Non-injection illicit drug use 

● Multiple sex partners

● Sex worker 

● Inmates

● Age ≤ 18 years at first sexual intercourse

● Sex with partner known to be HCV infected

● Sex with IDU 

● Tattooing performed by nonprofessional
75

Nonbehavioral Characteristics Identified by Low to High Quality Evidence from the Systematic 

Review

HIV

● STD 

● Marital status

HBV ● Hemodialysis

● STD 

● Marital status

HCV

● Hemodialysis

● Receipt of blood transfusion 

● Signs and symptoms (i.e., jaundice, elevated ALT)

● STD 

● Marital status

TOPIC III: DONOR INTERVENTIONS TO DECREASE TRANSMISSION OF HIV, HBV, OR HCV 

FROM INFECTED DONORS (Question 6)

Question 6. Which donor interventions reduce the probability of pathogen transmission

from an organ donor infected with HIV, HBV, or HCV to a previously uninfected 

recipient?

Q6.A. A single study found low quality evidence regarding interventions to diminish the risk of viral 

transmission from infected donors to uninfected recipients.180,181 (Table 60) Only one study met the inclusion 

criteria.180,181 The 1994 study described perfusion techniques to potentially inactivate virus in kidneys procured 

from HCV-positive deceased donors. The virus -reducing capacity of four inactivation protocols was 

investigated with the viral burden ranging from 69% to 99.7%. The response appeared to be dose dependent

(i.e., the longer the inactivation procedure, the greater the viral load reduction). (Table 58) 

Question 6 Recommendations

6.A. Further research is needed to assess interventions (e.g., pathogen reduction methods) to 

reduce or eliminate the viral burden of HIV, HBV, and HCV in donors or donor organs before or 

after recovery. (No recommendation/unresolved issue) (Question 6)

TOPIC IV: POTENTIAL RISKS AND BENEFITS OF TRANSPLANTANTING, OR NOT 

TRANSPLANTING, SOLID ORGANS FROM DONORS POSITIVE FOR HIV, HBV OR HCV

(Question 7)

Question 7. How do the clinical outcomes of recipients of organs from donors infected 

with HIV, HBV or HCV compare to those who remain on the transplant list?

This question involves whether patient survival will be better if an organ from a donor infected with HIV, HBV,

or HCV is transplanted or the patient remains on the waiting list for an organ from an uninfected donor. Due to 

the lack of evidence, the initial inclusion criteria was expanded to 1) compare results of organ transplants from 
76

infected and uninfected donors into recipients who were uninfected pre-transplant and 2) compare results of 

organ transplants from infected and uninfected donors into recipients who were infected pre-transplant. The use 

of organs from infected donors may be more acceptable for recipients who are infected pre-transplant (although 

co-infection with a different genotype is possible). Of 22 publications, there were 17 unique studies. None of 

the studies were randomized or prospective, but all 17 treated the groups concurrently, and 13 studies enrolled 

patients consecutively. Ten studies (two of HBV and eight of HCV) reported specific baseline patient 

characteristics to enable a comparison. Of the differing pre-transplant characteristics, four of the studies 

performed statistical adjustments of the results.75,78,182-184 There were no studies that met inclusion criteria for 

HIV likely due to OPTN policy that prohibits using organs from HIV infected donors.

Q7.A. HBV

Q7.A.1. Receiving Organs from HBV-positive Donors Compared to Remaining on the Waitlist

No studies were found that met the inclusion criteria.

Q7.A.2. Receiving Organs from HBV-positive Donors Compared to Organs from Negative Donors When the 

Recipients were Negative Before Transplant

Review of one available study77 revealed very low quality evidence comparing outcomes of receiving kidneys

from HBV-positive versus HBV-negative donors when recipients are negative pre-transplant. HBV positivity 

was defined as anti-HBc positive and HBsAg-negative. (Table 63) Both patient and graft survival favored 

receiving a kidney from a negative donor in univariate analysis. (Table 68, Figure 12) The study did not find

any pre-transplant differences between HBV-positive and HBV-negative donor groups, except for substantially 

higher rates of stroke among HBV-positive donors (Table 66).

Q7.A.3. Receiving Organs from HBV-positive Donors Compared to Organs from Negative Donors When the 

Recipients were Positive Before Transplant

We found very low quality evidence from studies comparing patient and graft survival outcomes for HBVpositive candidates who received organs from HBV-positive versus HBV-negative donors. (Table 63) There 

were three observational studies of renal transplant recipients where the donor was anti-anti-HBc-positive,

HBsAg-negative,77 IgG anti-HBc-positive, IgM anti-HBc-negative, HBsAg-negative,75 and HBsAg-positive,185-

187 and one of liver transplant recipients where the donor was anti-HBc-positive.188 Figure 13 shows no 

consistent trend in patient or graft survival outcomes. One study in kidney transplant recipients found 

significantly improved graft survival using HBsAg-positive donors if the donor was living, and using HBsAgnegative donors if the donor was deceased.185-187 The remaining kidney and liver studies found no statistically 

significant differences in graft survival.

77,188 When restricting the analysis to the two studies that used statistical 

adjustments to control for baseline prognosis,75,77 one study found poorer graft survival in the positive donor 

group,75 and the other study found no large differences in either graft survival or patient survival.77 (Table 68) 

The main difference in baseline characteristics included higher rates of HCV, older donor and recipient ages, 

and more African Americans donors (Tables 62 and 66) in the HBV-positive donor compared to HBV-negative 

donors. (Tables 62 and 66) Of three studies that reported patient survival, only one reported a statistically 

significant difference. Patient survival was higher in recipients receiving a kidney from an HBsAg-positive 

donor if the donor was deceased, but no statistical difference if the donor was living.185-187 Of the two studies 

that adjusted for potential confounding,75,77 one study found poorer graft survival in the HBV-positive donor 

group,75 and the other study found no significant differences in either graft or patient survival.77 (Table 68)

Q7.B. HCV

Q7.B.1. Receiving Organs from HCV-positive Donors Compared to Remaining on the Waitlist

Review of one observational study189 found very low quality evidence comparing survival outcomes for patients 

receiving an HCV-positive organ versus remaining on the waitlist. (Table 63) This study included patients with 
77

end-stage renal disease who had been on the transplant waiting list from April 1995 to August 2000, and were 

followed to August 2001. The adjusted hazard ratio of 0.76 was statistically significant favoring receipt of a 

kidney from an HCV-positive donor versus remaining on the transplant waitlist. An analysis comparing receipt 

of a kidney from any deceased donor (regardless of donor HCV status) and being on the waitlist favored 

transplantation substantially (adjusted hazard ratio of 0.47). 

Q7.B.2. Receiving Organs from HCV-positive Donors Compared to Organs from Negative Donors When the 

Recipients were Negative Before Transplant

There was low quality evidence on patient and graft survival outcomes from studies comparing receiving organs 

from HCV-positive versus HCV-negative donors when recipients were negative pre-transplant. (Table 63) Four 

observational study involved HCV-infected donors.37,44,99,101,182,183,190,191 Results for patient survival favored 

receiving an organ from an HCV-negative donor in two studies of heart and kidney donors;

99,101,182,183 a third 

study involving liver donors found no statistical difference 24 months post-transplant).37,44 Three of the four 

studies reporting on liver graft survival found no statistically significant difference 24-60 months posttransplant.

37,44,182,183,190,191 Only one study reported baseline characteristics to enable comparison. There were 

more male donors and older mean recipient age in the positive donor group.99,101 The reported hazard ratio of 

2.8 was not indicated as adjusted or unadjusted.99,101 Another study, which adjusted for pre-transplant 

differences,

182,183 found a significantly shorter survival in those who received organs from HCV-positive 

donors. (Table 66) The difference in baseline characteristics, and the possibility that the pre-transplant 

prognosis may have been poorer for recipients who received organs from infected donors make it difficult to 

interpret these raw results. All study results appear in Table 68 and Figure 12. 

Q7.B.3. Receiving Organs from HCV-positive Donors Compared to Organs from Negative Donors When the 

Recipients were Positive Before Transplant

We found very low quality evidence on patient and graft survival outcomes from studies that compared receipt 

of organs from HCV-positive versus HCV-negative donors when recipients were positive pre-transplant. (Table 

63) Six observational studies addressed kidney transplantation182,183,192-196 and seven addressed liver 

transplantation.

37,44,184,188,190,191,197-199,

For kidney (Figure 14) and liver transplants (Figure 15), data suggest a 

small but consistently better graft survival with HCV-positive donors than HCV-negative donors; however, the

studies may not have been powered to detect a statistical difference. Of the 11 studies that reported patient 

survival, one study favored recipients of organs from negative donors,182,183 and the other study favored 

recipients or organs from HCV-positive donors184 (statistical adjustments were applied to control for baseline 

differences). The remaining 9 studies found no significant difference.37,44,184,188,192-195,197-199 Of the 13 studies 

that reported graft survival, ,

37,44,182-184,188,190-199 significant difference were reported. (Table 68) The baseline 

characteristics between groups differed; donor/recipient ages were older and the recipient‟s time on the waitlist 

was shorter in HCV-positive donor groups.192,193 (Tables 62 and 66) 

Question 7 Recommendations

7.A. Transplantation of a liver allograft from an HBV-infected donor into an HBV-infected 

transplant candidate may be considered when risk-benefit is considered favorable by the patient 

and transplant center. (Category IIB) (Question 7)

7.B. Transplantation of a liver allograft from an HBV-infected donor into an HBV-uninfected 

transplant candidate should be avoided unless the risk to the recipient of not performing the 

transplant is elevated and deemed to be greater than the risk of disease development. Should 

liver transplantation occur, strategies to further minimize this risk should be considered (e.g., 

HBV vaccination of the transplant candidate, hepatitis B immune globulin, and anti-viral 
78

therapy). (Category IB) (Question 7) 

7.C. Transplantation of a non-hepatic organ from an HBV-infected donor into an HBVuninfected transplant candidate may be considered when risk-benefit is considered favorable by 

the patient and transplant center. (Category IIB) (Question 7)

7.D. When allografts from HBV-infected donors are utilized, transplant centers should obtain 

informed consent from the patient regarding the probability of HBV transmission and implement 

strategies to further minimize the consequences of acquiring an HBV infection, as appropriate 

(e.g., HBV vaccination of the transplant candidate if anti-HBs negative; hepatitis B immune 

globulin, and anti-viral therapy). (Category IB) (Question 7)

7.E. The use of a non-hepatic organ from an IgG anti-HBc positive only donor may be 

considered for transplantation, as a positive IgG anti-HBc with negative HBsAg and negative 

anti-HBs is of unclear clinical significance; the probability of HBV transmission to the 

uninfected recipient is likely low; and graft/patient survival post-transplantation is unknown. 

Strategies to further minimize this risk should be considered (e.g., HBV vaccination of the 

transplant candidate if anti-HBs negative; hepatitis B immune globulin, and anti-viral therapy). 

(Category IIB) (Question 7)

7.F. Testing with HBV NAT and ascertainment of IgM and IgG anti-HBc status should be 

considered for total anti-HBc positive only donors to better evaluate the HBV risk in the 

recipient post-transplantation. (Category IIB) (Question 7)

7.G. Transplantation of an organ from an HCV-infected donor into an HCV-infected transplant 

candidate may be considered given that the risk-benefit appears favorable, as patient and graft 

survival appear to be similar to receiving an organ from an HCV-uninfected donor. (Category 

IIB) (Question 7)

7.H. Transplantation of an organ from an HCV-infected donor into an HCV-uninfected 

transplant candidate should not be performed unless the risk to the recipient of not performing 

the transplant* is elevated and deemed to be greater than the probability of HCV transmission 

and risk of disease development. (Category IB) (Question 7) *Life-threatening illness requiring 

transplantation when no other organs are available and no other lifesaving therapies exist.

7.I. When organs from HCV-infected donors are utilized, transplant centers should obtain 

informed consent from the patient regarding the probability of HCV transmission and implement 

strategies to detect new infection quickly by post-transplant recipient testing using HCV NAT at 

minimum and also evaluating for the use of anti-viral therapy. (Category IB) (Question 7)

7.J. Since rates of infection transmission and recipient outcomes vary by organ, organ donor 

screening for deceased donors should still be done even if results cannot be obtained before the 

organ is transplanted, in order to guide recipient management post-transplantation. Specifically, 

screening results for HIV, HBV or HCV may be reported following organ transplantation in 

situations of life-threatening illness where benefits of transplantation outweigh potential risks of

infection transmission. (Category IB) (Question 7)

7.K. Research is needed concerning the risk-benefit of transplanting organs from HIV-infected

donors into HIV-infected recipients, given the need for transplants in HIV-infected recipients 
79

and improved outcomes with the availability of highly active anti-retroviral therapy (HAART). 

(No Recommendation/unresolved issue) (Question 7)

Figure 12. Clinical Outcomes of Negative Recipients: Positive vs. Negative Donors, HBV and HCV, 

Kidney or Liver

Note: The diagonal line represents no difference in survival between those who received an organ from a positive donor and those who 

received an organ from a negative donor. Points above the diagonal line favor recipients of organs from positive donors, whereas points 

below the diagonal line favor recipients of organs from negative donors. This figure only includes studies that reported graft or survival 

data as percentages, and it only includes the longest follow-up timepoint from each study. The full data are provided in Table 68. None 

of the plotted studies reported confidence intervals. Studies with a lower case „s‟ next to the point reported that the comparison of full 

survival curves was statistically significant; all other studies either did not report whether the difference was statistically significant, or 

reported that the difference was not statistically significant. One of the studies did not report results on a percentage scale, and so its 

results do not appear in the plot. This was the Abbott et al. (2003)182,183 study, which found an adjusted hazard ratio of death of 2.25 

(95% CI: 1.56 to 3.24) in favor of recipients of organs from HCV- donors.
80

Figure 13. Clinical Outcomes of Positive Recipients: Positive vs. Negative Donors, HBV, Kidney or 

Liver

Note: The diagonal line represents no difference in survival between those who received an organ from a positive donor and those who 

received an organ from a negative donor. Points above the diagonal line favor recipients of organs from positive donors, whereas points 

below the diagonal line favor recipients of organs from negative donors. This figure only includes studies that reported graft or survival 

data as percentages, and it only includes the longest follow-up timepoint from each study. The full data are provided in Table 68. None 

of the plotted studies reported confidence intervals. Studies with a lower case „s‟ next to the point reported that the comparison of full 

survival curves was statistically significant; all other studies either did not report whether the difference was statistically significant, or 

reported that the difference was not statistically significant.
81

Figure 14. Clinical Outcomes of Positive Recipients: Positive vs. Negative Donors, HCV, Kidney

Note: The diagonal line represents no difference in survival between those who received an organ from a positive donor and those who 

received an organ from a negative donor. Points above the diagonal line favor recipients of organs from positive donors, whereas points 

below the diagonal line favor recipients of organs from negative donors. This figure only includes studies that reported graft or survival 

data as percentages, and it only includes the longest follow-up timepoint from each study. None of the plotted studies reported 

confidence intervals. Studies with a lower case „s‟ next to the point reported that the comparison of full survival curves was statistically 

significant; all other studies either did not report whether the difference was statistically significant, or reported that the difference was 

not statistically significant. One of the studies did not report results on a percentage scale, and so its results do not appear in the plot. 

This was the Abbott et al. (2003)182,183 study, which found an adjusted hazard ratio of death of 2.04 (95% CI: 1.20 to 3.45) in favor of 

recipients of negative organs.
82

Figure 15. Clinical Outcomes of Positive Recipients: Positive vs. Negative Donors, HCV, Liver

Note: The diagonal line represents no difference in survival between those who received an organ from a positive donor and those who 

received an organ from a negative donor. Points above the diagonal line favor recipients of organs from positive donors, whereas points 

below the diagonal line favor recipients of organs from negative donors. This figure only includes studies that reported graft or survival 

data as percentages, and it only includes the longest follow-up timepoint from each study. The full data are provided in Table 68. None 

of the plotted studies reported confidence intervals around the data. Studies with a lower case „s‟ next to the point reported that the 

comparison of full survival curves was statistically significant; all other studies either did not report whether the difference was 

statistically significant, or reported that the difference was not statistically significant. One of the studies did not report results on a 

percentage scale, and so its results do not appear in the plot. These was the Marroquin et al. (2001)184 study, which found an adjusted 

two-year odds of graft failure of 0.88, in favor of recipients of positive organs, and an adjusted two-year odds of patient death of 0.51, 

also in favor of recipients of positive organs.
83

TOPIC V: POTENTIAL RISKS AND BENEFITS OF TRANSPLANTING, OR NOT 

TRANSPLANTING, ORGANS FROM DONORS WITH RISK FACTORS FOR HIV, HBV, OR HCV

(Questions 8,9,10)

Question 8. How do the clinical outcomes of transplant recipients who receive organs 

from donors with behavioral or nonbehavioral risk factors compare to those who remain 

on the transplant list?

This question differs from Question 7 since the donor is not known to be infected, but is identified as having an 

increased probability of infection due to certain behavioral or nonbehavioral characteristics. Two simulation 

studies met inclusion criteria,

200,201 but made different comparisons and, therefore, were considered separately. 

Due to the paucity of evidence, we also looked for studies comparing the clinical outcomes of recipients of 

organs from IRDs to recipients of organs from standard donors. No such comparative studies were identified.

Q8.A. Estimated recipient outcomes after renal transplantation comparing “transplant” and “discard” policies

There was very low quality evidence that examined clinical outcomes of transplant candidates receiving organs 

from donors with risk factors for HIV, HBV or HCV versus remaining on the transplant list. (Table 76) The 

study applied a Markov process to address whether kidneys of deceased IRDs should be transplanted or 

discarded.200 Four types of IRDs were considered: intravenous drug user (IDU), men who have sex with men 

(MSM), commercial sex workers (CSW), and prison inmates (inmates). The main outcome measures were 

patient survival, quality-adjusted life-years (QALYs), number of organs transplanted and cost of care. 

Comparisons were made between patients on the waiting list who received kidneys from either standard criteria 

or IRD donors (transplant group) or from standard criteria donors only (discard group). Having a risk of HIV or 

HCV infection only was considered. Assumptions about the incidence and prevalence of these infections within 

the general, potential donor and potential recipient populations are found in Tables 70 and 71. Of note, 

estimated incidence and prevalence rates of HIV and HCV in the specific behavioral risk population were used 

as a proxy for potential donors. Key assumptions about the donors, recipients, death rates, costs and quality-ofadjusted life years that were applied in the model are found in Table 69. The base case simulation assumed that 

IRD donors were current IDUs with negative immunoassay and NAT screening results for HIV and HCV. The 

“transplant” strategy resulted in lower mortality, more QALYs, lower cost, and slightly more HIV infections. 

(Table 72) For this case, more HCV infections occurred with the “discard” strategy. This strategy led to more 

time on hemodialysis with an assumption that the incidence of HCV is significantly higher when on dialysis 

than after kidney transplant. Separate analyses were performed for the three other types of IRDs (MSM, CSW, 

prison inmates) with results very similar to the base case for outcomes. (Table 73) Results of numerous one-way 

sensitivity analyses found that in most cases the conclusions of the base case “were not substantially changed,” 

except that HCV infections were strongly influenced by assumptions about incidence rates. Authors concluded 

that “the „Discard‟ policy would yield fewer HCV infections only in a setting where a recipient‟s risk of 

infection on dialysis is very low, while the probability of CDC-IRD infection in a donor is high.”200

Q8.B. Estimated mortality from receiving a kidney from an at-risk donor versus one-year waitlist mortalities

There was very low quality evidence that examined clinical outcomes of transplant candidates receiving organs 

from donors with risk factors for HIV, HBV or HCV versus remaining on the transplant list. (Table 76) This 

study was a comprehensive risk analysis of considerations pertaining to solid organ donation.201 The study 

emphasized that the risk of recipient death from a donor infection is only one among a set of competing risks, 

including the risk of dying while on the waitlist, the risk of dying after the transplant (regardless of the donor‟s 

status), and risks of dying from medications, employment, transportation, and recreation. Much of the data 

reported in the article was not relevant to the research question; therefore we were selective in the data reported 

here. One-year waitlist mortality estimates for a standard criteria donor were based on a Markov model that 
84

utilized 90-day waitlist mortality and transplantation probabilities from the OPTN/SRTR 2007 Annual Report. 

Mortality rates were reported separately for 12 different types of recipients. (Table 74) For at-risk donors, the 

study only addressed HIV. When considering disease transmission to a recipient, an infectious risk of 46 per 

100,000 for HIV was provided based on OPTN high-risk donor data. In a conservative analysis, the authors 

assumed that HIV is 100% fatal, which corresponds to a 0.046%, mortality rate. This estimate is much lower 

than all of the one-year waitlist mortality rates ranging from 2.7% to 21.8%. (Table 74) They concluded that the 

waitlist mortality risk far outweighs the risk of HIV-related mortality associated with receiving an organ from a 

serologically negative donor with a behavioral risk factor. They did not attempt to make mortality estimates for 

either HBV or HCV due to insufficient documentation in the literature.

Question 9. What is the impact of excluding potential solid organ donors with behavioral 

or nonbehavioral risk factors on the organ donor pool?

Q9.A. There was very low quality evidence estimating the number of donors that would be excluded from organ 

recovery based on having risk factors for HIV, HBV or HCV. (Table 76) One study included for this question

was described in detail under Question 8.

200 Over a 20-year period, the study estimated there would be a 25.3% 

reduction (250 fewer kidneys per 1,000 patients available for transplantation) if IRDs were excluded. The study

only considered HIV and HCV and four types of behavioral exclusions (IDU, MSM, CSW, and prison inmates). 

Exclusions for other reasons (e.g., HBV risk, or nonbehavioral risk factors for HIV or HCV) would likely result 

in a larger reduction in the organ donor pool.

Question 10. What is the impact of false positive tests on the organ donor pool?

10.A. Our search did not identify any studies that estimated the number of donors or organs excluded from 

recovery due to false positive results for HIV, HBV, or HCV.

Questions 8, 9, and 10 Recommendations

8/9. Further research is needed to evaluate transplant candidate and recipient outcomes if organ donors 

with behavioral or nonbehavioral risk factors were excluded from donating. This process may also 

require comparing incidence of infection among population subsets within risk factors. (No 

recommendation/unresolved issue) (Category8/9)

10. Research is needed to evaluate the rate of false positive immunoassay and NAT results for HIV, 

HBV and HCV among potential organ donors and the percentage of cases where donors are declined 

by organ type. (No recommendation/unresolved issue) (Category 10)
85

TOPIC VI: APPROACHES AS TO HOW RECIPIENTS CAN BE INFORMED ABOUT THE RISK OF 

HIV, HBV AND HCV TRANSMISSION AND BE EVALUATED FOR POSSIBLE EXPOSURE POSTTRANSPLANTATION (Expert Opinions 1, 2, and 3)

Expert Opinion 1 (EO.1.): How and when should informed consent be obtained from potential recipients 

to help them consider the risks of donor-derived HIV, HBV, and HCV?

Background and Justification

Organ transplantation always carries a risk of donor-derived disease transmission.202,203 Thus, donors 

without identified risk factors are not presumed to be risk-free, but rather are differentiated from donors 

with risk factors in that the former possess no known serological or historical characteristics that indicate 

elevated risk. Due to the scarcity of transplantable organs and that the loss of donated organs results in 

increased mortality of patients remaining on the transplant waitlist, donors with increased risk for infections 

are not barred from contributing to the organ supply, as they generally are from contributing to the blood or 

tissue supply. They are instead evaluated on a case by case basis by transplant centers weighing 

risks/benefits for each individual transplant candidate. Informed consent is an important part of this process. 

Current recommendations for obtaining informed consent from a potential recipient include the OPTN 

policy and recommendations from the 2009 consensus conference on NAT screening of potential donors.

The 1994 PHS exclusionary criteria for HIV have been used to assess risk for HIV, HBV, and HCV in 

potential donors. OPTN policy requires that the host OPO communicate to transplant centers information of 

donors meeting any of these criteria which it further defines as a “high risk”.18 Transplant centers must then 

inform the potential recipient of this information and maintain documentation of informed consent. If a 

potential recipient is unable to provide informed consent, the legal next of kin or other appropriate surrogate 

is required to do so. However, there is currently no uniform consent process resulting in variability among 

transplant centers. 

The 2009 consensus conference on NAT screening of potential donors, therefore, recommended 

establishing uniform consent standards across transplant centers, and made recommendations as to what 

specifics should be addressed at the time of listing and at the time of an organ offer.28 At the time of listing, 

they recommended discussing the following with potential recipients: that although transplantation carries 

the risk for potentially donor-derived transmission of infection, not performing the transplant often carries a 

higher risk of death than the risk attributable to donor-transmitted infection; relaying the risks of donor 

transmission of infections including HIV, HBV, and HCV; the limitations of available testing and the 

potential for both false-positive and false-negative test results; relaying the risk of transmission of infections 

placed in the broader context of risk including risks associated with the use of extended-criteria donors as 

well as everyday occurrences to make their magnitude understandable to the potential recipient; and that 

risk assessment using donor histories may be limited by the knowledge of the person providing the 

information. At the time of an organ offer, they recommended disclosing specific donor history and testing 

results to enable the potential recipient to understand the risk while protecting donor identity and 

emphasizing that the transplant team has assessed the risk of the donor with the risk of not performing the 

transplant.

Informed consent at the time of an organ offer has been controversial with some experts concerned that

patients may be less able to rationally weigh the risks of accepting or declining a particular organ at the time 

an organ is offered (i.e., choices made in such hurried circumstances do not reflect patients‟ underlying 

values or well-considered preferences).204,205 Alternatively, others have advocated for obtaining specific 
86

informed consent and providing full disclosure of the donors‟ risk behaviors to patients at the time of the 

organ offer to allow patients to make an informed decision based on the donor‟s specific characteristics.

206

Obtaining specific informed consent on multiple occasions would help to reinforce patient understanding of 

complex risk information critical to this decision, and to promote an informed treatment decision.

Expert Opinion 2 (EO.2.): When should testing of a transplant recipient be done to detect HIV, HBV, and 

HCV transmission from the donor?

Background and Justification

Unexpected transmission of donor-derived disease to uninfected organ transplant recipients appears to be 

rare.17 The exact incidence of disease transmission is unknown because disease transmission is not actively 

or uniformly assessed across transplant centers in the United States; this is particularly true for bloodborne 

viruses, such as HIV, HBV, and HCV.27 Furthermore, the OPTN does not have formal policies requiring 

post-transplant assessment of recipients, and therefore, does not collect results of the testing when 

performed.

There are two major goals in recommending testing of transplant recipients:

1. To identify donor-derived disease transmission and implement interventions (i.e. antiviral therapy) 

early post-transplant to try and minimize the impact of the disease on the recipient.

2. To provide insight into the true incidence of donor-derived disease transmission.

As such, testing needs to be conducted to allow recognition of infection early enough to permit timely 

intervention while at the same time providing sufficient follow-up to prevent missing disease transmission. 

There are currently several guidelines that provide a template for timing and frequency of screening 

individuals exposed, through occupational and non-occupational means, to HIV, HBV, and HCV.207-210

Because HIV, HBV, and/or HCV exposure via organ transplantation may be associated with a larger 

amount of virus transmission compared to occupational or non-occupational exposures and more rapid 

progression of disease secondary to the use of immunosuppressive medications, a modified recipient testing 

schedule of 1, 3 and 12 months post-transplant has been recommended by a 2009 consensus conference on 

NAT testing of potential donors.28,211 Sero-conversion of transplant recipients may be impeded by the 

immunosuppressive medications the patients receive.8,17,212 In most cases of known donor-derived HCV 

transmission, recipients failed to seroconvert to HCV seropositive status despite having high viral titers by 

NAT. 17,211,212 Likewise, in the confirmed HIV/HCV donor-derived transmission, 1 of 4 patients had an 

indeterminate western blot.212 As such, any post-transplant testing of recipients should include direct 

measure of the virus itself through antigen detection (i.e. HBsAg for HBV) or NAT (i.e., HIV and HCV).

Recipient baseline testing, done at the time the recipient is admitted for transplantation but before 

placement of the organ, should also be done to rule-out pre-existing disease prior to transplantation.
87

Expert Opinion 3 (EO.3.): How should donor and recipient specimens be collected and stored for 

potential investigation of donor-derived HIV, HBV, and HCV infection?

Background and Justification

The availability of both donor and recipient archived blood specimens are critical for investigations to 

determine if a recipient infected with HIV, HBV or HCV is donor-derived. Appropriate specimen 

collection, labeling, transportation, handling and storage facilitate the accuracy of reported results for

serologic and NAT screening. Collection of two separate archival samples (from all donors and those 

recipients who receive organs from donors at increased risk for HIV, HBV, or HCV) for immunoassay and 

NAT reduces the possibility of specimen cross contamination or deterioration of nucleic acids through

specimen handling and storage. Labeling each specimen with a minimum of two unique identifiers ensures

a confidential and unbroken chain of traceability to the identity of the donor and recipient.

Viral nucleic acid may deteriorate over time depending on storage conditions. For example, repeated freezethaw cycles can cause a moderate reduction in viral nucleic acid levels.213-215 Procedures to maximize 

sample quality include separating samples that might be used for NAT into multiple aliquots prior to long 

term storage with storage temperature maintained at -70oC. Furthermore, avoiding temperature extremes 

when archived samples are shipped for testing inhibits specimen hemolysis, which can result in both false 

positive serologic results and false negative NAT results.216 Therefore, transporting archived samples to a 

testing laboratory on dry ice is a common practice, as well as documenting the sample quality and 

condition, with respect to both temperature and hemolysis, on receipt in the testing laboratory. OPTN policy 

requires donor blood samples be retained for a minimum of 10 years after transplant.18

Massive blood loss and intravascular volume replacement by transfusion of crystalloid and colloid solution 

and blood products can cause hemodilution and result in unreliable test results for transmissible 

infections.3,217 If significant hemodilution, defined as ”a sample with plasma dilution sufficient to affect the 

results of communicable disease testing utilizing an FDA-approved hemodilution calculation,” is 

confirmed, the tests that used hemodiluted samples and the hemodilution calculation used are to be reported 

to the accepting transplant programs.18 Calculations of dilution effects should take into account blood 

products and colloid administered. It should also be noted that hemodilution calculation algorithms are not 

standardized and the limits of “acceptable” hemodilution have not been validated across all current versions 

of serologic tests.218 The impact and limits of hemodilution on NAT have not been extensively studied but,

from a theoretical perspective based on viral loads documented in acutely infected blood donors and the 

results of minipool testing in blood donors, may have a significantly greater impact on the detection of

some pathogens (e.g., HBV)219,220 compared to others (e,g., HCV, HIV).19,20

Administration of blood products (plasma, red blood cells, platelets) and intravenous or intramuscular 

immunoglobulin may result in the transfer of passive antibody and result in false positive test results.221

Although blood products are universally screened, many of the infectious disease markers of concern, for

organ donors and recipients who receive blood product, are significantly more likely to have false positive 

results for highly prevalent analytes that do not preclude blood donation (e.g., anti-HBs) but are important 

as part of the pre-transplant donor or recipient screen. Receipt of blood and immunoglobulin products by 

donors and recipients in the three months prior to screening should be recorded, if known. Passive maternal 

antibody may also be detectable in children less than 18 months of age; serostatus and infection status may 

be difficult to resolve. Recent HBV immunization may also result in false positive HBsAg testing results as 

HBsAg reactivity has been found in individual up to 5 days after (HBV) immunization.222 When screening

is urgent, efforts should be made to retrieve available pre-transfusion samples on the donor and recipients as 
88

close as possible to the time of transplant.

Expert Opinions 1, 2, and 3 Recommendations

EO1.A. A shared decision-making process between the prospective recipient and the listing clinician 

should start at the time that the patient is placed on the transplant waitlist. Patients should be counseled to 

consider all potential risks of both accepting and rejecting specific types of organs from donors known to 

be infected with HBV or HCV; or donors at increased risk for HBV, HCV, or HIV infection. (Category 

IB) (Expert Opinion 1)

EO1.B. Further research is needed to reduce the chance that decisions would be biased against specific 

donor risk behaviors. Consider development and evaluation of a relative or comparative risk-based 

quantitative process, such as a donor risk index, to allow a patient to accept or reject a donor based on 

level of risk for transmitting HIV, HBV, or HCV. (No recommendation/unresolved issue) (Expert

Opinion 1)

EO1.C. Patients should be allowed opportunities to discuss with clinicians issues related to organ and 

associated risk acceptance at any time while on the waiting list. (Category IB) (Expert Opinion 1)

E01.D. At the time of the organ offer, the transplant center team primarily responsible for the patient‟s 

care should have a discussion with the prospective recipient that includes more specific information 

regarding the probability that this specific donor may transmit HIV, HBV, or HCV based on the donor 

history and blood test results available at that time to enable the potential recipient to understand the risk. 

Since vessel conduits may be transplanted from a different organ donor than the primary organ 

transplant, with different associated donor risks, an additional informed consent discussion by the 

transplant center team may need to take place separately for the vessel conduit. (Category IB (Expert 

Opinion 1)

EO1.E. Transplant candidates should be informed that although all donors are screened for HIV, HBV, 

and HCV, there are limits to screening and no screening question or laboratory test can completely 

eliminate the risk for transmitting these infections. (Category IB) (Expert Opinion 1)

EO2.A. Transplant candidates, for whom follow-up testing is planned post-transplant, should have a 

serologic assessment of their HIV, HBV, and HCV status at the time that they are admitted to the 

hospital to undergo the organ transplant but prior to implantation of the organ. (Category IB) (Expert 

Opinion 2)

EO2.B. Post-transplant testing should be done for HIV, HBV, and HCV, unless infection has been 

documented pre-transplant, for all recipients of organs from living or deceased donors specifically 

when 1) recognized risk factors place them at increased probability of acquiring donor-derived HIV, 

HBV or HCV; 2) the donor screening specimens are hemodiluted; 3) a donor medical or social history is 

unavailable; or 4) the donor screening assay is repeatedly reactive. (Category IB) (Expert Opinion 2)

EO2.C. Where the donor (living or deceased) was infected with HBV or HCV, post-transplant recipient 

testing should be done, unless recipient infection has been documented pre-transplant. (Category IB)

(Expert Opinion 2)
89

EO2.D. Recipient testing should be conducted for HBV, with respect to Expert Opinion 2B and 2C 

recommendations, at a minimum of 3 times at intervals of 1, 3 and 12 months post-transplant and include 

screening for anti-HBs, anti-HBc, and HBsAg (unless known through prior testing to be infected pretransplant). (Category IB) (Expert Opinion 2)

EO2.E. Recipient testing should be conducted for HIV with respect to Expert Opinion 2B and 2C 

recommendations, at a minimum of 2 times at intervals of 1 and 3 months post-transplant and include 

HIV-1 and 2 antibody and HIV NAT or testing of equivalent sensitivity (unless known through prior 

testing to be infected pre-transplant). NAT or testing of equivalent sensitivity is important for HIV 

detection as infected recipients may remain seronegative due to immunosuppression. (Category IB)

(Expert Opinion 2)

EO2.F. Recipient testing should be conducted for HCV with respect to Expert Opinion 2B and 2C 

recommendations, at a minimum of 2 times at intervals of 1 and 3 months post-transplant and include 

HCV antibody and HCV NAT or testing of equivalent sensitivity (unless known through prior testing to 

be infected pre-transplant). NAT or testing of equivalent sensitivity is important for HCV detection as 

infected recipients may remain seronegative due to immunosuppression. (Category IB) (Expert Opinion

2)

EO2.G. Data on the results of pre- and post-transplant bloodborne pathogen infection assessments in 

recipients should be collected nationally and analyzed on a regular basis to inform policy decisions and 

future screening recommendations. Nationally aggregated data on donor-derived infections should be 

disseminated to allow the transplant community to have access to the data. (Category IB) (Expert 

Opinion 2)

EO2.H. Any documentation of new infection in a recipient must be reported to the OPTN as required by 

policy and to appropriate local and state health departments as required by local and state law. (Category 

IC) (Expert Opinion 2)

EO3.A. For archival blood specimens, consider collecting two separate samples from all donors (living 

and deceased) and those recipients who receive organs from donors at increased risk for HIV, HBV, or 

HCV to reduce the possibility of specimen cross-contamination. Ideally, one sample from each individual

of 10 ml in a serum separator tube would be collected and processed to create 5 ml aliquots of serum for 

serologic testing. A second plasma sample of 3-5 ml collected in EDTA would be processed to create 1 

ml aliquots for NAT screening. Smaller samples would be collected from pediatric donors and from 

pediatric recipients prior to implantation of the organ. Samples should be stored for at least 10 years. (If 

only one specimen tube is feasible, all FDA licensed-screening tests and/or FDA-approved tests are for 

use with serum or plasma specimens.) (Category IIB) (Expert Opinion 3)

EO3.B. For initial deceased donor screening, consider collecting a separate ethylenediaminetetraacetic 

acid (EDTA) plasma specimens for NAT rather than using serum samples for serologic assays. When an 

alternate specimen is not available and a previously assayed serum is used for NAT, documentation 

should be provided. (If only one specimen tube is feasible, all FDA licensed-screening tests and/or FDA 

approved tests are for with of serum or EDTA plasma specimens.) (Category IIB) (Expert Opinion 3)

EO3.C. When storage capacity exists and specimen volume permits, separating EDTA plasma samples 

that might be used for future NAT into multiple aliquots should be considered prior to long term storage
90

as repeated freeze-thaw cycles can cause moderate reduction in viral nucleic acid levels, with plasma

samples maintained at approximately minus 70oC. (Category IIB) (Expert Opinion 3)

EO3.D. Massive blood loss and intravascular volume replacement by infusion of crystalloid and colloid 

solution and transfusion of blood products can cause plasma dilution and result in unreliable test results 

for transmissible infections. Donors should be considered at increased risk for harboring HIV, HBV and 

HCV when donor samples are determined to be diluted by an accepted plasma dilution algorithm and 

calculation method, such as provided by FDA,13 designed to evaluate volumes administered in the 48 

hours before specimen collection, even when no risk factors are identified. (Category IB) (Expert 

Opinion 3) 

EO3.E. Further research is needed to identify the limits of acceptable plasma dilution. Plasma dilution 

algorithms and calculation methods are not standardized for organ donors and the limits of acceptable 

plasma dilution have not been validated across HIV, HBV and HCV serological assays used for organ 

donors. (No recommendation/unresolved issue) (Expert Opinion 3)
91

VIII. APPENDICES

GUIDELINE FOR REDUCING TRANSMISSION OF HUMAN 

IMMUNODEFICIENCY VIRUS (HIV), HEPATITIS B VIRUS (HBV), AND 

HEPATITIS C VIRUS (HCV) THROUGH SOLID ORGAN 

TRANSPLANTATION
92

APPENDIX: TABLE OF CONTENTS

Appendix 1 – Factors identified in the literature to be associated with increased likelihood of recent HIV, HBV or HCV 

Infection ............................................................................................................................................................................... 94

Appendix 2 – GRADE Tables (Organized by Key Question)

Key Question 1: What are the prevalence and incidence rates of HIV, HBV, and HCV among potential solid organ donors?

GRADE Table......................................................................................................................................................................................99

Key Question 2: What behavioral risk factors are associated with an increased probability of infection with HIV, HBV, or 

HCV? What is the prevalence of these factors among potential solid organ donors?

GRADE Table....................................................................................................................................................................................103

Key Question 3: What behavioral risk factors are associated with an increased probability of infection with HIV, HBV, or 

HCV? What is the prevalence of these factors among potential solid organ donors?

GRADE Table....................................................................................................................................................................................109

Key Question 4: What nonbehavioral factors are associated with an increased probability of infection with HIV, HBV, or 

HCV? What is the prevalence of these factors among potential solid organ donors?

GRADE Table....................................................................................................................................................................................112

Key Question 5: What are the test characteristics of the screening methods available to detect HIV, HBV, and HCV in 

potential solid organ donors? Do test characteristics differ in particular populations and with donor clinical status (i.e., heart 

beating vs. non-heart beating donors OR adult vs. pediatric donors)?

GRADE Table....................................................................................................................................................................................127

Key Question 6: Which donor interventions reduce the probability of pathogen transmission from an organ donor infected with 

HIV, HBV, or HCV to a previously uninfected recipient??

GRADE Table....................................................................................................................................................................................138
93

Key Question 7: How do the clinical outcomes of recipients of organs from donors infected with HIV, HBV, or HCV compare 

to those who remain on the transplant list?

GRADE Table....................................................................................................................................................................................139

Key Question 8: How do the clinical outcomes of transplant recipients who receive organs from donors with behavioral or 

nonbehavioral risk factors compare to those who remain on the transplant list?

GRADE Table....................................................................................................................................................................................143

Key Question 9: What is the impact of excluding potential solid organ donors with behavioral or nonbehavioral risk factors on 

the organ donor pool? ..............................................................................................................................................................................145

Key Question 10: What is the impact of false positive tests on the organ donor pool? ..........................................................................145
94

Appendix 1: Risk Factors

Given the paucity of literature identifying risk factors for incident infection, the potential risk factors identified from the evidence in 

the literature review in Table 9 of this document were reviewed with subjects matter experts on HIV and hepatitis to create a revised 

list of risk factors that would facilitate screening out incident (recent) HIV, HBV, or HCV infections in potential organ donors. The 

following risk factors associated with HIV, HBV and HCV infection supplant the identified factors from the evidence review listed in 

Table 9. Each factor reflects an increased risk of infection due to HIV, HBV and/or HCV as there may be overlap between pathogen 

risks for each listed factor; unless otherwise specified, a particular factor does not convey risk due to only one pathogen or to all 

pathogens equally.

Donors who have engaged in the behaviors listed below are identified as being at increased risk. The revised list takes into 

consideration that 1) certain risk factors are probably markers for other factors identified in the systematic review and 2) scientific 

evidence associating certain factors with the bloodborne pathogens exists, but may not have met the inclusion criteria of the systematic 

review or studies were of insufficient quality to draw conclusions.

Table 3. Factors identified in the literature to be associated with increased likelihood of recent HIV, HBV or HCV 

Infection

● Sexual contact

■ Persons who have had sex with ≥2 partners in the preceding 12 months

■ Persons who have had sex with a person known or suspected to have HIV, HBV or HCV infection in the 

preceding 12 months

■ Men who have had sex with another man (MSM) in the preceding 12 months

■ Women who have had sex with a man with a history of MSM behavior in the preceding 12 months

■ Persons who have had sex in exchange for money or drugs in the preceding 12 months

■ Persons who have had sex with a person who had sex in exchange for money or drugs in the preceding 12 months

■ Persons who have had sex with a person who injected drugs by intravenous, intramuscular, or subcutaneous route 

for non-medical reasons in the preceding 12 months

● Birth to a mother infected with HIV, HBV or HCV (for infants ≤2 years of age)

● Persons who have injected drugs by intravenous, intramuscular, or subcutaneous route for non-medical reasons in the 

preceding 12 months

● Intra-nasal use of an illicit drug (e.g., cocaine, heroin) in the preceding 12 months

● Inmate of a correctional facility (e.g., jail, prison, juvenile detention) >3 consecutive days in the preceding 12 months

● Persons who have, or have been treated for, syphilis, gonorrhea, or genital ulcers in the preceding 12 months

● Persons who have been on hemodialysis in the preceding 12 months (for HCV only)
95

● Persons who have immigrated to the United States in the preceding 12 months from a country of intermediate or high

hepatitis B prevalence (for HBV only)

Sexual Contact

Persons who have had sex with ≥2 partners in the preceding 12 months

● HIV: Review of the available studies reveals low quality evidence to suggest an association between having multiple sex partners 

and being at increased risk of HIV. 

● HBV: Review of the outlined studies demonstrated moderate quality evidence to support having multiple sex partners as risk 

factor for HBV infection. 

● HCV: Review of the outlined studies found moderate quality evidence confirming an association between HCV infection and 

having multiple sex partners. 

Persons who have had sex with a person known or suspected to have HIV, HBV or HCV in the preceding 12 months

● HIV: There was low quality evidence associating having sex with someone who is HIV-positive and having HIV. 

● HBV: There was very low quality evidence to support having a sex partner with a known HBV infection as a risk factor for HBV. 

● HCV: We found low quality evidence to support having sex with people known to be HCV infected as a risk factor for HCV 

infection.

Men who have had sex with another man (MSM) in the preceding 12 months

● HIV: There was moderate quality evidence identifying MSM as a risk factor for HIV. 

● HBV: The review demonstrated moderate quality evidence to support an association between MSM behavior and HBV.

● HCV: There was very low quality evidence to support MSM behavior as a risk factor for HCV infection. 

Females who have had sex with a male with a history of MSM behavior in the preceding 12 months

● Our search did not identify studies that examined the association between females who had sex with an ID with a male with a 

history of MSM behavior and acquiring HIV, HBV, or HCV

Persons who have had sex with a person who injected drugs by intravenous, intramuscular, or subcutaneous route for nonmedical reasons 

● HIV: Our search did not identify studies that examine the association between sex with an IDU and acquiring HIV.

● HBV: Review of the available studies revealed very low quality evidence supporting an association between HBV infection and 

having sex with an injection drug user. 

● HCV: Review of the outlined studies found moderate quality evidence supporting having sex with an IDU as a risk factor for 

HCV. 

Persons who have had sex in exchange for money or drugs in the preceding 12 months

● HIV: A single study found very low quality evidence which did not find an association between sex workers and HIV. 

● HBV: We found very low quality evidence relating sex work and HBV infection. 
96

● HCV: We found low quality evidence to suggest an association between sex work and HCV. 

Persons who have had sex with a person who had sex in exchange for money or drugs 

● HIV: No studies were identified that looked at the association between HIV and sex with a sex worker. 

● HBV: A single study of psychiatric inpatient veterans found very low quality evidence which did not find an association between 

HBV and having sex with a sex worker in univariate analysis. 

● HCV: We found very low quality evidence to suggest an association between having sex with a sex worker and having HCV. 

Persons who have had sex with a person who injected drugs by intravenous, intramuscular, or subcutaneous route for nonmedical reasons in the preceding 12 months

● HIV: Our search did not identify studies that examined the association between sex with an IDU and acquiring HIV.

● HBV: Review of the available studies revealed very low quality evidence supporting an association between HBV infection and 

having sex with an injection drug user. 

● HCV: Review of the outlined studies found moderate quality evidence supporting having sex with an IDU as a risk factor for 

HCV. 

Birth to a mother infected with HIV, HBV or HCV (for infants ≤2 years of age)

● HIV: Our search did not identify studies on behavioral risk factors in children, or on the risk of infection from mothers who 

engage in those risk behaviors. 

● HBV: Our search did not identify studies on behavioral risk factors in children, or on the risk of infection from mothers who 

engage in those risk behaviors. 

● HCV: Our search did not identify studies on behavioral risk factors in children, or on the risk of infection from mothers who 

engage in those risk behaviors. 

Persons who have injected drugs by intravenous, intramuscular, or subcutaneous route for non-medical reasons

in the preceding 12 months

● HIV: We found low quality evidence suggesting an association between IDU and HIV. 

● HBV: There was low quality evidence to support IDU as a risk factor for HBV infection. 

● HCV: This review demonstrated moderate quality evidence to support IDU as a risk factor for HCV. 

Intra-nasal use of an illicit drug (e.g., cocaine, heroin) in the preceding 12 months

● HIV: We found low quality evidence associating use of cocaine or street drugs and HIV infection. 

● HBV: There was very low quality evidence associating non-injection illicit drug use with HBV. 
97

● HCV: There was low quality evidence associating HCV with non-injection drug use. 

Inmate of a correctional facility (e.g., jail, prison, juvenile detention) >3 consecutive days in the preceding 12 months

● HIV: A single study found very low quality evidence to suggest an association between being incarcerated and having HIV. 

● HBV: We found very low quality evidence to suggest an association between being incarcerated and having HBV. 

● HCV: We found low quality evidence to support incarceration as a risk factor for HCV. 

Persons who have, or have been treated for, syphilis, gonorrhea, or genital ulcers in the preceding 12 months

● HIV: This review found low quality evidence associating HIV with having another infection (STD). 

● HBV: We found low quality evidence to suggest an association between having HBV and exposure to, or having, other types of 

infection (STDs). 

● HCV: We found low quality evidence to suggest an association between STD or other infections and having HCV. 

Persons who have been on hemodialysis in the preceding 12 months (for HCV only)

● HCV: Hemodialysis: There was low quality evidence which found an association between hemodialysis and HCV. 

Persons who have immigrated to the U.S. in the preceding 12 months from a country of intermediate or high prevalence

(for HBV only)

● HBV: This review found very low quality evidence to suggest a relationship between HBV and an individual‟s race, ethnicity or 

national origin. Grade of evidence specifically for national origin/birthplace was also rated very low.

The prevalence of chronic HBV infection is intermediate (≥2%) or high (≥8%) in the following geographic regions. These countries 

may be updated periodically as new information becomes available: 1) Africa: all countries; 2) Asia (comprising Southeast Asia, 

East Asia, and Northern Asia): all countries; 3) South and Western Pacific islands, except Australia and New Zealand; 4) Middle 

East, except Cyprus; 5) Eastern Europe, except Hungary; 6) Western Europe: Spain, Portugal and Greenland; 7) South America: 

Brazil, Ecuador, Guyana, Venezuela, French Guyana, Peru and Suriname, and Amazonian areas of northern Bolivia and southern 

Columbia; 8) Central America: Honduras, and Guatemala; 9) certain parts of the Caribbean: Haiti, Dominican Republic; 10) Alaska 

Natives and indigenous populations in Northern Canada
98

Prevalence of Hepatitis B Surface Antigen, 2010

Source: Centers for Disease Control and Prevention. CDC Health Information for International Travel 2010. Atlanta: U.S. 

Department of Health and Human Services, Public Health Service, 2009

http://wwwnc.cdc.gov/travel/yellowbook/2010/chapter-2/hepatitis-b.aspx
99

APPENDIX 2: GRADE TABLES

Question 1: What are the prevalence and incidence rates of HIV, HBV, and HCV among potential solid organ 

donors?

Table 1. GRADE Table for Question 1 (Epidemiology) Pathogen

Outcome

Quantity and 

Type of Evidence Findings

Starting Grade

Decrease GRADE Increase GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE of 

Evidence 

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose

Base

-response

Confounders would reduce the effect

HIV Incidence 1 study of potential 

tissue donors45

1 study of the U.S. 

general population46,47

In the study of potential tissue 

donors, incidence of 30.11 per 

100,000 person-years

In the general population 

study, incidence of 56,300 in 

2006, which corresponds to 

18.8 per 100,000 person years

High 0 -1 -1 0 0 0 0 0 Low
100

Pathogen

Outcome

Quantity and 

Type of Evidence Findings

Starting Grade

Decrease GRADE Increase GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE of 

Evidence 

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose

Base

-response

Confounders would reduce the effect

Prevalence 2 studies of potential 

organ donors34,36

1 study of potential 

tissue donors45

1 study of the U.S. 

general population52

In the studies of tested 

potential organ donors, 

prevalence of HIV was 

0/22 (0%), and prevalence of 

HIV or syphilis was and 

2/94 (2.1% or 1 in 48).

In the study of potential tissue 

donors, prevalence was 

10/10,910 (0.093% or 

1 in 1,090).

In the general population 

study, prevalence was 

1,106,400 in 2006 (0.37%, or 

1 in 270)

High 0 -1 -1 0 0 0 0 0 Low Low

HBV Incidence 1 study of potential 

tissue donors45

1 study of the U.S. 

general population48,49

In the study of potential tissue 

donors, incidence of 18.325 

per 100,000 person-years

In the general population 

study, 43,000 incidence in 

2007, which corresponds to 

14.4 per 100,000 person-years

High 0 0 -1 0 0 0 0 0 Moderate
101

Pathogen

Outcome

Quantity and 

Type of Evidence Findings

Starting Grade

Decrease GRADE Increase GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE of 

Evidence 

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose

Base

-response

Confounders would reduce the effect

Prevalence 1 study of HBV in 

potential organ donors35

2 studies of 

hepatitis(including HBV 

and HCV) in tested 

potential organ 

donors34,36

1 study of potential 

tissue donors45

1 study of the U.S. 

general population50

In the study of HBV in potential 

organ donors, prevalence was 

22/446 (4.9%, or 1 in 20).

In the two studies of hepatitis 

in potential organ donors, 

prevalence of 5/94 (5.3%, or 1 

in 19) and4/22 (18.2%, or 1 in 

6).

The study of potential tissue 

donors reported a prevalence 

of 25/10901 (0.229%, or 1 in 

436)..

In the general population 

study, prevalence of chronic 

infection was 1.1 million in 

2006 (0.36% or 1 in 274)

High 0 -1 -1 0 0 0 0 0 Low Low

HCV Incidence 1 study of potential 

tissue donors45

1 study of the U.S. 

general population48,49

In the study of potential tissue 

donors, incidence of 12.38 per 

100,000 person-years

In the general population 

study, 17,000 incidence in 

2007, which corresponds to 5.7 

per 100,000 person-years

High 0 -1 -1 0 0 0 0 0 Low
102

Pathogen

Outcome

Quantity and 

Type of Evidence Findings

Starting Grade

Decrease GRADE Increase GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE of 

Evidence 

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose

Base

-response

Confounders would reduce the effect

Prevalence 1 study of HCV in 

potential organ donors33

1 study of “hepatitis” in 

potential organ donors34

4 studies of prevalence 

among pre-1991 organ 

donors37-44

1 study of potential 

tissue donors45

1 study of the U.S. 

general population51

In the study of HCV in potential 

organ donors, prevalence was

2/55 (3.6%, or 1 in 28).

In the study of HBV and HCV 

in potential organ donors, 

prevalence was 5/430 (1.2%, 

or 1 in 86)

In the studies of pre-1991 

organ donors, combined 

estimate of prevalence of 4.0% 

or 1 in 25.

In the study of potential tissue 

donors, prevalence of 

119/10915 (1.091%, or 1 in 

92).

In the general population 

study, prevalence of chronic 

infection was 3.3 million in 

1999-2002 (1.1 % or 1 in 86)

High 0 -1 -1 0 0 0 0 0 Low Low
103

Question 2: What are the rates of transmission to recipients from donors infected with HIV, HBV, or HCV? Do 

the rates vary by the organ transplanted or when the donor was infected?

Table 2. GRADE Table for Question 2 (Transmission)

Definitions 

of Donor 

Positivity

Recipient 

tested for:

Quantity 

and Type of 

Evidence

Range of 

Results

Starting Grade

Decrease GRADE Increase GRADE

GRADE 

of 

Evidence 

for 

Outcome

Overall 

GRADE 

of 

Evidence 

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose

Base

-response

Confounders would reduce the effect

HBV and Liver Transplantation

Anti-HBc+ HBsAg 5 OBS56-63 0% to 94% High -1 -1 0 0 0 0 0 0 Low

Low

Anti-HBc+ HBeAg 2 OBS59-63 40% to 94% High -2 -1 0 0 0 0 0 0 Very Low

Anti-HBc+ anti-HBc 2 OBS56,57 0% to 78% High -1 -1 0 0 0 0 0 0 Low

Anti-HBc+ serum HBVDNA2 OBS59-63 40% to 94% High -1 -1 0 0 0 0 0 0 Low

Anti-HBc+ “Developed 

de novo 

infection”

1 OBS64 6% High -2 -1 0 0 0 0 0 0 Very Low

Anti-HBc+ anti-HBs 2 OBS56,57 0% to 44% High -1 -1 0 0 0 0 0 0 Low

Anti-HBc+ 

and HBsAgHBsAg 9 OBS54,55,65-

72

0% to 78% High -2 -1 0 0 0 0 0 0 Very Low

Anti-HBc+ 

and HBsAgHBeAg 2 OBS54,71 13% to 67% High -2 -1 0 0 0 0 0 0 Very Low

Anti-HBc+ 

and HBsAganti-HBs 2 OBS72,73 0% to 5% High -1 0 0 0 0 0 0 0 Moderate

Anti-HBc+ 

and HBsAganti-HBc 3 OBS67,68,73 0% to 37% High -1 -1 0 0 0 0 0 0 Low
104

Definitions 

of Donor 

Positivity

Recipient 

tested for:

Quantity 

and Type of 

Evidence

Range of 

Results

Starting Grade

Decrease GRADE Increase GRADE

GRADE 

of 

Evidence 

for 

Outcome

Overall 

GRADE 

of 

Evidence 

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose

Base

-response

Confounders would reduce the effect

Anti-HBc+ 

and HBsAgliver HBVDNA

2 OBS67,71 0% to 13% High -2 -1 0 0 0 0 0 0 Very Low

Anti-HBc+ 

and HBsAgserum HBVDNA

6

OBS54,67,69-

71,73,74

0% to 71% High -1 -1 0 0 0 0 0 0 Low

Anti-HBc+ 

and HBsAglymphocytes HBV-DNA

1 OBS70 0% High 0 -1 0 0 0 0 0 0 Moderate

HBV and Kidney Transplantation

anti-HBc+ HBsAg 1OBS63 0% High -2 0 0 0 0 0 0 0 Low

Low

anti-HBc+ HBeAg 1 OBS63 0% High -2 -1 0 0 0 0 0 0 Very Low

anti-HBc+ anti-HBc 1OBS63 0% High -2 0 0 0 0 0 0 0 Low

anti-HBc+ serum HBVDNA1 OBS63 0% High -2 -1 0 0 0 0 0 0 Very Low

anti-HBc+ anti-HBs 1 OBS63 0% High -2 -1 0 0 0 0 0 0 Very Low

HBsAg-, 

anti-HBc+

HBsAg 6

OBS65,66,72,75

-78

0% High -1 0 0 0 0 0 0 0 Moderate

HBsAg-, 

anti-HBc+

anti-HBs 4 

OBS72,75,78,79

0% to 11% High -1 0 0 0 0 0 0 0 Moderate

HBsAg-, 

anti-HBc+

anti-HBc 7

OBS65,66,72,75

-79

0% to 13% High -1 0 0 0 0 0 0 0 Moderate

HBsAg-, 

anti-HBc+

anti-HBs and 

anti-HBc

1 OBS78 0% High -1 -1 0 0 0 0 0 0 Low
105

Definitions 

of Donor 

Positivity

Recipient 

tested for:

Quantity 

and Type of 

Evidence

Range of 

Results

Starting Grade

Decrease GRADE Increase GRADE

GRADE 

of 

Evidence 

for 

Outcome

Overall 

GRADE 

of 

Evidence 

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose

Base

-response

Confounders would reduce the effect

HBsAg-, 

anti-HBc+

“HBV viremia” 1 OBS79 0% High -2 -1 0 0 0 0 0 0 Very Low

HBsAg-, 

anti-HBc+, 

serum HBVDNAHBsAg 1 OBS80 0% High -2 -1 0 0 0 0 0 0 Very Low

HBsAg-, 

anti-HBc+, 

serum HBVDNAanti-HBc 1 OBS80 0% High -2 -1 0 0 0 0 0 0 Very Low

HBsAg-, 

anti-HBc+, 

serum HBVDNAserum HBVDNA

1 OBS80 0% High -2 -1 0 0 0 0 0 0 Very Low

HBV and Heart Transplantation

anti-HBc+ HBsAg 2 OBS63,81 0% to 4% High -2 0 0 0 0 0 0 0 Low

Very Low

anti-HBc+ anti-HBc 2 OBS63,82 18% to 65% High -2 -1 0 0 0 0 0 0 Very Low

anti-HBc+ anti-HBs 3 OBS63,81,82 8% to 48% High -1 -1 0 0 0 0 0 0 Low

HBsAg-, 

anti-HBc+

HBsAg 1 OBS65,66 0% High -2 -1 0 0 0 0 0 0 Very Low

HBsAg-, 

anti-HBc+, 

anti-HBs+

HBsAg 1 OBS83,84 0% High -1 -1 0 0 0 0 0 0 Low
106

Definitions 

of Donor 

Positivity

Recipient 

tested for:

Quantity 

and Type of 

Evidence

Range of 

Results

Starting Grade

Decrease GRADE Increase GRADE

GRADE 

of 

Evidence 

for 

Outcome

Overall 

GRADE 

of 

Evidence 

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose

Base

-response

Confounders would reduce the effect

HBsAg-, 

anti-HBc+, 

serum HBVDNAHBsAg 1 OBS85 0% High -2 -1 0 0 0 0 0 0 Very Low

HBsAg-, 

anti-HBc+, 

serum HBVDNAanti-HBc 1 OBS85 0% High -2 -1 0 0 0 0 0 0 Very Low

HBsAg-, 

anti-HBc+, 

serum HBVDNAserum HBVDNA

1 OBS85 0% High -2 -1 0 0 0 0 0 0 Very Low

HBsAg-, 

anti-HBc+, 

serum HBVDNAlymphocyte 

HBV-DNA

1 OBS85 20% High -2 -1 0 0 0 0 0 0 Very Low

HBV and Lung Transplantation

HBsAg-, 

anti-HBc+

HBsAg 1 OBS86 0% High -1 -1 0 0 0 0 0 0 Low

Low

HBsAg-, 

anti-HBc+

anti-HBc 1 OBS86 0% High -1 -1 0 0 0 0 0 0 Low

HCV and Liver Transplantation

anti-HCV+ anti-HCV 1 OBS37,44 24% High -2 -1 0 0 0 0 0 0 Very Low

anti-HCV+, Low

serum HCVRNA+

anti-HCV 1 OBS87 67% High -1 -1 0 0 0 0 0 0 Low
107

Definitions 

of Donor 

Positivity

Recipient 

tested for:

Quantity 

and Type of 

Evidence

Range of 

Results

Starting Grade

Decrease GRADE Increase GRADE

GRADE 

of 

Evidence 

for 

Outcome

Overall 

GRADE 

of 

Evidence 

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose

Base

-response

Confounders would reduce the effect

anti-HCV+, 

serum HCVRNA+

HCV-RNA 1 OBS87 100% High -1 -1 0 0 0 0 0 0 Low

HCV and Kidney Transplantation

anti-HCV+ anti-HCV 8 OBS5,39-

43,88-94

6% to 91% High -2 -1 0 0 0 0 0 0 Very Low

Very Low

anti-HCV+ HCV-RNA 2 OBS91,92 50% to 100% High -1 -1 0 0 0 0 0 0 Low

anti-HCV+, 

serum HCVRNA+

anti-HCV 2 OBS38,96 0% to 19% High -2 -1 0 0 0 0 0 0 Very Low

anti-HCV+, 

serum HCVRNA+

anti-HCV or 

indeterminate 

1 OBS95,96 35% High -2 -1 0 0 0 0 0 0 Very Low

anti-HCV+, 

serum HCVRNA+

HCV-RNA 2 OBS38,95,96 0% to 57% High -2 -1 0 0 0 0 0 0 Very Low

anti-HCV+, 

serum HCVRNA+

RIA 1 OBS38 0% High -2 -1 0 0 0 0 0 0 Very Low

anti-HCV+

RIBA+

anti-HCV 1 OBS97 62% High -2 -1 0 0 0 0 0 0 Very Low

anti-HCV+

RIBA+

HCV-RNA 1 OBS97 67% High -2 -1 0 0 0 0 0 0 Very Low

HCV and Heart Transplantation
108

Definitions 

of Donor 

Positivity

Recipient 

tested for:

Quantity 

and Type of 

Evidence

Range of 

Results

Starting Grade

Decrease GRADE Increase GRADE

GRADE 

of 

Evidence 

for 

Outcome

Overall 

GRADE 

of 

Evidence 

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose

Base

-response

Confounders would reduce the effect

anti-HCV+ anti-HCV 3 OBS99-103 11% to 24% High -2 0 0 0 0 0 0 0 Low

Very Low

anti-HCV+ HCV-RNA 3 OBS99-103 12% to 75% High -2 -1 0 0 0 0 0 0 Very Low

anti-HCV+ liver HCV 1 OBS102 29% High -2 -1 0 0 0 0 0 0 Very Low

anti-HCV+ “Any HCV 

infection”

1 OBS102 43% High -2 -1 0 0 0 0 0 0 Very Low

anti-HCV+, 

serum HCVRNA+

anti-HCV 1 OBS98 44% High -2 -1 0 0 0 0 0 0 Very Low

anti-HCV+, 

serum HCVRNA+

HCV-RNA 1 OBS98 100% High -2 -1 0 0 0 0 0 0 Very Low

Note: The shaded rows denote evidence on rates where the donor was positive for anti-HBc but it was not reported whether the donor was positive for HBsAg; these were 

considered “critical” outcomes. The only expectation to this was when the recipient was being tested for anti-HBs, which was not considered critical. For HCV, we 

considered the result critical whenever the donor was positive for HCV RNA (thus the row was shaded).
109

Question 3: What behavioral risk factors are associated with an increased probability of infection with HIV, 

HBV, or HCV? What is the prevalence of these characteristics among potential solid organ donors?

Table 3. GRADE Table for Question 3 (Prevalence of Behavioral Risk Factors)

Factor

Quantity and Type of 

Evidence Findings

Starting Grade

Decrease GRADE Increase GRADE

GRADE of 

Evidence 

for 

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose

Outcome

-response

Associated Despite Confounders

Men who have 

sex with men

2 OBS*104,105 In two general population studies, one 

reported that 3.7% of men have sex with 

another man,104 while the other reported 

that 9.3% have a history of having sex 

with another man.135

High 0 -1 -1 0 0 0 0 0 Low

Injection drug 

abuse

4 OBS51,105,106,112 All four studies assessed general 

populations. Reported prevalences of 

injection drug use were 1.4%,105 1.7%,51

3.5%,112 and 7.9%.106 The lower two 

estimates were derived from NHANES 

data, and the higher two were drawn 

from patients and volunteers in urban 

areas.

Of the injection drug users in one study, 

63.2% reported they did not use needle 

exchange programs.106

High 0 -1 -1 0 0 0 0 0 Low

Sex Work 1 OBS106 One general population study reported 

2.3% of participants reported 

exchanging sex for money or drugs.106

High 0 -1 -1 0 0 0 0 0 Low

High-Risk Sex 

Partners: 

Injection drug 

user

1 OBS112 Among general population volunteers 

from a mainly urban area, 5% reported 

having sex with an injection drug use.112

High 0 -1 -1 0 0 0 0 0 Low
110

Factor

Quantity and Type of 

Evidence Findings

Starting Grade

Decrease GRADE Increase GRADE

GRADE of 

Evidence 

for 

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose

Outcome

-response

Associated Despite Confounders

High-Risk Sex 

Partners: Sex 

workers

1 OBS106 In the same population, 7.4% reported 

sex with a commercial sex worker.106

High 0 -1 -1 0 0 0 0 0 Low

Multiple Sex 

Partners: 

Multiple 

undefined

2 OBS105,112 26% of volunteers in one study reported 

having sex with multiple partners,112

while 22% of NHANES participants 

reported having multiple sex partners 

during the previous year.105

High 0 0 -1 0 0 0 0 0 Moderate

Multiple Sex 

Partners: At 

least 2 partners

2 OBS104,223 74% reported having sex with at least 

two partners,104 74% reported having 

sex with 2-49 partners.105

High 0 0 -1 0 0 0 0 0 Moderate

Multiple Sex 

Partners: At 

least 50 partners

2 OBS104,105 In one study, 3.5% reported having at 

least 50 sex partners,104 while in another 

6.6% did.105

High 0 -1 -1 0 0 0 0 0 Low

Age at first 

intercourse (<18 

years)

2 OBS51,104 The proportion of adults who reported 

having sex at age 18 or younger were 

58% 51 and 59%104 in two general 

population studies.

High 0 0 -1 0 0 0 0 0 Moderate

Same-sex 

partner (not 

restricted to 

men)

1 OBS106 8.2% of men and women reported 

having sex with same or both 

genders.106

High 0 -1 -1 0 0 0 0 0 Low

Noninjection 

substance 

abuse: Ongoing

1 OBS33 Among potential living donors, 5.5% had 

unspecified ongoing drug abuse.33

High 0 -1 0 -1 0 0 0 0 Low
111

Factor

Quantity and Type of 

Evidence Findings

Starting Grade

Decrease GRADE Increase GRADE

GRADE of 

Evidence 

for 

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose

Outcome

-response

Associated Despite Confounders

Noninjection 

substance 

abuse: Lifetime

3 OBS51,104,105 In the general population, 17% reported 

lifetime use of drugs other than 

marijuana,51 18% reported ever having 

used any drugs,105 and 21% reported 

ever using street drugs/cocaine.104

High 0 0 -1 0 0 0 0 0 Moderate

Alcohol 1 OBS122 Among heart donors, 20% reportedly 

drank alcohol heavily.122

High -1 -1 0 0 0 0 0 0 Low

Tobacco 1 OBS122 Among heart donors, 36% reportedly 

used tobacco.122

High -1 -1 0 0 0 0 0 0 Low

*Observational study
112

Question 4: What nonbehavioral factors are associated with an increased probability of infection with HIV, HBV, 

or HCV? What is the prevalence of these factors among potential solid organ donors?

Table 4. GRADE Table for Question 4 (Nonbehavioral Risk Factors)

Factor Virus

Quantity and 

Type of 

Evidence Findings

Starting 

Grade

Decrease Grade Increase Grade

GRADE 

of 

Evidence 

for 

Overall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose 

Outcome

Response

Associated Despite Confounders

Factors Identified in Original Guideline Exposure to Infected or Suspected Blood

HBV 1 OBS124 One study of embalmers who had a needle stick 

injury during embalming did not find an association 

between needlestick injuries with known or 

suspected HBV positive blood and HBV infection.

124

Low 0 -1 -1 -1 0 0 0 0 Very Low

HCV No studies - - - - - - - - - - Not 

Applicable 

(NA)

HIV - - - - - - - - - - - NA

Signs and Symptoms

HBV No studies - - - - - - - - - - NA

HCV 1 OBS121 Jaundice: Associated in one study121 Low 0 -1 0 0 0 1 0 0 Low

1 OBS119 ALT Reactivity: Associated in one study.119 Low 0 -1 0 0 0 1 0 0 Low

1 OBS51 ALT >40 U/L: Associated in one study51 Low 0 -1 0 0 0 1 0 0 Low

1 OBS109 Elevated liver enzyme: Associated in one study109 Low 0 -1 0 0 0 0 0 0 Very Low

HIV No studies - - - - - - - - - - NA
113

Factor Virus

Quantity and 

Type of 

Evidence Findings

Starting 

Grade

Decrease Grade Increase Grade

GRADE 

of 

Evidence 

for 

Overall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose 

Outcome

Response

Associated Despite Confounders

Receipt of Blood Transfusion

HBV 3 OBS111,112,115 Blood transfusion was associated with HBV infection 

in a general population,112 as was blood transfusion 

before 1991 in a special population.111 Blood 

transfusion was not associated with HBV in another 

special population study.115

Low 0 0 -1 0 0 0 0 0 Very Low

HCV 8 

OBS51,109,112,117,118,

120,121,129

All 8 studies associated having had a blood 

transfusion with HCV, and in eight of them the effect 

size was large. It was independently associated with 

HCV with large effect sizes in three blood donor 

studies117,120,129 and two general population 

studies.112,118 Two additional general population study 

performed univariate analyses only and found large 

effect sizes.109,121 The remaining general population 

study found an independent association between 

having a blood transfusion before 1992 and HCV, 

but the effect size was not large.51

Low 0 0 0 0 0 1 0 0 Moderate

HIV No studies - - - - - - - - - - NA
114

Factor Virus

Quantity and 

Type of 

Evidence Findings

Starting 

Grade

Decrease Grade Increase Grade

GRADE 

of 

Evidence 

for 

Overall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose 

Outcome

Response

Associated Despite Confounders

Accidental Needlestick with Unknown Blood

HBV 2 OBS107,112 According to data collected from a low-quality next-

of-kin, accidental needle sticks were not associated 

with HBV among potential corneal donors.107 A 

general population study found a lower prevalence of 

HBV among people who reported a needlestick.112

Low

000-10000 Very Low

HCV 4 OBS107,112,117,120 According to data collected from a low-quality next-

of-kin, accidental needle sticks were not associated 

with HCV among potential corneal donors.

107 A 

general population study found a lower prevalence of HCV among people who reported a needlestick.112

Among blood donors who work in a healthcare 

setting, needlestick injuries were not associated with 

HCV in one study,120 but “bloody” needlestick injuries 

were in another.117

Low

0-1000000 Very Low

HIV 1 OBS107 According to data collected from a low-quality next-

of-kin, accidental needle sticks were not associated 

with HIV among potential corneal donors107

Low

-1-10-10000 Very Low

Hemodialysis

HBV 2 OBS111,112 Hemodialysis was associated with HBV in one 

general population study112 and one special 

population study.111 Both analyses were univariate, 

and the special population study had a large effect 

size.

Low

00000100 Moderate

HCV 3 OBS112,118,121 In general population studies, “kidney dialysis” was 

associated with HCV in a univariate analysis in one 

study,121 and hemodialysis was associated with HCV 

with a large effect size in multivariate analysis in a 

second study.112 A third study did not find an 

association between hemodialysis and HCV.118

Low

00000000 Low

HIV No studies--

-------- NA
115

Factor Virus

Quantity and 

Type of 

Evidence Findings

Starting 

Grade

Decrease Grade Increase Grade

GRADE 

of 

Evidence 

for 

Overall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose 

Outcome

Response

Associated Despite Confounders

Surgery

HBV 3 OBS107,112,116 The corneal donor study did not associate having 

had surgery with HBV.107 One general population 

study found a lower prevalence of HBV among 

people who had surgery,112 and another found no 

relationship.116

Low

0-1000000 Very Low

HCV 5 

OBS107,109,112,117,11 9

The corneal donor study did not associate having 

had surgery with HCV.107 One blood donor study did 

not find any association with recent surgery119 and 

one general population study did not find any 

association with history of surgery.109 However, one 

blood donor study did find an independent 

association between HCV and lifetime history of 

surgery (or sutures).117 A general population study 

found no association.112

Low

0-1000000 Very Low

HIV 1 OBS107 The corneal donor study did not associate having 

had surgery with HIV.107

Low

-1-10-10000 Very Low

Organ Transplant 

Recipients

HBV 2 OBS107,113 HBV was not associated with having a organ 

transplant in one very low-quality study107 or 

a special population study.113

Low

000-10000 Very Low

HCV 1 OBS107 HCV was not associated with having a organ 

transplant in one very low-quality study.107

Low

-1-10-10000 Very Low

HIV 1 OBS107 HCV was not associated with having a organ 

transplant in one very low-quality study.107

Low

-1-10-10000 Very Low

Acupuncture

HBV 2 OBS113,116 Neither the general population study116 nor the 

special population study113 found an association 

between HBV and acupuncture.

Low

00000000 Low

HCV 3 OBS118,120,129 Acupuncture was not associated with HCV infection 

in two studies of blood donors120,129 or one study of a 

general population.118

Low

00000000 Low
116

Factor Virus

Quantity and 

Type of 

Evidence Findings

Starting 

Grade

Decrease Grade Increase Grade

GRADE 

of 

Evidence 

for 

Overall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose 

Outcome

Response

Associated Despite Confounders

HIV No studies - - - - - - - - - - NA

Dental Work

HBV 1 OBS116 Dental work within the last six months was not 

associated with acute HBV in one general population 

study.116

Low 0 0 0 -1 0 0 0 0 Very Low

HCV 2 OBS117,119 Dental work was not associated with HCV among 

blood donors in one study117; nor was having dental 

work in the six months before donation in another.119

Low 0 0 0 0 0 0 0 0 Low

HIV No Studies - - - - - - - - - - NA

Blood Draws

HBV 1 OBS107 The corneal donor study did not find an association 

between HIV testing and HBV, based upon next-ofkin interviews.107

Low -1 -1 0 -1 0 0 0 0 Very Low

HCV 2 OBS107,121 The low-quality corneal donor study did not find an 

association between HIV testing and HCV, based 

upon next of-kin interviews.

107 One general 

population study did find an association between 

having had a blood test for HBV and having an HCV 

infection.121 The same study also found that being a 

blood donor was associated with reduced risk of 

HCV.121

Low 0 0 0 -1 0 0 0 0 Very Low

HIV 1 OBS107 The corneal donor study did not find an association 

between HIV testing and HIV, based upon next of-kin 

interviews.107

Low -1 -1 0 -1 0 0 0 0 Very Low
117

Factor Virus

Quantity and 

Type of 

Evidence Findings

Starting 

Grade

Decrease Grade Increase Grade

GRADE 

of 

Evidence 

for 

Overall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose 

Outcome

Response

Associated Despite Confounders

Household Exposure

HBV 5 

OBS111,115,116,125,12

6

Having household contact with someone with 

hepatitis was associated with HBV in a special 

population study111, as was a family history of HBV in 

another special population study.125 However, having 

a household member with hepatitis was not 

associated with HBV in a third special population 

study;115 nor was being the wife of a man with HBV in 

a fourth special population study.126 Sharing a razor 

or toothbrush with a household member was not 

associated with HBV in a general population study 

either.116

Low 0 -1 -1 0 0 0 0 0 Very Low

HCV 3 OBS109,117,121 In one blood donor study, living with someone with 

hepatitis or having a relative with hepatitis was not 

associated with HCV , but living with a transfusion 

recipient and sharing a toothbrush or razor with 

person(s) unspecified was.117 In general population 

studies, having at least one family member treated 

for viral hepatitis was not associated with an 

increased risk of HCV in one study,109 but having at 

least one family member with HCV in another study 

was.121

Low 0 -1 0 0 0 0 0 0 Very Low

HIV No studies - - - - - - - - - - NA
118

Factor Virus

Quantity and 

Type of 

Evidence Findings

Starting 

Grade

Decrease Grade Increase Grade

GRADE 

of 

Evidence 

for 

Overall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose 

Outcome

Response

Associated Despite Confounders

Other Infections

HBV 2 OBS111,122 HBV surface antigen positivity was associated with 

HCV infection among heart donors in one study.122

HBV infection was associated with having had a 

sexually transmitted disease (STD) in a special 

population study.111

Low

00000000 Low

HCV 6 OBS51,118

-121,129 HCV was significantly associated with history of STD 

in two blood donor studies120,129 but not a general 

population study.121 HCV was associated with having 

a STD within six months of donating in another blood 

donor study.119 Herpes infection was associated with 

HCV in a general population study.

51 In addition, 

HCV was associated with seropositivity for other 

reactive infectious diseases in two blood donor 

studies.119,129 HIV infection was not associated with 

HCV infection upon univariate analysis of a general 

population study.118

Low

0-1000000 Very Low

HIV 4 OBS104

-106,108 In general population studies, HIV infection was 

associated with diagnosis of STD in one study,

106

HSV-2 in two studies,

104,105 and syphilis or other 

infection not apparently related to HIV in another 

study,108

Low

00000000 Low

Sex

HBV 6 OBS111

-

113,125,127,128

In one general population study112 and 2 special 

population studies113,125 males had higher prevalence 

of HBV. Two additional special populations studies 

found no difference127 or a lower prevalence.111 A study of children found no difference.128

Low

0-1-100000 Very Low

HCV 9 OBS51,109,112,119

-

122,129,130

One organ donor study found an increased 

prevalence of HCV in males.122 Among blood donors 

it was in one study129 but not in two others.119,120

Four general population studies found an increased 

risk among males.51,112,121,130 but one other did not.109

Low

0-1000000 Very Low
119

Factor Virus

Quantity and 

Type of 

Evidence Findings

Starting 

Grade

Decrease Grade Increase Grade

GRADE 

of 

Evidence 

for 

Overall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose 

Outcome

Response

Associated Despite Confounders

HIV 3 OBS106,123 None of three general population studies associated 

male sex with an increased prevalence of HIV.106,123

Low 0 0 0 0 0 0 0 0 Low

Age

HBV 8 OBS111-114,124-127 Every study tested the association of HBV and age in 

different ways, and the results are inconsistent and 

difficult to compare.

One general population study found an increased risk 

of HBV when >60 years.112 The rest of the studies 

were special population studies. One found an 

association with mean age (with older people having 

greater prevalence of HBV)111 while another did 

not.113 Increased prevalence was associated with 

age younger than 20 years,126 age over 35 years,124

and age over 50 years.114 In another study lower 

prevalence was found in people under 49 years.127

The remaining study did not find any association 

between age and HBV.125

Low 0 -1 -1 0 0 0 0 0 Very Low

HCV 7 OBS109,112,119-

122,130

Every study tested the association of HCV and age in 

different ways, and the results are inconsistent and 

difficult to compare. The organ donor study found 

that HCV infection was associated with older median 

age.122 One of the blood donor studies associated 

HCV with older mean age,119 the other did not.120

In general population studies, HCV was associated 

with increased mean age130 and decade of birth 

(with people born between 1940 and 1959 having the 

highest prevalence),121 but not age less than 

50 years109 or age less than 60 years.112

Low 0 -1 0 0 0 0 0 0 Very Low
120

Factor Virus

Quantity and 

Type of 

Evidence Findings

Starting 

Grade

Decrease Grade Increase Grade

GRADE 

of 

Evidence 

for 

Overall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose 

Outcome

Response

Associated Despite Confounders

HIV 3 OBS106,108,123 The HIV studies also measured age in different ways, 

complicating comparison. In general these studies 

found young adults to be at the highest risk. One 

study found younger adults (aged 18 to 30) had 

increased prevalence of HIV,123 another found adults 

aged 25 to 40 had higher prevalence of HIV than 

younger people aged 15 to 24 years,106 and the third 

found increased prevalence among adults aged 35 to 

44 years.108

Low 0 -1 0 0 0 0 0 0 Low

Race or Ethnicity

HBV 2 OBS112,113 White race or Hispanic ethnicity was associated with 

lower HBV prevalence in a general population study 

in a multivariate analysis112 but not in a special 

population study.113

Low 0 -1 0 -1 0 0 0 0 Very Low

4 OBS110,111,113,114 Non-Hispanic Black race was associated with a 

higher prevalence of HBV in a general population 

study multivariate analysis110 and two special 

population studies111,114 but not another special 

population study.113

Low 0 0 -1 0 0 0 0 0 Very Low

3 OBS110,111,113 Being Mexican-American was not associated with a 

different prevalence of HBV than non-Hispanic White 

race in a multivariate analysis of a general population 

study.110 In special population studies, Hispanic 

ethnicity113 and Hispanic or Latino ethnicity111 were 

not associated with HBV infection.

Low 0 0 -1 0 0 0 0 0 Very Low

1 OBS111 A special population study found an increased 

prevalence of HBV among Asian Americans 

compared with non-Hispanic White Americans.111

Low 0 -1 -1 0 0 0 0 0 Very Low

1 OBS116 Among African American, Caucasian, Asian, and 

Hispanic children who received blood transfusions, 

the prevalence was not significantly different.

Low 0 0 0 -1 0 0 0 0 Very Low
121

Factor Virus

Quantity and 

Type of 

Evidence Findings

Starting 

Grade

Decrease Grade Increase Grade

GRADE 

of 

Evidence 

for 

Overall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose 

Outcome

Response

Associated Despite Confounders

HCV 7 OBS51,119-

122,129,130

Because about half of the studies combined races in 

analyses (their results presented first), the different 

analyses are reported together here. The different 

analysis methods complicate side-by-side 

comparison, but the evidence rating would always be 

„very low‟ for these studies. (These results are all 

presented in the same row because of overlap within 

the studies.)

In organ donors, no relation between race and HCV 

infection was detected.122 Three general population 

studies did not find any relation either.51,121,130

White race was not associated with a difference in 

rate of HCV compared with other races.119

Black race was associated with increased rates of 

HCV compared to White race in two studies.120,129

Being Asian was associated with having a lower 

prevalence of HCV compared to White race among 

blood donors.129

Among blood donors, one study found that Hispanic

ethnicity had a higher risk of HCV than White

race,

129but another did not.119

Low 0 -1 0 0 0 0 0 0 Very Low

HIV 3 OBS105,106,123 In univariate analyses, two general population 

studies found increased prevalence of HIV among 

people of Black race105,106 but a third did not.123

Low 0 -1 0 0 0 0 0 0 Very Low

2 OBS105,106 In univariate analyses, neither of two general 

population studies found a difference in HIV 

prevalence in White race and Asians.105,106

Low 0 0 0 -1 0 0 0 0 Very Low
122

Factor Virus

Quantity and 

Type of 

Evidence Findings

Starting 

Grade

Decrease Grade Increase Grade

GRADE 

of 

Evidence 

for 

Overall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose 

Outcome

Response

Associated Despite Confounders

National Origin/Birthplace

HBV 5 

OBS110,112,116,125,12

6

National origin and birthplace were reported 

differently among studies and most factors cannot be 

considered side-by-side. However, since the rating 

for any factor in this group will be „very low‟ and there 

is some overlap among studies, we present the 

findings together.

In multivariate analysis of general populations, HCV 

was associated with being born in Southeast Asia or 

Africa in one study.112 A special population study 

found children born in Korea had higher prevalence 

of HBV than children born in the U.S.126 Other special 

population studies did not find significantly different 

rates of Asian Americans born in East Asia 

(excluding China) or Southeast Asia or Pacific 

Islands compared to Asian Americans born in 

China.125

Birth in an area with a high endemic rate or

household exposure to someone born in a high 

endemic rate was not in another general population 

study.116

In multivariate analyses, a general population 

study110 and a special population study125 found that 

being born in the U.S. was associated was lower 

prevalence of HBV.

Low 0 -1 -1 0 0 0 0 0 Very Low
123

Factor Virus

Quantity and 

Type of 

Evidence Findings

Starting 

Grade

Decrease Grade Increase Grade

GRADE 

of 

Evidence 

for 

Overall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose 

Outcome

Response

Associated Despite Confounders

HCV 5 

OBS51,112,119,121,129

One blood donor study did not associate foreign birth 

with HCV,119 but another did in a multivariate 

analysis.129 A general population study found people 

born outside of the U.S. had a lower prevalence of 

HCV.51 Birth in Southeast Asia or Africa was not 

associated with an increased prevalence of HCV in 

another general population study.112 A general 

population study found no association between HCV 

and U.S. citizenship.121

Low

0-1000000 Very Low

HIV No studies--

-------- NA

Preferred Language

HBV No studies--

-------- NA

HCV 1 OBS130 One general population study found an association

between preference of English or Spanish and

HCV.130

Low

0-1000000 Very Low

HIV 1 OBS123 One general population study found no difference in

prevalence of HIV among Spanish speakers.123

Low

0-10-10000 Very Low

Occupation

HBV 6 OBS110

-113,115,116 Occupation as a health care worker was protective 

against HBV in one general population study112 and 

not associated with HBV in another general 

population study110 or a special population study.113

However, having a healthcare-related job with 

frequent blood exposure was associated with HBV in 

one special population study.111

Another general population study did not associate 

healthcare employment or household contact with 

someone who is a health care worker with HBV,116

and a special population study did not associate 

being a health care worker or the spouse of one with 

HBV.115

Low

00000000 Low
124

Factor Virus

Quantity and 

Type of 

Evidence Findings

Starting 

Grade

Decrease Grade Increase Grade

GRADE 

of 

Evidence 

for 

Overall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose 

Outcome

Response

Associated Despite Confounders

1 OBS110 Ever being in the military was not associated with 

HBV in a general population study.110

Low 0 0 0 -1 0 0 0 0 Very Low

HCV 2 OBS109,117 In any occupation, occupational blood exposure was 

associated with HCV among blood donors in one 

study,117 but work contact with blood was not 

associated with HCV in a general population study.109

Low 0 -1 0 -1 0 0 0 0 Very Low

2 OBS112,119 Medical or dental job with frequent blood contact was 

not associated with HCV in one blood donor study119

and was associated with lower prevalence of HCV in 

a general population study.112

Low 0 -1 0 -1 0 0 0 0 Very Low

2 OBS51,109 Neither of two general population studies associated 

ever having served in the armed forces with 

HCV.51,109

Low 0 0 0 -1 0 0 0 0 Very Low

2 OBS119,121 Public safety job with frequent blood contact was not 

associated with HCV in one blood donor study.119

Another study did associate having a job at a prison 

with having HCV.

121

Low 0 -1 0 0 0 0 0 0 Very Low

HIV No studies - - - - - - - - - - NA

Education

HBV 3 OBS110,111,113 Having less than a high school education was 

associated with HBV in one general population study, 

compared with some college.110 In special population 

studies, one found a higher prevalence of HBV 

among students in 2-year colleges compared to 

those in 4-year colleges,111 and the other study found 

no relationship between years of education and 

HBV.113

Low 0 -1 -1 0 0 0 0 0 Very Low
125

Factor Virus

Quantity and 

Type of 

Evidence Findings

Starting 

Grade

Decrease Grade Increase Grade

GRADE 

of 

Evidence 

for 

Overall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose 

Outcome

Response

Associated Despite Confounders

HCV 5 OBS51,119-121,130 One blood donor study associated less education 

with HCV,119 and another associated having no 

college education with having HCV.120 One general 

population study associated having fewer than 

12 years of education with having HCV,51 but two 

others found no association between educational 

attainment and HCV.121,130

Low 0 -1 0 0 0 0 0 0 Very Low

HIV 2 OBS104,106 Neither of two general population studies found an 

association between having less than a high school 

education and having HIV.104,106

Low 0 0 0 -1 0 0 0 0 Very Low

Economic Factors

HBV 2 OBS113,114 One special population study did not associate 

homelessness with HBV.113 Another special 

population study did not associate homelessness, 

institutionalization, or other non-independent living 

arrangement with HBV.114

Low 0 0 -1 -1 0 0 0 0 Very Low

HCV 2 OBS51,121 In a general population, ever having been homeless 

was associated with an increased risk of HCV.121

In the same study, annual income was not 

associated with HCV. 

Another general population study did not find any 

association with family poverty level and HCV.51

Low 0 -1 0 -1 0 0 0 0 Very Low

HIV 2 OBS104,123 Being homeless was associated with an increased 

prevalence of HIV in one general population study.123

In another general population study, having a poverty 

index of less than one was not associated with 

HIV.104

Low 0 -1 0 0 0 0 0 0 Very Low

He

alth 

Ins

ura

nce

HBV No studies - - - - - - - - - - NA
126

Factor Virus

Quantity and 

Type of 

Evidence Findings

Starting 

Grade

Decrease Grade Increase Grade

GRADE 

of 

Evidence 

for 

Overall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose 

Outcome

Response

Associated Despite Confounders

HCV 1 OBS130 One general population study associated insurance 

with HCV infection, with people on Medicaid having 

the highest prevalence.130

Low 0 -1 0 0 0 0 0 0 Very Low

HIV 2 OBS106,123 One general population study found a higher 

prevalence of HIV among people with no insurance106

but a second did not.123

Low 0 -1 0 -1 0 0 0 0 Very Low

Marital Status

HBV 2 OBS110,114 Being divorced or separated was associated with a 

higher prevalence of HBV than any other status in 

one general population study.110 Being currently 

married was not associated with any difference in 

HBV prevalence than any other status in one special 

population study.114

Low 0 0 0 0 0 0 0 0 Low

HCV 1 OBS117 Being married was associated with a lower risk of 

HCV in one blood donor study.117

Low 0 0 0 0 0 0 0 0 Low

HIV 1 OBS104 Being married or cohabitating was associated with a 

lower risk of HIV in one general population study.104

Low 0 0 0 0 0 0 0 0 Low
127

Question 5: What are the test characteristics of the screening methods available to detect HIV, HBV, and HCV in 

potential solid organ donors? Do test characteristics differ in particular populations and with donor clinical status 

(i.e., heart beating vs. non-heart beating donors OR adult vs. pediatric donors)?

Table 5.GRADE Table for Question 5 (Performance - Sensitivity/Specificity)

Virus Test Trade Name Manufacturer Quantity and 

Type of 

Evidence

Findings (Point 

Estimates)

Starting 

GRADE 

(Study 

Design)

Decrease GRADE GRADE for 

Evidence for 

Outcome

QualityConsistencyDirectnessPrecisionPublication Bias

Tests currently in use in U.S. Organ Procurement Organization 176: Immunoassays

HIV

3

rd generation 

EIA

Genetics System 

(GS) HIV-1/HIV-2 

Plus 0 EIA

Bio-Rad 

Laboratories

1 A*132 Sensitivity: 99.8%A**

Specificity: 99.4%A

Main limitations: lack of 

diagnostic uncertainty, 

no blinding

Moderate -1 0 0 0 0 Low

HIVAB HIV-1/HIV-2 

(rDNA) EIA

Abbott 

Laboratories

2 A131,132 Sensitivity: 99.4%A132 and 

100%A131

Specificity: 97.7%A132 and 

99.74%A131

Main limitations: lack of 

diagnostic uncertainty, no 

blinding.

Study design and quality 

assessment equal for the 

two studies.

Moderate -1 0 0 0 0 Low

HBV (HBsAg; 

the surface 

antigen)

Abbott AxSYM 

HBsAg Assay

Abbott 

Laboratories

1 CDx†

155 Sensitivity: 100%C‡

Specificity: 99.4%C

Main limitation: no blinding

High -1 0 0 0 0 Moderate

Abbott PRISM 

HBsAg

Abbott 

Laboratories

No studies - - - - - - - -
128

Virus Test Trade Name Manufacturer Quantity and 

Type of 

Evidence

Findings (Point 

Estimates)

Starting 

GRADE 

(Study 

Design)

Decrease GRADE GRADE for 

Evidence for 

Outcome

QualityConsistencyDirectnessPrecisionPublication Bias

ADVIA Centaur 

HBsAg Assay

Siemens 

Healthcare 

Diagnostics

1 A156 Sensitivity: 100%A

Specificity: 97.9%A

Main limitations: lack of 

diagnostic uncertainty, 

no blinding 

Moderate -1 0 0 0 0 Low

Genetic Systems 

(GS) HBsAg EIA 3.0

Bio-Rad 

Laboratories

No studies - - - - - - - -

HBV 

(anti-HBs; 

antibodies to 

the surface 

antigen)

Ortho Antibody to 

HBsAg ELISA Test 

System 3

Ortho Clinical 

Diagnostics

No studies - - - - - - - -

HBV 

(anti-HBc; 

antibodies to 

the core 

antigen)

Abbott PRISM 

HBcore

Abbott 

Laboratories

No studies - - - - - - - -

ADVIA Centaur HBc 

Total Assay

Siemens 

Healthcare 

Diagnostics

No studies - - - - - - - -

AxSYM Core 2.0 Abbott 

Laboratories

No studies - - - - - - - -

CORZYME Abbott 

Laboratories

No studies - - - - - - - -

Ortho HBc ELISA 

Test System 

Ortho Clinical 

Diagnostics

No studies - - - - - - - -
129

Virus Test Trade Name Manufacturer Quantity and 

Type of 

Evidence

Findings (Point 

Estimates)

Starting 

GRADE 

(Study 

Design)

Decrease GRADE GRADE for 

Evidence for 

Outcome

QualityConsistencyDirectnessPrecisionPublication Bias

HCV Abbott HCV EIA 2.0 Abbott 

Laboratories

3 CDx166-168 Sensitivity: 73.2%C166

, 

85.7%C168, 100%C167

Specificity: 92.7%C167, 

99.8%C168, 99.9%C166

Main limitations: one study 

less appropriate reference 

standard, no blinding in 

any.

Anderson et al.166 used a 

less reliable reference 

standard. All other factors 

in study design and 

limitations assessment the 

same for all three studies.

High -1 0 0 0 0 Moderate

ADVIA Centaur HCV 

assay 

Siemens 

Healthcare 

Diagnostics

1 A172

1 DxC171

Sensitivity: Both 100%

Specificity: 94.4%C171, 

99.9%A172

Main limitations: one study 

suboptimal enrollment 

methods, no blinding in 

either.

Denoyel et al.172 did not 

report appropriate 

enrollment methods. 

All other study design and 

limitations assessments 

were the same.

High -1 0 0 0 0 Moderate

AxSYM Anti-HCV Abbott 

Laboratories

No studies - - - - - - - -
130

Virus Test Trade Name Manufacturer Quantity and 

Type of 

Evidence

Findings (Point 

Estimates)

Starting 

GRADE 

(Study 

Design)

Decrease GRADE GRADE for 

Evidence for 

Outcome

QualityConsistencyDirectnessPrecisionPublication Bias

Ortho HCV 

Version 3.0 ELISA 

Test System

Ortho Clinical 

Diagnostics

2 CDx169,171

1 A170

Sensitivity: All three 100%C

Specificity: 95.5%C171, 

99.7%C169, 99.9%A170

Main limitations: one study 

lack of diagnostic 

uncertainty, one study 

suboptimal enrollment 

methods, no blinding.

Vrielink et al.170 did not use 

samples with diagnostic 

uncertainty or report 

adequate enrollment 

methods. The rest of the 

study design and limitations 

assessment factors were 

the same for all three 

studies.

High -1 0 0 0 0 Moderate
131

Virus Test Trade Name Manufacturer Quantity and 

Type of 

Evidence

Findings (Point 

Estimates)

Starting 

GRADE 

(Study 

Design)

Decrease GRADE GRADE for 

Evidence for 

Outcome

QualityConsistencyDirectnessPrecisionPublication Bias

Tests currently in use in U.S. Organ Procurement Organization 176: NAT

HIV NAT COBAS AmpliScreen 

HIV-1 Test v. 1.5

Roche 

Diagnostics

1 DxC142

1 A132

Sensitivity: 7.7%C142 and 

92.6%A132

Specificity: 96.9%A132 and 

100%C142

Main limitations: one study 

inappropriate reference 

standard, other lack of 

diagnostic uncertainty, 

neither blinded

The main difference in 

findings appears to be due 

to the use of a reference 

standard inappropriate to 

calculate sensitivity in 

Bamaga et al.142

Moderate -1 0 0 0 0 Low

HCV NAT COBAS AmpliScreen 

HCV Test version. 

2.0

Roche 

Diagnostics

1 CDx142 Sensitivity: 20%C

Specificity: 99.4%C

Main limitations: 

inappropriate reference 

standards, no blinding

Moderate -1 0 0 0 0 Low

HBV NAT COBAS AmpliScreen 

HBV Test

Roche 

Diagnostics

1 CDx164 Sensitivity: 84.8%C

Specificity: 100%C

Main limitations: 

no blinding, potential for 

publication bias

Moderate -1 0 0 0 -1 Very Low
132

Virus Test Trade Name Manufacturer Quantity and 

Type of 

Evidence

Findings (Point 

Estimates)

Starting 

GRADE 

(Study 

Design)

Decrease GRADE GRADE for 

Evidence for 

Outcome

QualityConsistencyDirectnessPrecisionPublication Bias

HCV and 

HIV-1 NAT

ProCleix HIV-1/ 

HCV Assay

Gen-Probe 

Incorporated

1 CDx136

1 A135

HIV

Sensitivity: 99.9%A135 and 

100%C136

Specificity: 99.67%A135 and 

100%C136

HCV

Sensitivity: 99.3%C136 and 

99.6%A135

Specificity: 97.4%C136 and 

99.6%A135

Main limitations: one study 

lack of diagnostic 

uncertainty, one study 

no blinding, potential for 

publication bias.

Vargo et al.135 did not have 

diagnostic uncertainty, and 

Jackson et al. did not have 

blinding. The studies were 

on the same for the rest of 

the study design and 

limitations assessment 

factors.

Moderate 0 0 0 0 -1 Low
133

Virus Test Trade Name Manufacturer Quantity and 

Type of 

Evidence

Findings (Point 

Estimates)

Starting 

GRADE 

(Study 

Design)

Decrease GRADE GRADE for 

Evidence for 

Outcome

QualityConsistencyDirectnessPrecisionPublication Bias

Tests currently not in use in U.S. Organ Procurement Organization 176: 4th generation Immunoassays

HIV 

4

th generation

ARCHITECT HIV 

Combo

Abbott 

Laboratories

2 A145,150 Sensitivity: Both 100%A

Specificity: 99.6%A145 and 

100%A150

Main limitations: lack of 

diagnostic uncertainty, 

suboptimal enrollment 

methods, no blinding.

The study design and 

limitations assessments 

were the same for both 

studies.

Moderate -1 0 0 0 0 Low
134

Virus Test Trade Name Manufacturer Quantity and 

Type of 

Evidence

Findings (Point 

Estimates)

Starting 

GRADE 

(Study 

Design)

Decrease GRADE GRADE for 

Evidence for 

Outcome

QualityConsistencyDirectnessPrecisionPublication Bias

AxSYM HIV Ag/Ab 

Combo

Abbott 

Laboratories

1 CDx144

3 A145,147,148

Sensitivity: All 100%

Specificity: 98%A,145

99.65%C,144 99.8%A,147

99.9%/99.87%A148 (last two 

from same study, different 

data sets)

Main limitations: two 

studies lack of diagnostic 

uncertainty and/or 

suboptimal enrollment 

methods, all studies no 

blinding.

Bourlet et al.144 had 

diagnostic uncertainty and 

appropriate enrollment 

methods while the rest did

not. The studies were the 

same on all other study 

design and limitations 

assessment factors.

Moderate -1 0 0 0 0 Low

COBAS Core HIV 

Combi

Roche 

Diagnostics

2 A149,150 Sensitivity: Both 100%A 

Specificity: 99.3%A150 and 

99.73%A149

Main limitations: lack of 

diagnostic uncertainty, 

one study suboptimal 

enrollment methods, 

both no blinding.

The two studies were the 

same for study design and 

limitations assessment.

Moderate -1 0 0 0 0 Low
135

Virus Test Trade Name Manufacturer Quantity and 

Type of 

Evidence

Findings (Point 

Estimates)

Starting 

GRADE 

(Study 

Design)

Decrease GRADE GRADE for 

Evidence for 

Outcome

QualityConsistencyDirectnessPrecisionPublication Bias

Coulter HIV-1 p24 

Antigen Assay

Coulter 

Corporation

No studies - - - - - - - -

Enzygnost HIV 

Integral II

Siemens 

Healthcare 

Diagnostics

No studies - - - - - - - -

Genscreen Plus HIV 

Ag/Ab Combo

Bio-Rad 

Laboratories

1 DxC143

1A147

Sensitivity: Both 100%

Specificity: 82.5%C,143

99.9%A147

Main limitations: One study 

lack of diagnostic 

uncertainty, one suboptimal 

enrollment methods, 

neither blinded.

Ly et al.147 did not have 

diagnostic uncertainty or 

report appropriate 

enrollment methods. 

All other study design and 

limitation assessment 

factors were the same.

High -1 0 0 0 0 Moderate

Genscreen HIV Ultra 

Ag-Ab Assay

Bio-Rad 

Laboratories

1 A150 Sensitivity:100%A

Specificity: 99.8%A

Main limitations: lack of 

diagnostic uncertainty, 

suboptimal enrollment 

methods, blinding 

Moderate -1 0 0 0 0 Low

Modular HIV Combi Roche 

Diagnostics

No studies - - - - - - - -
136

Virus Test Trade Name Manufacturer Quantity and 

Type of 

Evidence

Findings (Point 

Estimates)

Starting 

GRADE 

(Study 

Design)

Decrease GRADE GRADE for 

Evidence for 

Outcome

QualityConsistencyDirectnessPrecisionPublication Bias

Murex HIV Ag/Ab 

Combo

Abbott 

Laboratories

1 A150 Sensitivity: 100%A

Specificity: 99.6%A

Main limitations: lack of 

diagnostic uncertainty, 

suboptimal enrollment 

methods, blinding

Moderate -1 0 0 0 0 Low

VIDAS DUO QUICK bioMerieux 

Clinical 

Diagnostics

No studies - - - - - - - -

VIDAS DUO ULTRA bioMerieux 

Clinical 

Diagnostics

2 DxC144,151

1 A150

Sensitivity: All 100% 

Specificity:99.5%C,150

99.5%A,151 99.86%C144

Main limitations: one study 

lack of diagnostic 

uncertainty, one study 

suboptimal enrollment 

methods, two studies lack 

of blinding

Ly et al.150 did not have 

diagnostic uncertainty or 

report appropriate 

enrollment methods. None 

of the studies besides 

Saville et al.151 used 

blinding. All other study 

design and limitation 

assessment factors were 

the same.

High -1 0 0 0 0 Moderate
137

Virus Test Trade Name Manufacturer Quantity and 

Type of 

Evidence

Findings (Point 

Estimates)

Starting 

GRADE 

(Study 

Design)

Decrease GRADE GRADE for 

Evidence for 

Outcome

QualityConsistencyDirectnessPrecisionPublication Bias

Vironostika HIV 

Uni-Form II Ag/Ab

bioMerieux 

Clinical 

Diagnostics

3 CDx152,224,225

1 A147

Sensitivity: All 100%

Specificity: 99.2%C,152

99.3%C,225 99.4%C,224

99.6%A147

Main limitations: one study 

lack of diagnostic 

uncertainty, no blinding

Ly et al.147 did not have 

diagnostic uncertainty or 

report appropriate 

enrollment methods. 

All other study design and 

limitation assessment 

factors were the same.

High -1 0 0 0 0 Moderate

HCV

4

th generation

INNOTEST HCV Ab 

IV

Innogenetics 

NV

No studies - - - - - - - -

Monolisa HCV Ag/Ab 

Ultra

Bio-Rad 

Laboratories

No studies - - - - - - - -

Murex 4.0 Abbott 

Laboratories

No studies - - - - - - - -

* A: Analytic study

** A: Analytic sensitivity/specificity

† CDx: Clinical diagnostic cohort

‡ C: Clinical sensitivity/specificity
138

Question 6: Which donor interventions reduce the probability of pathogen transmission from an organ donor 

infected with HIV, HBV, or HCV to a previously uninfected recipient?

Table 6. GRADE Table for Question 6 (Inactivation)

Comparison Outcome

Quantity and 

Type of 

Evidence Findings

Starting Grade

Decrease GRADE Increase GRADE

GRADE of 

Evidence for 

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose ResponseConfounders would reduce the effect

Outcome

Inactivating vs. 

not inactivating 

pathogens in 

solid organs

Viral 

burden

One study180,181 The four 

inactivation 

procedures 

reduced viral 

burden 69%% 

to 99.7% 

Low -1 -1 0 0 0 +1 +1 0 Low
139

Question 7: How do the clinical outcomes of recipients of organs from donors infected with HIV, HBV, or HCV 

compare to those who remain on the transplant list?

Table 7. GRADE Table for Question 7 (Clinical Outcomes of Known Positive Organs vs. Waitlist or Known Negative Organs)

Comparison Outcome

Quantity and 

Type of 

Evidence Findings

Starting Grade

Decrease GRADE Increase GRADE

GRADE of 

Evidence 

for 

Outcome

Overall

GRADE of

Evidence

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose R

Base

esponse

Confounders would reduce the effect

Receiving an HCV+ organ 

compared to remaining 

on the waitlist

Recipient 

survival

One 

observational 

study189

Adjusted hazard ratio 0.76

(95% CI: 0.6 to 0.96)

(in favor of transplantation 

over the waitlist)

Low -1 -1 0 0 0 0 0 0 Very Low Very Low

Receiving an HBV+ organ 

compared to receiving a 

negative organ for 

recipients who were 

NEGATIVE before 

transplant

Graft 

survival

One 

observational 

study77

Results favored receiving 

an organ from a negative 

donor:

1 year: D+ 87%, D- 88%

2 yrs.: D+ 78%, D- 83%

3 yrs: D+ 72%, D- 77%

Low -1 -1 0 0 0 0 0 0 Very Low

Very Low

Recipient 

survival

One 

observational 

study77

Results favored receiving 

an organ from a negative 

donor:

1 year: D+ 94%, D- 94%

2 yrs.: D+ 90%, D- 92%

3 yrs: D+ 86%, D- 90%

Low -1 -1 0 0 0 0 0 0 Very Low
140

Comparison Outcome

Quantity and 

Type of 

Evidence Findings

Starting Grade

Decrease GRADE Increase GRADE

GRADE of 

Evidence 

for 

Outcome

Overall

GRADE of

Evidence

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose R

Base

esponse

Confounders would reduce the effect

Receiving a HCV+ organ 

compared to receiving a 

negative organ for 

recipients who were 

NEGATIVE before 

transplant

Graft 

survival

Three 

observational 

studies44,182,18

3,190,191

No statistically significant 

difference was reported by 

any of the three studies.

Low -1 0 0 0 0 0 0 0 Very Low

Recipient Low

survival

Three 

observational 

studies44,99,101,

182,183

Two of the three studies 

reported results in favor of 

receiving an organ from a 

negative donor. The third 

study found a statistically 

nonsignificant result.

Low -1 0 0 0 0 +1 0 0 Low
141

Comparison Outcome

Quantity and 

Type of 

Evidence Findings

Starting Grade

Decrease GRADE Increase GRADE

GRADE of 

Evidence 

for 

Outcome

Overall

GRADE of

Evidence

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose R

Base

esponse

Confounders would reduce the effect

Receiving an HBV+ organ 

compared to receiving a 

negative organ for 

recipients who were 

POSITIVE before 

transplant

Graft 

survival

Four 

observational 

studies75,77,185-

188

Only one of the four studies 

reported any statistically 

significant difference. This 

study found that if the 

kidney donor was living, 

results slightly favored 

receiving an organ from an 

HBsAg+ donor, whereas if 

the kidney donor was 

deceased, results favored 

receiving an organ from an 

HBsAg- donor.

Low -1 -1 0 0 0 0 0 0 Very Low

Very Low

Recipient 

survival

Three 

observational 

studies77,185-

188

Only one of the three 

studies reported any 

statistically significant 

difference. This study found 

that if the kidney donor was 

living, there was no 

statistically significant 

difference, whereas if the 

kidney donor was 

deceased, results favored 

receiving an organ from an 

HBsAg- donor.

Low -1 -1 0 0 0 0 0 0 Very Low
142

Comparison Outcome

Quantity and 

Type of 

Evidence Findings

Starting Grade

Decrease GRADE Increase GRADE

GRADE of 

Evidence 

for 

Outcome

Overall

GRADE of

Evidence

Study QualityConsistency

Directness

Precision

Publication BiasLarge MagnitudeDose R

Base

esponse

Confounders would reduce the effect

Receiving a HCV+ organ 

compared to receiving a 

negative organ for 

recipients who were 

POSITIVE before 

transplant

Graft 

survival

13

observational 

studies37,44,182-

184,188,190-199

No statistically significant 

difference was reported by 

any of the 13 studies.

Low -1 0 0 0 0 0 0 0 Very Low

Very Low

Recipient 

survival

11 

observational 

studies37,44,182-

184,188,192-

195,197-199

Only 2 of the 11 studies 

found any statistically 

significant difference. 

One of the two favored 

recipients of organs of 

positive donors, and the 

other favored recipients of 

organs of negative donors.

Low -1 0 0 0 0 0 0 0 Very Low

Note: The shaded rows denote recipient survival, which was considered a “critical” outcome. Graft survival is unshaded because it was not considered “critical” for the purpose of evidence grading.
143

Question 8: How do the clinical outcomes of transplant recipients who receive organs from donors with 

behavioral or nonbehavioral risk factors compare to those who remain on the transplant list?

Table 8. GRADE Table for Question 8 (Clinical Outcomes of At-risk Organs vs. Waitlist or Not-at-risk Organs)

Comparison Outcome

Quantity and 

Type of 

Evidence Findings

Starting Grade

Decrease GRADE Increase GRADE

GRADE 

of 

Evidence 

for 

Outcome

Overall 

GRADE 

of 

Evidence 

Study

Base

Quality

Consistency

Directness

Precision

Publication BiasLarge MagnitudeDose ResponseConfounders would reduce the effect

Transplant vs. 

discard kidneys 

from at-risk 

donors who test 

negative

Recipient 

survival

One 

simulation200

91% survival in 

both groups at 

one year.

At five years, 

survival was 68% 

for the transplant 

group and 65% for 

the discard group.

At 10 years, 

survival was 49% 

for the transplant 

group and 45% for 

the discard group.

At 20 years, 

survival was 23% 

for the transplant 

group and 20% for 

the discard group.

Very 

Low

0 -1 0 0 0 0 0 0 Very Low

Very Low
144

Comparison Outcome

Quantity and 

Type of 

Evidence Findings

Starting Grade

Decrease GRADE Increase GRADE

GRADE 

of 

Evidence 

for 

Outcome

Overall 

GRADE 

of 

Evidence 

Study

Base

Quality

Consistency

Directness

Precision

Publication BiasLarge MagnitudeDose ResponseConfounders would reduce the effect

Quality of 

life

One 

simulation200

5.6 QALYs for the 

transplant strategy, 

compared to 

5.1 QALYs for the 

discard strategy

Very 

Low

0 -1 0 0 0 0 0 0 Very Low

Waitlist survival 

vs. survival of 

infected recipients 

of at-risk organs

Recipient 

survival

One 

simulation201

One-year waitlist 

mortality for 

kidneys was 3% to 

11% (increasing 

with age); for livers 

it was 4% to 37% 

(increasing with 

MELD score); for 

hearts it was 6% to 

22% (increasing 

with criticality 

status). No 

mortality estimates 

provided for all 

those who received 

at-risk organs. Of 

2,189 „high-risk‟

donors, there was 

only one confirmed 

cases of HIV 

infection.

Very 

Low

0 -1 0 0 0 0 0 0 Very Low Very Low
145

Question 9: What is the impact of excluding potential solid organ donors with behavioral or nonbehavioral risk factors on the organ 

donor pool? One study was included for this question. This study200 was described in Question 8. 

Question 10: What is the impact of false positive tests on the organ donor pool? No studies were identified that met the inclusion criteria.
146

References

1. CDC. Guidelines for preventing transmission of human immunodeficiency virus through transplantation of human tissue and organs. 

MMWR Recomm Rep. 1994;43(RR-8):1-17.

2. Wolf JL, Perkins HA, Schreeder MT, Vincenti F. The transplanted kidney as a source of hepatitis B infection. Ann Intern Med. Sep 

1979;91(3):412-413.

3. CDC. Epidemiologic Notes and Reports Human Immunodeficiency Virus Infection Transmitted From on Organ Donor Screened for 

HIV Antibody - North Caroli. MMWR. 1987 1987;36(20):306-308.

4. Kumar P, Pearson JE, Martin DH, et al. Transmission of human immunodeficiency virus by transplantation of a renal allograft, with 

development of the acquired immunodeficiency syndrome. Ann Intern Med. Feb 1987;106(2):244-245.

5. Pereira BJ, Milford EL, Kirkman RL, Levey AS. Transmission of hepatitis C virus by organ transplantation. N Engl J Med. 

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