Deceased Donors With HIV in the Era of the HOPE Act: Referrals and Procurement

Background. The HIV Organ Policy Equity Act legalizes organ procurement from donors with HIV (HIV D+). A prior survey of Organ Procurement Organizations (OPOs) estimated >2000 HIV D+ referrals/year; however, only 30–35 HIV D+/year have had organs procured. Given this gap, we sought to understand HIV D+ referrals and procurements in practice. Methods. We prospectively collected data on all OPO-reported HIV D+ referrals, including reasons for nonprocurement. We evaluated trends and compared HIV D+ characteristics by procurement status using regression, chi-squared tests, and Wilcoxon rank-sum tests. Results. From December 23, 2015 to May 31, 2021, there were 710 HIV D+ referrals from 49 OPOs, of which 171 (24%) had organs procured. HIV D+ referrals increased from 7 to 15 per month (P < 0.001), and the procurement rate increased from 10% to 39% (P < 0.001). Compared with HIV D+ without procurement, HIV D+ with procurement were younger (median age 36 versus 50 y), more commonly White (46% versus 36%), and more often had trauma-related deaths (29% versus 8%) (all P < 0.001). Nonprocurement was attributed to medical reasons in 63% of cases, of which 36% were AIDS-defining infections and 64% were HIV-unrelated, commonly due to organ failure (36%), high neurologic function (31%), and cancer (14%). Nonprocurement was attributed to nonmedical reasons in 26% of cases, commonly due to no authorization (42%), no waitlist candidates (21%), or no transplant center interest (20%). Conclusions. In the early years of the HIV Organ Policy Equity Act, actual HIV D+ referrals were much lower than prior estimates; however, the numbers and procurement rates increased over time. Nonprocurement was attributed to both medical and nonmedical issues, and addressing these issues could increase organ availability.

(OPOs) ultimately result in organ procurement and transplantation.Procurement rates are difficult to quantify due to a lack of national, publicly available OPO data. 6A recent study including >100 000 referrals from 10 OPOs reported that only 5.1% resulted in organ procurement. 7For HIV D+ referrals in particular, data are limited.Cash et al 8 performed a survey of all 58 OPOs that estimated >2000 HIV D+ referrals/year nationally.This survey predated HOPE Act implementation.Furthermore, it did not include whether HIV D+ referrals were suitable for organ procurement.Concerns have been raised that HIV D+ may have substantial medical contraindications to donation due to comorbidities or AIDSdefining illnesses. 4,5o better understand the potential of deceased HIV D+, we prospectively quantified and characterized OPO-reported HIV D+ referrals, procurement rates, and reasons for nonprocurement in the era of HOPE implementation.

Study Design
Starting October 1, 2015, we began collecting information from OPOs on HIV D+ referrals (Johns Hopkins University Institutional Review Board, study number IRB00041681).In practice, HIV D+ organs could be procured for transplant on December 23, 2015 when the first HOPE in Action Multicenter Pilot Trial of HIV D+/R+ Kidney and Liver Transplantation opened (NCT02602262).To study procurement rates, the study period was December 23, 2015, to May 13, 2021.All 58 OPOs were instructed to contact the study team in real time with any HIV D+ referrals, regardless of whether the OPO believed that the organs would be procured and utilized for transplant.The study team was available 24 h/d, 7 d/ wk, initially by phone and, starting in March 2018, by pager.This HIV D+ referral study period spanned multiple HOPE in Action HIV D+/R+ Kidney and Liver Transplantation Recipient Studies (NCT02602262, NCT03734393, NCT03500315), conducted at 35 transplant centers in the United States (Table S1, SDC, http://links.lww.com/TXD/A654).

Data Elements
We collected HIV D+ referral characteristics, including date of referral, specific OPO, Organ Procurement Transplantation Network (OPTN) region, donor age, sex, race, cause of death, mechanism of death, procurement status, and, when applicable, the reasons why organs were not procured and/or utilized.
The reasons for nonprocurement were grouped into several categories.If the donor was suspected or confirmed to have an AIDS-defining illness per Centers for Disease Control and Prevention definition, procurement was not allowed under the HOPE Act. 9 This was considered an HIV-related medical contraindication and infection type was collected.Alternatively, OPOs could cite medical contraindications not related to HIV, which were further divided into (1) acute or chronic organ failure, (2) high neurologic function (ie, perceived low probability of progressing to circulatory death within a suitable timeframe for organ recovery), (3) non-AIDS defining infection/sepsis, (4) cancer, and (5) hepatitis C virus in donors >60 y old (guidance suggested by HOPE in Action transplant center investigators).Lastly, on March 27, 2020, (6) SARS-CoV-2 infection in the donor was added as a reason as organs from donors with SARS-CoV-2 were not being utilized for transplantation early in the COVID-19 pandemic.In cases where multiple medical contraindications were reported (3.2%), a physician (C.M.D.) and an OPO coordinator on the study team (M.W.) adjudicated the primary reason.For example, if both cancer and acute/chronic organ failure were selected, cancer would be considered the primary cause, as this is a more absolute contraindication to donation.Nonmedical reasons that could be cited included authorization issues (ie, unregistered donor and next-of-kin did not authorize donation), no candidates listing as willing to accept HIV D+ on the match list, no interest from transplant centers, OPO concerns about HIV disclosure, and OPO decision not to pursue without other criteria met.

Statistical Analysis
All statistical analyses were conducted using Stata 18 software (StataCorp, College Station, TX).Descriptive statistics of categorical variables were reported as frequencies and percentages, and continuous variables were reported as medians and interquartile range.Wilcoxon rank-sum and chi-square tests were performed, for categorical and continuous variables respectively, to compare HIV D+ referrals by procurement status.We used univariable linear regression to visualize temporal trends in referral and procurement over the study period, and to determine whether referral and procurement rates increased or decreased over time, using calendar months as the unit of time.

Referral Outcomes of Deceased Donor Referrals With HIV
From December 23, 2015, to May 31, 2021, there were 710 HIV D+ referrals.Of these, 171 (24%) proceeded to procurement and 539 (76%) did not.Among those that proceeded to the operating room for procurement, 139 (81%) had organs utilized for transplant: 20 (12%) had organs procured but subsequently declined by transplant centers, and 12 (7%) did not experience circulatory death within a suitable timeframe for organ procurement (Figure 1).

Trends Over Time
During the study period, the number of OPOs reporting at least 1 HIV D+ referral increased from 1 to 49 and the number of centers in our consortium consenting at least 1 candidate increased from 1 to 31 (Figure 2A).Over the same period, the number of HIV D+ referrals/month increased from 7 to 15 (P < 0.001), the number of procurements increased from 0.3 to 5 per month (P < 0.001), and the procurement rate increased from 10% to 39% (P < 0.001) (Figure 2B).

DISCUSSION
In this national prospective study of deceased donor referrals with HIV (HIV D+), 84% of OPOs across the US reported 710 HIV D+ referrals over a time period of 5.4 y.Of these, 24% proceeded to procurement; HIV D+ with procurement     HIV D+ referrals from a prior OPO survey (2164/y). 8The OPO survey was based on retrospective records and/or OPO staff recollection before HOPE Act implementation, whereas our study was prospective and occurred when organs could truly be procured for transplantation.However, our study relied on OPOs voluntarily reporting all HIV D+ referrals, regardless of perceived procurement potential.Thus, it likely underestimated the total number of HIV D+ referrals.Notably, in both the survey and this prospective study, HIV D+ referrals were highest in the Southeast, which also aligns with the highest proportion of deaths among people with HIV in the United States, according to the Centers for Disease Control and Prevention. 10 We also found far fewer HIV D+ referrals who proceeded to procurement (32/y) compared with estimates of suitable HIV D+ donors projected by prior studies (range, 356-652). 3- 5The lower number in practice may be due to additional data on medical exclusions to donation (eg, granular data on neurologic function) or due to nonmedical exclusion factors, such as donor authorization status, that were not available in registry and retrospective studies of potential HIV D+.Of note, our observed 24% procurement rate for HIV D+ referrals is much higher than the 5% procurement rate for donors without HIV reported in a recent study of >100 000 referred donors. 7Our relatively high procurement rate might suggest that donor hospitals and/or OPOs were more likely to report HIV with a high probability of procurement.Alternatively, this might suggest that transplant center acceptance rates for HIV D+ offers are high.A prior study of OPTN data from Wilk et al 11 reported that the average organ acceptance rates across centers was higher for kidney and liver HIV D+ (47% and 60%, respectively) compared with donors without HIV (19% and 23%, respectively).Of note, we observed few HIV D+ referrals in which organs were procured but not utilized, occurring in only 4% of cases.
There were 123 HIV D+ who did not proceed to procurement because of a suspected or proven AIDS-defining illness.Notably, nearly half of these infections were Pneumocystis pneumonia or Cryptococcus meningitis.Since effective treatment is available for both infections, theoretically, organs could be used from these donors with appropriate prophylaxis in recipients (trimethoprim/sulfamethoxazole and fluconazole, respectively, which most recipients are already on as posttransplant prophylaxis). 12In practice, procurement is not currently allowed in these cases because a suspected AIDS-defining opportunistic infection is an absolute contraindication for HIV D+ under the HOPE Act Safeguards and Research Criteria. 9However, if HIV D+/R+ kidney and liver transplantation move from research to clinical care, as has been recommended by a federal advisory board, 13 criteria for HOPE donors will be at the discretion of clinical transplant teams.If donor acceptance criteria are liberalized, it might increase incentives for OPOs to pursue these donors.
Nonmedical barriers were also cited as reasons for nonprocurement.Lack of authorization was stated in 10% of nonprocurement cases, which could be due to lack of donor registration or lack of authorization from a donor's next-of-kin.A study by Nguyen et al 14 showed low donor registration rates (21%) among people living with HIV, but a high willingness to donate (87%).Our study did not collect data on how often OPO staff approached next-of-kin for authorization in these HIV D+ referral cases.However, studies of referred donors without HIV have shown a high variability in OPO authorization approach rates. 7ther nonmedical issues such as concerns regarding HIV disclosure and OPO decision not to pursue accounted for closure in 4% of HIV D+ referrals.Perceived barriers and disincentives to pursue HIV D+ at the OPO level have been identified in prior studies. 15,16A study by Predmore et al, 16 which included in-depth interviews with 20 OPO staff members, identified OPO concerns regarding HIV disclosure to next-of-kin and fear of HIV infection to procurement staff.In practice, these concerns should not be barriers to donation and procurement.HIV disclosure is not required to obtain authorization for donation.Moreover, standard universal precautions protect organ procurement staff from bloodborne transmissible diseases such as HIV.
Finally, a lack of waitlist candidates and no transplant center interest were cited in 17% of nonprocurement cases.This issue might be mitigated by broader transplant center participation in HIV D+/R+ transplantation.As of November 2022, only 31 transplant centers, roughly 13% of US transplant centers, had an OPTN variance to perform HIV D+/R+ transplants.Low transplant center participation might be due to current required experience thresholds under the HOPE Safeguards, 9,17 or it might be due to the additional administrative effort and cost required for a research protocol.These barriers may be lowered if HIV D+/R+ transplantation moves from research to clinical care.Under current research criteria, only 3% of heart programs and 0% of lung programs are eligible to perform HIV D+/R+ transplants; if these criteria were expanded, 39% of both heart and lung programs could participate. 17In a study of OPO decisions to pursue HOPE donors, the number of potential organs that could be recovered was the most important attribute. 15Thus, the possibility of having multiple organs utilized from a donor would likely influence OPOs to evaluate and procure organs from more HIV D+ referrals.
Our study had several limitations.As previously acknowledged, we relied on voluntary reporting from OPO staff and it is unlikely that we received data on all HIV D+ referrals.However, we found that 84% of OPOS reported at least 1 HIV D+ referral.In some instances, our data were missing, and we could not ascertain the reason for nonprocurement.Moreover, medical contraindications were based on the judgment of the OPO staff, and we did not collect objective data such as laboratory values or neurologic exam data to support this decision.Finally, we did not have a control group of referred donors without HIV.Despite these limitations, this study provides insight into the current real-world et al decision-making process for HIV D+ referrals across the United States.
In summary, since the implementation of the HOPE Act, >130 HIV D+ referrals have been made each year, with the opportunity for a potentially life-saving transplant.In most cases, these organs were not procured, for medical and nonmedical reasons.Overall, referrals were much lower than prior survey estimates, although the numbers increased over time.These data highlight potential areas for intervention to expand and optimize organ procurement from HIV D+.
were and more likely to have a trauma-related death compared with HIV D+ with nonprocurement.The total number of HIV D+ referrals and procurement rates increased over time.The majority of HIV D+ referrals were from the northeastern and southern regions of the United States.Nonprocurement was attributed to medical reasons in 63% of cases, 36% of which were due to possible AIDS-defining infections, primarily Pneumocystis and Cryptococcus.Nonmedical reasons related to authorization, number of transplant candidates on the waitlist, or transplant center/ OPO decision accounted for 26% of HIV D+ cases with nonprocurement.Overall, we observed a much lower annual number of HIV D+ referrals in practice (131/y) compared with estimates of

FIGURE 2 .
FIGURE 2. Trend over time in HOPE Act participation and HOPE donor procurement.Trends over time in (A) OPOs reporting HIV D+ referrals and transplant centers with consented candidates for HOPE trials.The cumulative number of OPOs that began reporting HIV D+ referrals is based on the first date of HIV D+ referral from that OPO.The cumulative number of transplant centers consenting candidates for HOPE is based on the first date a candidate was consented for HOPE at that center.B, HIV D+ referrals, procurements, and procurement percent.Each line represents the fitted univariable linear regression line of the displayed value over calendar months.HIV D+, donors with HIV; HOPE, HIV Organ Policy Equity; OPOs, Organ Procurement Organizations.

FIGURE 3 .
FIGURE 3. HOPE donor referrals and procurements by OPO.A, Overall procurement percent vs total HIV D+ referrals for each OPO and (B) total HIV D+ referrals for each OPO by OPTN region.Each point represents 1 OPO.Transparency and random jitter applied to illustrate overlap between OPOs.HIV D+, donors with HIV; OPO, Organ Procurement Organization; OPTN, Organ Procurement Transplantation Network.

TABLE 1 .
Characteristics of HIV D+ referrals by procurement status