Human immunodeficiency virus (HIV) Organ Policy Equity (HOPE)

Act Safeguards and Research Criteria for Transplantation of

Organs infected with HIV

HOPE Act – Update

Jonah Odim, MD, PhDChief, Clinical Transplantation Section

Transplantation Branch, NIAID Advisory Committee on Organ Transplantation (ACOT)

November 17, 2015

HOPE: Background

• HIV+ to HV+ organ TX only under IRB-approved research protocols

• While Muller (NEJM, 2015) has presented excellent results in 27 HIV+ to HIV+ kidney transplants [South Africa] there is no such evidence for safety, efficacy or effectiveness in North America

• In aligning with the HOPE Act, the Final Safeguards and Research Criteria are meant to support the acquisition of new clinical knowledge and mechanistic insights about HIV+ to HIV+ organ transplantation in the US

HOPE Act ENACTMENT

Public Law 113-51Signed into law by President

Obama, Nov. 21, 2013

Drafting the Criteria

• Final Delegation of Authority from NIH to NIAID: Jan. 20, 2015

• ACOT: April 13, 2015• ACOT: March 13, 2015• ATC: May 2, 2015

Research Protocol/Consent development and IRB approval

• Grant applications from the transplant community are starting to come in addressing the mandate of the HOPE Act

HHS-NIH working group• WTC: Town Hall meeting

July 28, 2014• ICAAC meeting Sept. 7,

2014• Delegation of Authority

from Secretary HHS to NIH: Nov. 25, 2014

2 YEARS POST ACT

ENACTMENT• Draft Safeguards and

Research Criteria [Federal Register]: June 18, 2015

• End 60-day comment: Aug. 17, 2015

• ACOT: Nov. 17, 2015• Final Safeguards and

Research Criteria: Nov. 21, 2015

• Secretary shall review the results of scientific research in conjunction with the OPTN

• Determine whether the results warrant revision of the standards of quality

4 YEARS POST ACT ENACTMENT (+ annually thereafter)

2013 2014 2015 2016 2017

HOPE Act: Safeguards and Research Criteria

Living Donors

• HIV-infected living donors may be at long-term risk for renal and/or liver disease and some centers would not use living HIV+ donors

• It is premature to embark on living HIV+ donors without prior experience with deceased HIV+ donors (recommended a staged approach)

• Desire to donate is strong and the evaluation of the risks and benefits of such a decision is personal and unique to a given D/R pair

• The HOPE Act (2013) does not include any language addressing use of living HIV+ donors

Living Donors (2)

• Evidence for the safety of organ donation by an HIV infected individual will only be generated by clinical research

• Participation in HIV+ to HIV+ clinical research is made freely, based on informed consent, without coercion

• Provision of a rigorous, transparent education, informed consent process describing alternatives, risks, potential benefits, unknowns and the need for long-term follow-up. Discussions must address how research injuries are managed and paid for in the long-run, available independent advocates not a part of research team

Independent Advocates

• Some strongly supported the requirement for independent advocates for both the HIV+ recipients and prospective HIV+ living donors. Others viewed this as unnecessary

• The advocate is an additional knowledgeable person who is neither a member of the research team nor the patient’s health care provider, whose role is to provide info, answer questions, and provide assurance of equal access to health care regardless of the patient’s decision regarding research participation

Transplant Hospital Experience

• Several from academic institutions, professional societies, and OPTN indicated the requirements for physicians’ and surgeons’ prior experience in HIV-negative to HIV+ organ transplants were excessive and would result in few centers being able to participate in the research allowed under the HOPE Act

• In response to the wide consensus on this issue we have accepted the specific suggestion of the ASTS to use the collective team experience rather than individual experience [5 cases of HIV negative to HIV+ organ transplantation over 4 years]

Donor eligibility criteria (CD4+ T-cell counts & HIV viral load)

• Concerns about the usefulness and relevance of requiring a minimum CD4+ T-cell count in the donor arguing these counts will not predict allograft function and among HIV+ to HIV+ transplants in South Africa excellent outcomes were observed in recipients of kidneys from donors with CD4+ cell counts well below the 200 minimum

• In response to these comments the Criteria were revised to acknowledge although collection of CD4+ T-cell counts during donor evaluation is required, no minimum criterion is imposed for organ acceptance

Donor eligibility criteria (2)

Some commenters preferred excluding any donors with detectable plasma viral load due to risk of transmitting drug resistance. Unfortunately, it will not be possible in all cases to mitigate the risk of transmitting viral resistance by setting viral load limits and/or assessing antiretroviral resistance profiles in the time available for donor evaluation. It is expected in many cases that potential donors will have adequate medical history available to inform the team’s assessment and maximally reduce the risk of transmitting resistance virus.

Biospecimens

Several commenters emphasized the importance of a pre-transplant donor organ biopsy. The Final Criteria includes a requirement for performance of a pre-implant “back-table” biopsy. Although there are no further specimen collection requirements, we strongly encourage the inclusion of serial biospecimens in the individual research protocols. These specimens will be a valuable resource to the community in studies related to superinfection risks, for example.

• Failure to collect such specimens, particularly in organ donors, would be a regrettable lost opportunity

Required Outcomes

• Several commenters expressed concerns about data collection, quality, and reporting.

• The HOPE Act requires the Secretary of HHS to review the results of research conducted under the Act.

• A purpose of the criteria presented in the Final Safeguards and Research Criteria is to ensure all investigators conducting research in HIV+ to HIV+ TX collect similar data elements. This standardization will facilitate the subsequent review mandated in the HOPE Act

Program Specific Reports (PSRs)

• Negative impact of adverse outcomes at transplant centers conducting research in HIV+ to HIV+ transplants on transplant PSRs. Commenter proposed:

“…transplants performed with HIV+ donor to HIV+ recipients are not included in the center specific reports. The risk of transplanting these patients is unknown, and there is no risk adjustment for it on the center specific reports. There will potentially be a strong disincentive for centers to take on these patients leading to fewer patients receiving life-saving organ transplants.”

Donor and Recipient eligibility criteria for HIV+ sero-concordant transplant pairs (D/R)

HIV+ variabl

es

DDNew Dx

DDKnown Dx

LivingDonor

Recipient

CD4+ T-cells(require)

None None ≥ 500 for 6 m before harvest( ≥ 200)

≥ 200 (kidney) and ≥100 (liver); Hx of OI ≥ 200

HIV-1RNA(require)

None

Pre-TX Biopsy

None

Pre-TX Biopsy

< 50 < 50*

OI No (invasiv

e)

No (invasive

)

None None

* Patients unable to tolerate ART due to organ failure or recent ART start

Independent Advocate

Independent Advocate

Pre-TX Biopsy

HHS appreciates the time and effort taken by the commenters to respond to the

Request for Comments. The comments represented the deliberative efforts of

truly dedicated individuals and organizations in transplantation and HIV

medicine. All the responses were helpful in revising the Draft HOPE Act Safeguards

and Research Criteria for Transplantation of Organs Infected with HIV

Special thanks to ACOT, AOPO, AST, ASTS, CDC, CMS, DHHS, FDA, HIVMA, HRSA, NATCO, NIH and the HIV community