Living donor liver transplant from an HIV-positive individual to an HIV-negative individual

Transplant centers worldwide face a huge shortage of organs, resulting in long-waiting lists even for the sickest patients. Various innovations have been and are being considered for expansion of the donor pools. In the United States, the HIV Organ Policy Equity Act, enacted in 2013, allowed transplantation of organs from HIV-positive living and deceased donors to HIV-positive individuals with end-stage organ disease. Concomitant with an increase in the prevalence of end-stage organ disease among HIV-infected individuals, there has been a marked rise in the demand for these organs. Today, patients with well controlled HIV on antiretroviral therapy (ART) who do not have opportunistic infections or cancer, and with specified minimum CD4+ cell counts are clearly appropriate transplant candidates [1]. Although the clinical experience with such transplants is still limited, there are encouraging results from a small number of deceased-donor kidney transplants from HIV-positive to HIV-positive persons in South Africa, as well as additional case reports from the United Kingdom and Canada; there have also been presentations of the results of HIV-positive-to-HIV-positive liver transplantations in the United States [2–6]. All so far suggest that this strategy is feasible, and that these organ transplant outcomes are comparable with those of other transplanted populations. In the current issue of AIDS, Botha et al.[6] have taken this one step further and, for the first time, report a successful liver transplant from an HIV-positive individual, in this case the recipient's mother, to an HIV-negative child. Indeed, the transplant team not only saved the life of a child who almost certainly would have otherwise died, but also raised the question whether, under circumstances of well controlled HIV replication in the living donor and well defined prophylactic measures for the recipient, HIV transmission may be prevented. Importantly, this type of transplant could potentially open up new therapeutic options for HIV-negative individuals urgently awaiting organ transplantation. Although so far this child has had a very successful course, the authors remain cautious about the child's HIV status. Noteworthy, although HIV has not been identified in the child in the year since the transplantation, the child seroconverted, though antibody titers are now decreasing. There is no ready explanation for the seroconversion and subsequent seroreversion. The child could be uninfected or could have been exposed to a limited cell-associated inoculum of HIV but subsequently cleared the infected cells and any ensuing free virus. As it is unclear whether the child has become infected, the timing of any potential ART interruption – even if brief – is hard to determine. Previous publications such as from the ‘Mississippi baby’, who was initially negative but subsequently found to be HIV positive, have underlined that HIV infection in a child is perplexingly difficult to document, particularly when under treatment [7]. How long must the child be free of detectable virus before it can be stated unequivocally that she/he is not infected? Is it ethical to stop ARVs at some point? Probably yes, as one could not justify a lifetime of ART absent proof of its necessity. But when will that be relatively safe? At that point, if there is still no virus detected, then the notion that transmission to a recipient can be managed will be more compelling. Although not completely analogous, since in the present case ART was initiated prior to any potential infection, a previous report indicated that initiation of ART in two patients 10 and 12 days after acute infection did not prevent infection [8]. Indeed, near complete or complete loss of detectable HIV in blood and tissues for sustained periods of time was insufficient evidence of lack of transmission, which was eventually discovered. Nevertheless, the small numbers of latently infected cells in these individuals treated during hyperacute infection may be associated with prolonged ART-free remission [8]. Animal studies further suggest that early antiviral therapy in simian immunodeficiency virus (SIV)-infected macaques can limit the SIV reservoir establishment and delay or prevent posttreatment viral rebound [9,10]. In the end, only treatment cessation and extended follow-up will clarify whether this child is infected or not. Although this is an important case report, the generalizable conclusions must be tempered. Before committing to a new approach regarding HIV-positive donors the question of potential HIV transmission and how far it is preventable needs to be answered reassuringly, and in more than one instance. Acknowledgements Conflicts of interest There are no conflicts of interest.

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