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contain replication-competent HIV virions. Small amount of Furthermore, the recipient’s ART regimen in Muller’s cohort
donor blood may remain in the organ despite flushing. had substantial activity against the donor strain in each case;
Furthermore, HIV can infect the renal tubular epithelial this may not be true of a patient cohort with more complicated
cells, podocytes and parietal epithelial cells of the kidney. 28,29,30 pre-transplantation ART histories. In addition, because none
Similarly, it is known that the liver’s Kupffer cells and of the donor patients were on protease inhibitors (PIs) or
sinusoidal endothelial cells may be infected by HIV, as are integrase strand transfer inhibitors (InSTIs) – only reverse
hepatoma cells. 31,32 In addition, HIV could be transmitted by transcriptase was sequenced for drug resistance mutations –
free virus or lymphocytes carried in the interstitium of the the effect of mutations involving protease or integrase
organ. Recent work suggests that HIV reservoirs probably remains to be determined. Lastly, the ability to detect
persist in all deep tissues, although replication-competent superinfection was limited by the low proviral loads found in
viruses likely comprise only a minority of viral strains. 27,33,34 the recipients (who were for the most part virally suppressed
post-transplantation) and by anti-thymocyte globulin-
Human immunodeficiency virus-positive induced T-cell depletion.
recipients
Most recently, Blasi et al. reported finding a donor’s HIV
There is concern that, despite being on ART for at least several strain in an HIV-positive recipient’s blood and urine up to
months at the time of transplantation, the HIV-positive 16 days after kidney transplantation, but not thereafter.
33
recipient may be at risk of acquiring a second strain of HIV Importantly, the donor HIV strain was susceptible to
via residual virus in the allograft. This strain could either the recipient’s ART regimen from the outset, though the
replicate independently or generate a new recombinant viral recipient’s regimen was additionally fortified with rilpivirine
strain. Both are rare phenomena that have previously been (RPV) from postoperative day 1 as a precaution.
documented in non-transplantation settings. 35,36,37,38 Of critical
concern would be the transmission of an HIV strain that is In summary, donor HIV viral strains appear to be detected in
unlikely to be controlled with ART in the recipient, either the blood of recipients in many cases within the first few
because of extensive resistance or because of recipient weeks after transplantation, although whether this represents
contraindications to particular antiretroviral drugs. In theory, productive infection of new cells, lysing of donor-derived
despite the flushing of blood, the risk of allograft transmission infected cells or a combination of both is unclear. Considering
would be higher with organs from donors with unsuppressed the potential risk of superinfection, we recommend that an
VLs at the time of donation (such as might be seen in some infectious diseases and/or HIV expert should review all
deceased HIV-positive donors). available donor HIV treatment history and resistance test
information prior to transplantation, and that an anticipated
Selhorst et al. recently reported on the impact of the donor inability of the recipient to control the donor HIV strain
strain on the recipient’s HIV control in Muller’s HIV- should be considered a contraindication to transplantation
39
positive-to-HIV-positive renal transplant cohort. Plasma (see ‘Recommendations’ section).
and peripheral blood mononuclear cell (PBMC) samples
were analysed from donor–recipient pairs. Donor virus was Human immunodeficiency virus-negative
detectable in 8/25 recipients (32%) on deep sequencing in recipients
plasma samples taken between 1 and 6 weeks post- The risk of an HIV-negative recipient acquiring HIV from an
transplantation. Deep sequencing of PBMC samples, organ from an HIV-positive donor is currently unknown, and
targeting reverse transcriptase and the env gene’s V3 region, is likely to be influenced by multiple donor and recipient
found drug resistance mutations in a minority of both characteristics, and the nature of the solid organ that is
donors and recipients, but without clear evidence of any transplanted. When the donor’s HIV infection is only
transmitted resistance from donor to recipient in 24/25 diagnosed subsequent to transplantation (because of the
recipients. Possible superinfection was detected in one donor inadvertently being in the window period of HIV
recipient from a sample taken 12 weeks post-transplantation.
However, donor sequences were not found in the recipient’s testing), HIV infection of the recipient appears highly likely.
PBMC samples taken before (6 weeks) or after (26 weeks) However, under the controlled conditions described by
that, nor when the 12-week sample was sequenced again. It Botha et al., where the donor has a stably suppressed VL and
is unclear whether donor proviral sequences detected in this the recipient is started on ART prior to transplantation, the
27
recipient in a single sample represent true superinfection or risk of HIV transmission to the recipient is far less certain. In
shedding of previously infected donor kidney cells into the the one such published case to date, the results of HIV testing
blood. None of the recipients have to date failed ART post- were equivocal, with initial seroconversion at day 43 and
transplantation. then slow waning of the serological response approaching
undetectable levels over the course of a year. No plasma or
Although somewhat reassuring, there are several limitations cell-associated HIV has been detected in the recipient even by
to these data. Only one of the donors had drug resistance using ultrasensitive assays, although this testing was only
mutations present at a level > 0.5% (levels thought to be possible on samples obtained from day 111 onwards. The
physiologically relevant), and no plasma or PBMC samples interpretation of these results is not straightforward,
from the recipient in that case were available for analysis. particularly in the post-transplantation setting, where

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