Peter Chin-Hong, MD

In this bleak time in our country, it is about time that we get some hopeful news. Durand and colleagues demonstrated that kidney transplantation from HIV-infected deceased donors to HIV-infected recipients is safe and effective in this pilot study of diverse participants. From the first cases of success reported by Elmi Muller in Cape Town in 2010 to the signing of the HOPE Act by President Obama in 2013, it is particularly gratifying to see how far we’ve come.

In a follow-up period just shy of 2 years, graft survival and mean estimated glomerular filtration were comparable if HIV-infected or HIV-uninfected kidney grafts were used, with no appreciable adverse effects or opportunistic infections.

There are several differences in this study population compared with the South African experience. This can give us further scientific insight. First, most of the donor kidneys in the Durand U.S. study were ART-experienced in contrast to those used in Cape Town. Given the higher prevalence of ART-resistance seen in the U.S., HIV superinfection was a concern from the onset. Fortunately, there was no breakthrough viral replication seen suggesting that superinfection was less of a clinical issue. However, we await the findings of the larger multicenter study by the same investigators that will also explore this possibility with finer resolution using molecular methods.

Second, while the South African recipients were primarily prescribed protease inhibitors as an ART backbone, 91% of the Durand study participants were on an INSTI-containing regimen. Nevertheless, a striking 50% of recipients who received kidney allografts from HIV-infected donors experienced organ rejection. This suggests that drug-drug interactions between pharmacologically boosted-PIs and calcineurin inhibitors may play less of a role, with immune dysregulation or chronic inflammation from HIV as a larger driver of the effect seen.

Nevertheless excellent graft function was observed at 1 year. The nature of the high proportion of HIV-infected individuals with rejection will need to be explored more fully in future studies. This may give insight into alternative forms of immunosuppression that may be used in this population.

But there are many silver linings in the study. First, an unexpected windfall of organs that would have normally been discarded were it not for the HOPE Act: donors who had false positive HIV-tests that accounted for two-thirds of the organs used. Demonstrating that everyone can become an organ donor-HIV — infected or not — can also help alleviate HIV stigma and harness the altruism that is so deep seated in the HIV community.

Ultimately, using data generated by this study, transplant professionals will be able to accurately speak to their HIV-infected patients about risk. But perhaps the greatest change will not be on the believers — those transplant centers already accustomed to transplanting HIV-infected organs, but rather the scores of hospitals and organ procurement organizations in the U.S., and globally — who wanted to pore over the evidence first before proceeding confidently. But the work is just beginning. We need to not only address the vexing problem of thousands of HIV-infected women and men awaiting kidneys, but also livers, hearts and lungs, and the use of living donors needs to be explored further. I yearn for a time in the not so distant future where this is all standard-of-care, not just investigational. And that gives us all something to hope for.