HOPE springs eternal: lack of HIV superinfection in HIV Organ Policy Equity Act kidney transplants

Abstract

Kidney transplantation from donors with HIV to recipients with HIV (HIV D+/R+) is an emerging practice that has shown substantial clinical benefit. Sustained HIV superinfection, whereby a transplant recipient acquires a new strain of HIV from their organ donor, is a theoretical risk, which might increase chances of viral failure. In this issue of the JCI, Travieso, Stadtler, and colleagues present phylogenetic analysis of HIV from kidney tissue, urine, plasma, and cells from 12 HIV D+/R+ kidney transplants out to five years of follow-up. Early after transplant, donor HIV was transiently detected in five of 12 recipients, primarily from donors with untreated HIV and high-level viremia, consistent with a viral inoculum. Long-term, donor HIV was not detected in any recipients, demonstrating no sustained HIV superinfection. These reassuring data support earlier findings from South Africa and the United States and further confirm the safety of HIV D+/R+ transplantation.

Figure 1. In HIV D⁺/R⁺ transplantation, donor HIV is detected early after transplant, but doesn’t manifest as persistent superinfection.

(A) Prior to transplant, recipients with HIV are on ART with undetectable plasma HIV RNA levels. In contrast, deceased donors with HIV may or may not be on ART; as such, some will have high-level plasma HIV RNA. In some cases, HIV can be amplified from donor kidney biopsies and occasionally constitutes a separate genetic cluster from HIV in the blood. (B) Early after transplant, a mix of recipient and donor-derived HIV can be detected in urine, urine-derived renal epithelial cells, peripheral blood mononuclear cells, and plasma from a subset of recipients. The presence of donor-derived HIV is more common in recipients who receive kidneys from donors with high HIV viral loads and represents a donor viral inoculum. Later after transplant, donor HIV is not detected in recipients, even in those who interrupt ART and experience high levels of plasma HIV RNA rebound. In summary, donor-derived HIV superinfection does not routinely occur in HIV D⁺/R⁺ transplantation, likely due to the protection of ART.