Impact of Protease Inhibitor–Based Anti-Retroviral Therapy on Outcomes for HIV+ Kidney Transplant Recipients

Abstract

Excellent outcomes have been demonstrated among select HIV-positive kidney transplant (KT) recipients with well-controlled infection, but to date, no national study has explored outcomes among HIV+ KT recipients by antiretroviral therapy (ART) regimen. Intercontinental Marketing Services (IMS) pharmacy fills (1/1/01-10/1/12) were linked with Scientific Registry of Transplant Recipients (SRTR) data. A total of 332 recipients with pre- and posttransplantation fills were characterized by ART at the time of transplantation as protease inhibitor (PI) or non-PI-based ART (88 PI vs. 244 non-PI). Cox proportional hazards models were adjusted for recipient and donor characteristics. Comparing recipients by ART regimen, there were no significant differences in age, race, or HCV status. Recipients on PI-based regimens were significantly more likely to have an Estimated Post Transplant Survival (EPTS) score of >20% (70.9% vs. 56.3%, p = 0.02) than those on non-PI regimens. On adjusted analyses, PI-based regimens were associated with a 1.8-fold increased risk of allograft loss (adjusted hazard ratio [aHR] 1.84, 95% confidence interval [CI] 1.22-2.77, p = 0.003), with the greatest risk observed in the first posttransplantation year (aHR 4.48, 95% CI 1.75-11.48, p = 0.002), and a 1.9-fold increased risk of death as compared to non-PI regimens (aHR 1.91, 95% CI 1.02-3.59, p = 0.05). These results suggest that whenever possible, recipients should be converted to a non-PI regimen prior to kidney transplantation.

Impact of antiretroviral regimen on renal transplant outcomes in HIV‐infected recipients

“…Interestingly, this favorable effect on graft survival is in contrast to results from a recent study analyzing SRTR data in 332 recipients, which found a 1.8 and 1.9‐fold increased risk in graft loss and death, respectively, in PI‐based regimens compared to non‐PI based regimens . Although the SRTR study contains a larger cohort than our patient population, one cannot discount the potential selection biases and unaccounted confounders in this type of study, which analyzed retrospective data from multiple centers.…”

“…to results from a recent study analyzing SRTR data in 332 recipients, which found a 1.8 and 1.9-fold increased risk in graft loss and death, respectively, in PI-based regimens compared to non-PI based regimens. 16 Although the SRTR study contains a larger cohort than our patient population, one cannot discount the potential selection biases and unaccounted confounders in this type of study, which analyzed retrospective data from multiple centers. Specifically, of the patients transplanted in the study's eligible timeframe, approximately 40% of patients were excluded due to missing post-transplant fill data.…”

“…Additionally, continued CNI overexposure can contribute to allograft loss through development of chronic allograft nephropathy . A recent study linking Scientific Registry of Transplant Recipients (SRTR) data to Intercontinental Marketing Services pharmacy fills data found an increased risk of graft loss associated with the use of PI‐based regimens . Furthermore, the complexity of dosing CNI in patients with this interaction leads to medication adherence concerns.…”

“…15 A recent study linking Scientific Registry of Transplant Recipients (SRTR) data to Intercontinental Marketing Services pharmacy fills data found an increased risk of graft loss associated with the use of PI-based regimens. 16 Furthermore, the complexity of dosing CNI in patients with this interaction leads to medication adherence concerns. While alternate strategies, such as daily "microdosing," have been explored, many clinicians prefer to convert patients to non-interacting antiretroviral agents prior to transplant, often choosing integrase-inhibitor based regimens.…”

Successful optimization of antiretroviral regimens in treatment‐experienced people living with HIV undergoing liver transplantation

“…This drug‐drug interaction is thought to have contributed to several cases of graft rejection, with case reports dating back to the late 1990s . Sawinski, et al found a 1.8‐fold increased risk of allograft loss in a national survey of renal transplant patients on a PI regimen . The American Society of Transplant (AST) Infectious Disease Community of Practice guidelines recommend caution with use of PI‐containing regimens due to these concerns …”