Impact of antiretroviral therapy on clinical outcomes in HIV+ kidney transplant recipients: Review of 58 cases

Abstract

Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients. We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV + kidney transplant recipients. Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV - to HIV + adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation. The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant. Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% ( p=0.06) and 82% vs. 100% ( p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02). Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01). Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV + kidney transplant recipients.

Clinical outcomes in HIV+/HCV+ coinfected kidney transplant recipients in the pre‐ and post‐direct‐acting antiviral therapy eras: 10‐Year single center experience

“…We have also reported that individuals receiving HIV PIs had a higher incidence of serious infections compared to those on PI‐sparing regimens (39% vs 8%, P = 0.01), which might explain why serious infections (and associated poor outcomes) in the present study were exclusively seen among patients in the pre‐DAA era, as most of them received PI‐based ART regimens . The increased risk of serious infections in PI‐treated patients could be related to increased exposure to immunosuppressants . Supporting this notion, we observed that three out of four PI‐treated patients with serious infections had supra‐therapeutic tacrolimus levels at the time of infection.…”

“…In a previous study, we have reported a higher incidence of serious infections in HIV+/HCV+ coinfected than in HIV‐monoinfected patients (80% vs 25%, P = 0.03) . We have also reported that individuals receiving HIV PIs had a higher incidence of serious infections compared to those on PI‐sparing regimens (39% vs 8%, P = 0.01), which might explain why serious infections (and associated poor outcomes) in the present study were exclusively seen among patients in the pre‐DAA era, as most of them received PI‐based ART regimens . The increased risk of serious infections in PI‐treated patients could be related to increased exposure to immunosuppressants .…”

“…Thus, it is conceivable that administration of HIV PI‐based ART in the patients from the pre‐DAA era might have negatively influenced outcomes in this group, and unfortunately, due to the small cohort size, logistic regression analyses to assess the influence of a specific ART regimen were precluded. Nonetheless, INSTI‐based (cobicistat free) ART is now the preferred regimen in HIV+ transplant recipients as such regimens pose no drug‐drug interactions with immunosuppressants or DAAs. As such, our data add to current clinical practices and newer standards of care.…”

Advanced heart failure therapies in patients with stable HIV infection

“…Kidney transplant outcomes in the HAART era are similar between HIV-positive and negative patients with the 3-year patient and graft survival of 90%. 4,5 Similar outcomes have been reported in liver transplantation with equivalent 1-, 3-, and 5-year patient and graft survival rates between HIV-positive and negative liver transplant recipients. 6 Orthotopic heart transplantation (OHT) is rarely performed in HIVpositive patients despite the fact that HIV-associated cardiomyopathy is a major long-term complication of HIV infection.…”

“…Kidney and liver transplants are performed often among HIV‐positive patients with excellent outcomes. Kidney transplant outcomes in the HAART era are similar between HIV‐positive and negative patients with the 3‐year patient and graft survival of 90% 4,5 . Similar outcomes have been reported in liver transplantation with equivalent 1‐, 3‐, and 5‐year patient and graft survival rates between HIV‐positive and negative liver transplant recipients 6 …”