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INSTIs and DAAs Boost Liver Transplant Survival in HIV+ and HIV+/HCV+ in US
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AASLD, The Liver Meeting, November 12-15, 2021
Mark Mascolini
Mortality after liver transplant dropped by two thirds in US residents with HIV or HIV/HCV with the arrival of anti-HIV integrase inhibitors (INSTIs) and anti-HCV direct-acting antivirals (DAAs) [1]. This retrospective study also found a yearly increase in HIV-positive liver donors starting in 2016.
Researchers from Baylor College of Medicine in Houston noted that for some time people with HIV or HIV/HCV had worse survival and more graft rejection after liver transplant than people in the general population [2,3]. But in the past decade, INSTIs have transformed medical therapy for people with HIV and DAAs have cured large majorities of people with HCV and HIV. The research team conducted this study to see whether those advances affected post-transplant survival of people with HIV or HIV/HCV.
This retrospective analysis involved US adults in the United Network for Organ Sharing (UNOS) database who had a single-organ liver transplant since 2002. Researchers divided people with HIV into a pre-INSTI group (March 2002 to December 2011) and an INSTI group (January 2012 to December 2020). They divided people with HIV/HCV into a pre-DAA group (March 2002 to December 2013) and a DAA group (January 2014 to December 2020).
The analysis included 548 liver transplant recipients with HIV, 225 in the pre-INSTI group and 323 in the INSTI group. The INSTI group had an older median age at transplant (56 vs 50, P < 0.001), a higher proportion of Hispanics (21.5% vs 12%, P = 0.006), and significantly more people with alcoholic liver disease, nonalcoholic steatohepatitis (NASH), and obesity.
Among 286 transplant recipients with HIV/HCV, there were 166 in the pre-DAA era and 120 in the DAA era. The DAA group was significantly older than the pre-DAA group (58 vs 55 years, P < 0.001) and included a significantly lower proportion of men (74.2% vs 83.7%, P = 0.047) and a lower proportion of whites (50.8% vs 62.2%, P = 0.046),
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From 2016 through 2020, numbers of HIV-positive liver donors rose by about 5 every year and totaled 27 HIV-positive donors during that period.
Comparing transplant recipients in the INSTI era and pre-INSTI years, Cox hazards analysis figured that 225 pre-INSTI people had almost a 60% lower chance of 3-year post-transplant survival than 323 people in the INSTI era (hazard ratio [HR] 0.423, 95% confidence interval [CI] 0.282 to 0.634, P < 0.001). Similarly, 166 people in pre-DAA years had a 51% lower chance of 3-year survival than 120 people in the DAA era (HR 0.487, 95% CI 0.274 to 0.652, P = 0.0122).
Three-year post-transplant mortality in pre-INSTI days was 47.1% in the HIV group and 36.9% in 548 propensity score-matched controls. After INSTIs arrived, 3-year mortality was much lower and virtually identical in the HIV group and controls (13.9% and 13.0%). Among people coinfected with HIV/HCV, pre-DAA post-transplant mortality stood at 44.6% in the HIV/HCV group and 31.3% in 286 propensity score-matched controls. After DAAs arrived those death rates plunged to 15.0% with HIV/HCV and 6.7% in controls.
These sizeable improvements in survival after liver transplant in people with HIV and HIV/HCV, the authors concluded, have allowed increasing use of HIV-positive donors while shifting demographics of the US transplant population to people with alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD).
References
1. Jacob JS, et al. Improved survival after liver transplantation for HIV positive and HIV/HCV co-infection in the INSTII and DAA eras. AASLD, The Liver Meeting, November 12-15, 2021. Parallel session 7: Immunosuppression, Outcomes, Complications.
2. Cooper C, Kanters S, Klein M, et al. Liver transplant outcomes in HIV-infected patients: a systematic review and meta-analysis with synthetic cohort. AIDS. 2011;25:777-786. doi:10.1097/QAD.0B013E328344FEBB.
3. Miro JM, Montejo M, Castells L, et al. Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study. Am J Transplant. 2012;12:1866-1876. doi:10.1111/J.1600-6143.2012.04028.X
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