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"Raising HOPE": Improved Outcomes for HIV/HCV-coinfected Liver Transplant Recipients in the Direct-acting Antiviral Era
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Transplantation Direct: July 2021 - Cotter, Thomas G. MB BCh1; Wang, Jennifer MD1; Lieber, Sarah R. MD2; Odenwald, Matthew A. MD1; Rich, Nicole E. MD2; Marrero, Jorge A. MD2; Singal, Amit G. MD2; Mitchell, Mack C. MD2; Aronsohn, Andrew MD1; Charlton, Michael MD1; Fung, John MD2
1 Division of Gastroenterology and Hepatology, Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL.
2 Division of Digestive and Liver Disease, UT Southwestern Medical Center, Dallas, TX.
3 Department of Surgery, Section of Abdominal Organ Transplantation, The University of Chicago Medicine, Chicago, IL.
Abstract
Background.
The 2013 HIV Organ Policy Equity Act has increased liver transplantation (LT) in HIV+ patients; however, transplant centers may remain reluctant to perform LT in HIV/hepatitis C virus (HCV)-coinfected patients due to inferior outcomes. We aimed to assess how direct-acting antivirals (DAAs) have impacted HIV+/HCV+-coinfected LT recipient outcomes.
Methods.
national data including 70 125 adult LT recipients between 2008 and 2019 were analyzed. Kaplan-Meier survival analysis and Cox proportional hazards model were used to analyze outcomes.
These data are prospectively collected from transplant programs and organ procurement organizations.23 Patients who underwent retransplantation or multiorgan transplantation apart from simultaneous liver-kidney (SLK) were excluded.
Donor livers were considered HIV+ if any of HIV antibody, HIV NAT, and HIV antigen/antibody combination test were positive, as OPTN allocates all donors with any positive HIV test result through the HOPE Act.7
Results.
LT for HIV+ individuals increased in the DAA era from 28 in 2014 to 64 in 2019 (23 had HIV+/HCV+ coinfection).
In the pre-DAA era, HIV+/HCV+-coinfected LT recipients had an increased risk of graft failure compared with HIV−/HCV−-uninfected LT recipients (hazard ratio [HR], 1.85; P < 0.001). In contrast, there was no difference in graft failure between HIV+/HCV+-coinfected versus HIV−/HCV−-uninfected LT recipients in the DAA era (HR, 1.24; P = 0.308).
Among coinfected LT recipients in the DAA era, 1- and 3-y cumulative graft survivals were 88.6% and 81.7% compared with 76.3% and 58.0% in the pre-DAA era, respectively (P = 0.006).
In Cox analysis, HCV coinfection was not associated with graft failure (HR, 1.00; 95% confidence interval, 0.53-1.89) among HIV+ LT recipients in the DAA era (n = 271). Black and Hispanic populations accounted for almost half of HIV+/HCV+ LTs in the DAA era.
Conclusions.
HIV+/HCV+-coinfected LT recipient outcomes have improved significantly in the DAA era. Our results should offer reassurance to transplant centers and encourage timely transplantation referral of HIV patients with decompensated cirrhosis, including patients coinfected with HCV.
RESULTS
Frequency and Demographics
Among 78 173 adult LTs during the study period, 4592 were excluded because of previous LT or multiorgan transplantation. Of the remaining 73 581, there were 3967 SLK transplants and 2985 living-donor liver transplants (LDLTs). HIV serostatus was not available for 3456 (4.7%) patients. The proportion with missing HIV serostatus was significantly less frequent over time, from 12.2% in 2008 to 1.9% in 2019 (P < 0.001). Among 70 125 LTs with known HIV serostatus, 416 (0.6%) were HIV+ LT recipients. A total of 5333 LTs were performed in 2013 and were thus omitted from analysis. The practice of LT for patients with HIV has increased since the HOPE Act, from 28 patients in 2014 to 64 patients in 2019 (of whom 23 had HIV+/HCV+ coinfection) (Figure 1).The Northeast (United Network for Organ Sharing regions 2 and 9) had the highest HIV+/HCV+ LT practice, which increased over time (Figure 1). For example, HIV+/HCV+ coinfection LTs made up 1.2% of all LTs in New York in 2019. Among the 138 LT centers who were active in the DAA era, less than half (65/138, 47%) performed HIV+ LTs, whereas 6 LT centers accounted for 39% (105/271) of all HIV+ LTs.
Table 1 outlines the demographic and clinical characteristics among the 4 DAA era groups and the HIV+/HCV+-coinfected pre-DAA group. Missing data comprised <1% of this final dataset. Table 2 provides a comparative analysis of the HIV+/HCV+-coinfected pre-DAA group with other pre-DAA groups. In the DAA era, there were 124 HIV+/HCV+-coinfected LT recipients, 147 HIV-monoinfected LT recipients, 11 231 HCV-monoinfected LT recipients, and 29 052 HIV−/HCV−-uninfected LT recipients, while there were 68 HIV+/HCV+-coinfected LT recipients in the pre-DAA era. HIV+/HCV+-coinfected LT recipients in the DAA era were older, had longer waitlist times, and received more HIV+ donors compared with HIV+/HCV+-coinfected LT recipients in the pre-DAA era. There have been shifts in racial group representation among LT recipients with HIV+/HCV+ coinfection from 2014 to 2019: a decrease was seen among White (61.8% to 46.8%) and Asian (4.6% to 3.2%) race, whereas an increase was observed among Black (23.5% to 25.8%) and Hispanic (14.7% to 20.2%) populations (P = 0.047). American Indians and other Pacific Islanders made up 4.0% of the HIV+/HCV+ coinfection LT DAA group, having 0% representation in the pre-DAA era. In the DAA era, HIV-monoinfected LT recipients had reduced waitlist time and higher MELD scores, as compared with HIV-monoinfected LT recipients in the pre-DAA era (Table 1).
INTRODUCTION
In the era of highly effective active antiretroviral therapy (HAART), there have been marked reductions in morbidity and mortality associated with HIV.1 In turn, a growing number of HIV+ patients are presenting with end-stage liver disease (ESLD) (~10% prevalence),2 predominantly from hepatitis C virus (HCV) due to shared routes of transmission.3 There are an estimated 2.3 million cases of HIV/HCV coinfection worldwide.4 Liver transplantation (LT) in select HIV+ patients with ESLD is effective with comparable outcomes to HIV− controls.5,6
The enactment of the HIV Organ Policy Equity Act (HOPE Act) in 2013 permitted the transplantation of organs from HIV+ donors into HIV+ recipients, thus expanding the donor pool for HIV+ patients. Although LT in HIV+ patients receiving HAART has been successful, the HOPE Act appears to be underused to date, with only 31 HOPE Act donor livers through 2018.7 This may be due to studies showing poor outcomes in HIV+/HCV+-coinfected LT recipients compared with matched HCV+-monoinfected patients with 5-y survival at 51%-54% (versus 71%-81%) in the pre-direct-acting antiviral (DAA) era.8-14 Graft loss due to recurrent HCV cirrhosis and the highly morbid fibrosing cholestatic hepatitis occurred at higher rates among HIV/HCV-coinfected patients.8-14 Moreover, HIV+ patients with hepatocellular carcinoma (HCC) had lower survival from time of waitlist listing and higher post-LT tumor recurrence compared with non-HIV-infected controls.15
In the DAA era, HCV+ patient outcomes have been transformed with high rates of sustained virologic response (SVR) (>90%), including HIV/HCV-coinfected patients.16,17 The success of DAA therapy has also translated into improved graft survival among HCV LT recipients.18,19 Treatment of pretransplant HCV patients with DAA therapy is often deferred to ensure that the patient's MELD score remains competitive in the MELD-based organ allocation system and help mitigate any posttransplant insurance coverage issues that may arise with the second request of HCV treatment should a patient receive an HCV-viremic donor liver.20 The recommended treatment regimen is either glecaprevir-pibrentasvir or sofosbuvir glecaprevir-pibrentasvir velpatasvir with particular attention to potential drug-drug interactions such as high-dose proton pump inhibitors and amiodarone with sofosbuvir-inclusive regimens and certain statins (eg, atorvastatin) with other DAAs.21 A recent study from Europe and the United States showed that HIV-infected LT recipient outcomes had improved in the DAA era through 2015; however, HCV coinfection still conferred a significantly increased risk of graft failure and death.22 We hypothesized that as we move forward into the DAA era, HCV infection will no longer confer an increased risk for graft failure in HIV+ LT recipients. Thus, our study aim was to assess if the DAA era has improved HIV/HCV-coinfected LT recipient outcomes. Furthermore, we planned to ascertain the latest trends in HIV+ LT and assess the ongoing impact of the HOPE Act.
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