Direct-acting antivirals are effective and safe in HCV/HIV-coinfected liver transplant recipients who experience recurrence of hepatitis C: A prospective nationwide cohort study

Abstract

Direct-acting antivirals have proved to be highly efficacious and safe in monoinfected liver transplant (LT) recipients who experience recurrence of hepatitis C virus (HCV) infection. However, there is a lack of data on effectiveness and tolerability of these regimens in HCV/HIV-coinfected patients who experience recurrence of HCV infection after LT. In this prospective, multicenter cohort study, the outcomes of 47 HCV/HIV-coinfected LT patients who received DAA therapy (with or without ribavirin [RBV]) were compared with those of a matched cohort of 148 HCV-monoinfected LT recipients who received similar treatment. Baseline characteristics were similar in both groups. HCV/HIV-coinfected patients had a median (IQR) CD4 T-cell count of 366 (256-467) cells/µL. HIV-RNA was <50 copies/mL in 96% of patients. The DAA regimens administered were SOF + LDV ± RBV (34%), SOF + SMV ± RBV (31%), SOF + DCV ± RBV (27%), SMV + DCV ± RBV (5%), and 3D (3%), with no differences between the groups. Treatment was well tolerated in both groups. Rates of SVR (negative serum HCV-RNA at 12 weeks after the end of treatment) were high and similar for coinfected and monoinfected patients (95% and 94%, respectively; P = .239). Albeit not significant, a trend toward lower SVR rates among patients with advanced fibrosis (P = .093) and genotype 4 (P = .088) was observed. In conclusion, interferon-free regimens with DAAs for post-LT recurrence of HCV infection in HIV-infected individuals were highly effective and well tolerated, with results comparable to those of HCV-monoinfected patients.

Challenges in solid organ transplantation in people living with HIV

“…HCV co-infection has negatively affected these results, as the cure rate with pegylated interferon and ribavirin was low. However, interferon-free DAAs have since changed this, and cure rates for LT are high, similar to those in HIV-negative recipients [9]. With HCV eliminated, the prognosis of liver and renal transplantation in HIV-infected patients is good (Table 1).…”

Sustained virological response with 16‐week glecaprevir/pibrentasvir after failure to sofosbuvir/velpatasvir in post‐transplant severe HCV recurrence in HIV

“…In HIV/HCV‐coinfected LT recipients, high SVR rates (93.6%‐96.6%) were observed with DAA in stable patients treated late after transplant (median 12‐71 months after) . Nonetheless, the few patients with FCH (n = 6) included in the CUPILT cohort showed a slower virological response compared with the others (HCV‐RNA below the limit of quantification after 9 weeks in FCH vs 6 weeks in F3‐F4 and 4 weeks in F1‐F2), suggesting a more difficult‐to‐treat condition compared with stable patients.…”

“…Moreover, genotype 4 patients appear to be underrepresented in the studies with SOF/VEL (5%) and GLE/PIB (4%), and in HIV/HCV‐coinfected LT recipients a trend to lower SVR rate compared with other genotypes (77.8% vs. 90.9%; P = .566) has been observed. Moreover, two cases of virological breakthrough have been described, even though with suboptimal regimen (simeprevir plus daclatasvir plus ribavirin) …”

“…DAA rapidly changed the scenario: Given their safety and efficacy, anti‐HCV treatment after LT became easier with high rates (>94%) of sustained virological response (SVR) in both HCV‐ and HIV/HCV‐coinfected patients . Despite this great improvement, challenges are not over.…”

Can HCV Viremic Organs Be Used in Liver Transplantation to HCV Negative Recipients?

“…Fortunately, the introduction of direct-acting antivirals (DAAs) has completely changed treatment of HCV infection. Randomized control trials and real-life cohort studies based on HCV-mono-infected LT recipients have shown positive results in terms of efficacy and safety [11].…”