Virologic Response of Antiviral Therapy in Hepatitis C Virus (HCV)-Human Immunodeficiency Virus (HIV) Coinfected Liver Transplant (LT) Recipients

Abstract

Recurrent HCV infection is a major barrier to graft and patient survival particularly in HCV-HIV coinfected recipients. A sustained virologic response (SVR) with post-LT HCV treatment significantly improves graft survival in HCV monoinfected LT patients. Risks/benefits of HCV therapy in HCV-HIV LT recipients are not established. Methods: Among 89 HCV-HIV LT recipients in the HIVTR study, 39 (44%) received ≥1 wk of peginterferon-a2a or a2b plus ribavirin (target dose 800 mg/day). HCV RNA was measured at wk12, end of treatment (EOTR), and ≥24 wks post-Rx (SVR). Histologic responses compared pre/post Rx biopsies (N=24). Results: Coinfected patients [82% male, median age 49 yrs, 23% Black, 79% genotype 1, CD4 count median (range) 195 (40-751) cells/mm3, 97% undetectable HIV-RNA, 90% on ART, median HCV RNA 6.89 log10, 83% stage F≤1, median ALT 135 (14-790) and total bilirubin 2.1 (0.4-29.8)] were treated a median 363 days (14-1373). On modified intent-to-treat basis, EOTR was achieved in 22%; 63% of those had SVR. By per-protocol analysis (completed 48-weektherapy ± dose reductions), 42% and 26% achieved EOTR and SVR, respectively.Table: [Treatment Outcomes]Severe AEs occurred in 85%, with 26% hospitalized infections, 72% anemia (Hgb < 10g/dL) and 13% acute rejection. Early discontinuations and dose reductions occurred in 38% and 82% respectively, despite use of growth factors in 85%. Eighteen (46%) subsequently died/had graft loss, with 10 (26%) attributed to recurrent HCV. Median treatment duration was shorter (33 vs 69 wks) and baseline bilirubin higher (4.6 vs 1.2) in those with graft loss vs survivors. Two-year graft survival (95% CI) post 48-week treatment was 88% (39-98) vs 67% (41-84) in patients with and without EOTR (log-rank test; p=0.21). Conclusion: Graft survival appears more likely in coinfected LT recipients with virologic responses (EOTR and SVR) following antiviral therapy. EOTR and SVR rates are lower than desired, especially in genotype 1 patients, and poor tolerability and risk of rejection are major limitations. These results highlight the critical need for better tolerated, safer (lower risk of rejection) and more efficacious HCV therapies for coinfected LT recipients.