Direct-acting antivirals (DAAs) are highly successful in HIV/HCV-coinfected patients with advanced fibrosis (F3) or cirrhosis (F4), but little is known about their impact on clinical events.
We studied coinfected patients with F3/F4 with a sustained viral response (SVR) following all-oral DAA-Rx (Rx) from 2014 to 2017 in observational GeSIDA cohorts (Spain). The censoring date was December 31, 2019. The primary outcome was time from the finalization of DAA-Rx to clinical progression (CP), defined as decompensation (DEC), hepatocellular carcinoma (HCC), or death, whichever occurred first. Variables included liver disease category (F3, compensated F4 [F4c], and decompensated F4 [F4d]), age, sex, current smoking, current high alcohol intake (>50 g/d), prior AIDS-defining conditions, metabolic syndrome (AHA/NHLBI criteria), CD4+ cell count, serum albumin, liver stiffness (LS), FIB4 index, triglyceride and glucose index (TyG), hepatic steatosis index (HIS); and % decrease in LS (D-LS) and % decrease in FIB4 (D-FIB4) 1 year after finalization of DAA-Rx. Multivariable Cox regression analysis, with multiple imputations by chained equations for missing data, was used to assess the effect of the independent variables on the outcome.
A total of 1300 patients were included with a median age of 52 years; 79% males; 87% prior injection drug use; 98% on ART; 94% with undetectable HIV-RNA; median CD4+ 525 cells/mm3. Liver disease: 384 (30%) F3, 761 (59%) F4c, and 155 (12%) F4d. After a median follow-up of 40.9 (34.5 – 45.1) months, 89 patients were lost, 85 died, 65 had a new LRE (DEC or HCC), and 30 were diagnosed with HCC. The frequency and indicence rate of outcomes by liver disesase category is shown in the Table. The following variables were found to be independently associated with CP: F4d (vs F3) (adjusted hazard ratio [aHR] 2.25; 95%CI 1.09-4.65, P=.029), male sex (aHR 1.99; 95%CI 1.17-3.37, P=.011), age (aHR 1.06; 95%CI 1.03-1.10, P=.001), LS (aHR 1.03; 95%CI 1.01-1.04, P<.001), D-LS (aHR 0.98; 95%CI 0.98-0.99, P<.001), and serum albumin (aHR 0.59; 95%CI 0.44-0.79, P<.001).
Our results suggest that among coinfected patients with well-controlled HIV and with advanced F3/F4, the risk of CP following DAA-induced SVR increased with liver disease severity at the beginning of therapy and with a lower decrease in LS one year after its finalization. Further work should be done to develop prediction scores to inform clinical decision-making in this population group.