Risk of Severe Clinical Events After Sustained Virological Response Following Direct-Acting Antiviral Therapy in HIV and Hepatitis C Virus Coinfected Participants

Mathieu Chalouni; Linda Wittkop; Firouzé Bani-Sadr; Karine Lacombe; Laure Esterle; Camille Gilbert; Patrick Miailhes; David Zucman; Marc Antoine Valantin; Sylvie Brégigeon-Ronot; Philippe Morlat; Eric Billaud; Lionel Piroth; Alissa Naqvi; Philippe Sogni; Dominique Salmon


HIV Medicine. 2021;22(9):791-804. 

In This Article

Abstract and Introduction


Objectives: Sustained virological response (SVR) decreases the risk of hepatitis C virus (HCV)-related events. Nevertheless, a substantial risk of events persists. We estimated incidences and identified factors associated with severe clinical events after SVR following treatment with a direct-acting antiviral (DAA) in HIV/HCV-coinfected patients.

Methods: Participants from the ANRS CO13 HEPAVIH were included if they reached SVR. Incidence rates of overall mortality, liver-related events, AIDS-defining events, ischaemic events and non-liver non-AIDS-defining cancers (NLNA) were estimated. Factors associated with the risk of those events were identified using Poisson models adjusted on age at SVR and sex.

Results: In all, 775 participants were included. Incidence rates (95% confidence interval) of liver-related events, overall mortality, AIDS-defining events, ischaemic events and NLNA cancers per 1000 person-years were 5.9 (3.3–10.3), 22.2 (16.8–29.5), 0.6 (0.1–4.5), 7.3 (4.4–12.2) and 13.7 (9.4–20.0), respectively. For all events, incidence rates were higher in cirrhotic than in non-cirrhotic participants. Cirrhosis, liver stiffness and CD4 count were associated with liver-related events. Factors associated with overall mortality were age, cirrhosis, liver stiffness and gamma-glutamyl transferase (GGT). For ischaemic events and NLNA cancers, associated factors were total cholesterol and CD4 count, respectively.

Conclusions: After SVR following a DAA treatment, liver-related and AIDS-defining events were observed less frequently than NLNA cancers. Severity of liver disease was associated with the risk of liver-related events and of overall mortality but not with ischaemic events and NLNA cancers. Factors reflecting HIV infection were associated with NLNA cancers and liver-related events.


Hepatitis C virus (HCV) infection is associated with several liver-related and non-liver-related complications and with mortality.[1–4] Indeed, notably, due to chronic inflammation, endothelial damage and lipid accumulation, HCV infection increased the risk of ischaemic events and of non-liver-related cancers due to up-regulation of oncogenic signals and down-regulation of tumour suppressive signals.[5] Since 2014 and the availability of direct-acting antivirals (DAAs) for the treatment of HCV chronic infection, the course of HCV disease has been largely modified. Direct-acting antivirals allow a sustained virological response (SVR) to be reached in more than 95%, in both HCV-monoinfected[6] and HIV/HCV-coinfected[7,8] patients. A SVR after anti-HCV treatment is associated with a reduction in risk of liver and non-liver-related complications related to HCV infection.[9–13] However, a risk of HCV-related events remains despite SVR, especially for cirrhotic patients.[14–17] In addition, historically, HIV coinfection negatively impacted the natural history of HCV infection, with a faster progression of liver fibrosis and a higher risk of HCV-related complications.[1,18] The emergence of antiretroviral therapies substantially decreased the impact of HIV infection on the course of HCV history.[19,20] In HIV/HCV-coinfected patients, few studies were conducted to identify factors associated with the risk of HCV-related events in participants who reached SVR, and especially for non-liver-related events. Our aim was to estimate incidence rates of HCV-related events, overall mortality, liver-related events, ischaemic events and non-liver-related non-AIDS-defining (NLNA) cancers and of AIDS-defining events, and to identify factors associated with the risk of these events, using an exploratory method, in HIV/HCV-coinfected participants who reached SVR. Despite that the effect of HCV infection on the natural history of HIV has not been clearly demonstrated, AIDS-defining events were studied as our population was at risk and could present specific risk factors for this event.