Unrestricted DAA use could reduce HCV incidence in HIV

Unrestricted access to direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection in individuals with HIV led to a substantial reduction in HCV incidence, particularly in the key subgroup of men who have sex with men (MSM), according to a retrospective Dutch study.

Data of participants were obtained from the ATHENA cohort which comprised adults (age ≥18 years) with HIV who received care at any of the 24 HIV treatment centres in the Netherlands in 2000–2019. The present analysis included 24,443 patients. HCV status – primary or reinfection rates – between 2000 and 2019 was identified. Treatment for primary HCV infection was pegylated interferon until 2011, pegylated interferon or pegylated interferon plus DAAs until 2016, and from 2016, DAAs. 

Of the 23,590 who did not have a prior history of HCV infection, 1,269 primary HCV infections were documented in the median 9.8-year follow-up period, corresponding to an incidence rate of 5.2 per 1,000 person-years. [Lancet HIV 2020;doi:10.1016/S2352-3018(20)30301-5]

New primary HCV infection occurred most frequently in MSM (92.7 percent of primary cases [1,176 infections]; 7.7 per 1,000 person-years), which peaked in 2007 (14.3 per 1,000 person-years) and remained at 8.7–13.0 per 1,000 person-years between 2008 and 2015. Following unrestricted access to DAAs in 2015, the incidence rate significantly declined to 6.1 cases per 1,000 person-years in 2016 (p=0.0004 vs 2015) and remained at 4.1–4.9 per 1,000 person-years in 2017–2019.

The overall primary HCV infection incidence rate was lower among people who inject drugs (PWIDs) and heterosexual or other populations (0.4 and 6.9 percent, respectively; 1.7 and 1.0 per 1,000 person-years, respectively). 

Among individuals with HIV with prior HCV infection* (n=1,866), 274 reinfections were documented over a median 4 years of follow-up, at an incidence rate of 26.9 per 1,000 person-years. The incidence of HCV reinfection was most common in MSM (86.9 percent; 38.5 per 1,000 person-years) compared with PWID (1.1 percent; 10.9 per 1,000 person-years) or heterosexual and other populations (12.0 percent; 8.9 per 1,000 person-years).

A total of 238 cases of HCV reinfection occurred in MSM, 134 and 104 after previous treatment-induced sustained virologic response (SVR) and spontaneous clearance, respectively. Reinfection rates were 38.0–88.9 per 1,000 person-years in 2006 to 2015, with a rate of 55.6 per 1,000 person-years in 2015. The rate declined to 41.4 per 1,000 person-years in 2016 (p=0.26 vs 2015) and to 24.4 and 11.4 per 1,000 person-years in 2017 and 2019, respectively (p=0.003 for 2017 vs 2015 and p<0.0001 for 2019 vs 2015).

Despite the increase in the proportion of MSM with undetectable HIV RNA as well as increasing CD4 counts at HCV diagnosis over the years, there was no apparent difference in HCV incidence with respect to HIV RNA viral load or CD4 counts.

“There is a consistent effect of decreasing HCV incidence following high DAA uptake during universal access to DAA,” said the researchers. “These changes in incidence were not due to changes in age structure, HIV RNA or CD4 levels, or possibly HCV testing frequency,” they pointed out.

MSM: A target population for HCV treatment

“[We] have observed that the HCV epidemic [in HIV patients] has disproportionally affected MSM with very few cases of primary HCV infection or reinfection in PWID or heterosexuals even before universal access to DAAs,” the researchers noted.

“MSM with HIV had a 61 percent overall drop in primary HCV incidence and 79 percent drop in HCV reinfection incidence in 2019 compared with 2015, 4 years after the introduction of universal access to DAAs for all individuals with HCV infection in the Netherlands,” they said. “[This] sharp decline … suggests a treatment-as-prevention effect.”

“However, infections are still occurring suggesting that other means of preventing HCV infection, possibly including increased HCV testing or reducing behaviours associated with HCV acquisition, are needed,” they said.