HCV Micro-Elimination in HIV-Positive Individuals in the Netherlands: Three Years After Universal Access to Direct-Acting Antivirals

Background: In the Netherlands, access to direct-acting antivirals (DAA) against hepatitis C virus (HCV) infection has been unrestricted for chronic infection since 2015. We evaluated whether this changed the nationwide incidence of HCV primary and re-infection among HIV-positive individuals. Methods: Individuals participating in the national ATHENA HIV cohort between 2000-2018 were included. Incidence rates (IR) of HCV primary infection and re-infection were calculated per calendar year using piecewise exponential survival models. Findings: Among 22,775 individuals without prior HCV, 651 cases of HCV primary infection were documented (IR=2·9/1,000 person-years, 95%CI=2·7-3·1). The highest IR was observed in men who have sex with men (MSM) (4·5/1,000 person-years, 95%CI=4·1-4·8) and much lower among people who inject drugs (PWID) (0·8/1,000 person-years, 95%CI=0·4-1·6) and other transmission groups (0·2/1,000 person-years, 95%CI=0·1-0·4). In MSM, IR increased dramatically in 2007 (IR=8·3/1,000 person-years) and fluctuated between 4·6 and 8·6/1,000 person-years from 2008-2015. In 2016, IR declined to 2·6 cases/1,000 person-years and remained steady in 2017 and 2018 (IR=2·8 and 1·7/1,000 person-years, respectively). Among 1917 individuals with a previous HCV infection, 249 HCV re-infections were documented (IR=26·0/1,000 person-years, 95%CI=23·0-29·5). The highest IR was again observed in MSM (38·4/1,000 person-years, 95%CI=33·6-44·0) and was lower among PWID (5·5/1,000 person-years, 95%CI=2·1-14·6) and other transmission groups (9·5/1,000 person-years, 95%CI=6·7-13·5). In MSM, re-infection IRs fluctuated until 2015, reaching 51·4/1,000 person-years. In 2016, re-infection incidence declined to 37·0/1,000 person-years, followed by a further decrease in 2017 and 2018 (IR=25·1 and 15·1/1,000 person-years, respectively). Interpretation: The observed sharp decline in HCV incidence among HIV-positive MSM shortly after unrestricted DAA access suggests a “treatment-as-prevention” effect. HCV incidence was already low in PWID and other groups prior to unrestricted access. Ongoing HCV transmission is occurring in MSM, as illustrated by a declining but nonetheless high rate of reinfection, stressing the need for additional preventive measures. Funding: Dutch Ministry of Health, Welfare and Sport Conflict of Interest: BJAR reports grants from MSD and Gilead, all outside the submitted work; he hasparticipated in advisory boards organized by MSD, Gilead, Pfizer, ViiV Healthcare, Jansen Cilag, and Abbvie. EMM reports participating an advisory board of Gilead. WB reports other funds from GSK and non-financial support from Janssen, all outside the submitted work. KB reports participating in advisory boards of ViiV, Gilead, MSD and Janssen; he has received research grants form ViiV and Gilead. JS reports grants from Gilead Sciences, outside the submitted work. MP reports grants, personal fees and other funds from Gilead Sciences,Roche, MSD and Abbvie, all outside the submitted work. JA reports other funding fromGilead Sciences, Janssen-Cilag, Abbvie, BSM, and MSD, all outside the submitted work.MvdV reports grants and personal fees from Abbvie, Gilead, Johnson & Johnson, MSD, ViiV Healthcare, all outside the submitted work. All other authors report no conflicts of interest. PR reports grants from Gilead Sciences, ViiV Healthcare, and Merck & Co, and other funds from Gilead Sciences, ViiV Healthcare, Merck & Co, and Teva Pharmaceutical Industries, alloutside the submitted work. Ethical Approval: At its inception, the ATHENA cohort was approved by the institutional review boards of all participating centres. Individuals can opt out after being informed by their treating physician of the purpose of data and sample collection. Data are pseudonymized and made available to investigators in a coded form. Coded data may be used for scientific purposes without further consent. For the purpose of our analysis, only existing data have been used and therefore no additional review or consent was required.