Interventions to Curb Hepatitis C Reinfections Among Men Who Have Sex With Men (ICECREAM)

ZonMw: The Netherlands Organisation for Health Research and Development, Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC), The National Institute for STI and Aids Control in the Netherlands (Soa Aids Nederland), Julius Centre for Health Sciences and Primary Care, UMC Utrecht, ANRS | Maladies infectieuses émergentes

Men who have sex with men (MSM) who cured from hepatitis C virus (HCV) infection are at substantial risk of HCV reinfection. In this study, the investigators aim to evaluate the effectiveness of an online behavioural intervention, a home-based testing intervention and a combination of both on risk behaviour, and ultimately preventing HCV reinfection and onward spread of HCV.

Rationale: As highly effective therapy against hepatitis C virus (HCV) infection is available with rapid uptake, there is newfound optimism for HCV elimination. Nevertheless, HCV reinfections cause great concern in at risk populations, including men who have sex with men (MSM). In the Netherlands, MSM account for the majority of new HCV (re)infections. Although HCV treatment uptake is high in this group, modelling data indicate HCV elimination would not be feasible without a reduction in risk behaviour. This finding highlights the urgent need for effective interventions aimed at reducing risk behaviour and preventing reinfections in MSM. Objective: To evaluate interventions aimed at reducing risk behaviour, and ultimately preventing HCV reinfections and onward spread of HCV. Study design: Using a 3-arm randomised trial comparing run-in and intervention periods, we will evaluate the effect of two interventions and its combination on risk behaviour in MSM previously infected with HCV. Study population: MSM aged 18 years or older with a history of a successfully treated or spontaneously cleared HCV infection. Interventions: Intervention I is a targeted, online behavioural intervention developed as part of the project. Intervention II aims to increase the frequency of testing by offering an additional patient-initiated, home-based HCV RNA testing service with the use of self-sampled dried blot spots. Intervention III is a combination of intervention I and II. Study parameters/endpoints: From run-in and post-randomization questionnaires, we will evaluate the proportion at risk of HCV infection (as determined by the HCV-MOSAIC score) as the primary outcome. The HCV-MOSAIC risk score is calculated by summing up the beta coefficients specific to six self-reported risk factors when present: receptive condomless anal sex (beta 1.1), sharing sex toys (beta 1.2), unprotected fisting (beta 0.9), injecting drug use (beta 1.4), sharing straws during nasally-administered drug use (beta 1.0), and ulcerative sexually transmitted infection (beta 1.4). Secondary outcomes include incidence of HCV reinfection, changes in the individual risk behaviour items and changes in sexual wellbeing.

A 3-arm multicenter randomized trial. The trial will start with a 6 month run-in period (standard care) to determine at-risk behaviour under no intervention.

Participants will receive the behavioural intervention and the home-based testing intervention in addition to standard of care.

An online tailored behavioural intervention. The intervention will be developed as part of the project and will be based on the principles of the Information-Motivation-Behavioural Skills (IBM) model for behavioural change. It will consist of four interactive text-based modules, and demonstration and modelling videos addressing information, motivation, and behavioural skills. The intervention will be offered on a website and able to be used on PCs as well as any mobile device. It will be provided to the participants after randomization at month 6 and available for a total period of 18 months.

An additional patient-initiated home-based HCV testing service. The service offers a maximum of 4 free-of-charge HCV-RNA tests, which involves HCV testing using self-sampled dried blood spots (DBS). The DBS obtained from a finger stick will be used for HCV-RNA testing in the laboratory. DBS test kits, along with instructions and package materials for returning the test kits with the self-collected DBS sample will be provided to the participants after randomization at month 6 and available for use for a total period of 18 months.

From run-in and post-randomization questionnaires, we will evaluate the proportion at risk of HCV infection (as determined by a HCV-MOSAIC score ≥ 2.0) during the run-in versus intervention periods. The HCV-MOSAIC risk score has been previously validated for acute HCV-infection and is calculated by summing up the beta-coefficients specific to six self-reported risk factors when present in the past 6 months: (i) receptive condomless anal sex (beta 1.1), (ii) sharing sex toys (beta 1.2), (iii) unprotected fisting (beta 0.9), (iv) injecting drug use (beta 1.4), (v) sharing snoring equipment during nasally-administered drug use (beta 1.0), and (vi) ulcerative sexually transmitted infection (beta 1.4).

Number of cases of HCV reinfection divided by total person-years of follow-up at risk for reinfection, self-reported and laboratory data.

Self-reported: month 0, month 6, month 12, month 18, month 24. Laboratory data: during total follow-up period of 2 years.

Number of cases of chlamydia, gonorrhoea, lymphogranuloma venereum (LGV), genital herpes and/or syphilis divided by total person-years, self-reported.

Change in the proportion of individuals sharing snoring equipment during nasally-administered drug use.

Change in the frequency of individuals engaging in group sex activities, including changes in number of events and maximum number of sex partners during an event.

The proportion of individuals reporting change in the risk behaviour identified in the goal setting module of the behavioural intervention.

Website statistics (e.g., frequency of use, time spent on the behavioural intervention and the proportion of individuals completing all modules of the intervention).

The proportion of free HCV tests used (the total number of free HCV tests used divided by the total number of distributed tests).

The proportion of HCV positive test results (the total number of HCV positive test results divided by the total number of free tests used).

Inclusion Criteria: Informed consent documented by signature. Male individual aged 18 years or older. History of a cured or spontaneously cleared HCV infection (positive HCV RNA test in the past and/or positive anti-HCV IgG). Self-reported MSM who are either (i) HIV-positive seeking care at an HIV treatment center or (ii) HIV-negative and seeking care at an STI/PrEP/sexual health center. Sufficient understanding of Dutch or English. Have internet access and an e-mail address. Exclusion Criteria: Acute or chronic HCV infection at time of enrolment. Under HCV treatment at time of enrolment. Unlikely, in the opinion of the clinician, to comply with the study procedures. Currently participating in an intervention study that offers extra HCV testing and/or a behavioural intervention targeting risk behaviour. Investigators or otherwise dependent persons.

Newsum AM, Stolte IG, van der Meer JT, Schinkel J, van der Valk M, Vanhommerig JW, Buve A, Danta M, Hogewoning A, Prins M; MOSAIC collaborators. Development and validation of the HCV-MOSAIC risk score to assist testing for acute hepatitis C virus (HCV) infection in HIV-infected men who have sex with men (MSM). Euro Surveill. 2017 May 25;22(21):30540. doi: 10.2807/1560-7917.ES.2017.22.21.30540.

Lambers FA, Prins M, Thomas X, Molenkamp R, Kwa D, Brinkman K, van der Meer JT, Schinkel J; MOSAIC (MSM Observational Study of Acute Infection with hepatitis C) study group. Alarming incidence of hepatitis C virus re-infection after treatment of sexually acquired acute hepatitis C virus infection in HIV-infected MSM. AIDS. 2011 Nov 13;25(17):F21-7. doi: 10.1097/QAD.0b013e32834bac44.

Lambers F, van der Veldt W, Prins M, Davidovich U; MOSAIC study. Changing the odds: motives for and barriers to reducing HCV-related sexual risk behaviour among HIV-infected MSM previously infected with HCV. BMC Infect Dis. 2018 Dec 18;18(1):678. doi: 10.1186/s12879-018-3571-1.