Going HCVree: Prevention of hepatitis C reinfection in HIV-infected men who have sex with men. A mixed methods study to enable scalability of a behavioral risk reduction intervention

Since the introduction of highly effective direct-acting antivirals (DAA), elimination of the hepatitis C virus (HCV) has become a realistic objective, leading the World Health Organization (WHO) to define elimination goals by 2030 [1]. Because HCV incidence and prevalence are more relevant within certain groups [2], focusing on key subpopulations for micro-elimination can be an effective strategy [3].
This requires the development of interventions tailored specifically for the target groups. In addition to screening and providing access to treatment, the overall intervention plan has to include the prevention not only of new infections but also of reinfection [3, 4].
In high-income countries, HIV-infected men who have sex with men (MSM) represent a high-impact treatment group. In recent years, members of this group have showed rap-idly increasing HCV incidence. For example, an 18-fold increase was observed between 1998 and 2011 in MSM participating in the Swiss HIV Cohort Study (SHCS) [5].
A major trigger for this HCV epidemic in HIV-infected MSM is sexual transmission. While related biological, behavioral and social factors are all discussed, behavioral factors ap-pear to be the most important drivers of transmission [6, 7]. Sexual practices that put MSM particularly at risk are currently a matter of discussion. For example, sexualized drug use is associated with additional risks, e.g., sharing of injection equipment or sexual encounters with increased potential for anal or rectal trauma [8-12]. And while some discussion remains as to the exact ranking of transmission drivers, current evidence in-dicates that an interplay between sexual and drug use behaviors is extremely influential [13].
Among HIV-infected MSM, the incidence-rate of HCV reinfection after successful treat-ment—5.93-9.2/100 person-years (py)—is the highest of any current grouping [14, 15]. Considering that reinfection is associated with complex behavioral risk factors, success-ful micro-elimination will demand a combination of behavior change and medical treat-ment as numerous researchers have argued [13, 16-18].
In 2015, noting the urgent need to prevent HCV reinfection in HIV-infected MSM, Swiss researchers decided to test an approach that combined pharmaceutical treatment with a behavioral counselling intervention [19]. Their decision was supported by a mathematic modelling study indicating that, without behavioral changes, micro-elimination would not be possible in Switzerland [20]. Until that time, no behavioral intervention focusing on HCV-related sexual risk reduction has been described or evaluated; five years later, to our knowledge, this is the first such study.
The overall immediate aim of this thesis was to strengthen the comprehensive behav-ioral prevention strategy, with the long-term aim of improving HCV micro-elimination. Guided by the Medical Research Council (MRC) framework for complex interventions in health [21, 22] in our process’s first phase, we developed an HCV-specific sexual risk reduction intervention by adapting an evidence-based HIV sexual risk reduction in-tervention. In the second, after feasibility testing the resulting intervention within the framework of the Swiss HCVree Trial, we evaluated its impact.
Chapter 1 provides an introduction to our topic in terms of content and methodology. Its first part focuses on HCV elimination and the strategies necessary to achieve that goal; the second presents arguments supporting our approach and choice of methods.
Chapter 2 presents our goals.
MRC framework phase I
Chapter 3 describes our development of a behavioral counselling intervention. We worked with the concept of scaling-out, i.e., the process of improving the intervention’s fit to a new context while maintaining its effectiveness [23]. This approach was influenced by our increased awareness of implementation research and the importance of “putting evidence into practice” [24]. The adaptation process was guided by the Intervention Map-ping (IM) Adapt approach [25] and a contextual analysis. At many steps, broad stake-holder involvement helped us discover the needed changes. The adapted intervention was called HCVree and me.
MRC framework Phase II
The project’s second phase focused on the evaluation of the HCVree and me feasibility test. We were especially interested in how the intervention worked in practice and to use this knowledge for further improvement when considering scalability [26, 27]. We used mixed methods, with methods chosen as appropriate for each evaluation question [26].
In the Swiss HCVree Trial, the decision was made to invite only men who reported in-consistent condom use with non-steady partners (nsCAI) in the previous year. In chapter 4, we examined the appropriateness of using this selection criterion for the behavioral intervention in 118 of our 122-man sample. We analyzed their self-reported sexual and drug use behaviors at baseline. While 72 (61%) qualified for the intervention, other po-tential HCV transmission risk behaviors were also frequent, e.g., 52 (44%) had used drugs, 44 (37%) reported sexualized drug use and 17 (14%) had injected drugs. This finding highlighted that the chosen screening question had excluded numerous men who indicated a need to develop prevention-centered behaviors.
Chapter 5 reports the results of a qualitative study in the behavioral intervention’s par-ticipants. For this, our aim was to understand the intervention program’s meaning for participants regarding their sexuality and risk behaviors. One-third of participants (n=17) agreed to semi-structured interviews. The narratives revealed one constitutive theme: Giving hepatitis C a place and living without it again, illustrating first how participants positioned themselves to the program and thereafter their sense-making work in relation to it.
All participants responded to the intervention program, but with considerable variation. Therefore, we differentiated three sense-making work: Avoid risks: get rid of hepatitis C for life; Minimize risks: live as long as possible without hepatitis C; and Accept risk: live with the risk of hepatitis C. This work summed up not only the range of the participants’ various responses to the intervention but also their later management of sexual risks. Also, regardless of their responses to the behavioral counselling intervention, the results also revealed that treatment had had a significant influence on their sense-making.
The fourth article, described in chapter 6, built on these sense-making groups. This study’s aim was to validate that the three groups also differed in the content of sexual risk reduction goal-setting and behavior change. To achieve this, we conducted a con-vergent mixed-method study. The qualitative analysis identified seven domains reflecting broader risk reduction strategies; the quantitative analysis largely supported the differ-entiation of the groups. The merged data validated our hypothesis. This finding is im-portant because the qualitatively generated sense-making work groups can now be used to inform further intervention development and tailoring. However, the analysis also indi-cated that our quantitative instrument was sub-optimal for measuring initiated diverse risk reduction strategies and emphasizes the need for better outcome variables/questionnaire items.
Chapter 7 presents a synthesis and discussion of the results, particularly three key find-ings. We begin by describing how the innovative combination of traditional and newer implementation frameworks facilitated the intervention’s successful scaling-out. Follow-ing the feasibility test, we identified and described the participants’ various responses regarding their sense-making work. The resulting groups reflected the diversity of their experiences with both the behavioral intervention and the DAA treatment. The chapter ends with an explanation of how the participants’ dynamic sexual behavior influenced not only our interpretation of evaluation findings but also the need for further adaptations to the intervention.
These studies’ findings highlighted various implications for future research and clinical practice. As a next step, we recommend revising the intervention according to the results of our evaluation, then preparing for the next trial—particularly to better cover sexualized drug use behaviors. For clinical practice, we recommend encouraging joint discussion within clinical teams to raise awareness of potential reinfection-related stigma, of assess-ment of problematic sexualized drug use behaviors and of how to use clinical appoint-ments as teachable moments. This will certainly impact patient-centered care and will very likely also improve patient outcomes.