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Behavioural trajectories following DAA treatment for HCV among people with HIV: findings from an international consortium of prospective cohort studies
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In our study, we found a slight decrease in the proportion of individuals engaging in any substance use and non-IDU following DAA treatment. IDU and sexual behaviours appeared to remain stable following DAA treatment. These findings highlight that primary prevention remains a key pillar in HCV elimination efforts alongside reinfection surveillance and the availability of retreatment among individuals with a cleared HCV infection.....high probability risk behaviour seemed to be the most present among somewhat younger individuals, and individuals belonging to the PWID and MSM+PWID (for drug use behaviours) and the MSM and MSM+PWID key population (for sexual behaviours).
Behavioural data were collected using self-reported questionnaires. These data included any recent (i.e., occurring within a maximum of up to twelve months) substance use, IDU, other recreational drug use (hereafter referred to as non-IDU), condomless anal sex (CAS) with any partner, and CAS with any casual partner (all yes/no). Data on non-IDU was inferred from the variables any substance use and IDU where individuals who did report any substance use but no IDU, were considered as non-IDU.
For most of the outcomes, younger age at baseline was associated with a higher risk of being in the "consistently high" profile [for outcomes any substance use (Supplementary Table 4,
https://links.lww.com/QAD/D728
), IDU (Supplementary Table 5,
https://links.lww.com/QAD/D728
), non-IDU (Supplementary Table 6,
https://links.lww.com/QAD/D728
) and CAS with any casual partner (Supplementary Table 7,
https://links.lww.com/QAD/D728)
]. Compared to the "consistently low" profiles, other behavioural profiles more often included PWID or MSM+PWID for drug use outcomes [i.e., any substance use (Supplementary Table 4,
https://links.lww.com/QAD/D728
), IDU (Supplementary Table 5,
https://links.lww.com/QAD/D728
) and non-IDU (Supplementary Table 6,
https://links.lww.com/QAD/D728
)] and MSM or MSM+PWID for sexual behavioural outcomes [i.e., CAS with any casual partner (Supplementary Table 7,
https://links.lww.com/QAD/D728
) and CAS with any partner (Supplementary Table 8,
https://links.lww.com/QAD/D728)].
High risk of reacquisition of hepatitis C virus infection in people with HIV with continued risk behavior
Download the PDF here
Given the limited behavioural change in some of the identified behavioural trajectories, including the consistent high probability of risk behaviours in the majority of individuals, and the varying patterns in behaviours in other trajectories, continuous assessment of behaviours should be encouraged to inform targeted HCV RNA testing strategies.
HCV infection incidence has declined in countries with broad access to DAA treatment [5]. However, the proportion of all incident HCV infections due to reinfection has increased from 23% in 2015 to 41% in 2019 in this cohort [6]. By 2023, one third of all DAAs dispensed in Australia were for retreatment, primarily due to HCV reinfection [23], suggesting that as primary infections decline, reinfections are playing an increasingly important role in the HCV epidemic in the DAA era.
Indeed, group-based trajectory modelling of any risk behaviour revealed four distinct trajectories, whereby roughly one-quarter of included individuals had a "consistently low" risk behaviour probability (29.3% of the total population) and the majority retained a high probability of risk behaviour (50.2%) during follow-up. These groupings were likely largely driven by differences in any substance use and non-IDU, as a majority of individuals also retained a high probability in these drug use behaviours
Conclusions:
Despite slight decreases in behaviours following successful DAA treatment, half of individuals had a consistently high probability of behaviours that put them at risk of HCV reinfection over time. As reinfections comprise a growing proportion of new incident HCV cases, these findings underscore the importance of ongoing primary prevention measures alongside testing and retreatment to eliminate HCV.
Characteristics of the study population
Of 33,105 individuals with HIV, 2,510 (7.6%) received treatment with DAAs. Of 2,510 individuals, 2,153 (85.8%) were successfully treated. Overall, 1,477 (68.6%) of 2,153 had at least two study visits with behavioural data ≥6 months apart following treatment completion and were included in the analysis (Fig. 1). Of those, DAAs were used to treat primary HCV infection in 1,393 (94.3%) and HCV reinfection in 84 (5.7%).
Main findings were that 30 cases of HCV reinfection occurred in the participants included in the study (0.74 per 100 persons-years). Incidence rate was lower than what was observed in a previous study [19], probably due in part to differences in inclusion criteria, that is, clearance following DAA treatment vs. all participants who cleared, and at least two visits with behavioral data instead of one. Overall, there were little changes in patterns of risk behavior associated with drug use or CAS over the follow-up period - there was only a modest decline in risk behaviors following DAA treatment. Incidence rate of HCV reinfection was highest in participants with the highest degree of risk behavior ('consistently high') (1.28 cases per 100 persons-years), this trajectory accounting for ~50% of all trajectories recorded in study participants. The majority of these individuals continued to engage in high-risk behavior for HCV acquisition, including injection drug use and CAS with casual partners. These participants include the youngest cohort participants; those who were most recently diagnosed with HIV infection; and those who were the least likely to be virologically suppressed in terms of undetectable HIV-1 viral load [16]. Overall, there was only a modest decline in risk behaviors following DAA treatment, and the majority of study participants admitted that they continued to engage in risk behaviors for HCV acquisition. This is indicative of limited behavioral changes and modification in risk behaviors in the majority of individuals - a sobering finding in light of the recently demonstrated importance of reinfections in key populations in the incidence rate of new HCV infections worldwide since the introduction of DAAs [20-25]. At the same time, these results clearly highlight a subgroup of participants towards whom the potentially most effective prevention practices and strategies should be targeted.
To limit the potential for forward transmission, horizontal or vertical, reinitiation of DAA treatment should be implemented in a wholly unprejudiced fashion in those persons who reacquire HCV infection, irrespective of how and why reinfection occurs or whether it occurs repeatedly: primary prevention; treatment; retesting; and retreatment. This is not a question of pointing fingers but one of sound public health policy.
For most of the outcomes, younger age at baseline was associated with a higher risk of being in the "consistently high" profile [for outcomes any substance use (Supplementary Table 4,
https://links.lww.com/QAD/D728
), IDU (Supplementary Table 5,
https://links.lww.com/QAD/D728
), non-IDU (Supplementary Table 6,
https://links.lww.com/QAD/D728
) and CAS with any casual partner (Supplementary Table 7,
https://links.lww.com/QAD/D728)
]. Compared to the "consistently low" profiles, other behavioural profiles more often included PWID or MSM+PWID for drug use outcomes [i.e., any substance use (Supplementary Table 4,
https://links.lww.com/QAD/D728
), IDU (Supplementary Table 5,
https://links.lww.com/QAD/D728
) and non-IDU (Supplementary Table 6,
https://links.lww.com/QAD/D728
)] and MSM or MSM+PWID for sexual behavioural outcomes [i.e., CAS with any casual partner (Supplementary Table 7,
https://links.lww.com/QAD/D728
) and CAS with any partner (Supplementary Table 8,
https://links.lww.com/QAD/D728)].
High risk of reacquisition of hepatitis C virus infection in people with HIV with continued risk behavior
Behavioural trajectories following DAA treatment for HCV among people with HIV: findings from an international consortium of prospective cohort studies
Download the PDF here
Hage, Krisa,b,c; Carson, Joanned; Hosseini-Hooshyar, Samirad; Sacks-Davis, Rachele,f,g; Stewart, Ashleigh C.e,f; Van Santen, Daniela K.a,e,f; Smit, Coletteh; Van Der Valk, Marcc,h; Wittkop, Lindai,j,k; Klein, Marina B.l; Doyle, Joseph S.e,m; Rauch, Andrin; Matthews, Gail V.d; Hellard, Margaret E.e,f,g; Boyd, Andersa,b,h,*; Prins, Mariaa,b,c,*; the InCHEHC study group
Objective:
Examine the proportion of people with HIV engaging in behaviours associated with hepatitis C virus (HCV) infection after successful direct-acting antiviral (DAA) treatment and establish longitudinal patterns of behavioural risk over time.
Design:
Multinational, prospective cohort study (International Collaboration on Hepatitis C Elimination in HIV Cohorts).
Study design and setting
Data from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC) were used [12]. Within this cohort, data from 11 different cohorts of people with HIV at risk of HCV infection or coinfected with HCV were pooled from six high-income countries (Australia, Canada, France, the Netherlands, Spain and Switzerland). Members from each cohort prepared and submitted data to the coordinating centre (Burnet Institute, Australia) based on the HIV Cohorts Data Exchange Protocol (HICDEP), including sociodemographic, HIV and HCV clinical and behavioural data, when available [12].
Methods:
Individuals with HIV successfully treated with DAAs and ≥2 follow-up visits with behavioural data were included. Changes in the proportion of any risk behaviour after treatment, which included sexual and drug use behaviours, were analysed using logistic regression with generalized estimating equations. We identified distinct trajectories of any risk behaviour over time using group-based trajectory models (GBTM).
Results:
Of the 1,477 individuals included, 487 (33.0%) were people who inject drugs, 378 (25.6%) were men who have sex with men and 442 (29.9%) were both. During a median 2.7 years (IQR = 1.6-3.9) of follow-up, the proportion engaging in any risk behaviour slightly decreased over time (adjusted odds ratio per half year = 0.97, 95% confidence interval = 0.95-0.99). GBTM revealed four distinct behavioural trajectories: consistently low (n = 433, 29.3% of total population), moderate at baseline and increasing (n = 119, 8.1%), high at baseline and decreasing (n = 184, 12.5%) and consistently high (n = 741, 50.2%).
Conclusions:
Despite slight decreases in behaviours following successful DAA treatment, half of individuals had a consistently high probability of behaviours that put them at risk of HCV reinfection over time. As reinfections comprise a growing proportion of new incident HCV cases, these findings underscore the importance of ongoing primary prevention measures alongside testing and retreatment to eliminate HCV.
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