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Low hepatitis C virus reinfection rate despite ongoing risk following universal access to direct-acting antiviral therapy among people living with HIV

Hosseini-Hooshyar, Samiraa; Martinello, Mariannea,b,c; Yee, Jasminea; Read, Phillipa,d; Baker, Davide; Post, Jeffrey J.f,g,h; Finlayson, Roberti; Bloch, Markj; Doyle, Joseph S.k,l; Shaw, Davidm; Hellard, Margaretk,l; Petoumenos, Kathya; Carson, Joannea; Dore, Gregory J.a,b; Matthews, Gail V.a,b; on behalf of the CEASE study team

Author Information
doi: 10.1097/QAD.0000000000002562

Abstract

Introduction

Globally, an estimated 2.2 million people are living with HIV/hepatitis C virus (HCV) coinfection [1]. HCV is a major cause of liver-related morbidity and mortality among people living with HIV (PLHIV) [2,3]. Further, an increase in HCV incidence has been noted in recent decades among HIV-positive gay and bisexual men (GBM) from less than 0.5 per 100 person-years before 2000 to at least one per 100 person-years after 2010 [4–6]. Within this population, both injecting drug use (IDU) and high-risk sexual behaviours such as condom-less anal intercourse (CLAI), fisting and group sex contribute to HCV transmission [7,8].

The introduction of oral direct-acting antivirals (DAAs) has dramatically changed the HCV treatment landscape [9,10]. In 2016, the United Nations and WHO called for the elimination of viral hepatitis as a public health threat by 2030 [11]. DAA-based treatment trials among people living with HIV/HCV coinfection have demonstrated very high efficacy [sustained virological response (SVR), ≥95%] [12,13]. Modelling studies have suggested that DAA treatment scale-up will lead to substantial reductions in HCV prevalence and potentially curb the HCV epidemic among PLHIV [14,15].

In populations with ongoing risk behaviour for transmission [including people who inject drugs (PWID) and GBM], the potential risk of HCV reinfection may compromise HCV elimination outcomes [16]. Rates of HCV reinfection among PLHIV are variable, ranging from 0.48 to 13.41 per 100 person-years [17–21]; but may be higher among HIV-positive GBM [17,18,22–25]. Risk of reinfection has been highlighted as a potential barrier to treatment among PWID and PLHIV [26,27].

Unrestricted access in Australia to DAAs since March 2016 [28] and a relatively small population of people living with HIV/HCV coinfection (estimated n = 2000–2500) [29], should make HCV elimination achievable among PLHIV in Australia. This could be compromised, however, if reinfection rates are high. The Control and Elimination of HCV from HIV-infected individuals within Australia (CEASE) study was designed to investigate the impact of DAA treatment scale-up on HCV disease burden among people living with HIV/HCV coinfection in Australia [30]. The objectives of this analysis were to evaluate patterns of injecting and sexual risk behaviours, and HCV reinfection incidence and knowledge among people living with HIV/HCV coinfection before and after unrestricted DAA access.

Methods

Study design and participants

CEASE is an ongoing prospective observational cohort study that enrolled participants between 31 July 2014 and 22 March 2017 from 14 sites in primary care (n = 12) and tertiary centres (n = 2) in New South Wales, Queensland, South Australia and Victoria (Supplemental Table S1, https://links.lww.com/QAD/B736).

Study inclusion required at least 18 years of age, HIV infection, and past (anti-HCV antibody positive, HCV RNA undetectable) or current (anti-HCV antibody positive, HCV RNA detectable) HCV infection. Participants with detectable HCV RNA were offered HCV treatment at the discretion of the site investigator and followed per standard-of-care. Follow-up assessments were conducted between 26 May 2017 and 31 May 2018, regardless of HCV RNA status at enrolment or treatment initiation during the study period.

Full details of the study design and procedures have been published previously [30].

Measures

Participants completed a questionnaire at enrolment containing sections on demographics (age, sex, sexual identity, country of birth, education, income and accommodation), drug and alcohol use, sexual behaviour (GBM only), and HCV acquisition, knowledge, treatment history and willingness, and reinfection risk perception. At follow-up, participants completed an abridged version of the questionnaire with sections on drug and alcohol use, sexual behaviour (GBM only) and HCV reinfection risk perception.

Injecting and non-IDU history were assessed for lifetime (ever), and in the 6 months and 1 month prior to enrolment and follow-up. Drugs most often injected, injection frequency and injecting risk behaviours (including use of an unsterile needle/syringe, and receptive sharing of ancillary injecting equipment) were assessed in month prior to each study timepoint. Hazardous alcohol consumption was assessed using the Alcohol Use Disorders Identification Test [31]. Information regarding sexual behaviour in the last 6 months was assessed among GBM at enrolment and follow-up, and included; presence and HIV and HCV status of regular male partner, presence and number of casual male partner(s), HIV and HCV disclosure to casual partner(s), and venue or site casual partner(s) were met as well as sexual practices [CLAI with casual male partner(s) and group sex]. Full questionnaire details can be found in Supplemental Appendix S1, https://links.lww.com/QAD/B751.

Outcomes and definitions

The two primary outcomes analysed for change in risk behaviours were IDU and CLAI with casual male partner(s) among GBM; both in the last 6 months.

Other injecting risk behaviour measures considered in the analysis were IDU in the last month; and among people reporting IDU in last month, frequency of IDU (≥weekly injecting), use of an unsterile needle/syringe and receptive sharing of ancillary injecting equipment. Other sexual risk behaviour measures among GBM considered in the analysis were any casual male partner(s) and group sex; both in the last 6 months.

Reinfection was defined by the presence of quantifiable HCV RNA after SVR12 or confirmed spontaneous clearance, or the presence of quantifiable HCV RNA between end of treatment and posttreatment week 12 with an HCV genotype or subtype distinct from the primary strain.

Study oversight

All study participants provided written informed consent before study procedures. The study protocol was approved by St Vincent's Hospital, Sydney Human Research Ethics Committee (primary study committee), as well as by the institutional review board or independent ethics committee at each participating site and was conducted according to the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice guidelines and local regulatory requirements. The study was registered with ClinicalTrials.gov (NCT02102451).

Statistical analysis

Descriptive statistics were used to summarize participants characteristics [mean and SDs or median and interquartile ranges (IQRs) for continuous variables, and frequency and percentages for categorical variables].

Drug use and sexual behaviour were reported for each time point. Changes in all drug use and sexual risk behaviour outcomes were evaluated from enrolment to follow-up. For the analysis of categorical outcomes, Chi-squared tests or exact equivalents (for small numbers) were used. In further sensitivity analyses for paired data, changes in the two primary outcomes [i.e. IDU in the last 6 months and CLAI with casual male partner(s)] between enrolment and follow-up were compared using the McNemar test (exact binomial probability). Results were considered significant if P values were less than 0.05. An additional sensitivity analysis was performed among participants with follow-up below the median (less than 2 years).

Reinfection incidence was calculated using person-time of observation, with confidence intervals (CIs) for rates calculated using Poisson distribution. The time at risk commenced at the end of treatment (if SVR12 was achieved post enrolment) or enrolment (if HCV RNA negative) and follow-up time was censored at estimated date of reinfection, date of last follow-up or death.

All analyses were conducted using the Stata v14.2 (StataCorp, College Station, Texas, USA).

Results

Characteristics of study participants

Between July 2014 and March 2017, 402 HIV/HCV antibody-positive individuals were enrolled in CEASE, of whom 393 (98%) completed the initial behavioural questionnaire. During follow-up, 53 participants either died (n = 10), were lost to follow-up (n = 21), moved to a nonstudy site (n = 7) or withdrew (n = 15), whereas 63 participants remained in follow-up, but did not complete their scheduled assessments (Supplemental Fig. S1, https://links.lww.com/QAD/B736). The present analysis included participants who completed the behavioural questionnaires at both enrolment and follow-up (n = 272). Total follow-up time was 762 person-years (median follow-up time: 2.91 years, IQR 2.23, 3.45); median time between completion of the behavioural questionnaires at enrolment and follow-up was 2.12 years (IQR 1.58, 2.59). There were no marked differences between the baseline characteristics of participants included in this analysis (n = 272) and those who completed the enrolment survey only (n = 121) (Supplemental Table S2, https://links.lww.com/QAD/B736).

Among 272 participants in this analysis, median age was 50 years (IQR 44, 55), 96% (n = 260) were male, and 83% (n = 226) identified as GBM (Table 1). The majority were born in Australia (71%, n = 192) and 2% (n = 7) identified as Aboriginal or Torres Strait Islander. Part-time or full-time employment was reported by 36% (n = 97), and 49% (n = 135) were receiving government financial assistance. Fifty-three percent (n = 143) had completed higher education, and 91% (n = 248) had stable housing.

Table 1
Table 1:
Enrolment demographic and clinical characteristics of Control and Elimination of HCV from HIV-infected individuals within Australia participants with available behavioural data at enrolment and follow-up.

HIV infection was well controlled, with median CD4+ cell count 590 × 106/l (IQR 404, 799) and HIV viral load below the limit of detection (<20 copies/ml) in 86% (n = 233), with most receiving antiretroviral therapy (n = 256, 94%). The most common clinician-determined mode of HCV acquisition was IDU (54%, n = 146) followed by sexual exposure (32%, n = 88). Thirty one percent (n = 83) had received HCV treatment prior to enrolment. A total of 199 (73%) had detectable HCV RNA at enrolment, predominantly genotype 1 (65%, n = 130) and 3 (24%, n = 48), of whom 187 (94%) were treated during the study period.

Drug use and sexual behaviour at enrolment

At enrolment, IDU ever and in the last 6 months were reported by 83 (n = 227) and 35% (n = 95), respectively (Table 2). Other noninjecting illicit drug use (excluding marijuana) ever and in the last 6 months was reported by 75 (n = 203) and 30% (n = 81), respectively. (Meth)Amphetamine use was predominant, both via injecting (ever, 66%; last 6 months, 28%) and noninjecting (ever, 60%; last 6 months, 18%) routes (Supplemental Table S3, https://links.lww.com/QAD/B736). (Meth)Amphetamine use in the last 6 months was more common among GBM (injecting 31%, noninjecting 20%) compared with women and heterosexual men (injecting 11%, noninjecting 7%).

Table 2
Table 2:
Patterns of drug and alcohol use among Control and Elimination of HCV from HIV-infected individuals within Australia participants with available behavioural data at enrolment and follow-up.

Among participants who reported IDU ever, median age at first injecting was 25 years (IQR 19, 33). Among those reporting IDU in the last month (n = 69), the drugs most often injected were (meth)amphetamine (71%), heroin (19%) and other opioids (1%). Use of an unsterile needle/syringe and receptive sharing of ancillary injecting equipment in the last month were reported by 16 (n = 11) and 19% (n = 13), respectively.

Among GBM, 34% (n = 78) reported having a regular male partner, of whom 58% were HIV-positive and 15% were HCV-positive. Most (57%, n = 129) reported having one or more casual male partner(s) in the last 6 months (Table 3). Almost half (48%, n = 108) reported having CLAI with casual partner(s) and 29% (n = 65) reported group sex in the 6 months prior to enrolment. Among those who had casual partner(s), 35% (n = 45) reported having more than 10 partner(s) in the last 6 months. Commonly reported ways of meeting casual partner(s) were via the Internet (60%, n = 77) and mobile apps (55%, n = 71). Participants were more likely not to disclose their HCV status with their casual partner(s) (‘never’ disclose, 48%, n = 62) than their HIV status (‘never’ disclose, 13%, n = 16).

Table 3
Table 3:
Sexual behaviour and attitudes among Control and Elimination of HCV from HIV-infected individuals within Australia gay and bisexual men with available behavioural data at enrolment and follow-up (N = 226).

Changes in injecting behaviour

The proportion reporting IDU in the last 6 months at enrolment (35%, n = 95) and follow-up (39%, n = 105) was similar (Fig. 1a). IDU in the last month was reported by 25% (n = 69) at enrolment and 29% (n = 79) at follow-up. Among individuals reporting IDU in the last month, the proportions reporting more than or equal to weekly injecting, use of an unsterile needle/syringe, and receptive sharing of ancillary injecting equipment were 32, 16 and 19%, respectively, at enrolment, and 32, 14 and 16%, respectively, at follow-up (Fig. 1a). (Meth)Amphetamines were the predominant drug injected at both enrolment (28%, n = 75) and follow-up (32%, n = 88) (Supplemental Fig. S2, https://links.lww.com/QAD/B736).

Fig. 1
Fig. 1:
(a) Injecting risk behaviours among Control and Elimination of HCV from HIV-infected individuals within Australia participants with available behavioural data at enrolment and follow-up. (b) Sexual risk behaviours among Control and Elimination of HCV from HIV-infected individuals within Australia gay and bisexual men with available behavioural data at enrolment and follow-up.

In a sensitivity analysis among participants with paired data (i.e. available responses for questions at both enrolment and follow-up; n = 266), there was no significant change in IDU in the last 6 months between enrolment (36%, n = 95) and follow-up (39%, n = 103; P = 0.268). Similar patterns of injecting risk behaviour were demonstrated among those with less than 2 years of follow-up (Supplemental Table S4, https://links.lww.com/QAD/B736).

Between enrolment and follow-up, eight participants commenced IDU (Table 2). The median age at enrolment for those commencing IDU during follow-up was 54 years (range 39, 59) and all were GBM. In addition, 29 individuals reported commencing non-IDU between enrolment and follow-up, of whom 26 were GBM. Again, among both those who commenced IDU and non-IDU during follow-up, (meth)amphetamine use was predominant (injecting: ever 88%, last 6 months 50%; noninjecting: ever 72%, last 6 months 24%).

Changes in sexual behaviour

Among GBM, the proportion reporting one or more casual partner(s) in the last 6 months was 57% (n = 129) at enrolment and 53% (n = 120) at follow-up (Fig. 1b). CLAI with casual partner(s) was reported by 48% (n = 108) at enrolment and 46% (n = 103) at follow-up. Group sex in the last 6 months was reported by 29% (n = 65) at enrolment and 26% (n = 58) at follow-up. Approximately one-quarter of GBM reported both high drug use and sexual risk behaviours [i.e. IDU and CLAI with casual partner(s) in the last 6 months] at enrolment (26%, n = 58) and follow-up (27%, n = 61).

In a sensitivity analysis among participants with paired data (n = 203), CLAI with casual partner(s) was reported by 53% (n = 108) at enrolment and 47% (n = 96) at follow-up (P = 0.073). Results of sensitivity analysis among those with less than 2 years of follow-up indicated similar patterns of sexual risk behaviour among GBM (Supplemental Table S5, https://links.lww.com/QAD/B736).

Reinfection

Reinfection was detected in five individuals (2%) during follow-up, after a median of 108 days (range 72, 405) posttreatment or enrolment (Table 4). All cases of reinfection occurred among GBM. Most reported coexisting risk behaviour of CLAI with casual partner(s) (n = 4) and IDU (n = 3) within the 6 months prior to follow-up; two participants with reinfection commenced IDU after enrolment. For one participant with reinfection, the mode of reinfection was unknown. One participant demonstrated spontaneous clearance and four received DAA retreatment of whom all achieved SVR (Table 4).

Table 4
Table 4:
Demographic, behavioural and virological characteristics of participants with reinfection in Control and Elimination of HCV from HIV-infected individuals within Australia study.

Among individuals at risk for reinfection (n = 254), reinfection incidence was 1.05 per 100 person-years overall (95% CI, 0.44–2.53; total follow-up time: 474 person-years; median follow-up time: 1.86 years, IQR 1.52, 1.99). Among those reporting IDU in the 6 months prior to enrolment, reinfection incidence was 0.64 per 100 person-years (95% CI, 0.09–4.53; total follow-up time: 157 person-years), and among GBM reporting CLAI with casual partner(s) at enrolment, reinfection incidence was 1.57 per 100 person-years (95% CI, 0.50–4.86; total follow-up time: 191 person-years). Following unrestricted access to DAA therapy, reinfection incidence in our cohort decreased from 2.20 per 100 person-years (95% CI, 0.71–6.82; total follow-up time: 136 person-years) in the period 2014–2016 [before Pharmaceutical Benefits Scheme (PBS) listing of DAAs], to 0.60 per 100 person-years (95% CI, 0.15–2.40; total follow-up time: 333 person-years) in the period 2017–2018 (immediately after PBS listing of DAAs).

Hepatitis C virus knowledge

Knowledge regarding risk behaviours associated with HCV transmission was variable. While most identified injecting risk behaviours [i.e. sharing needles (88%, n = 239), sharing other injecting equipment (76%, n = 206)] and CLAI (72%, n = 197) as behaviours increasing HCV risk, awareness of other sexual behaviours which may pose an HCV transmission risk [e.g. fisting (48%, n = 130), group sex (55%, n = 150) and use of sex toys (45%, n = 123)] was less common (Supplemental Table S6, https://links.lww.com/QAD/B736).

Most participants (69%) were aware that HCV reinfection could occur, but the majority felt they were at no or low likelihood of reinfection (73%, n = 198). Among the five participants with reinfection, three acknowledged that HCV reinfection was possible. Despite most reporting ongoing risk behaviour, only one of the five participants identified as being at high risk of reinfection in the future.

Discussion

The current study evaluated injecting and sexual risk behaviours pre and post unrestricted DAA access among a cohort of people living with HIV/HCV coinfection in Australia. Our results indicate that IDU in the last 6 months remained stable from enrolment to follow-up. Similarly, injecting frequency, use of an unsterile needle/syringe and receptive sharing of ancillary injecting equipment remained unchanged. We also documented ongoing sexual risk among GBM, with the proportion reporting CLAI with casual partner(s) and group sex remaining stable. Overall, these findings demonstrate that in the Australian setting of highly effective DAA therapy, there is no evidence of increasing risk behaviour or high levels of reinfection.

Despite ongoing risk behaviour, HCV reinfection was only observed in five individuals (incidence 1.05 per 100 person-years), all of whom were GBM and most had coexisting sexual and injecting risk. It is likely that this low incidence can be attributed to the rapid decline in HCV RNA prevalence following DAA scale-up among the CEASE population (from 82% in 2014 to 8% in 2018 [30]), and more broadly to overall high DAA uptake in Australia following universal access; 41% of people with HIV/HCV coinfection were estimated to commence DAA therapy in 2016 [32]. High cumulative HCV treatment uptake (91%) has considerably reduced the HCV viraemic pool, hence limiting further spread of HCV. These findings support a ‘treatment as prevention’ effect within this community. High DAA uptake accompanied by substantial decline in HCV RNA prevalence was also evident among the highest risk subpopulations including those reporting IDU in the last 6 months (cumulative treatment uptake, 88%) and GBM reporting CLAI with casual partner(s) (cumulative treatment uptake, 89%), suggesting that ongoing efforts to engage and treat these groups can produce substantial benefits.

Very little evidence is available regarding changes in risk behaviours in the DAA era. Several studies among PWID who received interferon-based therapies suggested that HCV treatment did not lead to increased risk behaviours [33–35]. Midgard et al.[34] observed a significant decrease in any IDU during and following treatment. Similarly, in a study by Alavi et al.[33], ancillary equipment sharing decreased significantly following treatment among PWID. Artenie et al.[35] indicated that PWID who received HCV treatment reported a reduction in IDU at 1 year, relative to those who did not engage. A very recent study among PWID [36] indicated that recent IDU and equipment sharing, significantly decreased following DAA therapy. However, participants in all these studies were highly selected and motivated, similar to CEASE population.

With DAA therapy simplifying HCV treatment, some concerns have been expressed that individuals may be less likely to seek health-improving changes such as risk reduction [37]. Reassuringly our study did not indicate any increase in risk behaviours after DAA roll-out. However, recent evidence suggests that sexual risk behaviours [including CLAI with casual partner(s)] among GBM have been on the rise [38–42], in part related to the widespread use of HIV preexposure prophylaxis [38,39], with a resultant increase in sexually transmitted infections [39,41,43]. Ongoing risk behaviours which may facilitate HCV transmission in this population highlight the importance of continued risk reduction education and surveillance among GBM.

The incidence of reinfection observed in the CEASE cohort is generally lower than rates reported in coinfected populations internationally. In Europe, there is a wide variation in reported reinfection rates ranging from 0.48 to 13.41 per 100 person-years (Supplemental Table S7, https://links.lww.com/QAD/B736[17,19,20,44]). Differences between our findings and those in Europe likely resulted from unrestricted access to DAA therapy in Australia that has led to an overall decline in HCV prevalence particularly among high-risk populations (including PWID [45] and PLHIV [30]). Modelling studies in the United Kingdom and Switzerland suggest that a combination of DAA scale-up and behavioural risk reduction is needed to reduce HCV incidence and prevalence among HIV-positive GBM [14,46]. Nevertheless, our data highlight the potential public health impact of a universal DAA access program with high treatment uptake in an urban Australian population without risk behaviour modification.

The study has some limitations. First, although the demographics of CEASE are similar to that of the broader HIV population in Australia [29,47], CEASE is not a random sample of the population. Although designed to include all anti-HCV antibody positive individuals, CEASE could have focused on individuals highly engaged in care. However, it should be noted that a high proportion of PLHIV (85%) are linked and retained in care in Australia [48]. It is noted that this is not the case globally and other HIV/HCV coinfected populations may differ. Further, given the participants were largely recruited from high case load services in NSW, the findings may not be generalizable to remote or rural settings. Second, our data may have been influenced by loss to follow-up. Although, the baseline characteristics of those lost to follow-up and those who remained in the study were not markedly different, it might be that some people were lost who had high sexual risk at baseline (Supplemental Table S8, https://links.lww.com/QAD/B736 and Table S9, https://links.lww.com/QAD/B736). Third, risk behaviour outcomes were based on self-report, which are prone to social desirability and recall biases, and may underestimate behaviours. However, our findings are consistent with those in other behavioural analyses of Australian GBM [49]. Finally, changes in risk behaviours have been measured at two time points (i.e. enrolment and follow-up) using a binary variable in periods immediately prior to and following unrestricted DAA access. As follow-up of the CEASE cohort is ongoing, future analyses will evaluate longer trajectories of risk behaviours and their relationship to HCV reinfection incidence.

In conclusion, the incidence of HCV reinfection following DAA therapy in an Australian HIV/HCV cohort was very low despite ongoing risk behaviours. The probable explanation is the rapid HCV RNA decline as a result of high levels of DAA uptake across all risk categories. However, ongoing risk behaviours, particularly high-risk sexual behaviours, may facilitate reinfection among this population. Regular screening and treatment of (re)infection alongside risk reduction education and access to harm reduction services will be required to achieve WHO goals.

Acknowledgements

The authors thank the study participants for their contribution to the research, as well as current and past researchers and staff. The authors acknowledge members of the study group:

Protocol Steering Committee – G.V.M. (Chair, The Kirby Institute, UNSW Sydney, Sydney, Australia), D.B. (East Sydney Doctors, Sydney, Australia), M.B. (Holdsworth House Medical Practice, Sydney, Australia), J.C. (The Kirby Institute, UNSW Sydney, Sydney, Australia), G.J.D. (The Kirby Institute, UNSW Sydney, Sydney, Australia), J.S.D. (The Alfred and Monash University, Melbourne, Australia), Tim Duck (NSW Health, Sydney, Australia), R.F. (Taylor Square Private Clinic, Sydney, Australia), M.H. (Burnet Institute, Melbourne, Australia), Hayden Jose (ASHM, Sydney, Australia), Sarah Lambert (ACON, Sydney, Australia), Stuart Loveday (Hepatitis NSW, Sydney, Australia), Pip Marks (The Kirby Institute, UNSW Sydney, Sydney, Australia), M.M. (The Kirby Institute, UNSW Sydney, Sydney, Australia), J.J.P. (The Albion Centre, Sydney, Australia), Leila Stennett (AFAO, Sydney, Australia), Vanessa Towell (ASHM, Sydney, Australia), Joseph Sasadeusz (Royal Melbourne Hospital, Melbourne, Australia).

Coordinating Centre, The Kirby Institute, UNSW Sydney, Sydney, Australia – G.V.M. (Coordinating Principal Investigator), J.C. (Study Coordinator), G.J.D. (Co-ordinating Principal Investigator), Ecaterina Filep (Data Manager), Lanni Lin (Study Coordinator), Pip Marks (Clinical Trials Manager), M.M. (Post-Doctoral Fellow, Statistician), K.P. (Statistician), Ineke Shaw (Systems Manager), J.Y. (Study Coordinator).

Site Principal Investigators – New South Wales – Eva Jackson (Blue Mountains Sexual Health, Sydney, Australia), Nicholas Doong (Dr Doong's Surgery, Sydney, Australia), D.B. (East Sydney Doctors, Sydney, Australia), M.B. (Holdsworth House Medical Practice, Sydney, Australia), P.R. (Kirketon Road Centre, Sydney, Australia), Archana Sud (Nepean Sexual Health, Sydney, Australia), G.J.D. (St Vincent's Hospital, Sydney, Australia), Anna McNulty (Sydney Sexual Health Centre, Sydney, Australia), R.F. (Taylor Square Private Clinic, Sydney, Australia), J.J.P. (The Albion Centre, Sydney, Australia), Shailendra Sawleshwarkar (Western Sydney Sexual Health, Sydney, Australia); Queensland – Diane Rowling (Brisbane Sexual Health Clinic, Brisbane, Australia); South Australia – D.S. (Royal Adelaide Hospital, Adelaide, Australia); Victoria – Richard Moore (Northside Clinic, Melbourne, Australia).

Site Coordinators – New South Wales – Vincenzo Fragomeli (Blue Mountains Sexual Health, Sydney, Australia), Shane Hewitt (Dr Doong's Surgery, Sydney, Australia), Melissa Benson (East Sydney Doctors, Sydney, Australia), Annabelle Caspersz (Holdsworth House Medical Practice, Sydney, Australia), Rosie Gilliver (Kirketon Road Centre, Sydney, Australia), Vincenzo Fragomeli (Nepean Sexual Health, Sydney, Australia), Alison Sevehon, Fiona Peet and Rebecca Hickey (St Vincent's Hospital, Sydney, Australia), Ruthy McIver (Sydney Sexual Health Centre, Sydney, Australia), Ching Tan (Taylor Square Private Clinic, Sydney, Australia), Raghib Ahmad (The Albion Centre, Sydney, Australia), Holly Miller, Tichaona Jaricha (Western Sydney Sexual Health, Sydney, Australia); Queensland – Fiona Taylor (Brisbane Sexual Health Clinic, Brisbane, Australia); South Australia – Catherine Ferguson (Royal Adelaide Hospital, Adelaide, Australia); Victoria – Susan Boyd and Sian Gowalds (Northside Clinic, Melbourne, Australia).

Author contributions: S.H.-H., M.M., J.Y., D.B., R.F., M.B., J.S.D., M.H., G.J.D. and G.V.M. contributed to study design, conceived the study proposal and developed the methodology. M.M., P.R., D.B., J.J.P., R.F., M.B., J.S.D., D.S., G.J.D. and G.V.M. were involved in participant recruitment and data collection. S.H.-H. conducted the data analysis, with oversight from M.M., K.P. and G.V.M. S.H.-H. led the writing of article, with critical revision by M.M., G.J.D. and G.V.M. All authors have seen and approved the final version of the article.

The Kirby Institute is funded by the Australian Government Department of Health and Ageing. M.M., G.J.D., G.V.M., J.S.D. and M.H. are supported through National Health and Medical Research Council (NHMRC) Fellowships (M.M.: Early Career Fellowship; G.V.M. and J.S.D.: Career Development Fellowship; G.J.D.: Practitioner Fellowships; M.H.: Principal Research Fellowship).

Conflicts of interest

S.H.-H., J.J.P., R.F., J.C.: No conflict. M.M. reports grants from Gilead Sciences. J.Y. has received grants from Gilead Sciences Inc. P.R. has received research funding to his institution from Gilead Sciences, as well as travel and speaking fees for Gilead Sciences, and speaking fees and advisory board participation fees from Merck Sharp and Dohme. D.B. has received research funding, advisory board payments and speaker payments from Gilead, Abbvie and Bristol-Myers Squibb. M.B. has received grants and personal fees from Gilead Sciences, grants and personal fees from BristolMyers Squibb, grants and personal fees from ViiV Healthcare, grants from Abbvie, grants and personal fees from Merck, Sharp and Dohme, and grants from Amgen. J.S.D. reports grants from Gilead Sciences, Bristol-Meyers Squibb, Abbvie, and Merck and personal fees from Gilead Sciences, Abbvie and Merck. D.S. reports personal fees from Kirby Institute. M.H. has received funding for investigator-initiated research from Gilead, BristolMyers Squibb and Abbvie. K.P. has received unrestricted grant funding grants from Boehringer-Ingelheim Pty Ltd, Bristol-Myers Squibb Australia Pty Ltd, Gilead Sciences Pty Ltd, Janssen-Cilag Pty Ltd, Merck, Sharp and Dohme (Australia) Pty Ltd, Viiv HealthCare. G.J.D. is an advisory board member and has received honoraria from Roche, Merck, Janssen, Gilead, Bristol-Myers Squibb and Abbvie; research grant funding from Roche, Merck, Janssen, Gilead, Bristol-Myers Squibb, Vertex, BoehringerIngelheim and Abbvie; and travel sponsorship from Roche, Merck, Janssen, Abbvie, Gilead and Bristol-Myers Squibb. G.V.M. has received research funding, advisory board payments and speaker payments from Abbvie, Gilead and Janssen. All other authors report no potential conflicts.

The views expressed in this publication do not necessarily represent the position of the Australian Government. Research reported in this publication was supported by Gilead Sciences Inc as an investigator-initiated study. The content is solely the responsibility of the authors. None of the authors had commercial relationships that might pose a conflict of interest in connection with this article.

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Keywords:

elimination; hepatitis C; HIV; men who have sex with men; reinfection; treatment-as-prevention

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