Treatment as prevention effect of direct-acting antivirals on primary hepatitis C virus incidence: Findings from a multinational cohort between 2010 and 2019

Daniela K van Santen^{1

2

3}, Rachel Sacks-Davis^{1

3}, Ashleigh Stewart^{1

3}, Anders Boyd^{2

4}, Jim Young⁵, Marc van der Valk^{4

6}, Colette Smit⁴, Andri Rauch⁷, Dominique L Braun⁸, Inmaculada Jarrin^{9

10}, Juan Berenguer^{10

11}, Jeffrey V Lazarus^{12

13}, Karine Lacombe¹⁴, Maria-Bernarda Requena¹⁴, Linda Wittkop^{15

16

17}, Olivier Leleux¹⁵, Dominique Salmon¹⁸, Fabrice Bonnet^{15

19}, Gail Matthews²⁰, Joseph S Doyle^{1

3

21}, Tim Spelman¹, Marina B Klein²², Maria Prins^{2

23}, Jason Asselin¹, Mark A Stoové^{1

3}, Margaret Hellard^{1

3

21}; InCHEHC study group

Affiliations

¹ Disease Elimination Program, Burnet Institute, Melbourne, Australia.
² Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, the Netherlands.
³ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
⁴ Stichting Hiv Monitoring, Amsterdam, the Netherlands.
⁵ Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada.
⁶ Department of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
⁷ Department of Infectious Diseases, Inselspital, University Hospital of Bern, University of Bern, Bern, Switzerland.
⁸ Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁹ Instituto de Salud Carlos III, Madrid, Spain.
¹⁰ Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain.
¹¹ Infectious Diseases. Hospital General Universitario Gregorio Marañón (IsSGM), Madrid, Spain.
¹² Barcelona Institute for Global Health, Hospital Clínic, University of Barcelona, Barcelona, Spain.
¹³ Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
¹⁴ Sorbonne Université, IPLESP INSERM UMR-S1136, St Antoine Hospital, APHP, Paris, France.
¹⁵ Univ. Bordeaux, INSERM, Institut Bergonié BPH U1219, CIC-EC 1401, F-33000, Bordeaux, France.
¹⁶ INRIA SISTM Team, Talence, France.
¹⁷ CHU de Bordeaux, Service d'information Médicale, INSERM, Institut Bergonié, CIC-EC 1401, F-33000, Bordeaux, France.
¹⁸ Université Paris Descartes, Service Maladies Infectieuses et Tropicales, AP-HP, Hôpital Cochin, Paris, France.
¹⁹ CHU de Bordeaux, Service de Médecine Interne et Maladies Infectieuses, F-33000, Bordeaux, France.
²⁰ The Kirby Institute, University of New South Wales, Sydney, Australia.
²¹ Department of Infectious Diseases, The Alfred and Monash University, Melbourne, Australia.
²² Division of Infectious Diseases and Chronic Viral Illness Service, McGill University Health Centre, Montreal, Canada.
²³ Department of Infectious Diseases, Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

PMID: 36618902
PMCID: PMC9816910
DOI: 10.1016/j.eclinm.2022.101810

Treatment as prevention effect of direct-acting antivirals on primary hepatitis C virus incidence: Findings from a multinational cohort between 2010 and 2019

Daniela K van Santen et al. EClinicalMedicine. 2022.

. 2022 Dec 30:56:101810.

doi: 10.1016/j.eclinm.2022.101810. eCollection 2023 Feb.

Authors

Affiliations

¹ Disease Elimination Program, Burnet Institute, Melbourne, Australia.
² Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, the Netherlands.
³ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
⁴ Stichting Hiv Monitoring, Amsterdam, the Netherlands.
⁵ Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada.
⁶ Department of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
⁷ Department of Infectious Diseases, Inselspital, University Hospital of Bern, University of Bern, Bern, Switzerland.
⁸ Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁹ Instituto de Salud Carlos III, Madrid, Spain.
¹⁰ Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain.
¹¹ Infectious Diseases. Hospital General Universitario Gregorio Marañón (IsSGM), Madrid, Spain.
¹² Barcelona Institute for Global Health, Hospital Clínic, University of Barcelona, Barcelona, Spain.
¹³ Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
¹⁴ Sorbonne Université, IPLESP INSERM UMR-S1136, St Antoine Hospital, APHP, Paris, France.
¹⁵ Univ. Bordeaux, INSERM, Institut Bergonié BPH U1219, CIC-EC 1401, F-33000, Bordeaux, France.
¹⁶ INRIA SISTM Team, Talence, France.
¹⁷ CHU de Bordeaux, Service d'information Médicale, INSERM, Institut Bergonié, CIC-EC 1401, F-33000, Bordeaux, France.
¹⁸ Université Paris Descartes, Service Maladies Infectieuses et Tropicales, AP-HP, Hôpital Cochin, Paris, France.
¹⁹ CHU de Bordeaux, Service de Médecine Interne et Maladies Infectieuses, F-33000, Bordeaux, France.
²⁰ The Kirby Institute, University of New South Wales, Sydney, Australia.
²¹ Department of Infectious Diseases, The Alfred and Monash University, Melbourne, Australia.
²² Division of Infectious Diseases and Chronic Viral Illness Service, McGill University Health Centre, Montreal, Canada.
²³ Department of Infectious Diseases, Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

PMID: 36618902
PMCID: PMC9816910
DOI: 10.1016/j.eclinm.2022.101810

Abstract

Background: Broad direct-acting antiviral (DAA) access may reduce hepatitis C virus (HCV) incidence through a "treatment as prevention" (TasP) effect. We assessed changes in primary HCV incidence following DAA access among people living with HIV (PLHIV).

Methods: We used pooled individual-level data from six cohorts from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC). Follow-up started from the first recorded negative HCV antibody test date and ended at last negative antibody test or estimated infection date. Follow-up was restricted to 2010-2019. We used segmented Poisson regression to model trends across pre-, limited- (i.e., restrictions on access) and broad-DAA access periods.

Findings: Overall, 45,942 participants had at least one HCV antibody negative result and follow-up between 2010 and 2019. We observed 2042 incident HCV infections over 248,189 person-years (PY). Pooled incidence decreased from 0.91 per 100 PY in 2015 to 0.41 per 100 PY in 2019. Compared to the average pre-DAA period incidence (0.90 per 100 PY), average incidence was similar during the limited-DAA access period (Incidence rate ratio [IRR] = 0.98; 95%CI = 0.87, 1.11), and 52% lower during the broad-DAA access period (IRR = 0.48; 95%CI = 0.42, 0.52). The average annual decline in HCV incidence was 2% in the pre-DAA period; an additional 9% annual decline in incidence was observed during the limited-DAA access period (IRR = 0.91; 95%CI = 0.82, 1.00) and a further 20% decline in the broad-DAA access period (IRR = 0.80, 95%CI = 0.73, 0.89).

Interpretation: Our findings suggest that broad DAA access has a TasP effect on primary HCV incidence among PLHIV. Based on the initial years of DAA availability, the countries in the InCHEHC collaboration are on track to meet the World Health Organization's 80% HCV incidence reduction target for PLHIV by 2030.

Funding: This study was funded by the Australian Government National Health and Medical Research Council (Grant number GNT1132902).

Keywords: Direct-acting antivirals; Elimination; HIV; Hepatitis C virus; Incidence; Trends.

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Conflict of interest statement

Juan Berenguer reports honoraria for advice or public speaking from 10.13039/100006483AbbVie, 10.13039/100005564Gilead, 10.13039/100012781MSD, JANSSEN, and 10.13039/100010877ViiV Healthcare; and grants from 10.13039/100006483AbbVie, 10.13039/100005564Gilead, 10.13039/100012781MSD, and 10.13039/100010877ViiV Healthcare. Dominique L Braun reports honoraria for advice or public speaking from, 10.13039/100005564Gilead, 10.13039/100012781MSD and 10.13039/100010877ViiV Healthcare. Marina Klein reports grants for investigator-initiated studies from 10.13039/100010877ViiV Healthcare, 10.13039/100006483AbbVie, 10.13039/100004334Merck, and 10.13039/100005564Gilead, and consulting fees from 10.13039/100010877ViiV Healthcare, 10.13039/100006483AbbVie, and 10.13039/100005564Gilead, all outside the submitted work. Marina Klein is supported by a Tier I Canada Research Chair. Jeffrey V Lazarus acknowledges grants and speaker fees from 10.13039/100006483AbbVie, 10.13039/100005564Gilead Sciences and 10.13039/100012781MSD and speaker fees from Genfit, Intercept, Janssen, 10.13039/100015758Novo Nordisk and 10.13039/100010877ViiV, outside of the submitted work. Andri Rauch reports support to his institution for advisory boards and/or travel grants from 10.13039/100006483Abbvie, 10.13039/100012781MSD, 10.13039/100005564Gilead Sciences, and 10.13039/100004319Pfizer, and an investigator initiated trial (IIT) grant from 10.13039/100005564Gilead Sciences. All remuneration to Andri Rauch went to his home institution and not to Andri Rauch personally, and all remuneration was provided outside the submitted work. Karine Lacombe reports honoraria for advice or public speaking from 10.13039/100006483Abbvie, 10.13039/100005564Gilead, 10.13039/100012781MSD, Janssen and 10.13039/100010877ViiV Healthcare. Fabrice Bonnet reports grants from 10.13039/100005564Gilead and honoraria from 10.13039/100005564Gilead, 10.13039/100005564ViiV healthcare and 10.13039/100012781MSD. Maria Prins reports unrestricted research grants and speaker/advisor fees from 10.13039/100005564Gilead Sciences and 10.13039/100012781MSD; all of which were paid to her institution and unrelated to the current work. Marc van der Valk reports unrestricted research grants from 10.13039/100005564Gilead and 10.13039/100012781MSD and fees for participation in advisory boards from 10.13039/100005564Gilead, 10.13039/100012781MSD and 10.13039/100010877ViiV (all paid to his institution). Joseph S Doyle reports funding to his institution for investigator-initiated research from 10.13039/100005564Gilead Sciences and 10.13039/100006483AbbVIe, and honoraria to his institution for educational events from 10.13039/100006483AbbVie. Linda Wittkop reports grants/financial support for the work under consideration from the French Agency 10.13039/501100003323ANRS Emerging Infectious Diseases (10.13039/501100003323ANRS—MIE) paid to her institution. Gail Matthews reports grants from 10.13039/100005564Gilead, 10.13039/100006483AbbVie and 10.13039/100010877ViiV, all paid to her institution and financial support for participating in advisory board from 10.13039/100005564Gilead and 10.13039/100010877ViiV. The CEASE study is supported by 10.13039/100005567Gilead. Inma Jarrin reports grants from 10.13039/100012781MSD and 10.13039/100010877ViiV healthcare, all paid to her institution, honoraria for lectures/presentations from 10.13039/100005564Gilead and 10.13039/100010877ViiV healthcare, support from 10.13039/100005564Gilead for attending meetings/travel, and support from 10.13039/100005564Gilead to participate in an advisory board. Margaret Hellard reports investigator-initiated research grants from 10.13039/100005564Gilead and 10.13039/100006483Abbvie. Dominique Salmon reports support for attending meetings/travel from 10.13039/100005564Gilead and 10.13039/100006483AbbVie. Mark Stoové reports funding from 10.13039/100005564Gilead and 10.13039/100006483AbbVie for investigator-initiated research unrelated to this work and consultant fees from 10.13039/100005564Gilead Sciences for activities unrelated to this work.

Figures

**Fig. 1**
**Participant selection for the primary incidence analysis from five InCHEHC countries.** InCHEHC: International Collaboration on Hepatitis C Elimination in HIV Cohorts; PLHIV: people living with HIV; HCV: hepatitis C virus; ACCESS: Australian Collaboration for Coordinated Enhanced Sentinel Surveillance; Ab: antibody; HCVsc: HCV seroconversions. We excluded ACCESS participants that only had data recorded prior to 2009 as data collection started from that year onwards (n = 244).

**Fig. 2**
**Overall HCV incidence per calendar year in the pooled dataset (2010–**2019). Black dots and bars represent the observed incidence and its 95% confidence interval. Grey line and band represent the predicted incidence and its 95%CI using Poisson regression modelling with calendar year using restricted cubic splines.

**Fig. 3**
**Piecewise exponential model, average primary incidence by DAA access period.** DAA: direct-acting antiviral; HCV: hepatitis C virus; PY, person-years; IRR: incidence rate ratio; CI: confidence interval; IR: Incidence rate. Random effect variance for the intercept was 0.11 (standard deviation = 0.34).

**Fig. 4**
**Changes in primary HCV incidence trends following access to DAAs by country.** HCV: hepatitis C virus; DAA: direct-acting antiviral. Predicted incidence based on the linear spline model.

See this image and copyright information in PMC

References

1. Polaris Observatory HCV Collaborators Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study. Lancet Gastroenterol Hepatol. 2022;7(5):396–415. - PubMed
1. World Health Organization Hepatitis C. 2022. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c
1. Sogni P., Gilbert C., Lacombe K., et al. All-oral direct-acting antiviral regimens in HIV/hepatitis C virus-coinfected patients with cirrhosis are efficient and safe: real-life results from the prospective ANRS CO13-HEPAVIH cohort. Clin Infect Dis. 2016;63(6):763–770. - PubMed
1. World Health Organization . 2021. Interim guidance for country validation of viral hepatitis elimination. - PubMed
1. Busschots D., Ho E., Blach S., et al. Ten years countdown to hepatitis C elimination in Belgium: a mathematical modeling approach. BMC Infect Dis. 2022;22(1):397. - PMC - PubMed

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Treatment as prevention effect of direct-acting antivirals on primary hepatitis C virus incidence: Findings from a multinational cohort between 2010 and 2019

Affiliations

Treatment as prevention effect of direct-acting antivirals on primary hepatitis C virus incidence: Findings from a multinational cohort between 2010 and 2019

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources

Miscellaneous