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University of Southampton Research Repository University of Southampton Research Repository Copyright © and Moral Rights for this thesis and, where applicable, any accompanying data are retained by the author and/or other copyright owners. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This thesis and the accompanying data cannot be reproduced or quoted extensively from without first obtaining permission in writing from the copyright holder/s. The content of the thesis and accompanying research data (where applicable) must not be changed in any way or sold commercially in any format or medium without the formal permission of the copyright holder/s. When referring to this thesis and any accompanying data, full bibliographic details must be given, e.g. Thesis: Author (Year of Submission) "Full thesis title", University of Southampton, name of the University Faculty or School or Department, PhD Thesis, pagination. UNIVERSITY OF SOUTHAMPTON FACULTY OF MEDICINE University of Southampton The social and genetic epidemiology of Hepatitis C in an isolated network of people who inject drugs By Dr Ryan Malcolm Buchanan Thesis for the degree of Doctor of Philosophy December 2017 Dedication: For Hannah & Benjamin i UNIVERSITY OF SOUTHAMPTON ABSTRACT FACULTY OF MEDICINE Thesis for the degree of Doctor of Philosophy THE SOCIAL AND GENETIC EPIDEMIOLOGY OF HEPATITIS C IN AN ISOLATED NETWORK OF PEOPLE WHO INJECT DRUGS Ryan Malcolm Buchanan Background and Aims Hepatitis C (HCV) causes liver cirrhosis, liver cancer and is a leading cause of death worldwide. In the UK the commonest risk factor for HCV is current or previous injecting drug use but many cases are undiagnosed and many known cases are disengaged from treatment services. The Isle of Wight (IOW) is a deprived, rural and geographically isolated population but suffers from the same obstacles to HCV care as larger nearby mainland populations. The overall aim of this thesis is to understand the burden of HCV in people who inject drugs (PWID) on the IOW and how their social network could be utilised in an HCV elimination strategy. Method A sequential mixed method research design was used. Qualitative methods informed the design of a quantitative survey, which recruited PWID via respondent driven sampling (RDS) for a social network questionnaire and HCV bio-behavioural survey. This was used to estimate the population prevalence of HCV and the total population size of PWID on the IOW. Data from the social network survey were combined with a phylogenetic analysis of HCV RNA positive cases and qualitative narratives to give a representation of the HCV transmission network in PWID. This network was then used in an individual- based model (IBM) testing different treatment strategies. i Results Sixty-nine PWID participated in the HCV bio-behavioural and social network surveys. The estimated prevalence of HCV was 29% (95% CI 13.3-44%) and the estimated total population size was 262 individuals. The social network survey described 179 PWID, connected together into a cohesive network component via injecting partnerships. Phylogenetic analysis indicated that a number of these partnerships had led to the transmission of HCV and that genotype 3a virus had been transmitted between PWID living on the IOW. In the IBM the preferential treatment of well-connected PWID, via injecting and social relationships, led to significantly fewer new infections of HCV than treating at random (9.56 vs. 6.58 P<0.01 and 9.56 vs. 7.84 p=0.011 respectively). Conclusion The burden of HCV in PWID on the IOW is lower than expected and existing case-finding initiatives are effective. The qualitative and quantitative results indicate that PWID are linked together in a dense network and the treatment of well-connected nodes within this network may be an effective treatment as prevention strategy for the elimination of HCV on the IOW. ii Table of Contents ABSTRACT ................................................................................................................... i List of tables ............................................................................................................. ix List of figures ............................................................................................................ xi List of accompanying materials ................................................................................ xv Published articles ............................................................................................................. xv Conference abstracts ....................................................................................................... xvi Acknowledgements ............................................................................................... xvii DECLARATION OF AUTHORSHIP .............................................................................. xix Abbreviations ......................................................................................................... xxi Overview of this thesis ............................................................................................. 23 1. Introduction ...................................................................................................... 25 1.1 Hepatitis C .............................................................................................................. 25 1.2 Genetic epidemiology of Hepatitis C ....................................................................... 27 1.3 Sampling in hidden populations .............................................................................. 30 1.4 Social networks and people who inject drugs .......................................................... 32 1.5 Mathematical modelling of Hepatitis C transmission and treatment in people who inject drugs ...................................................................................................................... 36 1.6 Hepatitis C treatment, people who inject drugs and the elimination agenda ........... 38 1.7 Hepatitis C on the Isle of Wight ............................................................................... 40 1.8 Rationale ................................................................................................................ 43 1.9 Research questions ................................................................................................. 44 1.10 Research objectives .............................................................................................. 44 1.11 Conclusion ............................................................................................................ 45 2. Hepatitis C bio-behavioural surveys in people who inject drugs – a systematic review of sensitivity to the theoretical assumptions of respondent driven sampling 47 2.1 Chapter overview ................................................................................................... 47 2.2 Introduction ........................................................................................................... 47 2.3 Method .................................................................................................................. 49 iii 2.3.1 Information sources and literature search ............................................................. 49 2.3.2 Inclusion criteria and study selection ..................................................................... 50 2.3.3 Data extraction ....................................................................................................... 51 2.4 Results ................................................................................................................... 52 2.4.1 Search results ......................................................................................................... 52 2.4.2 Overview of included surveys ................................................................................. 54 2.4.3 Sensitivity to RDS assumptions ............................................................................... 57 2.5 Discussion .............................................................................................................. 64 2.6 Conclusion ............................................................................................................. 66 3. Research design and qualitative methods used in this thesis ............................ 67 3.1 Research design & methodology ............................................................................ 67 3.2 Ethical considerations ............................................................................................ 70 3.3 Qualitative methods .............................................................................................. 71 3.3.1 Focus group with drug support centre staff ........................................................... 71 3.3.2 Semi-structured interviews in those with a history of injecting drug use .............. 73 3.3.3 Qualitative data analysis ......................................................................................... 74 3.3.4 Maintaining rigour in qualitative research ............................................................. 75 4. The social network of people who inject drugs on the Isle of Wight and the feasibility of undertaking respondent driven sampling ............................................ 77 4.1 Chapter overview ................................................................................................... 77 4.2 Introduction ..........................................................................................................
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