INTRODUCTION: Mortality associated with hepatitis C virus (HCV) infection is increasing, yet only a small percentage of HCV-infected individuals are aware of their infections, complete treatment, and achieve a cure, defined as a sustained virologic response. In March 2015, the Section of General Internal Medicine at Boston Medical Center (BMC), New England’s largest safety-net hospital, implemented the Adult Primary Care HCV Treatment and Triage Program to increase access to treatment. We are unaware of prior studies that have explored a pharmacist-centered primary care-based HCV treatment model in the era of newer direct-acting antiviral (DAA) medications. OBJECTIVES: To gain a deeper understanding of the roles of each program staff member, as well as an understanding of how primary care providers (PCPs) who refer patients to the program perceive and interact with the program. Such an understanding will help promote implementation and dissemination of the program. METHODS: We conducted in-depth semi-structured interviews with six staff members and with five PCPs in the Section of General Internal Medicine at BMC who refer patients to the program. We asked staff members about their roles and their perception of the program’s impact on patient linkage to HCV treatment. We probed PCPs about their experiences with HCV screening, referral, and follow-up processes, and differences in accessing HCV treatment for their patients prior to and following the implementation of the program. We audiotaped and transcribed interviews, and identified major themes through qualitative analysis. RESULTS: We identified five major themes that characterize how the HCV treatment program delivers care: 1) efficiency (“So here I feel like…they get evaluated…they get treated. Boom, it’s done”); 2) clear and open communication (“…one of the strengths of our program is that we have…a lot of direct contact with patients…”); 3) personalized medicine (“…I've set up the pill box for them [patients]…we tailor it to whatever they need”); 4) high patient engagement (“So if I get a referral for a patient…I call the patient three times. If I haven’t heard from the patient…I send them a letter and I tell the PCP”); 5) patient empowerment through education (“I think patient education is the best thing…if the patient is involved then… they’ll do what they need to do”). Additionally, the public health social worker and the pharmacist play key roles in the program. The social worker supports patients throughout treatment and addresses psychosocial barriers to treatment engagement (“I had a patient…who stopped taking his medication because his apartment was infested with bed bugs…[Social worker] got the patient furniture for free and got an exterminator…”). The pharmacist provides medication management during face-to-face patient visits (“…I go over everything imaginable...proper adherence…adverse effects, interactions…”). CONCLUSIONS: The HCV treatment program at BMC is a promising model to deliver HCV treatment to urban, underserved patient populations. Our findings suggest that public health social workers and pharmacists may be one approach to increasing access to HCV treatment in primary care settings in the era of DAA medications. Further study of the program’s efficacy in improving HCV outcomes is warranted.

Enveloped viruses acquire their membrane coat from the plasma membrane or intracellular organelles and rely on cellular machinery to facilitate envelopment and egress of virus progeny. This thesis examines egress-related interactions between host cell factors and proteins of two different enveloped viruses: hepatitis D virus (HDV) and herpes simplex virus 1 (HSV-1). HDV is a small RNA virus causing fulminant hepatitis or severely aggravating cirrhosis and hepatocellular carcinoma. HSV-1 is a large DNA virus infecting epithelial and neuronal cells. Infection with HSV-1 not only triggers the development of recurring sores on oral or genital mucosa, but can also cause severe disease in neonates and immunocompromised patients. The interaction between the large antigen of HDV (HDAg-L) and the N-terminal domain (NTD) of clathrin, a protein crucial for endocytosis and intracellular vesicular trafficking, was examined by structural, biochemical and biophysical techniques. Co-crystal structures of NTD bound to HDAg-L peptides derived from different HDV genotypes revealed that HDV interacts with multiple binding sites on NTD promiscuously, prompting re-evaluation of the binding between cellular peptides and NTD. Surprisingly, co-crystal structures and pull-down capture assays showed that cellular peptides containing clathrin-binding motifs can also bind multiple sites on the surface of NTD simultaneously. In addition, the structures of viral and cellular peptides bound to NTD enabled the molecular characterization of the fourth peptide binding site on NTD, the “Royle box”, and led to the identification of a novel binding mode at the “arrestin box” peptide binding site on NTD. The work in this thesis therefore not only identifies the molecular basis of HDV:clathrin interactions, but also furthers our understanding of basic clathrin biology. Even though many HSV-1 proteins have been implicated in the envelopment and egress of viral particles, only few interactions between HSV-1 and cellular proteins promoting these processes have been described. Therefore, the HSV-1 proteins gE, UL21 and UL56 were selected and characterized bioinformatically and/or biochemically. Cellular proteins interacting with UL56 were identified by yeast two-hybrid screening and quantitative mass spectrometry. Co-immunoprecipitation and pull-down experiments confirmed the Golgi-trafficking protein GOPC, components of the mammalian trafficking protein particle complex, and the ubiquitin ligase NEDD4 as novel binding partners of UL56, thereby suggesting exciting new avenues for the investigation of cellular mechanisms contributing to HSV-1 envelopment and egress.

Aprovados para o tratamento da hepatite C crônica (HCC) em 2011, os inibidores da protease (IPs) de primeira geração telaprevir (TVR) e boceprevir (BOC) representaram o início de uma nova era caracterizada pelo desenvolvimento de fármacos de ação direta contra o vírus da hepatite C (HCV). Os principais objetivos do presente trabalho foram descrever a efetividade e as incidências de eventos adversos ao uso de BOC ou TVR em esquema triplos com interferon peguilado (Peg-INF) e ribavirina (RBV), verificar a associação de fatores do hospedeiro e de fatores virais com a resposta virológica sustentada (RVS) e com a cirrose hepática (CH), além de realizar uma análise de custo-efetividade envolvendo a incorporação de TVR e BOC ao Sistema Único de Saúde (SUS). Foi realizado um estudo descritivo que incluiu pacientes cronicamente infectados pelo genótipo 1 do HCV cujo tratamento para HCC foi iniciado entre julho de 2013 e dezembro de 2015. Realizou-se ainda uma análise de custo-efetividade comparando as terapias triplas com a terapia dupla com RBV e Peg- INF alfa-2a. Foram incluídos 115 indivíduos, dos quais 58 (50,4%) tinham CH e 103 (89,6%) utilizaram TVR. A taxa de RVS global foi de 61,7% (62,1%, considerando TVR e 58,3%, considerando BOC). As análises bivariadas indicaram que ausência de CH, recidiva a tratamento prévio em relação a outros tipos de resposta, ausência de varizes de esôfago, presença dos alelos CC localizados no sítio rs12979860 do gene que codifica a interleucina-28 e razão entre o valor de aspartato aminotransferase (AST) pré-tratamento e o limite superior da normalidade menor que 3,0 são fatores associados com a RVS. A regressão logística evidenciou que o nível de AST e o tipo de resposta ao tratamento prévio seriam as variáveis mais fortemente associadas. Evidenciou-se ainda que valores maiores de transaminases estão associados ao diagnóstico de CH, sendo a alanina aminotransferase mais fortemente associada. Com relação às reações adversas a medicamentos, foi evidenciado que a inclusão de um dos IPs à terapia para HCC aumenta a incidência destas, com destaque para os eventos hematológicos que foram observados em quase 100,0% dos pacientes. Sobre a análise farmacoeconômica, os cálculos das razões de custo-efetividade, das razões de custoefetividade incremental e as análises de sensibilidade foram favoráveis à terapia dupla. As taxas de RVS foram superiores àquelas descritas nos estudos com terapia dupla e inferiores às taxas de efetividade encontradas nos principais estudos précomercialização com TVR ou BOC. Fatores relacionados à condição clínica do paciente infectado e ao seu sistema imune estão associados com a RVS aos IPs de primeira geração. As terapias triplas mostraram um perfil de segurança desfavorável em relação ao esquema com RBV e Peg-INF. O estudo sugeriu ainda que a incorporação de TVR ou BOC ao SUS não foi uma conduta custo-efetiva. / Approved for the treatment of chronic hepatitis C (CHC) in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC) were the beginning of a new era characterized by the development of direct action drugs against the hepatitis C virus (HCV). The main aims of the present study were to describe effectiveness and the incidence of adverse events to the use of BOC or TVR with pegylated interferon (Peg-INF) and ribavirin (RBV) in triple therapy, to verify the association of host factors and viral factors with sustained virological response (SVR) and with cirrhosis and to perform a cost-effectiveness analysis involving the incorporation of TVR and BOC to Brazilian Public Health System (BPHS). A descriptive study was carried out which included patients chronically infected with HCV genotype 1 whose treatment for CHC was started between July 2013 and December 2015. A cost-effectiveness analysis comparing triple therapies to a therapy with RBV and Peg-INF alpha-2a was also performed. A total of 115 subjects were included, of which 58 (50,4 %) had cirrhosis and 103 (89,6 %) used TVR. The overall SVR rate was 61,7 % (62,1 %, considering TVR and 58,3 %, considering BOC). Bivariate analyzes indicated that absence of cirrhosis, relapse of previous treatment in relation to other types of response, absence of esophageal varices, presence of the CC alleles located at the site rs12979860 of the gene coding the interleukin-28 and ratio between the pre-treatment aspartate aminotransferase (AST) value and the upper limit of normality less than 3.0 are factors associated to SVR. The logistic regression showed that the level of AST and type of response to previous treatment would be as variables more strongly associated. It was also evidenced that higher values of transaminases are associated to the diagnosis of cirrhosis, being the alanine aminotransferase more strongly associated. In relation to the adverse drug reactions, it was evidenced that the inclusion of one of the PIs to the therapy for CHC increases the incidence of these, highlighting the hematological disorders that were observed in almost 100,0% of the patients. About the pharmacoeconomic analysis performed, the calculations of the cost-effectiveness ratios, incremental cost-effectiveness ratios and the sensitivity analyzes were favorable to the dual therapy. The SVR rates were higher than those described in most studies with dual therapy and lower than the rates of effectiveness found in the main premarketing studies with TVR or BOC. Factors related to the infected patients clinical condition and to their immune system are associated with SVR to the firstgeneration PIs. The triple therapies showed an unfavorable safety profile in relation to dual regimen with RBV and Peg-INF. The study also suggested that incorporation of TVR or BOC to BPHS was not a cost-effective conduct.

mormaeche@dge.gob.pe / Objective: To assess the seroprevalence of hepatitis B virus (HBV), syphilis, and HIV and associated risk factors in pregnant women and their male partners from six indigenous populations of the Peruvian Amazon Basin. Methods: A cross-sectional study was performed in six indigenous populations from the Peruvian Amazon Basin. Blood samples were obtained and tested for HBV (antibodies to the hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg)), for syphilis (rapid plasma reagin and microhemagglutination assay for Treponema pallidum antibodies), and for HIV (ELISA and indirect immunofluorescence test). A survey was also performed to identify associated risk factors. Results: One thousand two hundred and fifty-one pregnant women and 778 male partners were enrolled in the study. The seroprevalence of anti-HBc in pregnant women was 42.06% (95% confidence interval (CI) 39.28–44.85%) and in their male partners was 54.09% (95% CI 50.32–57.86%). The seroprevalence of HBsAg in pregnant women was 2.11% (95% CI 0.78–3.44%) and in their male partners was 3.98% (95% CI 1.87–6.08%). The seroprevalence of syphilis in pregnant women was 1.60% (95% CI 0.86–2.33%) and in their male partners was 2.44% (95% CI 1.22–3.66%). HIV seroprevalence in pregnant women was 0.16% (95% CI 0.02–0.58%) and in their male partners was 0.29% (95% CI 0.04–1.03%). Sexual risk factors were strongly related to blood markers of syphilis and HBV. Conclusions: Hepatitis B was found to be hyperendemic and strongly related to sexual factors, suggesting an important sexual component in the transmission of the disease in the populations studied. Syphilis was found to have an endemicity in pregnant women above the national level and this may be indicative of high mother-to-child transmission. HIV has started to show its presence in indigenous populations of the Amazon Basin and the results suggest the epidemic is concentrated. / Revisión por pares

Determina la relación entre el nivel de conocimientos sobre hepatitis B y el estado de vacunación de los estudiantes de medicina que formarán parte del programa internado médico 2019 del Hospital Nacional Dos de Mayo (HNDM). Realiza un estudio transversal, analítico, observacional y correlacional. La población está constituida por los 120 estudiantes de medicina que formarán parte del programa internado médico del 2019 del HNDM. Del total de estudiantes de medicina el 61% presentan un mal conocimiento sobre el virus de la hepatitis B (VHB); el 53% presentan estado de vacunación incompleto. Asimismo, se aprecia que del total de estudiantes que recibieron vacunación el 86,2% tienen edad de 22 a 27 años; el 66% son de sexo femenino; el 79.8% provienen de universidad privada; el 71.3% recibió tres dosis de la vacuna contra el VHB y el 88.3% no presentaron eventos supuestamente atribuidos a la vacunación e inmunización (ESAVI). De los estudiantes que tienen un mal conocimiento sobre el VHB el 54,1% tiene un esquema de vacunación incompleta, mientras que el 76% de los estudiantes con conocimiento regular poseen un esquema incompleto. Finalmente, del total de estudiantes con un buen conocimiento sobre el VHB el 92,9% presenta un esquema de vacunación completa. Concluye que el nivel de conocimientos sobre el VHB está relacionado con el estado de vacunación del estudiante de medicina ingresante al programa de internado médico 2019 del HNDM. / Tesis

Introdução: O número de idosos representa uma parcela crescente da população devido ao aumento da expectativa de vida. Na epidemiologia, há diferenças importantes, em relação aos casos de hepatites virais que acometem os idosos quando comparados à população mais jovem. A Hepatite B é um problema de saúde pública mundial e uma das principais causas de doença hepática avançada, como cirrose hepática e hepatocarcinoma. O risco de hepatocarcinoma entre pessoas infectadas pelo Vírus da Hepatite B é maior em homens com mais de 60 anos, expostos cronicamente ao vírus. Alguns estudos apontam que a probabilidade de cronificação e complicações são maiores nos idosos, sendo uma preocupação para a saúde pública. Nota-se, todavia, escassez de estudos sobre Hepatite B para este grupo etário, sendo o intuito deste trabalho acrescentar informações nesta direção. Objetivo: Verificar a prevalência e fatores associados à infecção pelo vírus da Hepatite B entre idosos. Métodos: Estudo transversal de base populacional, realizado por meio de entrevista domiciliar e exames laboratoriais. Trata-se de amostra representativa de idosos (60 anos ou mais) residentes no Município de São Paulo, Brasil, participantes do Estudo Saúde, Bem-Estar e Envelhecimento, no ano de 2010. Resultados: No município de São Paulo, 14,7% (IC95%: 12,5-17,3%) dos idosos apresentaram diagnóstico positivo para infecção por Hepatite B. Na análise univariada, observou-se maior prevalência para Hepatite B no sexo masculino (19,8%), faixa etária entre 80 anos e mais (19,4%), sem companheiro (16,5%), residindo só (20,8%), com atividade sexual no último ano (19,8%). Na análise múltipla, observou-se que homens (OR= 1,60; IC95%: 1,01-2,52), indivíduos que indicaram morarem só (OR= 1,95; IC95%: 1,07-3,57) e pessoas idosas com relato de atividade sexual no último ano (OR= 1,76; IC95%: 1,05-2,94) apresentaram maior probabilidade de ter infecção pelo vírus da Hepatite B, em modelo controlado por idade e estado civil. Conclusão: A constatação desses fatores pode servir de base para a organização de ações educativas e a implementação de estratégias de prevenção da Hepatite B direcionadas para essa população. / Introduction: The elderly represent a growing portion of the population due to the increase in life expectancy. Epidemiologically, there are important differences between the cases of viral hepatitis in the elderly and those of the younger population. Hepatitis B is a public health concern in the whole world, and one of the major causes of severe liver disease, such as cirrhosis of the liver and hepatocellular carcinoma. The risk of hepatocellular carcinoma in the population infected by Hepatitis B virus is higher among men with more than 60 years of age, with chronic exposure to the virus. Some studies indicate that chronification and complications are more likely to occur in the elderly, making this a health care concern. However, there is a shortage of studies on Hepatitis B for this age group, and the purpose of this study is to add information in this direction. Objective: To verify the prevalence and associated factors of the Hepatitis B virus infection among the elderly. Methods: A cross-sectional population-based study, accomplished through home interviews and laboratorial blood tests. This is a representative sample of older adults residing in the city of São Paulo, Brazil, participants of the \"Health, Well-Being and Aging\" Survey, in the year of 2010. Results: In São Paulo, 14,7% (CI95%: 12,5-17,3%) of older adults showed positive diagnostic for Hepatitis B virus infection. In the univariate analysis, the highest prevalence of Hepatitis B was shown in the male population (19.8%), aged 80 or more years (19.4%), with no partner (16.5%), living alone (20.8%), reporting sexual intercourse in the last year (19.8%). In the multiple analysis, it was observed that men (OR = 1.60, 95% CI: 1.01-2.52), individuals living alone (OR = 1.95, 95% CI: 1.07-3.57) and elderly people that reported sexual activity in the last year (OR = 1.76, 95% CI: 1.05-2.94) were more likely to have Hepatitis B virus infection in a model controlled by age and marital status. Conclusion: The realization of these associations can ground the organization of educational practices and the implementation of strategies to prevent Hepatitis B virus -infection in this age group.

Estima-se que aproximadamente 400 milhões de indivíduos sejam portadores crônicos do vírus da hepatite B no mundo. Quando incide em adultos, a doença apresenta elevada proporção de evolução para a cura, ao passo que na ocorrência de transmissão vertical, o risco de cronificação chega a 90%, aumentando muito a possibilidade de graves conseqüências para a criança, entre as quais cirrose e hepatocarcinoma primário. A possibilidade de triagem para a identificação das gestantes portadoras do vírus da hepatite B e a conseqüente adoção de medidas profiláticas – imunização ativa e passiva – permite a prevenção segura da transmissão vertical. Em 1999, o Programa do Pré-Natal da Secretaria Municipal da Saúde de Ribeirão Preto introduziu em sua rotina o screening para o HBsAg, com a finalidade de identificar as gestantes portadoras do vírus. Este trabalho objetiva estudar alguns aspectos referentes à hepatite B entre as gestantes atendidas pela Rede Municipal de Saúde, bem como realizar uma avaliação sistematizada do Programa do Pré-Natal. Para este trabalho foram criados dois grupos de gestantes. O primeiro formado pelas pacientes com primeira avaliação sorológica do Pré-Natal para aquela gestação, realizada no período de 01 de novembro de 2001 a 31 de outubro de 2002, com a finalidade de estimar a prevalência do HBsAg e também verificar a proporção de recém-nascidos, filhos de mães portadoras deste marcador, que receberam os cuidados preconizados para tal situação. Já o segundo grupo foi formado pelas pacientes, na mesma condição, avaliadas no período de 01 de julho de 2002 a 30 de junho de 2003, com a finalidade de também estimar a prevalência do HBsAg, bem como a proporção de portadoras do HbeAg e anti-Hbe. Os valores de prevalência do HBsAg encontrados foram os seguintes: para o primeiro grupo 0,5 (IC 95% : 0,3 – 0,7) e, 0,4 (IC 95%: 0,2 – 0,6) para o segundo. Verificou-se que em 25,0% dos 24 partos realizados no município não foram realizados os procedimentos de profilaxia preconizados como ideais, no que diz respeito à rapidez da solicitação de vacina e imunoglobulina. Isso foi devido, parcialmente, a deficiências na qualidade de registro das informações em diferentes instâncias. As proporções de portadoras do HBeAg e anti-HBe foram respectivamente 5,9% (IC 95%: 0 – 17,1) e 90,5% (IC 95%: 77,9 – 100). Este trabalho procura apresentar informações que sirvam de base para reflexões a respeito do fluxo de procedimentos do Programa do Pré-Natal, visando elevar sua efetividade e superar os obstáculos encontrados. / It is estimated that about 400 million persons are chronic carriers of the hepatitis B virus worldwide. When it occurs in adults, the disease shows high proportions of benign evolution, meanwhile in vertical transmission the risk of becoming a chronic carrier approaches 90%, elevating the possibilities of serious consequences to the child, including cirrhosis and primary hepatocellular carcinoma. The possibility of performing screening tests for the identification of pregnant women carriers of the hepatitis B virus and the consequent adoption of prophylactic measures – active and passive immunization – allow safe prevention of the vertical transmission. In 1999, the Pre-Natal Program of the Municipal Secretary of Health of Ribeirão Preto, SP, Brasil, included in its routine services the screening for the HBsAg, towards the identification of pregnant carriers of the virus. This study aims to look into some aspects referring to hepatitis B among the pregnants being attended by the Municipal Health Network, as well as perform a careful systematic evaluation of the Pre-Natal Program. In order to perform this study, two groups of pregnants were selected. The first one formed by those patients having had their first pre-natal serological evaluation done for that pregnancy during the period of November 1, 2001 until October 31, 2002, with the purpose of estimating the HBsAg prevalence and also to verify the proportion of the new-borns of HBsAg carriers that received the recommended care for that situation. The second group was formed by those patients on the same condition, evaluated during the period of July 1, 2002 until June 30, 2003, with the purpose of also estimating the HBsAg prevalence, as well as estimating the proportion of HBeAg and anti-HBe carriers. The HBsAg prevalences were the following: for the first group of pregnants 0,5 (CI 95% : 0,3 – 0,7) and 0,4 (CI 95%: 0,2 – 0,6) for the second one. It was verified that in 25,0% of the 24 births that happened in the city, the recommended care were not taken, when it comes to the prompt request of the specific vaccine and immunoglobulin. This fact was, partially, due to deficiency in the data files quality of the different institutions. The proportions of HBeAg and anti-HBe carriers found were, respectively, 5,9% (CI 95%: 0 – 17,1) and 90,5% (CI 95%: 77,9 – 100). This study intends to present data that can be the starting point towards reflections on the established procedures of the Pre-Natal Program, in order to increase its effectiveness and surpass the found obstacles.

Malaria is a major health problem and an effective vaccine is essential for the eradication of the disease. Despite extensive efforts, a malaria vaccine remains elusive due to the parasite's complex life cycle, diverse morphology, and immune system evasion mechanisms. Antibodies against C terminal domain of merozoite surface protein 1 (MSP1-19), a highly conserved protein and the main vaccine candidate for blood-stage malaria, can inhibit erythrocyte invasion by the parasite and alleviate the disease symptoms. However, MSP1-19 is poorly immunogenic and classic protein-in-adjuvant MSP1-19-based vaccine formulations failed to induce strong immune responses due to low immunogenicity and generation of ineffective antibodies. The aim of this study was to use hepatitis B virus core (HBc) particles to increase the immunogenicity of MSP1-19. HBc forms particles with protruding spikes and induces a strong and specific immune response against foreign epitopes inserted at the tips of the spikes. In addition, positioning of MSP1-19 on the particle can influence the accessibility of certain antibody binding sites, possibly altering elicited antibody fine specificity and vaccine efficiency. MSP1-19 domain was inserted into the middle of the HBc sequence so that it is displayed at the tips of the HBc particle. Two HBc-MSP1-19 constructs, having different insert flanking linkers, displayed soluble particle formation after bacterial expression and lysis optimization. The particles were purified and the suitability of these two constructs as malaria vaccine candidates was assessed. Firstly, binding of the conformational anti-MSP1-19 antibodies indicated that MSP1-19 domain in the chimeric proteins has the correct disulphide bond pattern which is crucial for the protective properties of an MSP1-19-based vaccine. Furthermore, electron microscopy imaging and determination of initial 3D structures confirmed that both HBc MSP1-19 constructs form particles resembling the wild-type HBc particles, meaning the insertion of MSP1-19 did not heavily distort the overall HBc particle structure. In addition, it was shown that MSP1-19 domains are displayed at the tips of the particle spikes. Particle formation and foreign epitope display are important for the epitope's immunogenicity improvement. The immunogenicity of the chimeric particles was then assessed in mice. Both constructs elicited similar high antibody titres without the use of additional adjuvants, but no difference was observed between the particulate constructs and a non-particulate control (an MSP1-19-based protein). Interestingly, although both HBc-MSP1-19 and non-particulate MSP1-19-elicited antibodies recognized native malarial parasite, only the particulate construct antibodies demonstrated a moderate parasite growth inhibition while the antibodies from the control group did not show parasite inhibition above the background levels. In conclusion, it was shown that MSP1-19 can be expressed in bacteria as a soluble correctly folded protein fused to HBc. More importantly, the fusion protein is capable of forming immunogenic particles which generate antibodies that recognize native MSP1 and inhibit parasite growth more effectively than the protein without the HBc. Therefore, this work lays grounds and supports further chimeric HBc-MSP1-19 research and development.

Cheng Sze-Lok Alfred. / "March 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 175-211). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Hepatitis C (HCV) infection is associated with high rates of mortality and morbidity. Interferon alpha based treatment for HCV offers a good rate of viral clearance, however the associated neuropsychiatric side effects increase the risk of treatment interruption and disease progression. The HIV/HCV coinfection is of particular interest due to association with higher rates of HCV treatment side effects and earlier treatment discontinuation when compared with HCV mono-infection. Therefore, the aim of the thesis was to further explore the effect of coinfection on mood and cognition and how HCV interferon based treatment influences neuropsychiatric side effects in mono and co-infected samples. Firstly a meta-analysis was performed to explore cognitive impairment and depression in HIV HCV co-infection. The results suggested that there was consistent literature indicating that the coinfected group were more cognitively impaired and more likely to be depressed than the HCV and HIV monoinfected groups. Secondly empirical studies were conducted to analyse the profile of depression during interferon-based treatment, and explore potential risk factors, such as gender and immune profile. Co-infected patients appeared less vulnerable to the emergence of depressive symptoms during HCV treatment than HCV mono-infected patients. Additionally, neither female gender nor immune response were associated with increased vulnerability to depression. Finally, a longitudinal study investigating cognitive performance during interferon-based treatment was conducted. A significant effect of treatment on information processing speed level of executive function was observed. Overall the research reported in this thesis further clarifies the nature of interferon induced depression and cognitive effects differences between mono and coinfected groups. Having identified a neurovegetative symptom profile and speed of processing impairment of executive function during HCV treatment, the discussion considers the potential of targeted interventions via psychotropic medication and cognitive interventions to minimise the impact of these treatment effects and optimise outcomes in this clinical group.