It is now well established that gluten sensitivity comprises a spectrum of disorders, which affect different target organs. The small-intestine (coeliac disease), skin (dermatitis herpetiformis) and peripheral and central nervous systems are most frequently affected. These manifestations may occur alone or in combination with one another. Neurological complications affect approximately 6-10% of patients with gluten sensitivity with ataxia being the most frequent disorder seen in these patients. It has recently been established that previously undiagnosed gluten sensitivity may present solely with ataxia (gluten ataxia) and this disease entity may account for a large number of patients with sporadic idiopathic ataxia. Preliminary findings suggest an immune pathogenesis for gluten ataxia, in common with other manifestations of gluten sensitivity. The studies in this thesis are concerned with investigation of the humoral immune response in the pathogenesis of gluten ataxia. Assessment using enzyme-linked immunosorbent assay, immunohistochemistry and western blotting has shown the presence of elevated levels of circulating gluten sensitivity associated antibodies (anti-gliadin and anti-tissue transglutaminase antibodies) in patients with gluten ataxia. Studies have also shown the cross-reaction of anti-gliadin antibodies with epitopes on cerebellar Purkinje cells. In addition, patients with gluten ataxia possess circulating antibodies directed against cerebellar Purkinje cells, which are distinct from anti-gliadin antibodies although the target antigen remains unknown. Finally, studies have also shown that patients with gluten ataxia have elevated levels of circulating antibodies directed against glutamic acid decarboxylase. These studies suggest a role for the humoral immune response in gluten ataxia. However, preliminary evidence is also suggestive of a T-cell mediated response and the relative contributions of each in the pathogenesis of gluten ataxia remains to be elucidated.

In the UK, new HIV diagnoses are increasing in adults aged 50 years and over, a group that also has a higher likelihood of testing at an advanced stage of disease than younger people. Despite this, limited research has examined the pathway to HIV diagnosis and treatment experienced by this age group, or looked more broadly at the impact of living with HIV after diagnosis at this age. Using a mixed-methods approach, this thesis explores the acceptability and accessibility of HIV services in England to adults diagnosed at age 50+ years, from the perspective of these service users and healthcare professionals (HCPs) working in sexual health/HIV services and involved in caring for this age group. This thesis draws on semi-structured interviews with service users; an online survey and semi-structured interviews with HCPs; as well as national data on sexual health/GUM clinic attendance, HIV test coverage, and new HIV diagnoses by age. Adults aged 50+ years are found to experience often complex and non-linear journeys to HIV testing, particularly if they do not belong to a ‘risk group’ targeted in HIV prevention and testing efforts. Barriers to prompt HIV diagnosis include (i) the non-specific nature of HIV symptoms and their misattribution as being age-related, (ii) an age-associated decline in risk perception, and (iii) the decreased likelihood of HIV test offer in advancing age. Both service users and HCPs perceive HIV treatment services to provide exceptional care, which is associated with the benefits of closer health monitoring, clinician expertise in HIV, and consistency in care. General practitioners (GPs) by contrast appear to be underutilised in the management of older people with HIV, which may be particularly detrimental as these service users often develop additional, age-related morbidities, which extend beyond the remit of HIV clinician knowledge. The thesis concludes by highlighting a need to reconsider the model of HIV care in England, especially with respect to the role of GPs in HIV service provision. It is likely that increased GP involvement would optimise care and encourage the normalisation of HIV, which would promote testing and reduce stigma.

Background: The UNGASS target to reduce HIV prevalence by 25% among 15-25 year olds living in the most affected countries by 2005 has not been met. In the absence of a vaccine or cure, behavioural interventions are the main strategy for HIV control. The ability of specific behaviour change interventions to reduce HIV/STI incidence and unplanned pregnancies in young people remains unproven. Methods: Since January 1999, an adolescent sexual and reproductive health (SRH) intervention has been implemented in 10 randomly selected intervention communities in rural Tanzania, within a community randomised trial. The intervention consisted of teacher-led, peer-assisted in school education, youth-friendly health services, community activities and youth condom promotion and distribution. Process evaluation in 1999-2002 showed high intervention quality and coverage. From June 2007 to July 2008, in the specific research reported in this thesis, the long-term impact of the intervention was evaluated among 13,814 young people aged 17-27 years who had attended trial schools between 1999 and 2002. Findings: Prevalences of HIV and HSV2 were 1.8% and 25.9% in males and 4.0% and 41.4% in females, respectively. The intervention did not significantly reduce risk of HIV (males adjusted prevalence ratio(aPR)=0.91; 95%CI:0.50-1.65; females aPR=1.07; 95%CI:0.68-1.67) or HSV2 (males aPR=0.94;95%CI:0.77-1.15; females aPR=0.96; 95%CI:0.87-1.06). The intervention was associated with a reduction in number of lifetime sexual partners reported by males (aPR=0.87; 95%CI:0.78-0.97) and an increase in reported condom use at last sex with a non-regular partner among females (aPR=1.34; 95%CI:1.07-1.69). There was a clear and consistent beneficial impact on knowledge, but no significant impact on reported attitudes to sexual risk, reported pregnancies or other reported sexual behaviours. Interpretation: SRH knowledge can be improved and retained long-term, but this intervention had little effect on reported behaviour or HIV/STI prevalence. Youth interventions integrated within intensive, community-wide risk reduction programmes may be more successful and should be evaluated.

The worldwide Human Immuno-deficiency Virus (HIV) pandemic has now lasted more than three decades. Highly Active Antiretroviral Therapy (HAART) has revolutionised its impact (Anderson et al., 2000). HIV infection now produces a chronic, manageable illness. Nonetheless, a majority of people living with HIV (PLWHIV) suffer the psychological impact both of being infected and of accepting the diagnosis. In the United Kingdom (UK), HIV is highly prevalent in African women. Although Africans are the second largest group of PLWHIV after gay men in the UK (Prost Elford, Imrie, Petticrew & Hart, 2008), they are reported as reluctant in accessing available psychotherapy/counselling services (Malanda, Meadows & Catalan, 2001). Apart from the perception that such services are threatening, little is known about this reluctance. This is worrying, as Africans continue to be the most underrepresented HIV service users. One’s cultural background and language has an impact on service use. There is a profound existential impact of migration; and migration has an impact on illness and self-concept. Whilst there is a plethora of literature advocating culturally sensitive counselling services, there is a paucity of research relating to HIV-counselling. A notable exception is the Terrence Higgins Trust (THT). A 2001 service-user feedback survey conducted by this trust revealed some reasons why Africans LWHIV might not engage with available counselling provisions. These findings prompted the British Association of Counsellors and Psychotherapists (BACP) to establish the award-winning African Emotional Support culturally appropriate counselling model (AESC). Nevertheless, very little is known about how this initiative works, how it compares to the classical or conventional Western Counselling (CWC) model and how it relates to any gaps in cross-cultural counselling practice. The objectives of this study are to obtain an in-depth understanding through exploration of the lived experiences of 15 HIV sero-positive African childbearing migrant women living in London-UK; and to investigate and evaluate differences in efficacy between the AESC and the CWC models in terms of how the former works, and its strengths and limitations in practice. The research design had two arms: participants with CWC and later AESC (Arm 1); and those with AESC only (Arm 2). The 15 participants were purposively sampled and underwent in-depth qualitative semi-structured tape-recorded interviews. Subscribing to the constuctionist/ interpretivism paradigm, Interpretative Phenomenological Analysis (IPA) as a phenomenological, interpretative and analytic research methodology was considered appropriate for the study population and research question. After verbatim transcription, in-depth thematic mapping was used to examine the interviews and intellectual analysis using IPA. The findings were considered in the context of the existing literature, which was predominantly British. Participants emphasised the significant positive impact of situation-specific counselling by a counsellor from a similar cultural background compared to counselling by a therapist of a different cultural background. They explored their experiences and barriers to effective helping, comparing the CWC and AESC models. Tensions, links and paradoxes of the African philosophical sense of interdependent self-emerged in contrast to anxiety and isolation in the context of the stigma and discrimination associated with HIV diagnosis. Long-term was far preferable to time-limited counselling. Participants emphasised their sense of African heritage and identity, which instils distinct values. These are important aspects of counselling. Further emphasised was raising awareness in training about the impact of cross-cultural counselling, the impact of the patient's first language in counselling, and the power dynamics inherent in counselling. Othering, self-othering and social identity theories are proposed as possible tools for psychotherapeutic practice interventions. The findings might inform policy, existing NICE guidelines and BHIVA-BPS (2012) standards, and the development of existential psychotherapy/counselling psychology practice and training. Further research output includes research-informed teaching and local HIV services development.

Introduction: HIV/AIDS is a pandemic disease and its scourge has had a devastating impact on health, nutrition, food security and overall socioeconomic development in countries that have been greatly affected by the disease. The engagement of HIV/AIDS with under nutrition form a symbiotic relationship and one increases the prevalence and severity of the other. Aim: The main goal of the study was to evaluate the effectiveness of public health-nutrition intervention programme designed to attenuate the progression of HIV to AIDS among people living with HIV in Abuja, Nigeria. Methods: Local foods, which were known for their availability, accessibility, micro and macronutrient strengths were selected and optimised into a nutritional functional meal (Amtewa). 1000 PLWHIV were invited to participate in the research from all the HIV treatment centres in Abuja, Nigeria. Based on the sample size calculation, inclusion and exclusion criteria, 400 participants (adult, male and female from different religious background) were selected through simple randomisation. Out of these 400 participants, 100 were randomly selected for the pilot study. The participants in the pilot study overlapped to form part of the scale-up participants. The effect of daily consumption of Amtewa meal (354.92 kcal/d) for six and twelve months was ascertained through the nutritional status and biochemical indices of the study participants (n=100 pilot and n=400 scale-up interventions) who were/were not taking anti-retroviral drug therapy (ART). Results: Mean CD4 cell count (cell/mm3) for ART-Test group at baseline and sixth months increased by 12.12%. Mean mid upper arm circumference (MUAC) (cm) also increased by 2.52% within the same period (n=400). On the contrary, there were decreases in control groups of 14.9% CD4 count and 2.28% MUAC. Student‘s t-test analysis suggests a strong association between the intervention meal and mean CD4 count (It increased by 54.40 cells/mm3 in the ART Test group (p=0.05)) on prolong use of Amtewa (up to 12 months). Conclusion: These results ascertained the effectiveness of Amtewa meal on health status of HIV infected subjects and also underpinned its significant position within the National Health Services framework as innovative nutritional approach to delay the progression of HIV to AIDS in Nigeria.

Thailand introduced universal access to Anti-retroviral treatment (ART) service in 2003. This became the main factor increasing demands for services with increasing numbers of People living with the Human Immunodeficiency Virus (HIV) and the Acquired Immune Deficiency Syndrome (AIDS), (PLHIV) and those people living longer. Since 2011, two other factors altered the ART service provision: changes in enrolment criteria to allow PLHIV with high CD4 count (a blood test that establishes the stage of immunosuppression), access to the ART service, and decentralisation changes allowing easier access to ART at peripheral levels. This study therefore examined how service providers at all levels of care deliver ART services, and developed a tool to estimate future requirements for those providers. The case study uses mixed methods including both quantitative and qualitative approaches. Two stages of data collection were conducted; fieldwork to collect data on activities and flow of ART services, and time required for each type of service provider. These become the input data for a second stage to project staffing requirements based on Markov and Monte Carlo analysis to 2025. Three models of ART services were found, across all levels of facility in the public sector operating in high HIV/AIDS prevalence settings,: community-based, doctor-led and mixed-comprehensive. All models adapted their ART services from the national guidelines by applying HR strategies: task shifting, skill mix and community-based approach, to maintain/increase accessibility and quality of care. The estimation of time required to provide ART service of providers was estimated. 60 full time equivalent (FTE) providers (doctors, nurses, pharmacists, pharmacy technicians and non-healthcare providers) in 2012, projected to almost double in 2015. This study found negligible gaps (0.02-0.05%) between needs and availability of healthcare providers to deliver ART service. The HR strategies investigated, were sufficiently widespread to be worth recommending for wide application in human resource planning. Moreover, the tool developed to estimate the requirements for healthcare providers from this study could further support forward towards planning for HIV/AIDS services in Thailand and possibly elsewhere.

Owing to advances in HIV treatment, adolescents are now living long and healthy lives into adulthood and beyond. Research has been conducted in order to investigate the psychological and emotional responses of those who are HIV positive. However, there is a paucity of empirical research that investigates those responses in the siblings of adolescents who are diagnosed with HIV but who are not HIV positive themselves. This is an important area for research as clinicians recognise that healthy siblings of chronically unwell young people experience significant difficulties. Therefore, this project aimed to explore the psychosocial impact HIV is having on HIV discordant siblings, as well as considering the impact of this on the sibling relationship. Five sibling pairs (aged between 14 and 21), each consisting of one HIV positive and one HIV negative sibling, participated in face-to-face interviews with the author. This data was then subjected to Grounded Theory analysis which revealed 15 sub categories for the HIV positive group and 12 for the HIV negative group. Subcategories were subsequently arranged into a coherent framework before a group analysis was explored and a theoretical formulation describing the findings is offered. The theoretical formulation describes how the core categories that emerged from the research interact with one another whilst also detailing the systemic impact of HIV on the cognitive, affective and behavioural responses of participants. It emerged that both sibling groups struggle with the demands of secrecy in relation to HIV; both siblings manage disclosure anxiety and the threat of being exposed resulting from societal and cultural stigma associated with HIV. The sibling bond appears to be important to both. A family coping strategy of avoidance emerged for all families in that siblings offered a much needed source of support in discussing the taboo topic of HIV, often not openly discussed within the family. Participants discussed the influence HIV has had on their lives and the benefits of this were explored. The theoretical formulations proposed by this project are considered within the context of the existing literature and implications for future research and clinical practice are discussed.

This thesis explores how adolescent women see the risk of contracting AIDS in heterosexual relationships, 'how' in terms of viewpoints but also of the processes in which these viewpoints are constructed. The thesis is based on sociological theories of 'health' and 'risk' and sociological critiques of the scientific approach to 'risk' adopted by health promotion. The thesis draws on focus groups data gathered in twenty-four group meetings with adolescent women from a big city of the South of Brazil. The thesis develops the argument that 'sexual risk' in general and 'HIV/AIDS sexual risk' in particular are epistemological constructs, for 'risk' is not an event 'per se', but an event constructed through knowledge. The thesis assumes that it is important to investigate the many layers of knowledge that underpin adolescent women's conceptions of 'sexual risk' because this provides information about what they mean by that and how those meanings are constructed. The thesis challenges health promotion's idea that adolescent women's practice of 'unsafe sex' is the result of ignorance or incorrect perception of the risks of sex. The thesis demonstrates that adolescent women are very good learners of health promotion's messages on 'safe sex'. They know the risks and the available selfprotection strategies. They also know that it is their responsibility to take care of themselves and how important this is in a social environment that is continuously risky. The thesis argues that although sexual risk assessment is an operation influenced by a number of knowledges, health promotion's knowledge is the most influential of all. To learn the lessons of health promotion discourses on 'choice' implies to invest in 'self-governance'. The thesis concludes that this ideal of self-governance underpins adolescent women's conceptions of risky/safe sex and that it produces conceptions of risky/safe sex that are distinct from those used by health promoters.

HIV testing is an example of the separation between public health policy guidelines and practices of medical providers in urban Indian hospitals. An action-centred policy framework and interpretivist analytical approach was adopted to investigate problems of policy-practice gaps and identify strategies to resolve them. I conducted depth interviews with 61 respondents representing different groups of involved actors, including medical practitioners from public and private hospitals in five Indian cities, administrators, public health officials, regulators, educators, representatives of civil society organizations and international agencies, and with key informants. Respondents' perspectives on their participation in implementing the policies and on interactive processes between different groups were explored. There was a concentration on four aspects of HIV testing - selectivity in testing, pre-surgical testing, infonned consent, and confidentiality. I found that the actions of medical practitioners and other actors, and their respective interactions with each other, frequently diverged from expected nonns . of policy implementation. Explanations for divergences in actions included ambiguities around roles, conflicting valueorientations and practical considerations such as workplace relationships and systemic inadequacies. The nature of existing interrelationships between groups of actors was often inconsistent with a 'rational' top-down process of implementation. Irregularities in conveying meanings of policies also contributed to problems in their implementation. Different groups of actors are observed to inhabit discrete 'systems of meaning' and be guided by differing senses of purpose in their actions. This raises questions of the sufficiency and appropriateness, in isolation, of conventional prescriptions of strengthening regulations towards aligning implementers' practices with policymakers' intentions. In India's complex health policy ecosystem, the need for greater attention to the quality of interactive processes is identified. A renewed understanding of 'rationality' in the implementation of public health policies, based on good communicative practices and inclusion of different fonns of knowledge, is suggested as a standard for change.

South Africa is home to the largest number of people living with HIV in the world, as well as the world’s largest public-sector antiretroviral treatment (ART) programme. Despite the absolute majority of it being domestically funded, planning and budgeting for this programme has in the past been based on assumptions regarding target population and unit cost and on politically expedient coverage targets. The aim of this thesis was to improve on this situation by developing a budget impact model that could project the number of adults and children in treatment based on sound epidemiological methods, and calculate the cost of treating them based on the results of detailed bottom-up cost analyses at relevant clinics and hospitals in South Africa. The thesis describes the methods used in generating the inputs for the model, including the outpatient and inpatient cost of ART provision to adults and children of different ages, and the rates of CD4 cell count development, mortality, loss to follow-up, treatment failure, and regimen switches that were used in the model. The model was used to illustrate the budget impact of a number of guideline changes under discussion by the South African government in 2009/10, including 1.) expanding eligibility to all adults with CD4 cell counts < 350 cells/microl, as well as to all TB co-infected and pregnant patients and all children under the age of 12 months regardless of immunological status, and 2.) replacing stavudine in first-line regimens with tenofovir for adults and with abacavir for children, with concomitant changes to second-line regimens. Both 1.) and 2.) had been suggested by the 2009 World Health Organization (WHO) guidelines (“Full WHO guidelines”). A second scenario was considered that expanded eligibility at 350 CD4 cells/microl only to those adults who were pregnant or had active TB at initiation while also replacing the current drug regimens as under 2.) (“New guidelines”). Additional factors with an impact on cost that were considered in the model were a) the introduction of a task-shifting policy that allowed antiretroviral drugs to be prescribed by nurses instead of doctors, and dispensed by pharmacy assistants instead of pharmacists, and b) replacing the existing system of antiretroviral drug procurement via government tenders that favour domestic production with drugs sourced globally at ceiling prices based on the cheapest internationally available price for each drug, including fixed-dose combinations (FDCs) wherever possible. Combining all the inputs, the model showed that while the Full WHO guidelines scenario would increase total cost over the next two mid-term expenditure framework periods (2010/11 to 2016/17) by 35% to USD 19.1 billion, and the New Guidelines scenario by 19%, this increase could be more than offset by introducing the two additional policies. In this case, the total cost of the ART programme under the New Guidelines would be 32% less than under the Old Guidelines without FDCs and task-shifting (taken as government’s revealed willingness-to-pay), while reaching 14% more patients, and implementing the Full WHO Guidelines would still be 23% less costly than continuing the Old Guidelines, while reaching 23% more patients. Based in part on this analysis, the South African government increased treatment eligibility in two steps in April 2010 and in August 2011, introduced the improved drug regimens, established task shifting, and, using the proposed reference price list, negotiated significant drug price reductions for both the December 2010 and the December 2012 ARV drug tender. The budget impact model, named the National ART Cost Model, has been used in budget planning processes for the last seven financial years and, based in part on it, the government’s Conditional Grant for HIV/AIDS, the main vehicle for ART funding, was more than doubled in real terms over this time period. The thesis ends by presenting the results of a cost-benefit analysis of an alternative funding mechanism to public-sector funding, the provision of ART at the workplace, which was found from the company perspective to be cost-saving over no provision of ART, reducing the total cost due to HIV by 5%, and the cost per HIV-infected employee by 14%, over 20 years.