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HIV Medicine

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    HIV-specific CD8+ T cell responses in infected infacts enrolled on a study of early highly active antiretroviral treatment (HAART) and supervised treatment interruption (STI).
    (2011) Thobakgale, Christina Fanesa.; Kiepiela, Photini.; Ndung'u, Peter Thumbi.; Goulder, Philip Jeremy Renshaw.
    The manifestation of HIV-1 infection is different in children and adults. Most of the children who acquire HIV perinatally progress to disease within the first two years of life, while adults can remain asymptomatic for up to ten years. However, a small minority group of children can control the virus for years in the absence of antiretroviral therapy. We characterized CD8+ T cell responses critical for the containment of HIV infection in a cohort of infants HIV infected from birth using IFN- γ ELISPOT, multicolour flow cytometry and viral sequencing of the Gag protein. We investigated whether the age at the time of infection, specificity and functionality of the generated responses, genetic make up and the maternal immune responses to HIV, influenced disease progression in the child. We found that the majority of in-utero infected infants mounted CD8+ T cell responses from the first days of life. In contrast to chronically infected children or adults, the specificity of the initial response in acutely infected infants was directed towards Env and Rev proteins and CD4+ T cell responses were minimal during the first 6 months of life. Slow progression to disease was associated with possession of one of the protective HLA-B alleles by either the mother or the child (P=0.007) and targeting of Gag epitopes presented by the protective HLA-B alleles. Mothers who expressed protective alleles but whose children did not possess these alleles, transmitted less fit viruses that benefited their children. Furthermore, slow progressor children had more polyfunctional CD8+ T cell responses in early infection when compared to rapid progressors (P=0.05). The ability of infants to induce CD8+ T cell responses early in life is encouraging for vaccine interventions. The differences in the specificity of the initial responses between adults and children, insufficient priming of these responses as a result of minimal CD4+ T cell help during infancy and possession of non-protective HLA alleles shared between mother and child, may explain the rapid disease progression generally noted in most infants. However, slow progression to disease in the minority group of children may be attributed to functional capacity of the CD8+ T cells generated by the child, mediation by protective HLA alleles, acquisition of low fitness viruses from the mother or de novo attenuation of the virus by the child’s own immune responses.
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    Exploring the ancillary-care experiences of stakeholders in South African HIV vaccine trials.
    (2015) Slack, Catherine May.; Lindegger, Graham Charles.
    A controversial debate in research ethics comprises the responsibilities of sponsors and researchers to address participants’ medical needs in low-resource settings when this would not service the scientific objectives of the research, nor keep participants safe – their so-called ‘ancillary-care’ responsibilities – particularly when responses might be costly or demanding. The ancillary-care debate partially emerged out of the field of HIV vaccine trials. There has been surprisingly little effort to systematically explore the practices and perspectives of researchers (and other key role-players) regarding ancillary care in such trials. This qualitative study aimed to explore the experiences of key stakeholders involved in HIV vaccine trials in South Africa, specifically: their practices, how such practices are made sense of or understood, and contemporary concerns and complexities. It was funded by the Wellcome Trust Biomedical Ethics Program (087429/Z/08/Z). Semi-structured interviews were conducted with representatives of the coordinating network as well as Research Ethics Committees, Community Advisory Boards and research staff at five sites in the country implementing two HIV vaccine trial protocols. Key documents were obtained, including protocols, informed consent forms and supporting documentation. The study obtained necessary ethical approvals (UKZN BREC BE 241/09) and written consent was provided for study participation. Data was analyzed using Thematic Analysis to develop themes that captured meanings attributed by interviewees to their practices and experiences. Five master themes were developed namely Reciprocating, Engaging, Benefitting; as well as Reconciling, Privileging, Line-drawing, and Partnering. These master themes, and sub-themes, are discussed in terms of the ancillary-care literature. The study sets out implications of stakeholders’ ancillary-care experiences for leading accounts of ancillary care, as well as for current ethical guidelines. Recommendations are made to refine guidance so it is more responsive to the concerns and complexities experienced by stakeholders in the field. Recommendations are made to strengthen the practices of core stakeholders. It is hoped that through refined guidance and strengthened practices this study can contribute to the ethical rigor with which such trials are implemented.