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Studies of HIV and HCV co-infection in the context of haemophilia

Herrero-Martinez, Esteban; (2003) Studies of HIV and HCV co-infection in the context of haemophilia. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

HIV and HCV co-infection is highly prevalent in intravenous drug users and individuals with inherited bleeding disorders treated with clotting factor concentrates prior to the introduction of heat sterilisation in 1985. The presence of HIV accelerates HCV disease progression and the presence of HCV impairs CD4+ T-cell recovery post-HAART, although the underlying mechanisms for these effects remain to be elucidated. The aim of this thesis was to investigate HIV and HCV co-infection in the context of haemophilia. Initially, a quantitative competitive RT-PCR assay for HCV was developed. This assay was used in a retrospective cohort study of 96 men with haemophilia to determine the prognostic value of a single HCV RNA load measured early post HIV seroconversion. This study showed for the first time, that HCV RNA level early post HIV seroconversion is associated with progression to both AIDS and all-cause mortality over a period of at least 15 years. The effect of HAART on HCV replication is controversial, with some studies reporting no effect and others increases, reductions and clearances of HCV RNA post-therapy. I have investigated the effect of HAART on the titre of anti-HCV specific antibodies and on the relationship between these antibodies and HCV RNA level in a cohort of 24 patients with inherited bleeding disorders. A significant inverse correlation between anti-HCV antibodies was observed pre-HAART that disappeared or was obscured post-therapy. I have therefore shown that HAART affects HCV specific humoral immune responses without affecting HCV RNA level. Finally, I have investigated the effect of HCV co-infection on the expression of a range of memory markers on total CD8+ T-cells in HIV positive and negative patients. Significant differences in memory marker expression were observed in all four cohorts investigated; HIV mono-infected, HCV mono-infected, HIV and HCV co-infected and HIV and HCV negative controls.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Studies of HIV and HCV co-infection in the context of haemophilia
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; HIV; Hepatitis C
URI: https://discovery.ucl.ac.uk/id/eprint/10100332
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