Aim: To analyse the epidemiological, clinical and immunological aspects of a recent epidemic of acute HCV in HIV co-infected individuals.;Methods: The epidemiology was characterised using combined molecular and clinical studies. A phylogenetic analysis of the E1/E2 region of the HCV genome was performed to determine HCV transmission. Transmission risk factors were then explored in a multicentre case-control study. Data was collected on the early clinical course of HCV in HIV. Longitudinal cell-mediated responses to HCV and HCV evolution were studied with PBMCs and serum collected during the acute phase.;Results: The studies revealed significant differences in the epidemiology, natural history, cell-mediated responses and HCV evolution between acute HCV with and without HIV. The seven clusters demonstrated in the molecular study is strong evidence for common source transmission. The case-control study identified permucosal factors, including high-risk mucosally traumatic sexual and drug practices, were significantly associated with the recent transmission of HCV. HCV persistence was the outcome in the vast majority of HIV co-infected individuals and these rates are significantly higher than those for HCV mono-infection. The CD4 T-cell responses lacked the magnitude and breadth of response for control of HCV. The virological data supported this, revealing quasispecies evolution that appeared not to be driven by immune pressure.;Conclusions: The phylogenetic clusters cross both HCV genotype and subtype implying that the HCV transmission is not due to a specific viral change, but that patient and/or environmental factors are responsible for the recent infections. Permucosal rather than parenteral behavioural risk factors are associated with this transmission. The immuno-deficient state associated with HIV results in very low spontaneous clearance of HCV and the vast majority of these patients become persistently infected. In order to mitigate this important and ongoing epidemic, these factors need to be the focus of a concerted effort on the part of public health specialist, clinicians and HIV-positive individuals themselves
