Patients co-infected with HIV and HCV have increased risk of severe liver damage and ART exacerbates HCV disease in a sub-set of patients creating an immune restoration disease (HCV IRD). Immunological responses and histopathological changes in the liver associated with these events are poorly understood. A prospective cohort study of HCV-seropositive HIV patients was carried out at Cipto Mangunkusomo Hospital (Jakarta) with follow-up over 48 weeks. HCV IRD (defined as an increase in serum ALT ) affected 9 patients within 2 months on ART. Immunological and histochemical studies will be presented. Liver biopsies were collected at baseline and 48 weeks, Ishak scores were determined and intrahepatic CD4+ and CD8+ cells were counted. Levels of portal inflammation declined on ART, while fibrosis remained. Portal infiltration of CD4+ cells increased on ART, whilst CD8+ cellular infiltration subsided in portal and lobular regions. Numbers of infiltrating CD4+ cells at baseline correlate with circulating CD4+ T-cell counts, so intrahepatic CD4+ infiltration may be limited by global CD4 T-cell depletion. Baseline intrahepatic T-cell infiltration did not predict HCV IRD. Blood leukocytes were stimulated with antigens from HCV (core or NS3 proteins) and cells producing interferon-γ were enumerated by ELISpot. Responses to all antigens increased on ART, approaching levels seen in healthy controls. Responses to HCV antigens (notably NS3) were higher over several months in patients who experienced an IRD. This is consistent with Australian and Indonesian patients experiencing HCV IRD displaying elevated plasma CD26, marking T-cell activation. HCV IRD patients displayed low levels of HCV antibody assessed with the Roche Elecsys Anti-HCV Assay, before and on ART. In the same samples, levels of antibody to HCV core rose equivalently in IRD and non-IRD patients (marginally increased by IRD), whilst antibody to NS3, NS4 and NS5 declined irrespective of IRD. We examined the reactivity of antibodies and titres of neutralising antibodies (nAbs) using the HCV genotype 2a virus (JFH-1). Titres of nAb and reactivity to JFH-1 increased after 1 year of ART where HCV IRD patients had increased reactivity to JFH-1 antigen at baseline. Hence antibody or T-cell responses may identify patients at risk of developing HCV IRD, but the selection of antigens is critical. Disclosure of Interest: The project was funded by the University of western Australia and the University of Indonesia. No pharmaceutical grants were received in the development of this study.
Adherence to combination antiretroviral therapy (cART ) plays an important role on treatment outcomes. The TREAT Asia Studies to Evaluate Resistance – Monitoring Cohort Study (TASER-M) collects patients’ adherence based on a Visual Analogue Scale. The aim of this analysis was to assess the rates of, and factors associated with, suboptimal adherence in the first 24 months of initial cART in Asian patients.
REACH was a collaborative research and practice initiative to develop evidence building frameworks, capacity, tools and resources with the Victorian HIV community partnership.
HIV disease is associated with chronic inflammation and activation of the innate immune system. This state, as measured using plasma markers of inflammation, persists following suppression of HIV viremia using antiretroviral therapy, and may increase risk of non-AIDS co-morbidities. The causes of innate immune activation in the setting of virological suppression are unclear. Natural killer (NK) cells are innate immune cells that kill virus-infected and transformed cells without prior sensitization. We have shown that NK cells are activated both phenotypically (elevated expression of HLA-DR) and functionally (increased spontaneous degranulation measured by CD107a surface expression) in virologically suppressed (VS) HIV+ individuals. NK cells also lose expression of CD16, the receptor which mediates antibody-dependent cellular cytotoxicity.
Regular HIV testing is recommended in men who take sexual risks. We assessed the relationship between perceived barriers to HIV testing, and frequency of testing among men who engaged in unprotected anal intercourse with casual partners (UAIC), to inform HIV testing strategies.
The majority of HIV diagnoses including delayed diagnoses in Australia occur among men who report homosexual contact – hereafter called gay and bisexual men (GBM). Delayed diagnosis is strongly associated with increased HIV-related mortality and morbidity. People who are unaware of their HIV-positive status may also be unwittingly transmitting HIV. We assessed trends in delayed HIV diagnoses among GBM in Australia.
HIV-associated leishmaniasis, endemic in the Mediterranean basin is a growing problem in India, Brazil and East Africa. Despite surviving for than 20 years, the clinical course of our visceral-leishmania (VL)-HIV co-infected patient illustrates several management challenges including diagnosis, speciation and drug resistance; monitoring burden of disease; access to and use of VL-treatments; end-organ toxicity and the combined immunosuppressive effects of HIV-VL.
Early first sexual intercourse has been proposed as an important marker of later sexual and reproductive health. Discussions of what constitutes early sexual debut in this context, however, have been limited.