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Taylor L.E.,The Miriam Hospital | Swan T.,Treatment Action Group | Matthews G.V.,University of New South Wales | Matthews G.V.,Infectious Diseases Clinical Services Unit
Clinical Infectious Diseases | Year: 2013

Where active antiretroviral therapy (ART) is accessible, human immunodeficiency virus (HIV) is a survivable illness and effective ART can reduce HIV transmission. Chronic hepatitis C virus (HCV) has emerged as a threat to the survival of individuals harboring both HCV and HIV, due to high prevalence and aggressive disease course. The HCV/HIV coinfection epidemic has been driven by people who inject drugs (PWID), although incident HCV is rising among HIV-infected men who have sex with men in the absence of drug injection. Coinfected individuals warrant aggressive treatment of both viruses; although early ART initiation is recommended to reduce the rate of liver disease progression, the most effective way to decrease HCV-related morbidity and mortality in coinfection is to achieve HCV viral eradication. Direct-acting antiviral (DAA) agents will soon revolutionize HCV treatment. Clinical data are needed regarding the efficacy of DAAs in coinfected PWID. Drug-drug interaction studies between ART, DAAs, and opiate substitution therapy must be expedited. Coinfected PWID should have equitable and universal access to HIV/AIDS, HCV, and addiction prevention, care, and treatment. Essential basic steps include improving screening for both infections and engaging coinfected PWID in HIV and HCV care early after diagnoses. Developing strategies to expand access to HCV therapy for coinfected PWID is imperative to stem the HCV epidemic and limit the morbidity and mortality of those at greatest risk for HCV disease progression. The ultimate goal must be the elimination of HCV from all coinfected PWID. © 2013 The Author 2013.

Gidding H.F.,University of New South Wales | Law M.G.,University of Queensland | Amin J.,Royal Melbourne Hospital | MacDonald G.A.,John Hunter Hospital | And 5 more authors.
Medical Journal of Australia | Year: 2011

Objective: To determine uptake of treatment for hepatitis C virus (HCV) infection and predictors of deferral of treatment for HCV by using prospectively collected data from the Australian Chronic Hepatitis C Observational Study (ACHOS). Design, patients and setting: Cohort study involving interview and medical record review at enrolment and routine follow-up clinic visits of patients with chronic HCV and compensated liver disease attending a national network of 24 HCV clinics between April 2008 and December 2009. Eligible patients were those who had not been previously treated, were enrolled within 6 months of their first clinic visit, were eligible for treatment and had been enrolled for at least 6 months. Main outcome measure: Predictors of patients undergoing HCV treatment within the first 6 months of assessment. Results: 1239 patients were enrolled in ACHOS, of whom 406 met the criteria for inclusion in the subcohort for this study. Among this subcohort, 171 (42%) received treatment within 6 months of their first clinic visit. Current injecting drug use (odds ratio [OR], 0.26; 95% CI, 0.08-0.77), past and current treatment for drug dependency (OR, 0.34; 95% CI, 0.18-0.67, and OR, 0.42; 95% CI, 0.22-0.81, respectively) and alcohol use above 20 g/day (OR, 0.20; 95% CI, 0.08-0.46) were independent predictors of deferral of treatment. At least one of these factors applied to 41% of the subcohort. Clinical factors, including HCV genotype, HCV RNA level, and stage of liver disease were not associated with deferral of treatment for HCV. Conclusion: Factors related to drug and alcohol use, rather than clinical factors, influenced uptake of treatment for HCV. Further support for patients with drug and alcohol dependency is required to optimise treatment uptake.

Dore G.J.,University of New South Wales | Dore G.J.,Infectious Diseases Clinical Services Unit | Matthews G.V.,University of New South Wales | Matthews G.V.,Infectious Diseases Clinical Services Unit | Rockstroh J.,University of Bonn
Current Opinion in HIV and AIDS | Year: 2011

Purpose of review: The landscape of hepatitis C virus (HCV) therapy will change considerably over the next decade with the probable licensure of many HCV direct-acting antiviral (DAA) therapy agents. This review will outline the data on the initial two DAA agents licensed (protease inhibitors telaprevir and boceprevir) and cover potential future therapeutic strategies and challenges for DAA-based therapy, including in the context of HIV/HCV coinfection. Recent findings: Phase III trials evaluating the addition of telaprevir or boceprevir to pegylated interferon and ribavirin in both HCV treatment naïve and experienced populations with chronic HCV genotype 1 have demonstrated considerable improvements in sustained virological response, with many patients able to shorten total treatment duration from 48 to 24-36 weeks. Although these initial DAA-based treatment results are encouraging, additional toxicity, problematic dosing schedules, and potential drug-drug interactions pose challenges for clinical management, particularly in HIV/HCV coinfection. Phase II trials with telaprevir and boceprevir in HIV/HCV populations are underway. Subsequent DAA agents appear to have improved tolerability and dosing schedules and open the door for interferon (IFN)-free DAA-based combination therapy. Summary: Development of DAA therapy will lead to a major shift in HCV clinical management, particularly with the potential for IFN-free combination therapy. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Sasson S.C.,University of New South Wales | Sasson S.C.,Center for Immunology | Smith S.,Immunopathology Laboratory | Seddiki N.,University of New South Wales | And 16 more authors.
Cytokine | Year: 2010

The interleukin (IL)-7 receptor (IL-7R) is expressed on human pre-B but not mature B-cells. We hypothesised that aberrant expression of IL-7R contributes to B-cell oncogenesis. Surface expression of IL-7R components CD127 and CD132, and intracellular Ki-67 and Bcl-2 were examined by flow cytometry on peripheral blood or bone marrow mononuclear cells (PBMC; BMMC) from patients with B-cell derived neoplasms, chronic human immunodeficiency virus type-1 (HIV-1) infection alone, or healthy volunteers. Plasma IL-7, IL-2, IL-4, IL-6, IL-10, IL-21, TNF-α, IFN-γ and BAFF were measured by enzyme-linked immuno-sorbent assay or bead array. The effects of exogenous IL-7 on PBMC and BMMC were examined. CD127 expression was elevated in pre-B-cell acute lymphoblastic leukemia (pre-B-ALL) and in some cases of Non-Hodgkin's Lymphoma (B-NHL). Plasma IL-7 levels were higher in pre-B-ALL, B-cell chronic lymphocytic leukemia (B-CLL) and HIV-1 associated B-NHL (HIV-B-NHL) compared with control groups. CD127+ pre-B-ALL cells had higher expression of Ki-67, Bcl-2 and CD132 than CD127- counterparts. Unlike T-lineage cells, CD127+ pre-B-ALL cells did not down-regulate CD127 in response to exogenous IL-7. Patients with B-cell derived neoplasms had elevated circulating IL-10 and decreased BAFF. These findings support a role for the IL-7/IL-7R system in B-cell oncogenesis. © 2009 Elsevier Ltd.

Dore G.J.,University of New South Wales | Dore G.J.,Infectious Diseases Clinical Services Unit | Hellard M.,Burnet Institute | Hellard M.,Infectious Diseases Unit | And 14 more authors.
Gastroenterology | Year: 2010

Background & Aims: Patients with acute hepatitis C virus (HCV) infection who receive treatment achieve high rates of sustained virologic response (SVR), but few studies have examined outcomes among injecting drug users (IDUs). We evaluated the efficacy of treatment of recent HCV infection in IDUs with acute and early chronic HCV. Methods: We analyzed data from the Australian Trial in Acute Hepatitis C-a prospective study of the natural history and treatment outcomes of patients with recent HCV infection. Participants eligible for the study had their first anti-HCV antibody-positive test result within the past 6 months and either acute clinical HCV within the past 12 months or documented anti-HCV seroconversion within 24 months. Participants with HCV received pegylated interferon-alfa-2a (180 μg/wk, n = 74); those with HCV/human immunodeficiency virus (HIV) co-infection received pegylated interferon-alfa-2a (180 μg/wk) with ribavirin (n = 35) for 24 weeks. Results: From June 2004 to February 2008, 167 participants were enrolled in the Australian Trial in Acute Hepatitis C; 79% had injected drugs in the previous 6 months. Among 74 with only HCV, the SVRs were 55% and 72% by intention-to-treat and per-protocol analysis, respectively. In multivariate analyses, baseline factors independently associated with lower SVR included decreased social functioning and current opiate pharmacotherapy. Adherent participants had higher SVR rates (63% vs 29%; P = .025). Of the 35 participants with HCV/HIV co-infection, the SVRs were 74% and 75% by intention-to-treat and per-protocol analysis, respectively. Conclusions: Treatment of recent HCV infection among IDUs, including those with HIV co-infection, is effective. Strategies to engage socially marginalized individuals and increase adherence should improve treatment outcomes in this population. © 2010 AGA Institute.

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