Successful treatment of acute hepatitis C virus in HIV positive patients using the European AIDS Treatment Network guidelines for treatment duration
TL;DR: A retrospective cohort study of HIV-positive patients diagnosed with acute HCV infection between December 2006 and May 2010 finds that the high SVR rate of 91% supports the new NEAT treatment duration recommendations.
About: This article is published in Journal of Clinical Virology.The article was published on 2011-12-01. It has received 20 citations till now. The article focuses on the topics: Ribavirin & Hepatitis C.
Citations
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TL;DR: With multiple direct-acting antiviral agents in development to treat HCV, a unique opportunity exists to redefine the treatment paradigm for co-infected patients, which incorporates data on fibrosis stage as well as potential drug interactions with antiretroviral therapy.
Abstract: HCV and HIV co-infection is associated with accelerated hepatic fibrosis progression and higher rates of liver decompensation and death compared to HCV monoinfection, and liver disease is a leading cause of non-AIDS-related mortality among HIV-infected patients. New insights have revealed multiple mechanisms by which HCV and HIV lead to accelerated disease progression, specifically that HIV infection increases HCV replication, augments HCV-induced hepatic inflammation, increases hepatocyte apoptosis, increases microbial translocation from the gut and leads to an impairment of HCV-specific immune responses. Treatment of HIV with antiretroviral therapy and treatment of HCV have independently been shown to delay the progression of fibrosis and reduce complications from end-stage liver disease among co-infected patients. However, rates of sustained virologic response with PEG-IFN and ribavirin have been significantly inferior among co-infected patients compared with HCV-monoinfected patients, and treatment uptake has remained low given the limited efficacy and tolerability of current HCV regimens. With multiple direct-acting antiviral agents in development to treat HCV, a unique opportunity exists to redefine the treatment paradigm for co-infected patients, which incorporates data on fibrosis stage as well as potential drug interactions with antiretroviral therapy.
154 citations
North Manchester General Hospital1, Chelsea and Westminster Hospital NHS Foundation Trust2, Imperial College London3, University of Cambridge4, John Radcliffe Hospital5, Royal Free London NHS Foundation Trust6, Imperial College Healthcare7, Guy's and St Thomas' NHS Foundation Trust8, Brighton and Sussex University Hospitals NHS Trust9, University of Liverpool10, Birkbeck, University of London11, Western General Hospital12, University of Edinburgh13, Queen Elizabeth Hospital Birmingham14, University of Birmingham15, Barts Health NHS Trust16, University Hospitals of Leicester NHS Trust17, University College London18
68 citations
TL;DR: In this paper, the authors provide a review of the use of direct-acting antiviral agents (DAAs) for acute hepatitis C infection and highlight the potential effects of diagnosis and treatment of acute HCV infection in contributing to HCV elimination.
Abstract: The management of acute HCV infection has not been standardized following the availability of direct-acting antiviral agents (DAAs) for chronic HCV infection, and substantial uncertainty exists regarding the optimal treatment regimen and duration. Despite the lack of direct evidence, the 2016 American Association for the Study of Liver Diseases (AASLD)–Infectious Diseases Society of America (IDSA) guidelines supported “the same regimens for acute HCV as recommended for chronic HCV infection … owing to high efficacy and safety”, whereas the 2016 European Association for the Study of the Liver (EASL) guidelines recommended sofosbuvir–ledipasvir, sofosbuvir–velpatasvir or sofosbuvir plus daclatasvir for 8 weeks in acute HCV infection, with a longer duration of 12 weeks recommended for those infected with HIV and/or baseline HCV RNA levels >1,000,000 IU/ml. This Review outlines the epidemiology, natural history and diagnosis of acute HCV infection and provides contemporary information on DAAs for acute and recent HCV infection. The Review also discusses the 2016 AASLD–IDSA and EASL recommendations for acute HCV infection management in light of available evidence and highlights key differences in study populations and design that influence interpretation. We focus on populations at high risk of HCV transmission and acquisition, including people who inject drugs and HIV-positive men who have sex with men, and highlight the potential effects of diagnosis and treatment of acute HCV infection in contributing to HCV elimination. Direct-acting antiviral agents (DAAs) have revolutionized the management of chronic hepatitis C, but their use in acute infection is unclear. This Review outlines the epidemiology, diagnosis and management of acute HCV infection, providing insights into the use of DAAs in at-risk populations (such as people who inject drugs).
56 citations
TL;DR: Prevention and screening efforts along with early anti-HCV therapy have to be intensified to allow for control of viral dissemination as the current epidemic of AHC particularly among MSM is still ongoing.
Abstract: Almost 10 years ago clinicians started to note the first cases of an outbreak of acute hepatitis C (AHC) infections among human immunodeficiency virus- (HIV-) positive men who have sex with men (MSM) in Europe, soon followed by similar reports from the United States and Australia. In the absence of randomized controlled treatment trials in AHC, coinfection expert consensus recommendations based upon published data from uncontrolled clinical and cohort studies give guidance on best clinical management. Pegylated interferon in combination with weight-adapted ribavirin is still recommended as the treatment of choice for all HCV genotypes. For patients developing a rapid virologic response, treatment duration of 24 weeks is recommended. If antiviral therapy was initiated within 24 weeks after diagnosis, high sustained virologic response rates of 60 to 80% have been observed. Prevention and screening efforts along with early anti-HCV therapy have to be intensified to allow for control of viral dissemination as the current epidemic of AHC particularly among MSM is still ongoing.
31 citations
TL;DR: The capacity of the managing physician to recognize these tumours and refer to an ophthalmologist is essential for appropriate treatment, as they are the first point of contact for most HIV patients.
Abstract: PURPOSE OF REVIEW: Ocular surface malignancy is a serious complication in HIV infection, but can often result in successful treatment if diagnosed appropriately. In the literature, most reviews focus on information for the ophthalmic community. Here, we provide a review of the literature with the pertinent information for the nonophthalmologist, as they are the first point of contact for most HIV patients. RECENT FINDINGS: Ocular surface squamous neoplasia (OSSN) is the most common nonpigmented ocular surface malignancy. It can be treated well with surgery or topical chemotherapy, the newest method of treatment. When presenting in young patients, a high percentage have been found to be HIV positive. Kaposi's sarcoma is an AIDS-defining malignancy and critical to diagnose. It cannot be cured, but treatment is effective for keeping it controlled. Conjunctival lymphoma can be recognized with the salmon patch appearance. External beam radiation, systemic chemotherapy, and intralesional injections are the mainstays of treatment. SUMMARY: Ocular surface malignancy manifests significantly in the HIV population. OSSN, Kaposi's sarcoma and conjuctival lymphoma all have different clinical presentations. The capacity of the managing physician to recognize these tumours and refer to an ophthalmologist is essential for appropriate treatment.
22 citations
References
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TL;DR: Spontaneous clearance of acute HCV in HIV-positive men can be predicted by a rapid decline in viral load, high CD4 count, elevated bilirubin and ALT, and is associated with low viral diversity and strong T cell responses.
Abstract: Objective An epidemic of acute hepatitis C virus (HCV) infection in HIV-positive men-who-have-sex-with-men (MSM) is emerging in Europe, Australia and the USA. The aim of this study was to characterise the natural history of primary HCV in this setting and to assess host and viral factors which predict spontaneous clearance. Methods This prospective longitudinal cohort study was carried out in 112 HIV-positive patients who were followed in a single centre (the St Mary’s Acute HCV Cohort). Plasma and peripheral blood mononuclear cells (PBMCs) were obtained at monthly intervals for 3 months and at 3-monthly intervals thereafter for a median of 45 months (IQR¼29e69 months). The primary end point was spontaneous clearance of HCV. Cox regression was used to assess the impact of clinical and virological variables on outcome, including liver function, CD4 count, rate of HCV RNA decline, T cell response and clonal sequence evolution within the HCV E2 envelope gene. Results 15% of patients cleared HCV spontaneously, while 85% progressed towards chronicity. The latter group included a significant proportion of ‘fluctuating’ progressors (37.5%), in whom a fall followed by a rise (>1 log10) in viraemia was observed. This was associated with superinfection with new HCV strains and partially effective T cell responses. Spontaneous clearance was strongly associated with a 2.2 log10 viral load drop within 100 days of infection (HR¼1.78; p<0.0001), elevated bilirubin ($40 mmol/l; HR¼5.04; p¼0.006), elevated alanine aminotransferase (ALT; $1000 IU/ml; HR¼2.62; p¼0.048) and baseline CD4 count $650310 6 /l (HR¼2.66; p¼0.045), and only occurred in patients with genotype 1 infection. Evolution to spontaneous clearance occurred in patients with low viral diversity in the presence of an early multispecific T cell response. Conclusions Spontaneous clearance of acute HCV in HIV-positive men can be predicted by a rapid decline in viral load, high CD4 count, elevated bilirubin and ALT, and is associated with low viral diversity and strong T cell responses.
175 citations
TL;DR: This study was undertaken to determine whether within clinics, changes in the number of individuals being diagnosed with acute HCV infection were occurring and to ascertain risk factors for acquisition in these individuals.
Abstract: Although the principal mode of hepatitis C (HCV) transmission in the United Kingdom is injecting drug use (IDU), the risk for a third of infections is unknown.1 The contribution of sexual transmission between men who have sex with men (MSM) to the spread of hepatitis C is unclear, however evidence is accumulating that both co-infection with HIV2 and the presence of other sexually transmitted infections (STIs) facilitate sexual transmission of HCV.3 With the reported increases in unsafe sex and STIs in HIV positive MSM we questioned whether these circumstances may lead to an increase in the number of HCV infections.
This study was undertaken to determine whether within our clinics, changes in the number of individuals being diagnosed with acute HCV infection were occurring and to ascertain risk factors for acquisition in these individuals.
A case note review of all patients within the HIV and sexual health clinics of St Stephen’s Centre with diagnosed acute HCV infection between January …
153 citations
TL;DR: The authors' data support phylodynamic findings that HCV incidence had already increased among HIV-infected MSM from the mid-1990s, however, the main expansion of the HCV epidemic started after 2002.
Abstract: BACKGROUND
Outbreaks of acute hepatitis C virus (HCV) infection among HIV-infected MSM have been described since 2000 However, phylogenetic analysis suggests that the spread of HCV started around 1996 We estimated the incidence of HCV in HIV-infected MSM with well estimated dates of HIV seroconversion from 1990 to 2007
METHODS
Data from 12 cohorts within the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) Collaboration were used HCV incidence was estimated using standard incidence methods and methods for interval-censored data We accounted for the fact that routine HCV data collection in each cohort started in different calendar years
RESULTS
Of 4724 MSM, 3014 had an HCV test result and were included Of these, 124 (4%) had only positive HCV test results, 2798 (93%) had only negative results and 92 (3%) had both In 1990, HCV incidence ranged from 09 to 22 per 1000 person-years, depending on the analysis strategy used HCV incidence increased up to 1995 when it was estimated to range between 55 and 81 per 1000 person-years From 2002 onwards, it increased substantially to values between 168 and 300 per 1000 person-years in 2005 and between 234 and 511 per 1000 person-years in 2007
CONCLUSION
Our data support phylodynamic findings that HCV incidence had already increased among HIV-infected MSM from the mid-1990s However, the main expansion of the HCV epidemic started after 2002 Incidence estimates obtained from cohort studies may help identify changes in the spread of important infections earlier and should guide routine testing policies to minimize further disease burden
138 citations
Pasteur Institute1, Carlos III Health Institute2, University College London3, University of Bonn4, Hannover Medical School5, University of Brighton6, French Institute of Health and Medical Research7, Imperial College London8, University of Bern9, Hoffmann-La Roche10, Goethe University Frankfurt11, University of Amsterdam12, Istituto Superiore di Sanità13, Université libre de Bruxelles14, University of New South Wales15
TL;DR: Four working groups prepared draft guidelines for consideration at the conference on case definition and diagnosis; transmission risk and epidemiology; pathogenesis and natural history; and acute HCV infection management in the HIV-infected population.
Abstract: There is increasing awareness of an ongoing epidemic of acute hepatitis C virus (HCV) infection in HIV-infected MSM. The epidemiology has been reviewed in this journal recently [1]; however, there is a lack of guidance on the management of acute HCV infection in HIV-infected individuals. To address this issue, the European AIDS Treatment Network (NEAT) invited members of the European AIDS Clinical Society (EACS) hepatitis group, the European Association for the Study of the Liver (EASL), the European Study Group on Viral Hepatitis of the European Society of Clinical Microbiology and Infectious Diseases, the European AIDS Treatment group and other experts to draw up a consensus statement at a conference held in Paris, France, in May 2010. Four working groups prepared draft guidelines for consideration at the conference on case definition and diagnosis; transmission risk and epidemiology; pathogenesis and natural history; and acute HCV infection management in the HIV-infected population. A literature search using the PubMed database of the National Library of Medicine and abstract databases of the Conference on Retroviruses and Opportunistic Infections, the Interscience Conference on Antimicrobial Agents and Chemotherapy, the Liver Meetings of the American Association for the Study of Liver Disease and EASL was utilized by all groups. Statements and recommendations were graded by the strength of recommendation and level of evidence (Table 1) [2]. A consensus was reached if 80% or more of the participants were in favour.
134 citations
TL;DR: Sustained virologic response rates in HIV-positive patients treated for acute HCV infection are lower than inAIDS subjects, and treatment should be delayed until after 12 weeks because a high percentage of individuals seroconvert spontaneously.
Abstract: OBJECTIVE To evaluate treatment outcome of acute hepatitis C virus (HCV) in HIV-positive individuals. DESIGN Open-label, prospective study conducted in London, January 1997-December 2003. METHODS Patients in whom acute HCV infection had been diagnosed had sequential HCV RNA levels measured at 0, 4, 12, 24, 32, and 48 weeks. If HCV RNA positive at 12 weeks, patients were offered pegylated interferon alpha-2b 1.5 microg/kg/wk and ribavirin 800-1200 mg/d for 24 weeks. Patients with increasing HCV RNA titers were offered treatment earlier. RESULTS Fifty male homosexuals with a mean age 37 years were identified: 44 from abnormal liver function test results, 4 from sexual contact with an HCV-positive partner, and 2 at HIV seroconversion. Overall, 12 individuals became HCV RNA negative spontaneously. This was significantly associated with high baseline median CD4(+) count (P = 0.029), CD4(+) count >500 cells/mm(3) (P = 0.017), and lower HCV RNA titers (P = 0.017). Only 27 patients accepted treatment, 16 (59%) of whom reached sustained virologic response. This was associated with higher peak mean alanine aminotransferase (P < 0.001) and higher baseline CD4% (P = 0.041). CONCLUSIONS Sustained virologic response rates in HIV-positive patients treated for acute HCV infection are lower than in HIV-negative subjects. Because a high percentage of individuals seroconvert spontaneously, treatment should be delayed until after 12 weeks.
133 citations