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Introduction: HIV-controllers have the ability to spontaneously maintain viraemia at low or undetectable levels in the absence of antiretroviral treatment. Furthermore, HIV-controllers seem to have a superior capacity to spontaneously clear hepatitis C virus (HCV) compared to non HIV-controllers. Some of these subjects eventually lose HIV-controller status (transient controllers), whereas some HIV-controllers show a persistent natural HIV control (persistent controllers). We aimed to analyse whether persistent controllers have superior capacity to spontaneously clear HCV compared to transient controllers. Methods: We recruited HIV-controllers from January 1981 up to October 2016 with available antibodies to HCV (anti-HCV) data (n = 744). Factors associated with HIV spontaneous control in relation to HCV status were analysed in persistent and transient HIV-controllers with anti-HCV positive (n = 202 and n = 138 respectively) in comparison with 1700 HCV positive non HIV-controllers recruited from January 1981 up to March 2018, bivariate and multivariate analyses, following a logistic regression model, were applied. In addition, the factors related to the loss and time to lose HIV-controller status were explored (n = 744) using Log rank test and Kaplan-Meier curves, in this case the multivariate analysis consisted in a Cox regression model. Results: A higher frequency of HCV spontaneous clearance was found in persistent HIV-controllers (25.5%) compared to non-controllers (10.2%). After adjusting for potential confounders, as sex, age, HIV transmission risk, [CD4.sup.+] T-cell nadir and time of follow-up, HCV clearance was independently associated with persistent HIV spontaneous control (p = 0.002; OR (95% Cl) = 2.573 (1.428 to 4.633) ), but not with transient spontaneous control (p = 0.119; 1.589 (0.888 to 2.845) ). Furthermore, persistent HIV-controllers were more likely to spontaneously clear the HCV in comparison with transient controllers (p = 0.027; 0.377 (0.159 to 0.893). Finally not to lose or lengthen the time of losing this control was independently associated with HCV spontaneous clearance (p = 0.010; 0.503 (0.297 to 0.850). Conclusions: This study shows an association between spontaneous persistent HIV-control and HCV spontaneous clearance. The study findings support the idea of preserved immune mechanisms in persistent HIV control implicated in HCV spontaneous clearance. These results highlight persistent HIV-controllers but not transient controllers as a good model of functional HIV cure. Keywords: HIV; HCV; HIV-controllers; persistent; transient; HCV spontaneous clearance Additional information may be found under the Supporting Information tab for this article., 1 | INTRODUCTION HIV-controllers are a small group of subjects ( On the other hand, HIV-controllers as a whole seem to have a higher capacity to spontaneously clear hepatitis C [...]

Background Modelling suggests that achieving the WHO incidence target for hepatitis C virus (HCV) elimination in Pakistan could cost US$3.87 billion over 2018 to 2030. However, the economic benefits from integrating services or improving productivity were not included. Methods and findings We adapt a HCV transmission model for Pakistan to estimate the impact, costs, and cost-effectiveness of achieving HCV elimination (reducing annual HCV incidence by 80% by 2030) with stand-alone service delivery, or partially integrating one-third of initial HCV testing into existing healthcare services. We estimate the net economic benefits by comparing the required investment in screening, treatment, and healthcare management to the economic productivity gains from reduced HCV-attributable absenteeism, presenteeism, and premature deaths. We also calculate the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for HCV elimination versus maintaining current levels of HCV treatment. This is compared to an opportunity cost-based willingness-to-pay threshold for Pakistan (US$148 to US$198/DALY). Compared to existing levels of treatment, scaling up screening and treatment to achieve HCV elimination in Pakistan averts 5.57 (95% uncertainty interval (UI) 3.80 to 8.22) million DALYs and 333,000 (219,000 to 509,000) HCV-related deaths over 2018 to 2030. If HCV testing is partially integrated, this scale-up requires an investment of US$1.45 (1.32 to 1.60) billion but will result in US$1.30 (0.94 to 1.72) billion in improved economic productivity over 2018 to 2030. This elimination strategy is highly cost-effective (ICER = US$29 per DALY averted) by 2030, with it becoming cost-saving by 2031 and having a net economic benefit of US$9.10 (95% UI 6.54 to 11.99) billion by 2050. Limitations include uncertainty around what level of integration is possible within existing primary healthcare services as well as a lack of Pakistan-specific data on disease-related healthcare management costs or productivity losses due to HCV. Conclusions Investment in HCV elimination can bring about substantial societal health and economic benefits for Pakistan., Author(s): Aaron G. Lim 1,*, Nick Scott 2, Josephine G. Walker 1, Saeed Hamid 3, Margaret Hellard 2, Peter Vickerman 1 Introduction Recent scientific advances in hepatitis C virus (HCV) [...]

TABLE OF CONTENTS I. INTRODUCTION II. THE DRUG PRICING TRAP A. Rising Drug Prices B. Narrowing Drug Access: The Case of Hepatitis C III. THE THEORETICAL CASE FOR GOVERNMENT USE [...], High drug prices are creating serious health and fiscal problems in the United States today. This reality is vividly illustrated by recently approved medicines to treat Hepatitis C. These new medicines can cure nearly everyone with this potentially fatal infection and may even enable the elimination of this disease. But the drugs' sticker price--close to $100,000--has meant that very few patients who could benefit from them can access them. This Article describes an approach, available under existing law, to bring about transformative reductions in the prices of these medicines, at least for federal programs and possibly beyond. Under 28 U.S.C. § 1498, the U.S. government can buy generic versions of these medicines at less than 1% of their list price plus a reasonable royalty. This power has received almost no academic attention, despite the fact that it is regularly used by the government in other sectors, including defense. Indeed, though it has now been forgotten, the federal government relied on this provision numerous times to procure cheaper generic drugs in the 1960s. We recover this history and show how § 1498 can once again be used to increase access to life-saving medicines, addressing several important interpretive questions about the application of the provision along the way. We also offer the first sustained efficiency defense of this approach. This power, we show, can be analogized to the eminent domain power over land and similarly justified as a means to address hold out problems. We show that courts or agencies can fashion damages remedies that provide robust returns to investment, and so protect dynamic incentives while permitting radical improvements in static efficiency. Our remedy involves some risk, as do all policy innovations. But the status quo is so deeply dysfunctional--with millions of Americans unable to benefit from medicines that could halt the spread of a major disease--that the case for action is overwhelming.

Acylsulfonamide and acylsulfamide as surrogates for the carboxylic acid function of N-acetamide-indole-6-carboxylic acids were evaluated as allosteric inhibitors of hepatitis C virus (HCV) NS5B polymerase. Several analogs displayed excellent antiviral potency against both 1a and 1b HCV genotypes in cell-based subgenomic replicon assays. Structure-activity relationships (SAR) are discussed in the context of the crystal structure of an inhibitor--NS5B polymerase complex. Absorption, distribution, metabolism, and excretion pharmacokinetic (ADME-PK) properties of this class of inhibitors are also described. Key words: hepatitis C virus (HCV), NS5B polymerase, allosteric inhibitors, antivirals, structure-activity relationship. On a evalue les acylsulfonamides et les acylsulfamides comme substituts de la fonction acide carboxylique des acides N-acetamide-indole-6-carboxylique comme inhibiteurs allosteriques de la polymerase du virus de l'hepatite C (VHC) NS5B. Plusieurs analogues presentent des activites antivirales excellentes contre les genotypes 1a et 1b du VHC dans les essais de replication sous-genomiques a base de cellules. On discute de relations structure-activite (RSA) dans le contexte de la structure cristalline d'un complexe inhibiteur--polymerase NS5B. On decrit aussi les proprietes pharmacocinetiques, telles les taux d'absorption, de distribution, de metabolisme et d'excretion (PC-ADME), de cette classe d'inhibiteurs. Mots-cles: virus de l'hepatite C (VHC), polymerase NS5B, inhibiteurs allosteriques, antiviraux, relation structure- activite. [Traduit par la Redaction], Introduction The hepatitis C virus (HCV) is a blood-borne ribonucleic acid (RNA) virus that infects an estimated 170 million people worldwide and can cause severe liver damage such as cirrhosis [...]

The article discusses the transmission of Hepatitis C virus among patients receiving hemodialysis at an outpatient unit in New York. The results of an investigation carried out by the New York State Department of Health (NYSDOH) following this transmission highlighted the need to adhere to recommendations for infection control and ensure appropriate precautions and comprehensive HCV surveillance.

Efficient in vitro systems to study the life cycle of hepatitis C virus (HCV) were recently developed for JFH1 (genotype 2a), which has unique replication capacity in Huh7 cells. We developed 4a/JFH1 intergenotypic recombinants containing the structural genes (Core, E1, and E2), p7, and all or part of NS2 of the 4a prototype strain ED43 that, after transfection of Huh7.5 cells with RNA transcripts, produced infectious viruses. Compared with the J6/JFH control virus, production of viruses was delayed. However, efficient spread of infection and high HCV RNA and infectivity titers were obtained in serial passages. Sequence analysis of recovered viruses and subsequent reverse genetic studies revealed a vital dependence on one or two NS2 mutations, depending on the 4a/2a junction. Infectivity of ED43/JFH1 viruses was CD81 dependent. The genotype 4 cell culture systems permit functional analyses as well as drug and vaccine research on an increasingly important genotype in the Middle East, Africa, and Europe. We also developed genotype 1a intergenotypic recombinants from H77C with vital mutations in NS3. Using H77C/JFH1 and ED43/JFH1 viruses, we demonstrated high homologous neutralizing antibody titers in 1a and 4a patient sera, respectively. Furthermore, availability of JFH1 viruses with envelope proteins of the six major HCV genotypes permitted cross-neutralization studies; 1a and 4a serum cross-neutralized 1a, 4a, 5a, and 6a but not 2a and 3a viruses. Thus, the JFH1 intergenotypic recombinants will be of importance for future studies of HCV neutralization and accelerate the development of passive and active immunoprophylaxis. Egypt | hepatitis C virus strain ED43 | in vitro infection | intergenotypic recombinant | vaccine

One way to dissect the antibody response to an invading microorganism is to clone the antibody repertoire from immune donors and subsequently characterize the specific antibodies. Recently, methodological advances have allowed investigations of neutralizing antibodies against hepatitis C virus (HCV) in vitro. We have investigated three human mAbs, previously isolated from an individual infected with HCV of genotype 2b, that are known to cross-react in a binding assay to the envelope E2 protein of genotypes 1a and 1b. We now report that two of them have a neutralizing activity with a breadth not previously observed. Indeed, mAbs 1:7 and A8 recognized E2 from all of the six major genotypes, and they neutralized retroviral pseudoparticles [HCV pseudoparticles (HCVpp)] carrying genetically equally diverse HCV envelope glycoproteins. Importantly, these antibodies were also able to neutralize the cell culture infectious HCV clone JFH-1 in vitro, with [IC.sub.50] values of 60 ng/ml and 560 ng/ml, respectively. The conformational epitopes of these two broadly reactive antibodies were overlapping yet distinct and involved amino acid residues in the 523-535 region of E2, known to be important for the E2-CD81 interaction. The third antibody clone, representing a dominant population in the initial screen for these antibodies, was less broadly reactive and was unable to neutralize the genotype 2a infectious clone JFH-1. Our results confirm at the clonal level that broadly neutralizing human anti-HCV antibodies can be elicited and that the region amino acids 523-535 of the HCV envelope glycoprotein E2 carries neutralizing epitopes conserved across all genotypes. immunoglobulins | liver disease | viral hepatitis

The evolution of the APRI (alanine aspartyl transferase (AST)-to-platelet ratio index) and its predictive value for hepatic outcomes in a cohort of HIV and HIV-hepatitis C virus (HCV)-coinfected patients with more than 10 years of follow-up are evaluated and the effects of highly active antiretroviral therapy (HAART) on liver disease progression is assessed. The results have shown that APRI is a useful marker for longitudinal evaluation of the progression of liver disease in HIV-HCV coinfection.

Byline: G. Borgia (1), L. Reynaud (1), I. Gentile (1), M. Piazza (1) Abstract: Hepatitis C virus (HCV) infection occurs in about one-third of HIV-seropositive patients and in about 90% of HIV-positive drug abusers. After the introduction of highly active antiretroviral therapy (HAART) and the subsequent reduction in mortality from opportunistic infections, HCV-related liver failure has become a frequent cause of death in HIV-positive patients. In HIV-seropositive patients, the course of HCV infection is accelerated and there is evidence that HCV is an important factor for HIV progression. Consequently, it is important to establish the appropriate treatment for HCV infection in HIV-seropositive patients. This review examines the epidemiology, physiopathology, diagnostics and treatment of HIV/HCV coinfection with particular regard to the impact of HAART. Author Affiliation: (1) Dept. of Public Medicine and Social Security, Institute for Infectious Diseases--Ed 18, Federico II University of Naples, via Pansini 5, I-80131, Naples, Italy Article History: Received Date: 02/07/2002 Accepted Date: 23/12/2002

Byline: L. De Cock (1), R. Vranckx (1) Abstract: Background: Given that both pathogenicity and the response to treatment are possibly associated with hepatitis C virus (HCV) serotype, it appeared sensible to establish the prevalence of the different HCV types in Belgium. Materials and Methods: The HCV serotypes were determined in 68 HCV-RNA and anti-HCV-positive samples taken from Belgian patients and compared with the results of the genotyping assay. Possible associations with age and sex were investigated. Results: Antibodies were identified in 55 (80.9%) of the 68 samples, with serotype 1 (58.8%) and serotype 3 (19.1%) showing the highest prevalence. 17 samples contained several serotypes with serotype 1 being detected in 82.4% of cases. Nine of the 11 samples undetermined by serotyping could be determined by genotyping. There was no significant difference in the distribution of HCV types with respect to gender. Compared with genotype 3 (p &lt 0.01) and genotypes 2 and 4 (p = 0.05), genotype 1 was detected among older patients. Conclusion: Our data showed a 96.0% correlation between the serotyping and genotyping assays. Genotypes 1 and 3 are the most prevalent types among Belgian patients. The data suggest that genotype 1 spread earlier than genotypes 2, 3 and 4. This corroborates previous European studies. Author Affiliation: (1) Dept. of Microbiology, Section Virology, Scientific Institute of Public Health, Juliette Wytsmanstr. 14, B-1050 Brussels, Belgium. liesbet.decock@iph.fgov.be, BE Article note: Received: January 3, 2002 * Revision accepted: December 2, 2002 Liesbet De Cock (corresponding author)

Byline: D. Siagris (1), N. Pharmakakis (2), M. Christofidou (3), J.K. Petropoulos (2), C. Vantzou (2), A. Lekkou (1), C.A. Gogos (1), C. Labropoulou-Karatza (1) Keywords: Key Words Hepatitis C virus; Keratoconjuctivitis sicca; Cryoglobulins; Genotypes Abstract: Background: The aim of this study was to determine the prevalence of keratoconjunctivitis sicca (KCS) in Greek patients with chronic hepatitis C virus (HCV) infection and its association with HCV genotypes and liver histology. Patients and Methods: 93 HCVAb (+) patients underwent lacrimal function testing (Schirmer-1 test, break-up time test and Rose-Bengal staining test) and estimation of serum cryoglobulins and autoantibodies. 80 healthy volunteers were included in the study as controls. Results: 34 out of 93 HCV patients (36.6%) and eight out of 80 healthy subjects (10%) had at least two abnormal lacrimal function tests suggestive of KCS (p &lt 0.001). Cryoglobulinemia was evident in 20 patients (21.5%), rheumatoid factor (RF) in 43 (46.2%), antinuclear antibodies (ANA) in 19 (20.4%), antinuclear antigens (anti-SS-A and anti-SS-B) in one (1.1%) and two (2.2%) patients, respectively. Reduced prevalence of KCS was found in patients with genotype 3a compared to those with other genotypes (5/30, 16.7% vs 20/42, 47.6%, p = 0.007), probably because of their younger age. In patients with KCS a higher staging score was noted in liver biopsy compared to those without KCS (4.50 +- 1.65 vs 3.06 +- 1.88, p = 0.005). Conclusion: Greek patients with chronic HCV infection have a high prevalence of KCS (36.6%). The tow frequency of antiSS-A and anti-SS-B antibodies in these patients denotes different pathogenetic associations from primary Sjogren's syndrome. Author Affiliation: (1) Dept. of Internal Medicine, Patras University Hospital, 4 Tertseti Str, Patras G-26442, Greece Phone: (+3o/610) 438980, Fax: -993982, e-mail: dsiagris@mland.gr, GR (2) Dept. of Opthalmology, Patras University Hospital, Rio, Greece, GR (3) Dept. of Microbiology, Patras University Hospital, Patras, Greece, GR Article note: Received: May 5, 2001 * Revision accepted: April 4, 2002

Byline: C. Campello (1), A. Poli (2), G. Dal Molin (1), F. Besozzi-Valentini (3) Keywords: Key Words Hepatitis C virus; Genotypes; Epidemiology; Risk factors; General population Abstract: Background: Our aim was to define the burden of HCV infection and the related risk factors in a sample of the general population of northern Italy Materials and Methods: This is a survey on the prevalence of hepatitis C virus (HCV) infection carried out in a cohort (861 males and 1,293 females aged 17--67 years) from the general population of northern Italy. Results: The crude HCV seroprevalence rate was 3.3%, higher in females than in males (p &lt 0.01) and with a clear age-related effect (test for linear trend: p &lt 0.01). When adjusted for sex and age in relation to the reference population, the prevalence was 3.7% )95% CI: 2.9--4.5%). In the univariate analysis, HCV infection was related to intravenous drug use (IVDU) (p &lt 0.001) transfusion (p &lt 0.001) tattooing (p = 0.02) chiropodist/manicure (p &lt 0.001) number of children (p &lt 0.01) educational level (p &lt 0.001). In the multivariate analysis sex, age over 50 years, transfusion, IVDU and tattooing were confirmed as risk factors, while the educational level seems to be a protective factors. Separate multivariate analysis for males and females points out that the age shift, the protective effect of education and the number of children as risk factor were present only in females. HCV viremia was detected in the 71.8% of the seropositive, resulting in an infection rate of 2.4% (95% CI: 1.7--3.0%). Genotype 1b accounted for 64.7% of isolates. Conclusion: In the general population of our area, HCV infection is mesoendemic and current infections are mostly sustained by genotype 1b. Author Affiliation: (1) Dept. of Public Medical Science, UCO Preventive Medicine, University of Trieste, IRCCS 'B.Garofolo', Via dell'Istria 65/1, I-34137 Trieste, Italy Phone: (+39/40) 7-73433 Fax: -600324, e-mail: campello@burlo.trieste.it, IT (2) Dept. of Public Health and Medicine, University of Verona, Strada le Grazie 8, I-37134 Verona, Italy, IT (3) Distretto Valle Trompia ASL Brescia, Via Beretta 3, I-25063 Gardone Val Trompia (BS), Italy, IT Article note: Received: November 29, 2000 * Revision accepted: October 7, 2001

Byline: B. Othman (1), F. Monem (2) Keywords: Key Words Prevalence; HCV; Hemodialysis; Transplant recipients; Damascus Abstract: Background: Evaluation of the epidemiology of hepatitis C virus (HCV) infection was made possible by the development of a serological assay to detect antibodies to epitopes of HCV. Hemodialysis (HD) is considered to be one of the main risk factors of HCV transmission. Therefore, the prevalence of antibodies to HCV (anti-HCV) was studied in patients undergoing maintenance dialysis therapy. Patients and Methods: Anti-HCV were detected using a third-generation assay. The study group consisted of HD patients, transplant recipients and staff members from two dialysis units in Damascus, Syria. Results: The overall prevalence of anti-HCV among HD patients was 48.9% 24,4% in one center (Al-Mouassat Hospital) and 88,6% in the other (Kidney Hospital). There was a significant correlation between prevalence of anti-HCV and duration of HD. The prevalence was 36.7% for patients on HD for &lt 3 years and 65% in patients on HD for &gt 3 years (p &lt 0.05). There was a significant correlation beteen anti-HCV positivity and elevated liver enzymes: alanine aminotransferase (ALT) and asparate aminotransferase (AST). However, there was no significant correlation between anti-HVC positivity and history of blood transfusion, exposure to hepatitis B virus, age and sex. The prevalence of anti-HCV among kidney transplant recipients was 48%, among staff members of the dialysis units it was 5.8%. Conclusion: Factors related to infrastructure and operational system might be responsible for the very high prevalence of anti-HVC found in one of the two units. There was no data available on anti-HCV status of transplant recipients prior to transplantation. However, the prevalence among those patients, which is very similar to that of HD patients, suggests that HD may be responsible for such high prevalence among this group. An intensive educational program for staff members and proper evaluation of the HD situation in the two units are needed. Author Affiliation: (1) P.O. Box 511, Al-Tal, Damascus, Syria Phone:, (+96/31) 1-2820668, Fax: -6119809, SY (2) Al-Assad University Hospital, Clinical Laboratory Dept., Damascus, Syria. E-mail: fawzamon@scs-net.org, SY Article note: Received: November 27, 1999 * Revision accepted: March 2, 2001

To the Editor: The Fundacao de Hematologia e Hemoterapia do Amazonas is a public health service in Manaus, Brazil, that is responsible for serologic screening the serum of all blood [...]

The article discusses epidemiology, natural history, treatment and pathogenesis of the prevalence of hepatitis C virus (HCV) in the HIV-infected patients. It demonstrates the need of development of new strategies for the destruction of HCV, as the HCV-related liver disease leads to death of most of the patients.

As expected, the US Food and Drug Administration has approved what is only the second drug to directly target the hepatitis C virus. Telaprevir (Incivek), marketed by Vertex Pharmaceuticals in [...]