CROI 2016 Abstract eBook

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Oral Abstracts

potential drug-associated neuronal toxicity and vascular abnormalities will be presented. Following a brief description of the pharmacokinetic determinants of antiretroviral penetration and activity in the CNS (including cellular targets), the available evidence on the effect of different antiretrovirals on CNS HIV will be reviewed as well as the studies involving ARV combinations for treating patients with CNS disorders including the ongoing discussion on the use of the CNS concentration/effectiveness (CPE) score and the effect of unconventional antiretroviral regimens (based on more or less than three drugs). Finally, studies on adjunctive therapies will be presented and potential therapeutic targets reviewed. 64 Hepatitis C: Global Epidemiology ImamWaked , Natl Liver Inst, Shebeen El Kom, Egypt Hepatitis C virus (HCV) is a major global health burden and the leading cause of liver disease and hepatocellular carcinoma in many parts of the world. New treatment options are available that have the potential to change the epidemiology and natural history of the disease, and there is a need to precisely characterize its epidemiology and disease burden. Total global sero-prevalence is estimated at 120-180 million cases, with around two thirds viremic (viremic infections estimated at 80-120 million infections). Egypt is the country with highest prevalence, with 12% of the population sero-positive, and close to 8% of the population chronically infected. The 5 countries with largest number of patients (China, Pakistan, Egypt, Nigeria and India) have close to 50% of the global viremic patients despite their limited resources. Transmission routes are different in different areas globally. In developed countries where prevalence is low, transmission is mainly through needle sharing among PWID, as high- risk behavior and nosocomial transmission has decreased. In under-developed and limited resources countries, transmission is still ongoing mainly through blood transfusion and non-sterile equipment use in the healthcare settings, and reuse of needles for medical injections. Mass spread of HCV coincided in Egypt with the intravenous mass-treatment of schistosomiasis, and coincided in many areas of Africa with the introduction of population vaccination in the 1960s and 1970s. In addition, HCV is genetically diverse, with seven genotypes and many subtypes. There are regional variations in genotype prevalence, and genotypes respond differently to different therapies. Genotype 1 (G1) is the most common worldwide (44%-48%%) with around 50-60 million viremic cases, with most in East Asia, followed by G3 (20%-22%, 30-35 million cases), G2 (12%-15%, 15-20 million cases), and G4 (12%-15%, 15-20 million cases). Genotypes 5 and 6 comprise a limited minority. G1 and G3 are predominant in most countries, and genotypes 4 and 5 and more prevalent mainly in lower-income countries. Not all countries report anti-HCV prevalence; and HCV viremic rates and genotype distribution are more scarce. More recent and accurate geographical epidemiological data is needed to direct treatment development and availability, and to guide vaccine development efforts. 65 Hepatitis C in Egypt: A National Approach to Treatment Manal H. El-Sayed , Ain Shams Univ, Cairo, Egypt Egypt has one of the highest global burdens of hepatitis C virus (HCV) infection, with an estimated 7%, over 6 million people between 15-59 years, being chronically infected. Tragically, an estimated 150,000 new people are being infected annually, and thousands die every year. In recognition of the enormity of the problem, in 2006, the Ministry of Health established a National Committee for Control ofViral Hepatitis (NCCVH), a team of experts who published the first national strategy for control of viral hepatitis in Egypt and established a nationwide treatment program in 26 specialized viral hepatitis units treating 350,000 patients through the Ministry of Health program. In 2012, and in collaboration with stakeholders includingWHO, US-CDC and Pasteur Institute, the NCCVH and MOH developed the“Plan of Action for the Prevention, Care &Treatment ofViral Hepatitis, Egypt” (PoA) which focuses on the seven main components of viral hepatitis prevention and control: surveillance, infection control, blood safety, hepatitis B virus (HBV) vaccination, care & treatment, communication, and research. In addition, in 2014, Sofosbuvir was introduced for nationwide treatment of HCV infection at 1% of its international price.The NCCVH is also introduced other approved direct antiviral agents consecutively during 2015, in addition to encouraging the local manufacturers to produce prequalified generics to effectively implement the elimination program in the shortest possible duration. A web-based registration system has been established mid-September 2014 to schedule patients’appointments to receive treatment at its specialized units. So far, more than one million patients with known HCV infection have registered and are being evaluated at the NCCVH centers.The numbers treated increase by at least 15,000 on monthly basis with almost 200,000 treated in by the end of 2015.The success of the Egyptian endeavor in collaboration with national and international partners would provide an exemplary model that can be replicated in other resource-limited countries. 66 Hepatitis C Therapeutics: Pangenotypic Therapeutics on the Horizon Karine LaCombe , Sorbonne Univs, Paris, France With more than 185 million individuals affected worldwide, chronic hepatitis C virus (HCV) infection has emerged as a major public health problem. More than one million deaths are attributed to chronic HCV, together with chronic hepatitis B, ranking it among the top ten causes of death in the Global Burden of Diseases. The advent of direct antiviral agents, targeting multiple steps in the viral replication cycle, has led to substantial improvement in the management of chronically infected patients. By increasing rates of sustained virological response to 90% in the 12 weeks after end of treatment, HCV therapy has dramatically improved clinical outcomes for all patients, including those with more severe disease (i.e. cirrhotics or with liver transplants). However, there are still a number of issues needing to be addressed alongside the continuum of care, among which simplifying virological evaluation is paramount. One of the keys to alleviate the burden of costs will be the use of pangenotypic drugs. These agents help reduce the need for genotyping and possibly extensive viral load monitoring, thereby easing HCV-associated care for all. As we aim towards global elimination of hepatitis C, the use of pangenotypic drugs will constitute a major step forward. 67 Hepatitis B Virus: Is a Cure Possible? Chloe Thio , Johns Hopkins Univ, Baltimore, MD, USA Worldwide, about 2 billion people have had a hepatitis B virus (HBV) infection and 248 million are chronically infected. Once an HBV infection occurs, a stable, intranuclear form, known as the cccDNA persists not only in those with chronic infection but also in those who resolve infection with production of protective hepatitis B surface antibody. Cure of hepatitis B can be defined as a functional cure or an eradication cure. A functional cure is similar to what occurs naturally with resolution of an acute infection where the immune system can control HBV replication without medication and protective hepatitis B surface antibody is produced. In the functional cure, the cccDNA is still present. An eradication cure is a therapy that eliminates the cccDNA. In this talk, I will discuss both types of cure and progress towards each of them. 68 Delivery of PrEP: From Evidence to Practice C. Bradley Hare , Kaiser Permanente Northern California, San Francisco, CA, USA The efficacy and effectiveness of HIV pre-exposure prophylaxis (PrEP) have been shown in randomized clinical trials, demonstration projects and real-world cohort studies. Despite this, uptake of the use of PrEP in the US was initially slow after its FDA approval in July 2012. More recent data indicate increased awareness, acceptability and uptake in some – but not all – at-risk populations and geographic areas. As PrEP use increases, many questions remain unanswered about the optimal models for PrEP delivery. In what settings and by whom should PrEP be provided? What population(s) should be targeted, and how do we reach those who could most benefit from PrEP? What is the appropriate monitoring and follow-up? What additional services should be provided and how are they best integrated with PrEP? How do you predict interest and plan for increasing capacity and sustainability? What staffing and resources are needed to provide PrEP safely and effectively? This presentation will explore these questions using published reports and real- world experience to provide a framework for conceptualizing and implementing sustainable delivery models for PrEP.

Oral Abstracts

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CROI 2016