CROI 2020 Abstract eBook

Abstract eBook

Oral Abstracts

disorders including depression, anxiety disorders, and substance use disorders is higher in people living with HIV (PLHIV) compared to the general population. Reported prevalence estimates of mental and substance use disorders in PLHIV in low- and middle-income countries (LMIC) range between 19% and 50%, with depression being the commonest. This increased risk is often mediated by a mix of factors which could be biological- related the virus and its treatment, psychological- related to stigma and coping, as well as behavioral-related to adherence to medication and retention in care. The presence of mental disorders in PLHIV is often associated with an increased risk of HIV disease progression, poor adherence to antiretroviral therapy and excess mortality. An often overlooked and less well researched aspect of this relationship is the higher risk of HIV amongst people with serious mental disorders such as bipolar affective disorders, schizophrenia and schizoaffective disorders. Patients with comorbid mental disorders and HIV are more likely to delay HIV treatment initiation and more likely to engage in HIV risk behaviors and hence are potential drivers for the continued spread of the virus especially in parts of sub-Saharan Africa with high HIV prevalence rates. Whilst mental health services have become widespread in HIV care and support services in high-income countries (HIC), low- and middle-income countries that bear a disproportionate burden of the HIV infection are still lagging behind in developing appropriate services to meet the mental health needs of PLHIV. Health systems in low- and middle-income countries are commonly overburdened and characterized by poor human and financial resources which are particularly worse for mental health care. Adoption of a stepped care, task sharing approach is likely to be the most viable option. However, research evidence for the most appropriate models that can deliver effective and cost-effective integrated care in LMIC is still sparse. Meeting the UNAIDS 90-90-90 goal will require commitment to expanding culturally appropriate mental health services for PLHIV, especially in LMICs, that include prevention of transmission of the infection in people with mental disorders, early identification of mental disorders in PLHIV and the provision of evidence-based care. 102 CEREBROVASCULAR DISEASE AND HIV IN THE GLOBAL SETTING: DATA FROM ASIA AND BEYOND Felicia C. Chow , University of California San Francisco, San Francisco, CA, USA Stroke is the second leading cause of death worldwide. An estimated 1 in 4 25-year-olds globally will have a stroke during their lifespan. The largest burden of stroke (over 75% of stroke mortality and 80% of disability-adjusted life years) is shouldered by low-and-middle income countries (LMIC) where, in sharp contrast to high-income countries (HIC) that have been experiencing a decline in stroke incidence, stroke rates are steadily rising. Furthermore, strokes in LMIC occur at a younger mean age, affecting individuals during the peak of their productivity. This global stroke crisis poses a major threat to many of the same regions of the world where HIV prevalence is high. This presentation will focus on cerebrovascular disease in persons living with HIV (PLWH) in Asia, with its exceedingly high global lifetime risk of stroke, and sub-Saharan African (SSA), which has seen a rapid acceleration in stroke rates. We will review available data on the epidemiology of HIV-associated stroke in LMIC, drawing attention to similarities and differences in stroke risk factors, pathogenesis, and outcomes between LMIC and HIC. One recurring theme is the strong association between HIV and stroke in younger age groups and, similar to in the general population in LMIC, a younger age at diagnosis of first-time stroke in PLWH, underscoring the pivotal role that HIV plays in stroke in the young. We will also discuss the implications of increased cerebrovascular risk in PLWH on cognitive impairment and potential differences in the contribution of cerebrovascular dysfunction to cognitive health between women and men living with HIV. Finally, with the overall paucity of data on cerebrovascular disease in PLWH from LMIC, we will underscore gaps in knowledge where research efforts should be focused. Gilles Wandeler , University of Bern, Bern, Switzerland Chronic hepatitis B virus (HBV) infection affects 250 million persons worldwide and is the most important cause of liver cirrhosis and cancer. In 2017, the World Health Organization outlined specific targets along the prevention and care cascade to be met if the elimination of HBV as a global health threat was to be achieved. Among the proposed core interventions, global service coverage of the HBV vaccine birth dose, as well as the uptake of testing and antiviral therapy remain largely insufficient. This presentation will highlight the key determinants of global HBV elimination and discuss the main challenges that 103 GLOBAL ELIMINATION OF HEPATITIS B VIRUS

will be faced during the implementation of prevention and care interventions. It will also insist on the importance of addressing logistic and sociocultural barriers, especially in resource-limited countries where the HBV burden is highest. As many of the challenges expected to arise on the road to HBV elimination are similar to those experienced during the fight against HIV, it will be critical to learn the lessons from the past 30 years and avoid making the same mistakes. Recent improvements in the understanding of the HBV life cycle and the development of promising treatment modalities to achieve the functional cure of HBV have helped move HBV elimination up the global political agenda. However, HBV elimination will only be achieved if these scientific achievements are accompanied by the rapid uptake of HBV vaccination, testing and treatment. To succeed, HBV elimination efforts will heavily rely on innovative public health strategies, education and political will. Approximately 257 million people worldwide are chronically infected with the hepatitis B virus (HBV). About 900,000 people die from HBV-related liver failure and/or hepatocellular carcinoma each year, which makes HBV more deadly than HIV and malaria. Unfortunately, the incidence of HBV-related mortality is projected to increase further in the coming decades. The goal of curative treatments for chronic HBV infection is a functional cure, defined as sustained loss of hepatitis B surface antigen (HBsAg) with or without anti-HBsAg antibodies. Clearance of HBsAg is a durable endpoint and associated with improved long-term clinical outcome. Unfortunately, nucleos(t)ide analogues are not sufficient to achieve cure, because they do not eliminate the covalently closed circular HBV DNA nor the HBV DNA that has integrated into the human genome. Treatment with pegylated IFNalpha can achieve this cure, albeit only in a minority (2-10%) of chronically HBV infected patients. Its immunomodulatory effects are thought to be important in this process. Although we understand many features of acute self- limited hepatitis B and natural and vaccine-induced immunity, our understanding of immune response in chronic hepatitis B is still limited. One of the keys to curing chronic infection lies in a better understanding of innate and adaptive immune responses in early childhood and the first two decades of life. New insights are emerging that HBV induces innate immune cell maturation and T-helper type 1 cell differentiation (trained immunity) in early life and that an age-related increase in inflammation contributes to changes in disease activity during later life. This presentation will review the role of innate and adaptive immune responses in the control of acute HBV infection, their modulation during the distinct clinical phases of chronic infection and immune therapeutic strategies to induce a functional cure. Raymond T. Chung , Harvard University, Cambridge, MA, USA The goals of hepatitis B virus (HBV) treatment are to: 1) achieve sustained suppression of HBV replication, 2) decrease liver injury and 3) prevent cirrhosis, liver failure, hepatocellular carcinoma (HCC) and death. Currently available FDA-approved therapies have been able to deliver on each of these clinical goals, using well-tolerated nucleos(t)ide analogues with high barriers to resistance. However, they are limited in their ability to yield functional cure (loss of HBsAg with or without anti-HBs seroconversion). Hence, there remains a large unmet clinical need. The ultimate clinical goal is to achieve functional cure of HBV with a finite course of treatment. However, there are many challenges to HBV functional cure. Most importantly, like HIV, HBV has a latent form, covalent closed circular DNA (cccDNA), a highly stable episomal form of the HBV genome that serves as the template for new HBV transcription in the nucleus. Moreover, a fraction of HBV DNA is also integrated into the host genome, and there is evidence that a portion of integrated HBV DNA, particularly HBsAg, can be translated. These stable forms are largely untouched by current therapies. There is also evidence that in chronic hepatitis B (CHB), the adaptive virus-specific immune response becomes exhausted, further contributing to chronicity. The latest therapies in the pipeline seek to achieve HBsAg loss using approaches that target other, discrete steps in the HBV lifecycle as well as modulate the immune environment essential for clearance. Novel antiviral therapies in clinical development include entry inhibitors, capsid assembly modifiers to block assembly and possibly replenishment of cccDNA, RNA interference (siRNA) to block viral protein production, and nucleic acid polymers to block HBsAg release. Immunomodulatory therapies include strategies both to stimulate ADAPTING THE IMMUNE RESPONSE TO CURE HEPATITIS B Barbara Rehermann , NIH, Bethesda, MD, USA

Oral Abstracts

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CROI 2020