CROI 2020 Abstract eBook

Abstract eBook

Oral Abstracts

160

GETTING IT RIGHT: PRACTICAL APPROACHES TO ADHERENCE WITH MODERN ARVs Jose R. Castillo-Mancilla , University of Colorado Denver, Denver, CO, USA Along with the remarkable advancements in antiretroviral therapy (ART), new paradigms have emerged on the importance of adherence. Early studies with older antiretrovirals (ARVs) proposed that >95% adherence was required to achieve and maintain virologic suppression, which led to the concept that an undetectable HIV viral load (VL) was equivalent to full adherence. However, the potency and favorable pharmacology of the new ARVs have allowed for more forgiveness to missed doses, with recent studies demonstrating that the “minimal” level of ART adherence required to sustain viral suppression may range between 80-85% (and as low as 75%). While advantageous, achieving viral suppression despite variable ART adherence has de-emphasized the focus on adherence in clinical practice, limiting our understanding of its consequences at the individual (i.e., biological, virological) and population (i.e., transmission) levels. This is essential to maximizing the benefit of ART and controlling the HIV epidemic, since maintaining an undetectable HIV VL (mainly driven by adherence) is indispensable for the U=U (Undetectable=Untransmittable) strategy to be effective, and because adherence remains a lifelong challenge. However, despite its critical importance, we currently lack a gold-standard measure to quantify ART adherence. In response to this gap, several innovative methods and strategies to objectively measure ART adherence have emerged in recent years. These include: a) pharmacologic methods that inform about cumulative adherence and recent dosing by quantifying drug concentrations in plasma, urine, hair and dried blood spots; b) advances in electronic medication dispensers that monitor pill-taking behavior, and; c) digital pills that confirm medication ingestion. These novel methods have proven more accurate than self-report, can predict adverse clinical outcomes (i.e., viremia), and provide real-time adherence information that can lead to actionable interventions during a routine clinical visit. Moreover, pharmacologic methods can assess inter-individual pharmacokinetic differences not captured by HIV VL monitoring or other adherence measures. This symposium talk will address these and other questions by exploring the benefits and potential risks of forgiveness of modern ARVs (including long-acting agents), evaluating the pearls and pitfalls of existing and new ART adherence measures, and providing the audience with some practical strategies for integrating these tools into clinical practice. In 2017, WHO published its Global Hepatitis Report, which described the status of the viral hepatitis epidemic in 2015, at the baseline of the Global Health Sector Strategy (GHSS)on viral hepatitis that aims for elimination. In 2020, 4 years into the strategy, we can reflect on what is known and what is unclear in terms of incidence, prevalence, and mortality of HCV infection. With respect to incidence, using a model from the Centre for Data Analysis (CDA), WHO estimated that in 2015, 1.75 million new infections occurred. Surveillance for acute hepatitis C and age-specific seroprevalence suggests that in most countries, the incidence has been on the decline. However, a recrudescence of transmission because of injection drug use, unsafe health care or unsafe practices among men who have sex with men is always possible. This calls for enhanced case reporting of acute hepatitis to describe trends and risk factors for infection. With respect to prevalence, on the basis of a CDA systematic review of biomarker surveys adjusted with modeling, WHO estimated that 71 million persons were living with HCV in 2015. This number is decreasing because of curative treatments. Also, the heterogeneity of prevalence needs to be better characterized so that testing and treatment policies can be adapted. A limited number of high-prevalence countries (> 2-5%) faced substantial morbidity and mortality that require testing in the general population. However, most infections are located in settings where prevalence is under 2% and where focused testing may be more cost-effective. Given this heterogeneity, local biomarker surveys and data on the prevalence of HCV infection in subgroups being tested are needed to guide testing and treatment policies. Finally, on the basis of death certificates and attributable fractions, WHO estimated that in 2015, about 400,000 persons died from the sequelae of HCV infection, including cirrhosis and hepatocellular carcinoma. While on average HCV-associated mortality is increasing worldwide, there are differences. In countries where transmission occurred many decades ago, mortality already started to decrease. In countries where transmission took place more recently, mortality is still increasing or in some cases, may not even have started to increase. Therefore,

Our host defenses have evolved over millions of years and in general they work pretty well, except when they don’t. In HIV infection, defenses are broadly dysregulated resulting in both a heightened risk of infection and a systemic proinflammatory environment. Thus host defenses and the immune activation and inflammation that mediate these defenses cannot be viewed on a simple two-dimensional scale. These perturbations are improved with antiretroviral therapy, but they are not completely normalized and in particular, inflammatory morbidities persist as does a reservoir of replication-competent virus. If properly monitored, targeted interventions to alter this environment can provide insight as to how immune and inflammatory pathways interact but we should be prepared to expect the unexpected as these pathways are complex, dynamic and difficult to orchestrate smoothly with the simple yet blunt interventions that we possess. 157 NOVEL ANTIRETROVIRAL AGENTS: TRANSFORMING THE CARE OF PEOPLE WITH HIV Rajesh T. Gandhi , Massachusetts General Hospital, Boston, MA, USA In this state-of-the art overview, we will discuss new approaches to treating HIV, including agents with novel mechanisms of action; long-acting medications; and innnovative delivery systems. We will review novel options for optimizing treatment of HIV for a broad array of patients, including those initiating therapy for the first time and those who have multi-drug resistant virus. And we will highlight treatments that are on the horizon but that have the potential to transform the care of people with HIV. PEDIATRIC AND ADOLESCENT ART: A ROAD LESS TRAVELLED Carolyn Bolton Moore , Centre for Infectious Disease Research in Zambia, Lusaka, Zambia Over the last three decades, advances in antiretroviral therapy and improvements in overall clinical management and service provision have dramatically reduced both morbidity and mortality in children with HIV across the globe. However, in general, outcomes remain much poorer than those seen in adults and data from both the developing and developed world show that children have consistently lower rates of viral suppression than adults. Adherence to ART is critical for optimal treatment outcomes. Proper adherence to treatment results in viral suppression, improved symptoms, fewer opportunistic infections and less chance of viral resistance. Barriers to poor adherence are diverse and those affecting young children may differ significantly from those largely affecting older children and adolescents. Developing more palatable, child-friendly formulations of ART which do not require specialized cold chain management is likely to significantly increase adherence amongst younger children. But improving treatment outcomes in older children and adolescents likely requires a multi-pronged approach combining innovative behavioral interventions, stigma reduction strategies and simplification of treatment regimens. Several strategies for reducing and simplifying antiretroviral therapy for adolescents and children are currently under investigation and aim to maximize adherence, reduce toxicity, preserve future treatment options, and reduce costs. Development of pediatric formulations of antiretroviral drugs have historically lagged 10-15 years behind that of adult versions of the drugs, partly as a result of diminishing markets for these drugs in wealthier countries and partly due to the complexity of the physiological and developmental changes associated with childhood and adolescence. Over the past few years, various efforts have enabled better alignment and agreement on key principles in pediatric drug development and research including defining dosing by weight bands, applying innovative study designs, synergizing work across research networks to achieve common goals, including adolescents in adult trials and the establishment of a global prioritized research agenda. However, despite these advances, accelerating the pediatric agenda and prioritizing new/ more effective agents and formulations remains a priority. Keeping up the momentum, and finding newmomentum, is key to ending the epidemic and allowing our children and adolescents to be happy, healthy and free of HIV. 158

Oral Abstracts

161 GLOBAL EPIDEMIOLOGY OF HEPATITIS C Yvan J. Hutin , WHO, Geneva, Switzerland

159 METABOLIC COMPLICATIONS OF HIV AND ITS THERAPIES Jordan E. Lake , University of Texas at Houston, Houston, TX, USA

This talk will discuss the contributions of current ART agents and combinations to metabolic disease, including the potential impact of weight gain on co-morbid conditions, and possible interventions to mitigate metabolic complications of ART.

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CROI 2020