CROI 2016 Abstract eBook

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Oral Abstracts

were in sub-Saharan Africa. Almost two-thirds of all adolescents and youth with HIV are females. Capturing adolescent data is particularly complex because these data represent a combination of perinatally and behaviorally infected ALHIV – a factor that is critical to understanding clinical and programmatic outcomes, but which is not disaggregated in surveillance or program evaluation. These groups have substantially different social contexts and HIV disease experiences. Perinatally infected ALHIV are frequently orphaned, highly treatment experienced, and experiencing long-term complications of their disease after a lifetime of immunosuppression. Behaviorally infected ALHIV are coping with a relatively recent diagnosis, more often from key affected populations, have less severe disease and better immune function, and poorer treatment uptake. Adherence and retention research has shown that older adolescents, who are more likely to be behaviorally infected, are twice as likely to be lost to follow-up compared to younger adolescents and older adults. However, HIV-related mortality among ALHIV is more frequently due to deaths of the perinatally infected. The persistent increase in ALHIV death compared to a 41% decrease observed in adults since 2005 represents a serious failure of the global HIV response. When it was reported in 2014 that HIV was the second leading cause of death of adolescents worldwide and the most common cause of death in sub-Saharan Africa, policy makers and advocates began campaigning to promote investment into the continuum of prevention, testing, and care for adolescents. In order to achieve current targets for reduction of new infections and expansion of care and treatment, resources would have to increase by at least 45%. In addition, the quality of the strategic information used to monitor the ALHIV epidemic and the impact of programmatic interventions would need to improve by disaggregating surveillance data by age, sex, mode of exposure, and key population. 175 Blame It On the Brain Lisa K. Simons , Ann and Robert H. Lurie Children’s Hosp of Chicago, Chicago, IL, USA Adolescence is understood to be a period of tremendous growth and development: physically, cognitively, emotionally and socially. While most adolescents experience their peak physical health during this time, morbidity and mortality during adolescence rise substantially. This paradoxical increase is largely related to an upsurge in risk-taking behaviors observed in adolescence. Over the past fifteen years, advancements in neuroimaging studies have offered enhanced understanding of structural and functional changes which occur in the brain during adolescence. One model of conceptualizing adolescent risk-taking behavior (proposed by developmental psychologists such as B.J. Casey and Laurence Steinberg) relies in part on the differential timing and rate of maturation of regions of the brain implicated in modulating reward sensitivity and exerting cognitive control. While these neurodevelopmental processes should not be presumed to be the singular cause for increased risk-taking behaviors during adolescence, they suggest some neural explanation for adolescents’ propensity towards risk-taking behaviors. This expanded understanding of adolescent neurodevelopment has important implications for clinicians caring for adolescents living with HIV and for those developing interventions targeted at adolescents. 176 Finding and Engaging Adolescents With HIV in Low- and Middle-Income Countries Rashida A. Ferrand , London Sch of Hygiene & Trop Med, London, UK Adolescents are the only group in which HIV-associated mortality continues to rise, despite the remarkable global scale-up of antiretroviral therapy. This is mainly due to delayed diagnosis with less than a third aware of their HIV status globally. HIV testing strategies for adolescents to date have primarily been similar to those employed for adults and fail to take into account the specific legal, sociocultural and structural barriers to HIV testing faced by this age-group. Innovative strategies to identify adolescents living with HIV that are context- and age-appropriate, sustainable and acceptable to both adolescents and their caregivers are required. Adolescents fare disproportionately poorly across the HIV care continuum following diagnosis and therefore testing strategies must be accompanied by strategies to engage adolescents who test HIV-positive with care services. Evidence for such strategies is sparse. The talk will review existing evidence base for innovative interventions to identify adolescents living with HIV, including both health facility and community-based strategies, and describe how these can overcome barriers to HIV testing and engagement with HIV care in this age-group. It will highlight research priorities to address the burden of undiagnosed HIV in this age-group in lower and middle-income countries. 177 Thinking About the Future: Transition for Adolescents With HIV Allison L. Agwu , Johns Hopkins Univ, Baltimore, MD, USA The HIV epidemic among adolescents and youth includes a heterogeneous mixture of survivors of perinatally-acquired HIV infection and those acquiring infection during the second decade of life. Youth living with HIV (YLHIV) have poorer rates of diagnosis, engagement and retention in care, and initiation of combination antiretroviral therapy (cART); and higher rates of cART discontinuation than older adults. All perinatally HIV-infected and approximately 20% (in the U.S.) of non-perinatally HIV-infected youth initially engage in care in pediatric/youth HIV clinics. Studies have demonstrated better ART initiation, retention, and virologic suppression for YLHIV followed in pediatric/youth compared to adult HIV care. However, given the limitations in the structure of these pediatric/youth clinics, YLHIV must transition to adult care, between the ages of 15 and 25 years, depending on the region where they reside. There are a multitude of logistic, structural, and psychosocial barriers to transitioning YLHIV from pediatric/youth to adult care. Therefore, YLHIV are at increased risk of loss to care and associated negative outcomes (e.g., nonadherence, viremia, immunologic deterioration, morbidity, and HIV transmission) during and after this transition period. Guidelines recommend strategic comprehensive, youth-friendly, integrated transition approaches to effectively transition the care of these YLHIV from pediatric/ youth to adult HIV care. However, there is limited data on transition strategies, best practices, and clinical outcomes. The aging up of YLHIV creates a critical need to define successful transition, assess different transition strategies, including their implementation, cost, feasibility and sustainability, and importantly, determine the clinical outcomes of the strategies employed. This information is needed to inform guidelines and best practices to optimize retention and clinical outcomes, during and after transition, for YLHIV. 178 NK Cell-Mediated Recognition of HIV Marcus Altfeld , Heinrich Pette Inst, Hamburg, Germany NK cells represent the main cytotoxic effector cell population of the innate immune system, and play an important role in the control of viral infections. The mechanisms by which NK cells can recognize HIV-1-infected cells remain incompletely understood. On this presentation, new data will be presented on the receptor/ligand interactions that allow NK cells to recognize and kill HIV-1-infected cells, and on the mechanisms by which HIV-1 can evade NK cell-mediated recognition. 179 Natural killer (NK) cells play critical roles in immune defense and reproduction, but remain the most poorly understood major lymphocyte population. NK cells contribute to control of chronic HIV infection, yet their role in protection from infection is less clear. NK cell activation is controlled by a variety of combinatorially expressed activating and inhibitory receptors, making NK cell diversity and function closely linked. We recently defined that the human NK cell repertoire is remarkably diverse, with an estimated 6000 to 30,000 phenotypic populations within an individual and >100,000 phenotypes in a small population. Furthermore, our studies revealed immune experience diversifies and specializes the NK cell repertoire. Finally, high NK diversity is associated with increased risk of HIV-1 acquisition in a Kenyan cohort. Overall, these studies suggest that NK diversity may decrease the flexibility of the antiviral response, and that human NK diversity is a previously undefined metric of immune history and function that may be clinically useful in predicting the outcomes of viral exposure. 180 Supercharging NK Cells for Cure Jonathan Karn , Case Western Reserve Univ, Cleveland, OH, USA We are developing a novel HIV eradication strategy that combines proviral reactivation, ex vivo stimulation, expansion of natural killer (NK) cells, and enhancement of NK cell killing specificity and cytotoxicity via antibody-dependent cell-mediated cytotoxicity (ADCC). Our main hypothesis isthat MHC Class I downregulation induced by the expression of Nef Signatures of Protective NK Cell Responses Catherine A. Blish , Stanford Univ, Stanford, CA, USA

Oral Abstracts

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CROI 2016