CROI 2016 Abstract eBook

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clinic-based administrative records, for example, can reveal the extent to which undocumented deaths (including deaths among patients who were well engaged) as well as “silent transfers” (undocumented movement across clinic settings) contribute to attrition in a particular setting. In addition, patient-provider communication and quality of care itself represent critical but under-explored dimensions of retention. Second, diverse barriers to retention have been documented in the literature and include depression, stigma, work demands, and long waiting times at clinic among many others. Application of qualitative and causal methodologies can elucidate the causal relationships between these factors, retention, and downstream outcomes such as productivity and HIV RNA suppression. Insight into this complex behavioral “anatomy” of retention can inform “retention 2.0” interventions. For example, exciting approaches seek to enhance patient activation, leverage social capital, and apply behavioral economics to create greater and more consistent demand for treatment. Health systems are evolving to use community based delivery strategies, mHealth and peers to enhance the accessibility, efficiency and quality of the supply of care. In addition, adaptive approaches offer the promise of “personalized public health.” Adaptive approaches and seek to minimize expenditures where less is sufficient (optimizing efficiency), but intensify where more is needed (optimizing effectiveness). Insights from implementation science such as standardization of intervention specification, routine use of mixed methods, attention to implementation outcomes, and elucidating mechanisms to inform transportability can strengthen the next generation of research on retention in HIV care. 122 Innovations in Antiretroviral Therapy Delivery Anna Grimsrud , IAS, Cape Town, South Africa In September 2015, WHO announced “Treat all” recommending antiretroviral viral therapy (ART) for everyone living with HIV. The most recent UNAIDS estimates suggest that 15.8 million people are accessing ART and 36.9 million people globally are living with HIV. If we are to reach the ambitious “90-90-90” targets and more than double the treatment cohort, innovations in ART delivery are needed. There are a growing number of examples of differentiated models of ART delivery that provide quality, patient-centred care and in turn, free up the capacity of the health care system to support those most in need. Examples from the field will be presented, alongside data of their effectiveness, evidence of their broader implementation and some insights on what may be needed to support expansion and inclusion in national guidelines. While the principles of differentiation have primarily focused on simplifying models of care for the “stable” patient, the case will be made for their application across other groups of patients, in different contexts and for all sub-populations. Global funders, normative agencies, implementers and civil society acknowledge that innovations to service delivery are urgently required. However, questions remain about how to ensure quality care to the millions of people living with HIV, to what extent differentiated models lead to efficiency gains, and howmodels of ART delivery can support the HIV continuum of care and other chronic diseases. 123 Visceral Adiposity in the Modern HIV Treatment Era Grace A. McComsey , Case Western Reserve Univ, Cleveland, OH, USA Lipohypertrophy or gains in fat depots, the most concerning of which being visceral abdominal and ectopic fat, occur commonly after the initiation of treatment for chronic illnesses including HIV infection. Although incidence of lipoatrophy or peripheral fat loss was drastically attenuated by the avoidance of thymidine NRTI agents, a different picture is surfacing for lipohypertrophy. Recent data revealed that accumulation of visceral fat occur occurring with contemporary antiretroviral regimens perceived to be metabolically- friendly. These central fat changes are clinically important as they can predispose to cardiovascular disease and could have devastating consequences on quality of life, and importantly have been shown to predict mortality. There are limited data on the pathogenesis of central fat accumulation, and the advent of these changes with all antiretroviral classes should make us question the importance of HIV itself, directly or indirectly thru inflammation and immune activation. Associations with viral-specific factors will be therefore emphasized, and discussions of potential mechanisms will include specific dietary factors that could have major impact on gut barrier integrity. Finally, strategies to prevent or treat visceral fat accumulation will be discussed. 124 NAFLD and NASH in HIV Infection Elizabeth C. Verna , Columbia Univ, New York, NY, USA Liver disease is a leading cause of morbidity and mortality among persons with HIV, and in this era of safer and more effective hepatitis C therapy, non-alcoholic fatty liver disease (NAFLD) may emerge as the most common liver disease in this population. For a variety of reasons, NAFLD is extremely common in patients with HIV, and may be more likely to progress to its more ominous forms, including steatohepatitis (NASH) and NAFLD-related fibrosis or cirrhosis. Significant work has been done to identify mechanisms of NAFLD formation, including the influence of intestinal permeability as well as metabolic and immunologic factors, all which may be of particular importance in patients with HIV. Current treatment strategies are largely based upon modification of NAFLD risk factors, however several drugs are now being studied to assess both reduction in hepatic steatosis as well as reversal of fibrosis. Thus it is increasingly important for clinicians to accurately identify and stage patients with NAFLD in order to determine prognosis and evaluate them for available and future treatments. 125 Immunopathogenesis of Metabolic Complications in Treated HIV Infection Suzanne M. Crowe , Burnet Inst, Melbourne, Australia Despite effective antiretroviral therapy (ART), HIV-infected individuals remain at higher risk than the general population for several morbidities including metabolic complications. While innate immune activation declines during suppressive ART, it also persists in many individuals and may contribute to these metabolic complications. HIV persistence, microbial translocation, and co-infections may all contribute to persistent macrophage activation in tissues as well as both local and systemic inflammation. These immunologic perturbations may contribute to the risk of metabolic diseases as described in the other talks of this session. In some cases, metabolic derangements including oxidized lipoproteins may further contribute to immune activation and the inflammatory state. These processes may highlight several potential interventional targets to decrease the risk of metabolic complications in treated HIV infection. 126 What Exactly Does Antiretroviral Therapy Do to Bone? Patrick Mallon ; for the UCD HIV Molecular Research Group, Univ Coll Dublin, Dublin, Ireland Both low bone mineral density (BMD) and fractures are prevalent in people living with HIV, with HIV an independent risk factor for low BMD in some studies. In addition, there is a well established association between exposure to antiretroviral therapy (ART) and loss of BMD, largely limited to the first year after initiation of either first-line or second line ART in viraemic patients. Although the extent of BMD loss varies depending on the ART regimen used, that the effect occurs with all ART suggests a role for both ART and host response to ART in its pathogenesis, with a temporary uncoupling of bone metabolism leading to discreet losses of BMD as a viable underlying explanation. The pathogenesis underlying development of low BMD and ostoeporosis in HIV is complex, with systemic effects from immunological and virological changes, disruptions to vitamin D metabolism and subclinical renal dysfunction all potentially implicated. Once the initial bone loss with ART initiation has occurred, the relative contribution of specific ART when compared to other factors to ongoing bone health remains debated, with signifcant gaps remaining in our knowledge of the natural history of changes in BMD, changes in underlying bone quality and ultrastructure and the association between these factors and fracture prevalence, type and severity, particularly in the setting of a persistently high bone turnover state. Addressing these gaps should be a major research focus in an ageing population to prevent fractures, with innovative interventions focused on preserving bone health through optimising vitamin D status and exploratory use of bisphosphonates at ART initiation currently underway.

Oral Abstracts

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CROI 2016