CROI 2016 Abstract eBook

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Oral Abstracts

rates of SVR even in the setting of chronic immunosuppression. However significant questions remain about the optimal timing of treatment in individual patient scenarios. Thus, HCV treatment should remain individualized. 12 The availability of efficacious oral HCV treatments of short duration with limited side effects has removed a key barrier to HCV treatment in high risk groups. These groups such as injection drug users with potential to transmit HCV to others are high priority for HCV treatment. Several challenges however remain with respect to delivery of treatment and eventual control of HCV at the population level. HCV reinfection in particular represents a major obstacle to control of HCV in injection drug using populations. HIV infected men who have sex with men are also at risk for HCV reinfection. By presenting a case of HCV in an HIV/HCV co-infected injection drug user, we will review data to support treatment of HCV in injection drug users. Current knowledge of rates and predictors of HCV reinfection after successful treatment and potential strategies for HCV reinfection prevention will also be highlighted. 13 T Cell Control of HIV: Implications for Vaccines and Cure Bruce D. Walker , Ragon Inst of MGH, MIT, and Harvard, Cambridge, MA, USA HIV infection results in progressive and ultimately profound immune suppression in the absence of treatment; moreover, there is no evidence that the infection is ever eradicated by host defenses. However, the remarkable ability of some HIV infected persons to maintain viral loads below the limits of detection in the absence of antiretroviral therapy provides evidence that the immune system can achieve the upper hand in this infection. Since the discovery of HIV-specific CD8 T cells in 1987, numerous laboratories have contributed to a convincing array of data from patients indicating that these cells are the main contributors to controlling acute and chronic HIV infection. Massive induction of HIV-specific CD8 T cells occurs following onset of viremia in hyperacute infection, the rapidity and magnitude of which are associated with set point viral control. However, in most persons dysfunction and dysregulation of these responses as well as immune escape rapidly ensue. Emerging data provide insights to harnessing and maintaining the antiviral efficacy of CD8 T cells , which will be key to key to functional and sterilizing cure strategies. 14 N’Galy-Mann Lecture: Confronting HIV and TB From the Bronx, NY, to Tugela Ferry, South Africa Gerald H. Friedland , Yale University School of Med, New Haven, CT, USA Among the most striking features of the global pandemic of HIV/AIDS has been its early unrecognized and subsequent explosive arrival and its entwined disastrous relationship with tuberculosis, particularly among vulnerable populations locally and globally. In the 1980’s, early in the pandemic, this relationship featured prominently in the AIDS urban epicenter of NYC and its most impoverished borough, the Bronx, and particularly among people who inject drugs and their sexual partners and children. Both HIV and TB and their complex interaction required appreciation of and attention to their shared personal, clinical and epidemiologic characteristics and their social, political and human rights context. They raised issues, as well, of how health professionals, governments and civil society respond to such unanticipated, explosive and challenging threats. The occurrence these two diseases, in this setting, presaged the repetition of these issues globally in similar impoverished global communities. Twenty years later, 8,000 miles distant, eerily similar ingredients resulted the explosive rise of in both HIV and TB and of multiple and extensively drug resistant (M/XDR) TB in urban and rural Sub Saharan Africa. This talk will explore the differences and also the similarities in the etiology and the social and human rights contexts of the entwined epidemics, focusing on the recurring themes and events in the Bronx, NY and more recently in Tugela Ferry in rural KwaZulu-Natal, South Africa. Particular attention will be focused on success and challenges of strategies elaborated to control and reverse the epidemics and their resultant morbidity and mortality in both settings. Although distinct in time and place these may have more general relevance to recent, current and inevitable future epidemics and to the challenges of the full realization of the goals of both HIV and TB elimination. 15 Harnessing Antibodies for HIV-1 Prevention and Treatment John R. Mascola , VRC, NIAID, NIH, Bethesda, MD, USA Passive immunization with polyclonal or monoclonal IgG antibodies has been used to for prevention or early post-exposure treatment of numerous infectious pathogens, particularly viruses such as Hepatitis A and B, Varicella-Zoster, Rabies and Respiratory Syncytial virus. Thus, the recent isolation of broadly neutralizing monoclonal antibodies (mAbs) against the HIV-1 has engendered interest in testing these antibodies for prevention or treatment of HIV-1 infection. Numerous preclinical studies in non-human primates demonstrate the ability of neutralizing mAbs to completely block SHIV infection when administered prior to, or shortly after, viral exposure. For prevention of infection in humans, potential advantageous characteristics of passive immunization with human mAbs include likely clinical safety and prolonged plasma concentrations, with potential to mediate protection for weeks or months after a single dose. In contrast to prevention, where mAbs need to interrupt a viral transmission event, mAbs administered in the setting of established HIV-1 infection face the obstacle of viral escape variants. Thus, combinations of mAbs may be required. A key question is whether antibody Fc-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), can lead to killing of HIV-1 infected cells and impact the cell associated viral reservoir. Clinical trials to address questions of HIV-1 prevention and treatment are underway. 16 Antiretroviral therapy has dramatically changed the course of HIV-1 infection for those infected persons who have access. As of 2014 over 13 million people world-wide have received antiretroviral therapy. In many centers in developed and developing countries 80% or more of patients on ART have plasma HIV RNA suppressed to below the limit of detection and in clinical trials of initial ART success rates are greater than or equal to 90% at a year. Later lines of therapy have increasingly higher success rates. Life expectancy for people on therapy has increased dramatically and in countries with a high percentage of infected people on therapy new HIV-1 infections have declined. Antiretroviral therapy has also become simpler and safer with better tolerated regimens, frequently including integrase inhibitors, becoming standard in many treatment guidelines. The durability of these simple, safe and effective regimens has increased and virologic failure with emergent resistance has become less common. For many patients the future of antiretroviral therapy is now. Patients with virologic failure and multi-drug resistant virus are uncommon although there exists a much larger pool of patients with multi-drug resistant virus who are currently suppressed on more complex and perhaps fragile regimens. Therefore new agents that have activity against resistant variants will continue to be needed and those inhibiting HIV-1 via a newmechanism of action will be more likely to have activity. For other patients adherence to oral ART presents a substantial challenge. Long-acting antiretroviral agents may provide a means to serve a greater proportion of infected people either long-term or through chaotic periods in their lives. Long-acting injectable ART holds promise for the near future and alternatives such as once weekly oral therapy or implantable sustained release combination ART or vector delivery of broadly neutralizing antibody combinations may be considerations in the future. With our current therapies and new strategies in development we will have an array of antiretroviral therapies that will serve virtually all people with HIV infection and support the treatment goals of the WHO. Treatment of HCV Infection in Groups at High Risk for Reinfection Oluwaseun Falade-Nwulia , Johns Hopkins Univ, Baltimore, MD, USA Antiretroviral Therapy: Where AreWe Now? Where AreWe Going? Joseph J. Eron , Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Oral Abstracts

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CROI 2016