CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

76 The Médecins Sans Frontières Experience with the Current Ebola Outbreaks Gilles Van Cutsem Médecins Sans Frontières, Mowbray, Cape Town, South Africa

In December 2013 a two year old child in the village of Meliandou in the southern Guinean forest was infected with the Ebola virus, most likely acquired from a bat. This single zoonotic transmission event has led to the largest Ebola virus disease outbreak in history, which has killed more than 8,000 and infected more than 22,000 people in Guinea, Liberia and Sierra Leone. More than 800 health care workers have been infected; more than 500 have died. As a consequence, the extremely fragile health systems of West Africa almost came to a standstill, resulting in morbidity and mortality of other diseases adding to that of Ebola. Yet most of the response has been carried by West African health workers and communities, while the international response was slow and uncoordinated. Since March 2014 Médecins Sans Frontières (MSF), in partnership with Ministries of Health, has admitted more than 7,700 patients, among whom nearly 5000 were confirmed with Ebola. MSF provides care in 8 Ebola Case Management Centres and two transit centres, with approximately 650 beds, and has over 300 international and 3800 national staff on the ground in January 2015. Last year, 28 MSF staff members were infected with Ebola, the vast majority in the community; 14 have died. More than 1,400 tonnes of supplies have been shipped. MSF’s strategy to control Ebola is organised into six elements: isolation and supportive medical care for cases, including laboratory capacity to confirm infection; safe burial activities; awareness raising; alert and surveillance in the community; contact tracing; and access to healthcare for non-Ebola patients, including protection of health facilities and health workers. These activities are interdependent and all must be in place to contain the epidemic. As was demonstrated in previous outbreaks as well as recently in the D.R.C., Mali, Nigeria, Norway, Senegal, Spain, the U.K. and the U.S., Ebola outbreaks can be controlled early on by rapid and vigorous outbreak control measures. Yet, the world was unable to contain this epidemic. This presentation will present challenges and lessons learned by MSF during the first year of the response. Incidence has decreased recently yet many challenges remain unaddressed. MSF has called repeatedly on the international community to provide a strong, flexible, and coordinated response, with limited success. The first lesson we must retain is that thousands have died because of international negligence.

77 Ebola Treatment and Vaccine Development and Implementation: Challenges and Opportunities H. Clifford Lane National Institute of Allergy and Infectious Diseases, Bethesda, MD, US

WEDNESDAY, FEBRUARY 25, 2015 Session PL-1 Plenary

4AB Auditorium

8:30 am– 9:00 am Preventing Pediatric HIV and Managing HIV-Infected Children: Where AreWe Now andWhere AreWe Going? 78 Preventing Pediatric HIV and Managing HIV-Infected Children: Where AreWe Now, andWhere AreWe Going? Diana M. Gibb University College London, London, United Kingdom

Oral Abstracts

By 2015, the MDGs and ‘Double Dividend’ Initiatives aimed for ‘virtual’ global elimination of perinatal HIV. 2015 also marks 30 years since ACTG 076 trial showed MTCT reduction with AZT; new paediatric HIV is now rare in rich countries. However, globally, 240,000 children acquired HIV in 2015; >90% live in 22 high-burden countries, 21 in Africa. WHO 2013 guidelines recommended ‘Option B’ pMTCT (endorsed by recent results from the PROMISE trial) or ‘Option B+’ (ART for life, in high fertility/high HIV countries; now adopted by 15 countries). With pMTCT expansion, new child infections have fallen by ~50% since 2007. Option B+ is also aiding ART rollout to lower-level clinics but challenges of retention on postnatal ART, partner testing and concerns about bone safety of tenofovir for exposed children need further research. Infant HIV diagnosis remains a major challenge; in 2013, <45% exposed infants had DNAPCR by age 2months. More importantly, as >90% HIV-infected children will be born to undiagnosed mothers or those not on ART and 50% children die by their 2nd birthday, a shift is urgently needed to early clinical recognition, HIV diagnosis, and ART with cotrimoxazole prophylaxis initiated locally, alongside pMTCT/treatment for adults. Early infant ART reduced mortality 4-fold in the CHER trial; over >5 years, even ART for 1 or 2 years was superior to delayed ART. Pragmatically, WHO 2013 guidelines recommend ART for children <5years, extended to <15yrs in some countries; recent data suggest this may improve pubertal development and long-term immunological health. By 2013, 760,000 children worldwide had started ART; however, coverage for those needing ART was only 24% (36% in adults), emphasizing need for integration with MCH services and ART harmonization with adults, where possible. Paediatric solid-based combination ARTs are available, dosed by weight bands backed by African data, and as daily regimens (eg 3TC/ABC+EFV). Children respond very well to ART, with few side-effects and even after perinatal ART exposure. Daily dolutegravir for 1 st /2nd-line ART is promising, will be evaluated in the planned ODYSSEY trial and may allow better future harmonisation with adults and across paediatric weight bands. With ART, children are reaching young adulthood; global cohort study collaboration through an IAS initiative is focused on adolescent outcomes and linkage of paediatric/adult cohorts; this is vital to study long-term effects of early childhood HIV/ART.

Session PL-2 Plenary

4AB Auditorium

9:00 am– 9:30 am Directing Chronic Virus Infection Through Viral Regulation of Innate Immune Defenses 79 Directing Chronic Virus Infection Through Viral Regulation of Innate Immune Defenses Michael Gale University of Washington, Center for Innate Immunity and Immune Disease, Seattle, WA, US

Innate immune defenses are essential for restricting virus replication and spread, and for programming the adaptive immune response for protection against infection. Our studies have revealed key features of innate immunity, starting with nonself discrimination for identification of virus infection, to innate immune effector genes and responses that serve to restrict viral replication and spread. Studies of hepatitis C virus (HCV), a heptotropic RNA virus, have identified RIG-I-like receptors (RLR) signaling of interferon regulatory factor (IRF)3 activation as a critical event initiating the innate immune response to infection fromwithin the host cell. This process propagates through induction of innate immune effectors genes, including type 1 and 3 interferons and interferon stimulated genes (ISGs). ISG products include antiviral factors that restrict virus replication, and proinflammatory cytokines and chemokines that facilitate innate immune cell activation and lymphocyte response toward the infected liver. HCV disrupts these process through the actions of the viral NS3/4A protease that cleaves MAVS, a key adaptor protein in the RLR pathway, resulting in loss of IRF3 activation and target gene expression, thus supporting viral persistence. Comparison of innate immune signaling outcomes within cells infected with HCV or HIV defines viral regulation of IRF3, and suppression of ISG products, as shared feature of

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CROI 2015