CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

approach for the SIV model system and engineered sterilizing immunity in monkeys against a virulent SIV challenge virus. Importantly, antibody levels in “immunized” monkeys have been stable for over 6 years. We have nowmoved this concept into Phase 1 human clinical trials. 67 Broadly Neutralizing Antibodies for HIV-1 Eradication Strategies Dan H. Barouch Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, US We have previously shown that the broadly neutralizing monoclonal antibody PGT121 afforded substantial therapeutic efficacy in viremic, chronically SHIV-SF162P3-infected rhesus monkeys. In a recent study, we have also explored the efficacy of PGT121 in ART-suppressed, SHIV-SF162P3-infected monkeys. In addition, we recently observed that the viral reservoir is established very early following infection and prior to viremia. These data demonstrate new challenges facing HIV-1 eradication strategies and suggest novel approaches to target the viral reservoir. 4:00 pm– 6:00 pm Current Issues in HIV-Related Malignancies 68 HIV-Associated Malignancies: TheWorldwide Epidemic James J. Goedert National Cancer Institute, Bethesda, MD, US Background : Malignancies in people with HIV are a major cause of morbidity and mortality. With improving control of HIV infection, the burden and complexities of malignancies are increasing. Methods : Recent publications and public data were reviewed, focusing on international patterns and differences between AIDS-defining cancers (ADC) and non-ADC. Results : In the USA, the incidence and burden (total number of cases) of malignancies fell dramatically from 1993-1998, but this was exclusively ADC, specifically Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL). Since 1998, age-adjusted incidence has been stable while burden of non-ADC has increased. From 2012-2015, ADC incidence increased 5-10% outside North America and Europe. Southern and especially east Africa continue to have the highest burden of KS. Cervix cancer has had the highest incidence and burden especially in Africa, but most cases do not have HIV. Aging is increasing the importance of ADC, the most important of which are cancers of the lung, anus and liver. Lung cancer is by far the most common ADC, but incidence fell from 1996-2010, perhaps due to smoking reduction. Anus and liver cancers are increasing, probably due to longer survival with HPV and HCV, respectively. Hodgkin lymphoma is decreasing, probably with better control of HIV. Mortality due to NADC has been increasing in most populations. Conclusions : Implementation of programs to address malignancies are needed, especially in low and middle-income countries. Global access and use of effective antiretroviral therapy is paramount, but research is needed to integrate and optimize combined antiretroviral and cancer therapies. Reducing the burden of cervix and anus cancers will require global access and use of HPV vaccines, but VIA with simplified HPV screening could be a useful interim approach. Liver cancer burden would be reduced with broader use of HBV vaccine and HCV direct-acting agents. Smoking cessation is needed to reduce the morbidity and mortality from lung cancer and many other diseases. 69 Viral Oncogenesis: Evolving Concepts Shannon C. Kenney University of Wisconsin, Madison, WI, US AIDS-related malignancies are often associated with oncogenic viruses, in particular Epstein-Barr virus (EBV) and Kaposi Sarcoma herpesvirus (KSHV). This lecture will discuss how viruses contribute to AIDS-related cancers (with particular emphasis on EBV), and describe novel virus-targeted therapies. 70 AIDS Lymphoma: Advances and Existing Challenges Ariela Noy Memorial Sloan Kettering Cancer Center, New York, NY, US Despite dramatic advances in anti-retroviral therapy, HIV related lymphoma remains a challenge. Lymphoma is the largest contributor to cancer deaths among HIV infected persons and accounts for about 10% of all deaths. Though the incidence has changed, HIV infected person with good CD4 counts still have a marked increase risk of lymphoma with the exception of primary central nervous system lymphoma Gibson et al. (AIDS 2014) have recently estimated an 11 fold increase overall and 17 fold increase for AIDS defining Session S-2 Symposium Room 6D One of the hallmarks of AIDS has been the elevated risk of developing cancers linked to immunosuppression. The introduction of highly active antiretroviral therapy (HAART) has greatly changed the natural history of HIV infection and associated morbidities. In Western countries the cumulative risk of developing and dying from AIDS defining cancers (ADCs) such as Kaposi’s sarcoma, non-Hodgkin’s lymphoma (NHL) and invasive cervical cancer, has significantly declined. On the other hand, non-AIDS-defining cancers (NADCs), such as hepatocellular carcinoma, anal cancer, lung cancer significantly increased. Cancers therefore still represent a significant burden of HIV-associated morbidity in the current era of HAART worldwide. Few studies have highlighted clearly the impact of scale up of HAART on cancer burden in resource-limited settings such as in Sub-Saharan Africa. It is prudent to state that the highest burden of HIV and cancers are currently found in these countries. It is ironic that in practice linkage between HIV and cancers at this point in LMIC is based on extrapolation from the developed world experience. This has probably contributed to the challenges being faced in translating this model for intervention in LMIC. The resources available and background cancer risks factors in these two settings are diametrical at best. By and large, the epidemiology of malignancies in the developing world are driven by infectious agents mainly viruses such Human Herpes virus 8(HHV8), Epstein Barr Virus (EBV), human papilloma virus (HPV) infection and hepatitis B and C (HBV and HCV). The observations from these countries still show that the cancers common in HIV-infected individual are very much reminiscent of the era before wide spread use of HAART; given the magnitude of AIDS-defining cancers such as Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer. subtypes. These authors also note an increased risk for lymphomas not previously associated with HIV. 71 HIV Malignancies in Low- and Middle-Income Countries: A Double Burden of Disease Jackson Orem Uganda Cancer Institute, Kampala, Uganda

Oral Abstracts

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CROI 2015