Cancer has become one of the most common complications of long-term HIV infection in the US, and may come to be an even greater threat in sub-Saharan Africa because of the delayed and incomplete access to antiretroviral therapy, the high prevalence of viral oncogens, and a larger number of years a person may be at risk for developing cancer due to pediatric HIV infection. In this region, the three """"""""AIDS-Defining Cancers"""""""", including Kaposi sarcoma (KS), non-Hodgkin Lymphoma (NHL), and invasive cervical cancer (ICC), remain among the most common cancers in the entire population. Over the past decade, the Fred Hutchinson Cancer Research Center has collaborated with the Uganda Cancer Institute to conduct collaborative research and training on infection-related cancers;and define the natural history, biology and treatment of HlV-associated malignancies (HIVAM). This work has revealed HIV-infected individuals with cancer are at significantly increased risk of death when compared with similar HIV-negative persons with cancer, and that the response to therapy varies dramatically within HIV-infected persons with the three ADCs. In the current proposal, we seek to understand the biologic basis for the differential natural history of ADCs in Uganda through the following Specific Aims: 1) To characterize the viral genetic diversity among two viral oncogens, human herpesvirus-8 (HHV-8) and human papillomavirus (HPV), and begin to explore the relationship between genetic variants and the natural history of KS and ICC, respectively;2) To describe the evolution of the cellular immune response among persons with AlDS-defining malignancies who initiate antiretroviral therapy and chemotherapy;3) To expand the capacity to conduct state-of-the-art translational research in HIVAM in Uganda through optimizing scientific leadership among Ugandans who have been trained in HIVAM research, maintaining a unique and extraordinary biorepository for the study of HIVAM in Uganda, expanding the enrollment of patients with ADCs into translational studies of the natural history of their malignancies, and providing the administrative support for collaborative biomedical research across two continents.
This proposal examines how host and viral factors impact the response to therapy among persons with HIV associated cancers in Africa. We will study how the genetic diversity of viruses that cause cancer affects the natural history of these malignancies, and characterize the evolution of the cellular immune response among patients treated for HIV and cancer in Uganda. This work could lead to novel therapeutic and diagnostic strategies for persons with HlV-associated cancers both in sub-Saharan Africa and the US.
|Beima-Sofie, Kristin; Wamalwa, Dalton; Maleche-Obimbo, Elizabeth et al. (2018) Toll-like receptor 9 polymorphism is associated with increased Epstein-Barr virus and Cytomegalovirus acquisition in HIV-exposed infants. AIDS 32:267-270|
|Coghill, Anna E; Schenk, Jeannette M; Mahkoul, Zeina et al. (2018) Omega-3 decreases IL-6 levels in HIV and human herpesvirus-8 coinfected patients in Uganda. AIDS 32:505-512|
|Menon, Manoj P; Coghill, Anna; Mutyaba, Innocent O et al. (2018) Association Between HIV Infection and Cancer Stage at Presentation at the Uganda Cancer Institute. J Glob Oncol :1-9|
|Bender Ignacio, Rachel; Ghadrshenas, Matine; Low, Daniel et al. (2018) HIV Status and Associated Clinical Characteristics Among Adult Patients With Cancer at the Uganda Cancer Institute. J Glob Oncol :1-10|
|Phipps, Warren; Kansiime, Rachel; Stevenson, Philip et al. (2018) Peer Mentoring at the Uganda Cancer Institute: A Novel Model for Career Development of Clinician-Scientists in Resource-Limited Settings. J Glob Oncol :1-11|
|Low, Daniel; Merkel, Emily C; Menon, Manoj et al. (2017) Chemotherapy Use at the End of Life in Uganda. J Glob Oncol 3:711-719|
|Coghill, Anna E; Schenk, Jeanette M; Mahkoul, Zeina et al. (2017) Omega-3 decreases interleukin-6 levels in HIV and HHV-8 co-infected patients: results from a randomized supplementation trial in Uganda. AIDS :|
|Okuku, Fred; Krantz, Elizabeth M; Kafeero, James et al. (2017) Evaluation of a Predictive Staging Model for HIV-Associated Kaposi Sarcoma in Uganda. J Acquir Immune Defic Syndr 74:548-554|
|Casper, Corey; Fitzmaurice, Christina (2016) Infection-related cancers: prioritising an important and eliminable contributor to the global cancer burden. Lancet Glob Health 4:e580-1|