Despite the success of the roll-out of antiretroviral therapy (ART) in sub-Saharan Africa, not all patients prescribed ART have their health fully restored. For example, one of the most common cancers in the pre- ART era Kaposi's sarcoma (KS) continues to be amongst the most frequent even after ART. Surprisingly, there has been no prospective account of KS that develops after start of ART. Thus, the specific aims of Research Project 3 of the Uganda-UCSF Consortium are to:
Aim 1 : Describe the clinical and labor3tory ch3r3cteristics of p3tients who develop KS despite being prescribed ART. We will determine, in addition to routine characteristics available in existing data sources (e.g., sex and age), a more comprehensive and germane set of clinical and laboratory characteristics heretofore not systematically recorded at the immediate time of KS diagnosis after start of ART.
Aim 2 : Evaluate determinants of incident KS despite ART-mediated virologic suppression. Among individuals with virologic suppression (i.e., undetectable plasma HIV RNA), we will evaluate several biological mechanisms for KS development. Specifically, we will assess, with several biomarkers, the roles of CD4+ lymphopenia, systemic inflammation, and immunosenescence in the development of KS.
Aim 3 : Determine survival after KS occurrence 3mong p3tients prescribed ART 3nd compare this to survival of KS that occurs prior to ART and to patients without KS. Because we expect most patients who develop KS after ART initiation to have early clinical stage of disease, we hypothesize that survival will be better than patients diagnosed with KS pre-ART. However, we hypothesize that survival among those diagnosed with KS after ART will be worse than comparable patients without KS who are on ART. To address these aims, the Consortium will take advantage of its collaboration with East Africa IeDEA, one of the only networks large enough to prospectively study cancer in Africa. Through the established KS biopsy services in IeDEA, we will characterize KS diagnoses through rapid case ascertainment. We will also use the well-enumerated population to perform a nested case-control study of the determinants of KS. We expect this work to become a resource to understand the pathogenesis of KS in the ART era, setting the stage for new interventions above and beyond ART to further reduce KS risk.

Public Health Relevance

Even with the new therapy for HIV infection, the cancer known as Kaposi's sarcoma continues to occur. This is true in resource-rich settings like the U.S, and particularly true in resource-limited settings like sub- Saharan Africa. This research project will investigate which types of patients develop Kaposi's sarcoma despite being prescribed ART, why this occurs, and how long such patients live after being diagnosed.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZCA1-RPRB-O (M2))
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Dominguez, Geraldina
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University of California San Francisco
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