Positron emission tomography imaging utilizes radiolabeled compounds with unique properties to determine the sites and intensity of tissue activity in the whole body. This nonivasive methodology has been applied to tumor imaging, studies of metabolic activity, and more recently by use to studies of lymphoid tissue activation in HIV infected patients. PET imaging with flurodeoxyglucose (FDG) as the radiotracer identifies tissues with highest metabolic activation. During HIV infection, very high rates of glucose incorporation in virus infected lymphoid tissues distinguished clearly these sites from unaffected tissues and organs. FDG/PET studies in HIV-infected patients revealed a pattern of lymphoid tissue activation that was associated with diagnosis. In these initial studies, FDG/PET showed a clear pathology (splenomegaly with activation) in acutely infected patients without CD4 depletion and distinguished acute infection from both peripheral generalized lymphadenopathy and long term nonprogressing infection. Yet another pattern was associated with late disease stages where peripheral lymphoid tissues were not evident and a distinct activation of abdominal lymphoid tissue sites became apparent. Our principal goals for the proposed study are to confirm the relationship between unique FDG/PET images and natural history of HIV infection. Specifically, we test the hypothesis that lymphoid tissue activation during acute and early infection stages is limited to peripheral lymph nodes and spleen. This patter is also evident in long term nonprogressors irrespective of the duration of HIV-1 infection. The switch from early to late disease stages is accompanied by loss or activated peripheral tissue sites and increased activity in deep lymphoid tissues and gut-associated sites. Little is known about the pattern of HIV-1 dissemination and its relationship to disease progression. Noninvasive imaging methods that correlate tissue activity with virus replication can provide a unique view of viral pathogenesis and may facilitate novel intervention approaches for attacking major sites of virus replication.
