Fluorodeoxyglucose imaging in healthy subjects with HIV infection: impact of disease stage and therapy on pattern of nodal activation.

OBJECTIVES: Nodal uptake in areas of lymphocyte activation can be visualized using fluorodeoxyglucose. Various patterns of fluorodeoxyglucose accumulation in HIV-positive patients have been described previously and hypothesized potentially to represent regions of active HIV replication or nodal activation. We evaluated the utility of fluorodeoxyglucose scanning as a tool to study HIV pathogenesis. DESIGN: We evaluated fluorodeoxyglucose biodistribution visually and quantitatively in HIV-negative individuals and various groups of HIV-infected patients to determine the impact on the pattern of nodal activation of HIV infection, the stage of HIV infection and degree of viremia, and HAART. In addition, we attempted to image anatomical site(s) of ongoing HIV replication in patients with suppressed HIV viremia on HAART, but subsequently discontinued HAART. METHOD: We performed fluorodeoxyglucose imaging on five groups: HIV-negative, HIV-positive individuals with early infection, HIV-positive patients with advanced disease, HIV-positive patients with suppressed viral loads, and HIV-positive patients who stopped HAART. RESULTS: Healthy HIV patients with suppressed viral loads and HIV-negative individuals had no or little fluorodeoxyglucose nodal accumulation or any other hypermetabolic areas, whereas viremic individuals with early and advanced HIV had increased fluorodeoxyglucose in the peripheral nodes, indicating that fluorodeoxyglucose potentially identifies areas of HIV replication. Fluorodeoxyglucose biodistribution was similar between early and advanced-stage disease. Four of five patients taken off HAART had negative baseline scans but developed nodal uptake and increases in viral loads. CONCLUSION: Abnormal fluorodeoxyglucose accumulation occurs in the nodes of individuals with detectable viral loads. Interruption of effective HAART results in the activation of previously quiescent nodal areas.

Fluorodeoxyglucose imaging in healthy subjects with HIV infection: impact of disease stage and therapy on pattern of nodal activation.

OBJECTIVES: Nodal uptake in areas of lymphocyte activation can be visualized using fluorodeoxyglucose (FDG). Various patterns of FDG accumulation in HIV-positive subjects have been described previously and hypothesized to potentially represent regions of active HIV replication and or nodal activation. We evaluated the utility of FDG scanning as a tool to study HIV pathogenesis. DESIGN: We evaluated FDG biodistribution visually and quantitatively in HIV-negative individuals and various groups of HIV-infected subjects to determine the impact on pattern of nodal activation of: HIV infection; stage of HIV infection and degree of viremia; and HAART. In addition, we attempted to image anatomical site(s) of on-going HIV replication in subjects with suppressed HIV viremia on ART, but who subsequently discontinued ART. METHOD: We performed FDG imaging on five groups: HIV-negative, HIV-positive with early infection, HIV-positive with advanced disease, HIV-positive with suppressed viral loads, and HIV-positive who stopped ART. RESULTS: Healthy HIV subjects with suppressed viral loads and HIV-negative individuals had no or little FDG nodal accumulation or any other hypermetabolic areas, whereas viremic subjects with early and advanced HIV had increased FDG in peripheral nodes, indicating that FDG potentially identifies areas of HIV replication. FDG biodistribution was similar between early and advanced-stage. Four of five subjects taken off ART had negative baseline scans but developed nodal uptake and increases in viral load. CONCLUSIONS: Abnormal FDG accumulation occurs in nodes of subjects with detectable viral loads. Interruption of effective ART results in activation of previously quiescent nodal areas.

HIV through the looking glass: insights derived from Hepatitis B.

BACKGROUND: Although higher levels of hepatitis B virus (HBV) replication in HIV-HBV co-infection may relate to liver disease progression, this has not been completely elucidated. We used expression of hepatitis B core antigen (HBcAg) in liver biopsies from HIV-HBV co-infected and HBV mono-infected patients as a marker for HBV replication, and related these findings to clinical and histological parameters. METHODS: Data from 244 HBV patients were compared with 34 HIV-HBV patients. Liver biopsies were scored for inflammation, fibrosis, HBcAg, and hepatitis B surface antigen. Univariate and multivariate analyses were performed. RESULTS: HBcAg, but not hepatitis B surface antigen, staining was stronger in HIV co-infected than in HBV mono-infected. Co-infected and HBV mono-infected had similar alanine aminotransferase, inflammatory and fibrosis scores, and hepatitis B e antigen status. HBcAg staining correlated with HIV after correcting for HBV DNA and hepatitis B e antigen. CD4 counts and HIV RNA level did not correlate with intensity of HBcAg staining. HBV DNA levels were higher in HIV co-infected and correlated with HBcAg staining. CONCLUSIONS: By looking at HBcAg as a reflection of HBV replication in HIV-HBV co-infected with controlled HIV, our findings suggest that these patients may have subtle immune function defects, which could lead to adverse liver disease outcomes.

Three cases of autoimmune hepatitis in HIV-infected patients.

Autoimmune hepatitis (AIH) is an uncommon liver disease that has previously been reported only 4 times in HIV-infected patients. Our report describes 3 new cases of AIH, 2 probable, and 1 definite. Two of these cases developed while the patient was virologically suppressed on antiretroviral therapy. Liver biopsy findings were critical in establishing the diagnosis of AIH. Because abnormal liver function tests in HIV-positive patients are often ascribed to antiretroviral medications and/or comorbid conditions, AIH may be underdiagnosed in this population. These cases underscore the value of liver biopsy in evaluating hepatitis of unclear etiology in HIV-positive patients. The clinical course of these cases also suggests that standard immunosuppressive therapy for AIH remains the optimal treatment regimen, even in HIV-positive patients.

A pilot study of the use of 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography to assess the distribution of activated lymphocytes in patients with systemic lupus erythematosus.

OBJECTIVE: The 2-[(18)F]-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) technique provides information on uptake and metabolism of glucose in various tissues. Compared with resting cells, activated lymphocytes take up radioactively labeled glucose analog at a higher rate, which makes it possible to identify lymphoid organs with higher concentrations of activated lymphocytes. This study was undertaken to compare the pattern of PET images and quantitative FDG uptake in lymphoid organs of patients with active systemic lupus erythematosus (SLE) versus patients with inactive SLE and to correlate these findings with peripheral blood lymphocyte phenotypes. METHODS: Ten patients with active SLE and 9 patients with inactive SLE were studied. FDG-PET images were obtained from the inguinal region to above the ear, starting at 60 minutes after injection of FDG. Standardized uptake values using lean body mass were determined over areas of interest. RESULTS: Both patients with active lupus and those with inactive lupus had increased FDG uptake in lymph nodes when compared with healthy volunteers, and there was no statistically significant difference between the 2 groups of lupus patients. Thymic uptake was demonstrated in 5 of 10 patients with active lupus compared with 0 of 9 patients with inactive disease. Three of the 5 patients with active SLE who were over 29 years of age had thymic uptake. Of the activation markers tested, only the CD3/CD71 population of cells was significantly different between the patient groups, with an increased percentage in the active disease group (P = 0.0247). CONCLUSION: Increased FDG uptake in lymph nodes of both patients with active SLE and patients with inactive SLE suggests that metabolic, and probably immunologic, activity is enhanced not only in active, but also in clinically quiescent, disease. The increased thymic uptake observed only in patients with active disease suggests that the thymus plays an important role during periods of disease activity.