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18F-FDG PET in HIV Infection: Correlation with Virological and Immunological Parameters in Different Clinical Stages of Disease
miriam cesari*1, K marzo2, E orunesu3, M pacei4, G bechi4, F franzetti1, G lucignani3, M clerici4, A gori5, and A chiti2
1Luigi Sacco Hosp, Univ of Milan, Italy; 2Inst Clin Humanitas, IRCCS, Milan, Italy; 3Inst of Radiological Sci, Univ of Milan, Italy; 4LITA VIALBA, Univ of Milan, Italy; and 5San Paolo Hosp Univ Med Sch, Milan, Italy
Background: ART leads to suppression of measurable HIV
plasma viral load and partial immunological recovery but HIV lingers in
lymphatic tissues. We examined lymphatic tissue uptake by 18F-fluoro-deoxy-glucose
(FDG) positron emission tomography (PET), as well as immune parameters in
antiretroviral ART-treated and -naive HIV-infected individuals in different
stages of disease progression.
Methods: We cross-sectionally
investigated 26
consecutive HIV outpatients and divided them into 5 groups according to HIV
plasma viral load, CD4+ count, clinical diagnosis, and presence or absence
of ART. Recruitment within the group was unbiased. A visual score for degree
and pattern of FDG uptake was adopted: no
uptake, faint uptake, intense uptake. Maximum standardized uptake value (SUVmax)
in each identified lesion as well as SUVmax of spleen and oral
lymphoid tissue was measured in all patients. Activation markers expressing T lymphocytes
and lytic/apoptotic proteins in HIV-specific CD4+ and CD8+
T lymphocytes were also evaluated in all patients by flow cytometric analysis.
Statistical analyses were based on non-parametric test (Mann-Whitney);
comparisons between the different groups were made using a 2-tailed t-test.
Results: FDG
uptake was observed in 9 patients, mostly ART-naive and patients initiating ART
after a diagnosis of AIDS. FDG uptake by spleen and oral lymphoid tissues was
augmented in ART-naive patients, as well as in immunological non-responders and
in patients initiating ART after a diagnosis of AIDS. Activation markers expressing
CD4+ and CD8+ T lymphocytes were increased in FDG+
patients; gag-specific, perforin- and granzyme-positive CD8+ T
lymphocytes were reduced in these same individuals.
Conclusions: Absence
of ART, a previous AIDS diagnosis, and the persistence of low CD4 count
correlate with increased FDG uptake; immune activation and impaired synthesis
of CD8+ T lymphocyte lytic/apoptotic molecules is seen in FDG+
patients. FDG PET is an accurate tool for assessing lymphatic tissue
activation, adding independent information to virologic and immunologic
parameters.
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