Whole-body positron emission tomography in patients with HIV-1 infection

doi:10.1016/S0140-6736(03)14366-8

The Lancet

Volume 362, Issue 9388, 20 September 2003, Pages 959-961

https://doi.org/10.1016/S0140-6736(03)14366-8 Get rights and content

Summary

Positron emission tomography with fluorine-18-deoxyglucose (FDG-PET) detects active lymphoid tissues during HIV-1 infection in man. We used FDG-PET to study anatomical correlates of HIV-1 infection in man. Whole-body FDG-PET images from 15 patients with HIV-1 showed distinct lymphoid tissue activation in the head and neck during acute disease, a generalised pattern of peripheral lymph-node activation at mid-stages, and involvement of abdominal lymph nodes during late disease. Unexpectedly, HIV-1 progression was evident by distinct anatomical correlates, suggesting that lymphoid tissues are engaged in a predictable sequence. Understanding the anatomy of HIV-1 infection could encourage use of surgical or radiological interventions to supplement chemotherapy.

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Tuberculosis remains one of the main infectious diseases globally. It contributes significantly to morbidity and mortality and remains the leading cause of death from a single infectious agent.
Conventional tools for the diagnosis and follow-up of patients afflicted with TB suffer from significant limitations, which become even more evident in patients that are dually infected with HIV and TB and in those with extra-pulmonary TB involvement.
¹⁸F-FDG PET/CT imaging provides an attractive surrogate marker that combines both morphological and metabolic information in a single, non-invasive whole-body study with the potential to direct and change patient management. ¹⁸F-FDG accumulation depends mainly on the metabolic activity of macrophages, neutrophils and lymphocytes and therefor suffer from non-specificity and potential false positives.
Potentially the most attractive clinical applications include the differentiation of active from latent infection with early identification of those at risk of reactivation, detection of suspected extra-pulmonary involvement and in the early treatment response evaluation to individualize standard treatment regimens. Larger prospective studies with standardized protocols are needed in order to obtain the evidence needed for inclusion in routine clinical management protocols.
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Nonetheless, the potential to supplement the initial whole-body FDG-PET/computed tomography (CT) scan with focused PET/MR imaging of suspicious findings is not far-fetched in our time with novel fast reconstruction algorithms that allows for almost instantaneous image interpretation. The same is probably true for other whole-body disorders, where the FDG-PET/CT scan is finding its place, but where the literature is still lacking, for example, in human immunodeficiency virus infection, where studies have demonstrated correlation between FDG uptake pattern in lymph nodes, disease stage, and viral load.8,9 A specific challenge is the effect of treatment on FDG-uptake, which not only is exploited in monitoring treatment response, but also may cause false-negative findings if patient preparation is not controlled sufficiently, especially in vasculitides.
How I treat classical Hodgkin lymphoma in patients infected with human immunodeficiency virus
2015, Blood
Citation Excerpt :
Clinical evaluation includes a history and physical, complete blood count with differential, albumin level, liver and kidney function, baseline pulmonary function test for patients undergoing bleomycin-containing regimens, and 18FDG-PET with integrated or concurrent CT of the neck, chest, abdomen, and pelvis.50 18FDG-PET must be interpreted with caution because HIV viremia and certain OIs can cause 18FDG-avid nodes.51-53 Although not validated in the setting of HIV-cHL, 18FDG-PET is both sensitive and specific for detecting bone marrow involvement in cHL.
HIV-associated classical Hodgkin lymphoma (HIV-cHL) is an important complication of HIV disease in the era of effective combination antiretroviral therapy (cART). Generally, newly diagnosed HIV-cHL should be managed with curative intent. With modern HIV therapeutics, HIV-cHL treatment outcomes are largely comparable to those of the background population with cHL (non–HIV-cHL). To achieve these outcomes, particular attention must be given to managing HIV. This management includes understanding HIV as a comorbid condition with a spectrum of impact that is unique to each patient. Meticulous attention to drug-drug interactions is required to avoid toxicity and pharmacokinetic effects that can undermine cure. Relapsed and refractory HIV-cHL poses additional therapeutic challenges. The standard management in this setting should also be based on that for non–HIV-cHL, and includes the use of salvage chemotherapy followed by autologous stem cell transplant in chemosensitive disease. The role of allogeneic hematopoietic stem cell transplant is less clear but may be useful in select cases. Newer agents with activity in cHL are being tested as part of primary and salvage therapy and are also highly relevant for HIV-cHL.
Contribution of <sup>18</sup>fluoro-deoxyglucose PET/CT for the diagnosis of infectious diseases
2014, Medecine et Maladies Infectieuses
The diagnosis of some infectious diseases is sometimes difficult to make and new diagnostic tools have been regularly assessed to that end. 18fluoro-deoxyglucose (¹⁸FDG) positron-emission tomography (PET) coupled with computed tomography (CT) is one of these new procedures. It has been evaluated for numerous infectious diseases with uneven results. A literature review allowed drawing some conclusions. First, ¹⁸FDG-PET/CT is not currently a first-line procedure for infectious diseases. Second, it has proved useful for the evaluation of patients presenting with fever of unknown origin (FUO). Its negative predictive value is 100%: the symptoms of patients experiencing FUO with negative first-line investigations and a negative ¹⁸FDG-PET/CT will almost always spontaneously disappear. Third, ¹⁸FDG-PET/CT also seems to be contributive for the diagnosis of vascular prosthesis infections or osteomyelitis. Fourth, it has promising results for patients presenting with infective endocarditis, especially for secondary infectious foci, or for patients presenting with suspected infection of pacemakers or implanted defibrillator; but results are still preliminary and must be confirmed. Finally¹⁸FDG-PET/CT cannot be recommended yet for other infectious diseases due to lack of published data.
Le diagnostic de certaines maladies infectieuses peut être parfois difficiles et de nouvelles procédures diagnostiques sont évaluées régulièrement pour répondre à cette problématique. La tomographie par émission de positron au ¹⁸fluorodeoxyglucose couplée au scanner (¹⁸FDG-PET/CT) a été évaluée dans de nombreuses maladies infectieuses et ses résultats sont contrastés. L’analyse de la littérature permet tout de même de tirer quelques conclusions. Premièrement, le ¹⁸FDG-PET/CT n’est en l’état actuel des choses, pas un examen de première intention dans le contexte des maladies infectieuses. Deuxièmement, son utilité semble acquise dans l’évaluation des patients présentant une fièvre d’origine indéterminée. Sa valeur prédictive négative est notamment de 100 % : les patients présentant ce symptôme avec un premier bilan et un ¹⁸FDG-PET/CT négatifs voient quasi systématiquement leur fièvre spontanément disparaître sans qu’aucune pathologie n’apparaisse dans le suivi. Troisièmement, le ¹⁸FDG-PET/CT semble également avoir un intérêt dans le diagnostic des infections de prothèses vasculaires ou d’ostéomyélite. Quatrièmement, ses performances chez les patients présentant une endocardite infectieuse notamment pour le diagnostic de localisations infectieuses secondaires ou chez les patients avec suspicion d’infection de pace maker ou de défibrillateur implantable sont prometteuses mais encore préliminaires. Enfin, les résultats des études s’étant intéressés au ¹⁸FDG-PET/CT dans d’autres maladies infectieuses ne permettent actuellement pas de le recommander pour ces autres situations.
FDG-PET imaging in HIV infection and tuberculosis
2013, Seminars in Nuclear Medicine
Citation Excerpt :
Increased tissue FDG uptake preceded fulminant virus replication at these sites, suggesting that a diffusible factor of host or viral origin was responsible for lymphoid tissue changes. In humans, Scharko et al31 performed FDG-PET imaging in 15 patients suffering from HIV-1. They observed distinct lymphoid tissue activation in the head and neck during acute disease, a generalized pattern of peripheral LN activation at midstages, and involvement of abdominal LNs during late disease, suggesting that lymphoid tissues are engaged in a predictable sequence.
The intersection and syndemic interaction between the human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics have global prevalence with devastating morbidity and massive mortality. Using FDG-PET imaging it was shown that in HIV-infected individuals, involvement of the head and neck precedes that of the chest and of the abdomen. The sequence of lymph node involvement observed suggests the existence of a diffusible activation mediator that may be targeted via therapeutic intervention strategies. Furthermore, the degree of FDG uptake proved directly related to viral load and inversely related to CD4 cell count. Available data in acquired immune deficiency syndrome (AIDS)-defining cancers further suggest that FDG-PET/CT imaging may be useful for prognostication of cervical cancer and for identifying appropriate sites for biopsy, staging, and monitoring lymphoproliferative activity owing to HIV-associated Kaposi sarcoma and multicentric Castleman disease. Inversely, in HIV-associated lymphoma, FDG uptake in HIV-involved lymphoid tissue was shown to reduce the specificity of FDG-PET imaging findings, the effect of which in clinical practice warrants further investigation. In the latter setting, knowledge of viremia appears to be essential for FDG-PET image interpretation. Early HIV-associated neurocognitive disorder, formerly known as AIDS dementia complex, proved to be characterized by striatal hypermetabolism and progressive HIV-associated neurocognitive disorder or AIDS dementia complex by a decrease in subcortical and cortical metabolism. In lipodystrophic HIV-infected individuals, lipodystrophy proved associated with increased glucose uptake by adipose tissue, likely resulting from the metabolic stress of adipose tissue in response to highly active antiretroviral therapy. Furthermore, ongoing chronic low-grade infection in arteries of HIV-infected individuals could be depicted by FDG-PET/CT imaging. And there is promising data that FDG-PET/CT in HIV may serve as a new marker for the evaluation of thymic function in HIV-infected patients. In the setting of TB, FDG-PET has proven unable to differentiate malignancy from TB in patients presenting with solitary pulmonary nodules, including those suffering from HIV, and thus cannot be used as a tool to reduce futile biopsy or thoracotomy in these patients. In patients presenting with extrapulmonary TB, FDG-PET imaging was found to be significantly more efficient when compared with CT for the identification of more sites of involvement. Thus supporting that FDG-PET/CT can demonstrate lesion extent, serve as guide for biopsy with aspiration for culture, assist surgery planning and contribute to follow-up. Limited available data suggest that quantitative FDG-PET findings may allow for prediction or rapid assessment, at 4 months following treatment instigation, of response to antituberculostatics in TB-infected HIV patients. These results and more recent findings suggest a role for FDG-PET/CT imaging in the evaluation of therapeutic response in TB patients.

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Research LettersWhole-body positron emission tomography in patients with HIV-1 infection

Summary

Virology

Evolutionary pattern of human immunodeficiency virus (HIV) replication and distribution in lymph nodes following primary infection: implications for antiviral therapy

Nat Med

Research Letters
Whole-body positron emission tomography in patients with HIV-1 infection