Increased Metabolic Activity on 18F-Fluorodeoxyglucose Positron Emission Tomography–Computed Tomography in Human Immunodeficiency Virus–Associated Immune Reconstitution Inflammatory Syndrome

Hammoud, Dima A.; Boulougoura, Afroditi; Papadakis, Georgios Z.; Wang, Jing; Dodd, Lori E.; Rupert, Adam; Higgins, Jeanette; Roby, Gregg; Metzger, Dorinda; Laidlaw, Elizabeth; Mican, JoAnn M.; Pau, Alice; Lage, Silvia Lucena; Wong, Chun-Shu; Lisco, Andrea; Manion, Maura; Sheikh, Virginia; Millo, Corina; Sereti, Irini

doi:10.1093/cid/ciy454

Cited by 35 publications

(29 citation statements)

References 32 publications

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“…Taken together, these findings suggest ART-associated functional cellular immune recovery directed at the site of antigen may be contributing to incident lung inflammation in patients with pulmonary TB via an IRIS-like phenomenon. Also consistent with this are findings from Hammoud et al [33] that demonstrated correlations between changes in body glycolytic activity on ART and soluble inflammatory biomarkers associated with IRIS risk, including TNF-α.…”

Section: Discussionsupporting

confidence: 87%

Lung Injury on Antiretroviral Therapy in Adults With Human Immunodeficiency Virus/Tuberculosis

Ravimohan

Auld

Maenetje

et al. 2019

Clinical Infectious Diseases

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Background Immune restoration on antiretroviral therapy (ART) can drive inflammation in people living with human immunodeficiency virus (HIV) who have pulmonary tuberculosis (TB), but its effects on the lungs have not been assessed. We evaluated associations between pulmonary inflammation, recovery of pathogen-specific CD4 T-cell function, and lung injury prior to and after ART initiation in adults with HIV and pulmonary TB. Methods This was a prospective cohort study in South Africa, following adults with HIV and pulmonary TB prior to and up to 48 weeks after ART initiation. Pulmonary-specific inflammation was defined as total glycolytic activity (TGA) on [18]F-fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET-CT) at baseline and 4 weeks after ART initiation. Spirometry, respiratory symptom tests, and flow cytometry were performed at the same times to assess lung involvement and the frequency of mycobacteria-specific CD4 T-cells. In addition, we evaluated lung function longitudinally up to 48 weeks after ART initiation. Results Greater lung TGA on FDG PET-CT was associated with worse lung function and respiratory symptoms prior to ART initiation, and nearly half of subjects experienced worsening lung inflammation and lung function at Week 4 of ART. Worsening Week 4 lung inflammation and pulmonary function were both associated with greater increases in pathogen-specific functional CD4 T-cell responses on ART, and early decreases in lung function were independently associated with persistently lower lung function months after TB treatment completion. Conclusions Increases in pulmonary inflammation and decreases in lung function are common on ART, relate to greater ART-mediated CD4 T-cell restoration, and are associated with the persistent impairment of lung function in individuals with HIV/TB.

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Section: Discussionsupporting

confidence: 87%

Lung Injury on Antiretroviral Therapy in Adults With Human Immunodeficiency Virus/Tuberculosis

Ravimohan

Auld

Maenetje

et al. 2019

Clinical Infectious Diseases

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“…In totality, a global Warburg phenotype has now emerged as a classic manifestation of HIV infection. 53,64,65 Thus, the plasma metabolite signatures we observed are likely a snapshot of the global and intrinsic cellular metabolic ux that occurs during ATI in individual patients.…”

Section: Discussionmentioning

confidence: 96%

Non-Invasive Plasma Glycomic and Metabolic Biomarkers of Post-treatment Control of HIV

Giron

Palmer

Liu

et al. 2020

Preprint

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Non-invasive biomarkers that predict HIV remission after antiretroviral therapy (ART) interruption are urgently needed. Such biomarkers can improve the safety of analytic treatment interruption (ATI) and provide mechanistic insights into the pathways involved in post-ART HIV control. We identified plasma glycomic and metabolic signatures of time-to-viral-rebound and probability-of-viral-rebound using samples from two independent cohorts. These samples include a large number of post-treatment controllers, a rare population demonstrating sustained virologic suppression after ART-cessation. The signatures remained significant after adjusting for key demographic and clinical confounders. We also confirmed a mechanistic link between biomarkers and HIV latency reactivation and myeloid inflammation in vitro. Finally, machine learning algorithms selected sets of biomarkers that predict time-to-viral-rebound with 74–76% capacity and probability-of-viral-rebound with 97.5% capacity. In summary, we fill a major gap in HIV cure research by identifying non-invasive biomarkers, with potential functional significance, that predict duration and probability of viral remission after treatment interruption.

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“…In a cohort of patients with multidrug-resistant TB treated with second-line TB therapy for 2 years, quantitative changes in 18 F-FDG uptake 2 months after starting treatment were associated with long-term outcomes, offering valuable early prognostic information (81). Similarly, early pathological metabolic activity on 18 F-FDG PET, before initiation of antiretroviral therapy (ART), was associated with subsequent development of HIV-related immune reconstitution inflammatory syndrome (IRIS) after initiation of ART (82).…”

Section: Clinical Translationmentioning

confidence: 99%

Molecular Imaging: a Novel Tool To Visualize Pathogenesis of Infections In Situ

Gordon

Ruiz-Bedoya

Ordoñez

et al. 2019

mBio

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Increased Metabolic Activity on 18F-Fluorodeoxyglucose Positron Emission Tomography–Computed Tomography in Human Immunodeficiency Virus–Associated Immune Reconstitution Inflammatory Syndrome

Abstract: NCT02147405.

Cited by 35 publications

References 32 publications

Lung Injury on Antiretroviral Therapy in Adults With Human Immunodeficiency Virus/Tuberculosis

Lung Injury on Antiretroviral Therapy in Adults With Human Immunodeficiency Virus/Tuberculosis

Non-Invasive Plasma Glycomic and Metabolic Biomarkers of Post-treatment Control of HIV

Molecular Imaging: a Novel Tool To Visualize Pathogenesis of Infections In Situ

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