Comparison of HIV-Infected and Noninfected Patients Undergoing Bariatric Surgery: The ObeVIH Study

Pourcher, Valérie; Capeau, Jacqueline; Dudoit, Yasmine; Boccara, Franck; Soulié, Cathia; Ndoadoumgue, Aude Laetitia; Charlotte, F.; Fellahi, Soraya; Bastard, J.-P.; Béréziat, Véronique; Lagathu, Claire; Marcelin, Anne‐Geneviève; Peytavin, Gilles; Boutron-Ruault, M.-C.; Tubbax, Candice; d’Auerstaedt, Ariane d’Avout; Valantin, Marc Antoine; Schneider, Luminita; Costagliola, Dominique; Katlama, Christine; Assoumou, Lambert; Pourcher, Guillaume

doi:10.1097/qai.0000000000002939

Cited by 4 publications

(4 citation statements)

References 36 publications

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“…Regarding inflammation, in accordance with our present results, we observed, in SCAT samples from obese PLWH, the absence of inflammation (macrophage infiltration with crown-like structures) in samples issued from INSTI-treated patients by contrast to non-INSTI PLWH and HIV-negative controls [17]. Interestingly, increased weight in INSTI-treated PLWH was associated with decreased VAT density suggesting a lower inflammation level [18].…”

Section: Discussionsupporting

confidence: 90%

Altered subcutaneous adipose tissue parameters after switching ART-controlled HIV+ patients to raltegravir/maraviroc

Bastard

Pelloux

Alili

et al. 2021

Aids

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Objective: To evaluate the effect on anthropometric, metabolic and adipose tissue parameters of switching ART-controlled persons living with HIV (PLWH) from a proteaseinhibitor regimen to raltegravir/maraviroc. Design: Substudy of ROCnRAL-ANRS157 with investigation of subcutaneous abdominal adipose tissue (SCAT) biopsy at inclusion and study end.Methods: We performed lipoaspiration of paired SCAT samples, histology on fresh/fixed samples and examined the transcriptomic profile analyzed using Illumina microarrays after RNA extraction. Statistical analyses used Wilcoxon-paired test.Results: The patients (n=8) were mainly male (7/8), aged (mean±SEM) 54.9±1.2 years, BMI 26.1±1.2 kg/m 2 , CD4: 699±56 cells/mm 3 , all viral load (VL)<50 copies/mL. After a follow-up of 6±0.5 months, all PLWH remained with VL<50 copies/mL. BMI, trunk and limb fat amounts were unchanged yet systemic insulin resistance increased. Adipose tissue histology was unchanged except for borderline increased adipocyte diameter (P=0.1). Amongst the 16,094 RNA transcripts, 458 genes were up-regulated and 244 down-regulated. Analyses of the KEGG and GO databases, evaluating modifications in the main functional pathways, revealed that genes related to immune recognition/function were less expressed as were genes encoding T-cell receptor and receptor signaling pathways. The gene expression profiles indicated decreased inflammation but genes involved in adipogenesis and insulin resistance were overexpressed.Conclusion: After 6 months of raltegravir/maraviroc, adipogenesis-related gene profile was enhanced in SCAT, in agreement with a tendency for increased adipocyte size.Enhanced SCAT insulin resistance-related profile was concordant with higher systemic insulin resistance. However, immune activation/inflammation profile was globally lowered. We propose that raltegravir/maraviroc might favor SCAT gain but reduce inflammation/immune activation.

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Section: Discussionsupporting

confidence: 90%

Altered subcutaneous adipose tissue parameters after switching ART-controlled HIV+ patients to raltegravir/maraviroc

Bastard

Pelloux

Alili

et al. 2021

Aids

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“…In SIV-infected ART-controlled macaques [28], the inflammatory profile was modified with a mixed phenotype: higher expression of anti-inflammatory genes (as CD163 indicating M2 macrophages) and of pro-inflammatory genes. In SAT from obese PWH, INSTI use was associated with a lower content of phagocytic crown-like structures formed by macrophages compared to non-INSTI users and non-HIV infected controls [34]. As well, in five INSTI-treated PWH compared to noninfected controls, the number of macrophages and of CD9þ metabolically active macrophages was markedly reduced [35].…”

Section: Mechanismsmentioning

confidence: 91%

Recent data on the role of antiretroviral therapy in weight gain and obesity in persons living with HIV

Capeau,

Lagathu,

Béréziat

2023

Current Opinion in HIV and AIDS

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Purpose of review Antiretroviral therapy (ART) has long been implicated in fat alterations and weight variations leading to cardiometabolic consequences. Recent largely prescribed antiretrovirals (ARVs) from the integrase-strand-transfer-inhibitor (INSTI) class have been associated with excessive weight gain/obesity in a minority of persons with HIV (PWH). As well, in the nucleoside reverse transcriptase inhibitors (NRTI) class, tenofovir-alafenamide (TAF), often replacing tenofovir-disoproxil-fumarate (TDF), has been associated with weight gain, a worrying concern in the present worldwide obesogenic environment. The respective role of the different ARV, the risk factors and the mechanisms remain questionable. Recent findings The INSTIs dolutegravir (DTG) and bictegravir (BIC) and TAF have a proper effect on weight gain, while efavirenz (EFV) and TDF inhibit it. These effects are reported in ART-naïve PWH, in addition to weight gain resulting from the return to health process, and in ART-controlled PWH. Also, INSTIs induce weight gain in adolescents and excessive weight gain during pregnancy. The effects of INSTIs and TAF are additive. Their trajectory differs. Most of the weight gain is observed during the initial 12-month period. The main risk factors are low CD4+ and high viral load (VL) in ART-naïve PWH, Black race or originating from some African countries and female gender. The role of age and BMI differs between studies. The reversibility of the effect of INSTI and TAF appears limited. Regarding the mechanisms, the INSTIs can directly alter adipose tissue in particular through inhibition of fat beiging, resulting in fat fibrosis and hypertrophy. Macrophage infiltration is decreased. The mechanisms explaining the opposite effects of TDF and TAF remain elusive. Summary The specific impact of DTG, BIC and TAF on weight gain/obesity in PWH is confirmed in different populations independently of the weight limiting effect of EFV and TDF. ART-linked excessive weight gain is uncommon. African origin and female sex are risk factors that need to be considered. The mechanisms are better understood for INSTIs but unknown for TDF/TAF. The reversibility of weight gain/obesity when stopping INSTI or TAF remains limited.

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“…However, the available in vivo data are difficult to interpret because they concern the study of subcutaneous adipose tissue (SCAT) from obese PLWH with metabolic complications [21] or from lipodystrophic areas in patients on ART [22,23]; these SCAT samples featured the underexpression of adiponectin and leptin and the overexpression of IL-6 and TNF-α, relative to healthy donors [22]. Given the invasive nature of the biopsy, few studies have evaluated changes in visceral adipose tissue (VAT); however, it appears to be less affected than SCAT [24,25]. The AT inflammation associated with HIV infection thus remains to be characterized in detail.…”

Section: Introductionmentioning

confidence: 99%

Prolonged Antiretroviral Treatment Induces Adipose Tissue Remodelling Associated with Mild Inflammation in SIV-Infected Macaques

Mausoleo

Olivo

Desjardins

et al. 2022

Cells

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During chronic SIV/HIV infection, adipose tissue (AT) is the target of both antiretroviral treatment (ART) and the virus. AT might subsequently contribute to the low-grade systemic inflammation observed in patients on ART. To evaluate the inflammatory profile of AT during chronic SIV/HIV infection, we assayed subcutaneous and visceral abdominal AT from non-infected (SIV−, control), ART-naïve SIV-infected (SIV+) and ART-controlled SIV-infected (SIV+ART+) cynomolgus macaques for the mRNA expression of genes coding for factors related to inflammation. Significant differences were observed only when comparing the SIV+ART+ group with the SIV+ and/or SIV− groups. ART-treated infection impacted the metabolic fraction (with elevated expression of PPARγ and CEBPα), the extracellular matrix (with elevated expression of COL1A2 and HIF-1α), and the inflammatory profile. Both pro- and anti-inflammatory signatures were detected in AT, with greater mRNA expression of anti-inflammatory markers (adiponectin and CD163) and markers associated with inflammation (TNF-α, Mx1, CCL5 and CX3CL1). There were no intergroup differences in other markers (IL-6 and MCP-1). In conclusion, we observed marked differences in the immune and metabolic profiles of AT in the context of an ART-treated, chronic SIV infection; these differences were related more to ART than to SIV infection per se.

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Comparison of HIV-Infected and Noninfected Patients Undergoing Bariatric Surgery: The ObeVIH Study

Cited by 4 publications

References 36 publications

Altered subcutaneous adipose tissue parameters after switching ART-controlled HIV+ patients to raltegravir/maraviroc

Altered subcutaneous adipose tissue parameters after switching ART-controlled HIV+ patients to raltegravir/maraviroc

Recent data on the role of antiretroviral therapy in weight gain and obesity in persons living with HIV

Prolonged Antiretroviral Treatment Induces Adipose Tissue Remodelling Associated with Mild Inflammation in SIV-Infected Macaques

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