Association Between the Development of Subclinical Cardiovascular Disease and Human Immunodeficiency Virus (HIV) Reservoir Markers in People With HIV on Suppressive Antiretroviral Therapy

Turcotte, Isabelle; El‐Far, Mohamed; Sadouni, Manel; Chartrand-Lefèbvre, Carl; Filali‐Mouhim, Ali; Fromentin, Rémi; Chamberland, Annie; Jenabian, Mohammad-Ali; Baril, Jean-Guy; Trottier, Benôit; Thomas, Réjean; Tremblay, Cécile; Durand, Madéleine; Chomont, Nicolas

doi:10.1093/cid/ciac874

Cited by 6 publications

(8 citation statements)

References 16 publications

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“…The detection of IL-17A-producing CD4 + T-cells in the atherosclerotic plaque of mice [2–4,6,13,18,20,28,33,81,94–96] supports the possibility that subsets of Th17 cells may be recruited into the vascular beds and locally fuel atherosclerosis. In line with this scenario, in our study TPV + compared to TPV − ART-treated PLWH exhibit increased plasma levels of CCL20, a chemokine essential for CCR6 + Th17 cell trafficking [80–82].…”

Section: Discussionmentioning

confidence: 90%

“…Third, we did not study alterations in the Th17/Tregs ratios in relationship with the size of HIV reservoirs. However, studies performed by our group on the CHACS samples revealed an increased HIV-DNA reservoir in CD4 + T-cells of TPV + versus TPV − HIV + [96], pointing to the possibility that Th17 depletion is a consequence of their infection. Fourth, we were not able to confidently conclude on immunological differences between HIV − participants with and without subclinical CAA due to the reduced number of individuals enrolled at the time we performed the study.…”

Section: Discussionmentioning

confidence: 99%

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A Blood Immunological Signature of Subclinical Coronary Artery Atherosclerosis in People Living with HIV-1 Receiving Antiretroviral Therapy

Wiche Salinas,

Zhang,

Gosselin

et al. 2023

Preprint

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Cardiovascular disease (CVD) remains an important co-morbidity in people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Our previous studies performed on the Canadian HIV/Aging Cohort Study (CHACS) (>40 years-old; Framingham Risk Score (FRS) >5%), revealed a 2-3-fold increase in non-calcified coronary artery atherosclerosis (CAA) plaque burden, measured by Computed tomography angiography scan (CTAScan) as total (TPV) and low attenuated plaque volume (LAPV) in ART-treated PLWH (HIV+)versusuninfected controls (HIV-). In an effort to identify novel correlates of subclinical CAA, markers of intestinal damage (sCD14, LBP, FABP2); cell trafficking/inflammation (CCL20, CX3CL1, MIF, CCL25); subsets of Th17-polarized and regulatory (Tregs) CD4+T-cells, classical/intermediate/non-classical monocytes, and myeloid/plasmacytoid dendritic cells, were studied in relationship with HIV and TPV/LAPV status. The TPV detection/values coincided with higher plasma sCD14, FABP2, CCL20, MIF, CX3CL1 and triglyceride levels, lower Th17/Treg ratios, and classical monocyte expansion. Among HIV+, TPV+versusTPV−exhibited lower Th17 frequencies, reduced Th17/Treg ratios, higher frequencies of non-classical CCR9lowHLADRhighmonocyte, and increased plasma fibrinogen levels. Finally, Th17/Treg ratios and non-classical CCR9lowHLADRhighmonocyte frequencies remained associated with TPV/LAPV after adjusting for FRS and HIV/ART duration in a logistic regression model. These findings point to Th17 paucity and non-classical monocyte abundance as novel immunological correlates of subclinical CAA that may fuel the CVD risk in ART-treated PLWH.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

A Blood Immunological Signature of Subclinical Coronary Artery Atherosclerosis in People Living with HIV-1 Receiving Antiretroviral Therapy

Wiche Salinas,

Zhang,

Gosselin

et al. 2023

Preprint

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“…Alternatively, the lack of association between sgp120 alone and the reservoir might be due to the fact that measures of HIV reservoir were performed in the blood and not in the tissues, which may be a preferential site for persistence of the active reservoir [44]. Finally, it has been demonstrated that the size of the viral reservoir in PLWH on ART was associated with subclinical CVD [26,45], whether this association is linked to the persistence of sgp120 in those individuals remains to be determined. Future studies are needed to elucidate the mechanism by which sgp120 persists over time and whether it may represent a potential therapeutic target to reduce the risk of early onset comorbidity for PLWH.…”

Section: Discussionmentioning

confidence: 99%

“…HIV DNA was measured as described previously [26]. Briefly, CD4 + T cells were isolated from PBMCs by negative selection using the EasySep Human CD4 + T cell Enrichment Kit (StemCell).…”

Section: Measurement Of Hiv Dnamentioning

confidence: 99%

Plasmatic HIV-1 soluble gp120 is associated with immune dysfunction and inflammation in ART-treated individuals with undetectable viremia

Benlarbi,

Richard,

Bourassa

et al. 2023

Preprint

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Background Chronic inflammation persists in some people living with HIV (PLWH), even during antiretroviral therapy (ART) and is associated with premature aging. The gp120 subunit of the HIV-1 envelope glycoprotein can shed from viral and cellular membranes and can be detected in plasma and tissues, showing immunomodulatory properties even in the absence of detectable viremia. We evaluated whether plasmatic soluble gp120 (sgp120) and a family of gp120-specific anti-cluster A antibodies, which were previously linked to CD4 depletion in vitro, could contribute to chronic inflammation, immune dysfunction, and sub-clinical cardiovascular disease in participants of the Canadian HIV and Aging cohort (CHACS) with undetectable viremia. Methods Cross-sectional assessment of plasmatic sgp120 and anti-cluster A antibodies was performed in 386 individuals from CHACS. Their association with pro-inflammatory cytokines, as well as subclinical coronary artery disease measured by computed tomography coronary angiography was assessed using linear regression models. Results In individuals with high levels of sgp120, anti-cluster A antibodies inversely correlated with CD4 count (p=0.042) and CD4:CD8 ratio (p=0.004). The presence of sgp120 was associated with increased plasma levels of IL-6. In participants with detectable atherosclerotic plaque and detectable sgp120, sgp120 levels, anti-cluster A antibodies and their combination correlated positively with the total volume of atherosclerotic plaques (p=0.01, 0.018 and 0.006, respectively). Conclusion Soluble gp120 may act as a pan toxin causing immune dysfunction and sustained inflammation in a subset of PLWH, contributing to the development of premature comorbidities. Whether drugs targeting sgp120 could mitigate HIV-associated comorbidities in PLWH with suppressed viremia warrants further studies.

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“…HIV DNA was measured as described elsewhere [ 25 ]. A detailed description is provided in the Supplementary Materials .…”

Section: Methodsmentioning

confidence: 99%

Plasma Human Immunodeficiency Virus 1 Soluble Glycoprotein 120 Association With Correlates of Immune Dysfunction and Inflammation in Antiretroviral Therapy–Treated Individuals With Undetectable Viremia

Benlarbi,

Richard,

Bourassa

et al. 2023

The Journal of Infectious Diseases

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Background Chronic inflammation persists in some people living with human immunodeficiency virus (HIV) during antiretroviral therapy and is associated with premature aging. The glycoprotein 120 (gp120) subunit of HIV-1 envelope sheds and can be detected in plasma, showing immunomodulatory properties even in the absence of detectable viremia. We evaluated whether plasma soluble gp120 (sgp120) and a family of gp120-specific anti–cluster A antibodies, linked to CD4 depletion in vitro, contribute to chronic inflammation, immune dysfunction, and subclinical cardiovascular disease in participants of the Canadian HIV and Aging Cohort Study with undetectable viremia. Methods Cross-sectional assessment of sgp120 and anti–cluster A antibodies was performed in 386 individuals from the cohort. Their association with proinflammatory cytokines and subclinical coronary artery disease was assessed using linear regression models. Results High levels of sgp120 and anti–cluster A antibodies were inversely correlated with CD4+ T cell count and CD4/CD8 ratio. The presence of sgp120 was associated with increased levels of interleukin 6. In participants with detectable atherosclerotic plaque and detectable sgp120, anti–cluster A antibodies and their combination with sgp120 levels correlated positively with the total volume of atherosclerotic plaques. Conclusions This study showed that sgp120 may act as a pan toxin causing immune dysfunction and sustained inflammation in a subset of people living with HIV, contributing to the development of premature comorbid conditions.

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Association Between the Development of Subclinical Cardiovascular Disease and Human Immunodeficiency Virus (HIV) Reservoir Markers in People With HIV on Suppressive Antiretroviral Therapy

Cited by 6 publications

References 16 publications

A Blood Immunological Signature of Subclinical Coronary Artery Atherosclerosis in People Living with HIV-1 Receiving Antiretroviral Therapy

A Blood Immunological Signature of Subclinical Coronary Artery Atherosclerosis in People Living with HIV-1 Receiving Antiretroviral Therapy

Plasmatic HIV-1 soluble gp120 is associated with immune dysfunction and inflammation in ART-treated individuals with undetectable viremia

Plasma Human Immunodeficiency Virus 1 Soluble Glycoprotein 120 Association With Correlates of Immune Dysfunction and Inflammation in Antiretroviral Therapy–Treated Individuals With Undetectable Viremia

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