Jean-Pierre Routy

McGill University | McGill · Department of Medicine

Chronic inflammation is associated with higher risk of cardiovascular disease (CVD) in people living with HIV (PLWH). We have previously shown that interleukin-32 (IL-32), a multi-isoform proinflammatory cytokine, is chronically upregulated in PLWH and is linked with CVD. However, the mechanistic role of the different IL-32 isoforms in CVD are yet...

Background Aging people with HIV (PWH) on antiretroviral therapy face high rates of metabolic dysfunction and nonalcoholic fatty liver disease (NAFLD). Fat alterations are frequent in PWH and predict worse cardiometabolic outcomes. Visceral adipose tissue (VAT) is an important compartment of body fat tissue releasing bioactive molecules. As a hormo...

The phenotype of the rare HIV-infected cells persisting during antiretroviral therapies (ART) remains elusive. We developed a single-cell approach that combines the phenotypic analysis of HIV-infected cells with near full-length sequencing of their associated proviruses to characterize the viral reservoir in 6 male individuals on suppressive ART. W...

Candida albicans (C. albicans) is a ubiquitous fungal commensal component of the human microbiota, and under certain circumstances, such as during an immunocompromised state, it may initiate different types of infection. Moreover, C. albicans continuously and reciprocally interacts with the host immune system as well as with other elements of the g...

Human cytomegalovirus (CMV) infection drives the expansion and differentiation of natural killer (NK) cells with adaptive-like features. We investigated whether age and time on antiretroviral therapy (ART) influenced adaptive NK cell frequency and functionality. Flow cytometry was used to evaluate the frequency of adaptive and conventional NK cells...

Introduction: Chronic cytomegalovirus (CMV) infection is very frequent in people living with HIV (PLWH). High anti-CMV IgG titres, which may be linked to transient CMV replication, have been associated with earlier mortality, CD8 T-cell expansion, lower CD4/CD8 ratio and increased T-cell senescence. We previously showed that anti-CMV IgG titres co...

Chronic inflammation persists in people living with HIV (PLHIV) despite antiretrovial therapy (ART) and is involved in their premature development of cardiovascular diseases (CVD) such as atherosclerosis. We have previously reported that an excess of “B-cell activating factor” (BAFF), an important molecule for the selection and activation of first-...

Background: With anti-inflammatory properties, cannabinoids may be a potential strategy to reduce immune activation in people living with HIV (PLWH) but more information on their safety and tolerability is needed. Methods: We conducted an open-label interventional pilot study at the McGill University Health Centre in Montreal, Canada. PLWH were...

We have reported excess B-cell activating factor (BAFF) in the blood of HIV-infected progressors, which was concomitant with increased frequencies of precursor-like marginal zone (MZp) B-cells, early on and despite antiretroviral therapy (ART). In controls, MZp possess a strong B-cell regulatory (Breg) potential. They highly express IL-10, the orph...

Objectives: Many vaccines require higher/additional doses or adjuvants to provide adequate protection for people with HIV (PWH). Our objective was to compare COVID-19 vaccine immunogenicity in PWH to HIV-negative individuals. Design: In a Canadian multi-center prospective, observational cohort of PWH receiving at least two COVID-19 vaccinations,...

Background: Fat alterations are frequent in people with HIV (PWH) and predict worse cardiometabolic outcomes. Visceral adipose tissue (VAT) is associated with ectopic fat accumulation in the liver. We aimed to investigate nonalcoholic fatty liver disease (NAFLD) diagnosed by controlled attenuation parameter (CAP) as a potential marker of visceral a...

The Aryl hydrocarbon receptor (AhR) identifies “ non-pathogenic ” Th17-polarized CD4 ⁺ T-cells in autoimmune models. Thus, we explored whether AhR restricts HIV-1 in Th17-cells, consistent with its antiviral role in macrophages. AhR-specific CRISPR/Cas9-mediated knockout and pharmacological blockade decreased AhR target gene expression (CYP1A1/IL-2...

Background Immune checkpoint blockade (ICB) partially reverses the dysfunctional state of antigen-specific T cell in chronic infections. However, its impact on the diverse subsets of CD4+ T cells in humans is largely unknown. Methods We examined immune checkpoint (IC) expression and function in HIV-specific CD4+ T cells of viremic individuals (≥50...

The phenotype of the rare HIV-infected cells persisting during ART remains elusive. We developed a single-cell approach that combines the phenotypic analysis of HIV-infected cells with near full-length sequencing of their associated proviruses. Individual cells carrying clonally expanded identical proviruses displayed very diverse phenotypes, indic...

This study aimed to explore the experiences of migrant people living with HIV (MLWH) enrolled in a Montreal-based multidisciplinary HIV care clinic with rapid antiretroviral treatment (ART) initiation and cost-covered ART. Between February 2020 and March 2022, 32 interviews were conducted with 16 MLWH at three time-points (16 after 1 week of ART in...

Background Increased rates of cardiovascular diseases (CVD) and larger subclinical high-risk coronary plaques in coronary CT angiography have been observed in people living with HIV (PLWH) treated with antiretroviral therapy (ART) compared to HIV-uninfected people. Growth differentiation factor-15 (GDF-15) is a cytokine emerging as an optimal marke...

Chronic inflammation persists in people living with HIV (PLHIV) despite antiretrovial therapy (ART), and is involved in their premature development of cardiovascular diseases (CVD) such as atherosclerosis. We have previously reported that an excess of "B-cell activating factor" (BAFF), an important molecule for the selection and activation of first...

We have shown that excess B-cell activating factor (BAFF) in the blood of HIV-infected individuals, is concomitant with increased frequencies of precursor-like marginal zone (MZp) B-cells, early on and despite successful antiretroviral therapy (ART). We have recently reported that in HIV-uninfected individuals, MZp possess a strong B-cell regulator...

Background: Clinical management and optimal treatment are essential to improving outcomes for people living with HIV (PLWH). We assessed trends and outcomes of chronic kidney disease (CKD) in PLWH in a resource limited centre of central China. Methods: All PLWH who were followed up in a tertiary referral centre in Wuhan, China, from July 2016 to...

The unprecedented worldwide spread of SARS-CoV-2 has imposed severe challenges on global health care systems. The roll-out and widespread administration of COVID-19 vaccines has been deemed a major milestone in the race to restrict the severity of the infection. Vaccines have as yet not entirely suppressed the relentless progression of the pandemic...

Objectives Besides CD4 regulatory T-cells (Tregs), immunosuppressor FoxP3 ⁺ CD8 T-cells are emerging as an important subset of Tregs, which contribute to immune dysfunction and disease progression in HIV infection. However, FoxP3 ⁺ CD8 T-cell dynamics in acute HIV infection and following early antiretroviral therapy (ART) initiation remain understu...

Introduction: HIV cure research requires interrogating latent HIV reservoirs in deep tissues, which necessitates autopsies to avoid risks to participants. An HIV autopsy biobank would facilitate this research, but such research raises ethical issues and requires participant engagement. This study explores willingness to participate in HIV cure res...

The Nobel Prize in Physiology or Medicine 1953 was shared between Sir Hans Adolf Krebs, a German-British biochemist, and Fritz Albert Lipmann, a German-Amer-ican biochemist for their pioneer work on metabolism. 1 The former earned it for his discovery of tricarboxylic (TCA) or Krebs cycle, and the later earned it for his discovery of coenzyme A tha...

Background Because inflammation is associated with mortality and has been linked to HIV transcription in lymphoid tissues during ART, it is necessary to address the long-term effects of switching 3-drug (3DR) to 2-drug regimens (2DR) on inflammation. Methods Nested study in the Spanish AIDS Research Network. We selected PWH ART-naive initiating 3D...

HIV elite controllers (ECs) are characterized by the spontaneous control of viral replication, and by metabolic and autophagic profiles which favor anti-HIV CD4 and CD8 T-cell responses. Extracellular acyl coenzyme A binding protein (ACBP) acts as a feedback inhibitor of autophagy. Herein, we assessed the circulating ACBP levels in ECs, compared to...

Background: Like other chronic viral illnesses, HIV infection necessitates consistent self-management and adherence to care and treatment, which in turn relies on optimal collaboration between patients and healthcare professionals (HCPs), including physicians, nurses, pharmacists, and clinical care coordinators. By providing people living with HIV...

We performed retrospective chart reviews and describe the clinical characteristics, exposure risks, and disease severity of people living with HIV (PLWH) attending the Chronic Viral Illness Service (CVIS) in Montreal, Canada, who developed COVID-19 during September 2020-August 2021, coinciding with the 2nd and 3rd waves of the pandemic. A total of...

Growth differentiation factor 15 (GDF-15) is a transforming growth factor (TGF)-β superfamily cytokine that plays a central role in metabolism regulation. Produced in response to mitochondrial stress, tissue damage or hypoxia, this cytokine has emerged as one of the strongest predictors of disease severity during inflammatory conditions, cancers an...

Dolutegravir/Lamivudina (DTG / 3TC) é um regime completo de 2 medicamentos (2DR) para o tratamento do HIV-1. A eficácia virológica não inferior foi comprovada ao longo de 3 anos em pessoas virgens de tratamento PARA HIV e 2 anos em um ambiente de troca estável. TANGO, um estudo randomizado, aberto e de não inferioridade, avalia a eficácia e a segur...

Among CD4+ T-cells, T helper 17 (Th17) cells play a sentinel role in the defense against bacterial/fungal pathogens at mucosal barriers. However, Th17 cells are also highly susceptible to HIV-1 infection and are rapidly depleted from gut mucosal sites, causing an imbalance of the Th17/Treg ratio and impairing cytokines production. Consequently, dam...

The intestinal epithelial layer acts as a mechanical and functional barrier between the intraluminal microbiota and the immunologically active submucosa. A progressive loss of gut barrier function (leaky gut) leads to enhanced translocation of microbial products, which in turn contributes as endotoxins to inflammaging. Th17 T cell represents the ma...

Background Switching to dolutegravir/lamivudine (DTG/3TC) was non-inferior to continuing tenofovir alafenamide (TAF)-based regimens for maintaining virologic suppression at Week 48 of the TANGO study. Here we present Week 144 outcomes (efficacy, safety, weight, and biomarkers). Methods TANGO is a randomized (1:1, stratified by baseline third agent...

Introduction Despite the success of antiretroviral therapy (ART) in transforming HIV disease into a chronic infection, people living with HIV (PLWH) remain at risk for various non-AIDS inflammatory comorbidities. Risk of non-AIDS comorbidities is associated with gut dysbiosis, epithelial gut damage and subsequent microbial translocation, and increa...

Early establishment of HIV reservoir represents the main impediment to an HIV cure. Mainly composed of infected memory CD4 T-cells and macrophages, HIV reservoirs are found in several organs including lymph nodes, gut, and testes. In men, and as seen in brain and eyes, testes represent a distinctive organ characterized by an immune privilege, allow...

The intestinal microbiome is an essential so-called human “organ”, vital for the induction of innate immunity, for metabolizing nutrients, and for maintenance of the structural integrity of the intestinal barrier. HIV infection adversely influences the richness and diversity of the intestinal microbiome, resulting in structural and functional impai...

Background DTG/3TC is a complete 2-drug regimen (2DR) for the treatment of HIV-1 infection. Non-inferior virologic efficacy has been proven over 3 years in treatment-naive people living with HIV (PLWH) and 2 years in a stable switch setting. Methods TANGO, a randomized, open-label, non-inferiority study, evaluates efficacy and safety of switching...

Introduction Most existing vaccines require higher or additional doses or adjuvants to provide similar protection for people living with HIV (PLWH) compared with HIV-uninfected individuals. Additional research is necessary to inform COVID-19 vaccine use in PLWH. Methods and analysis This multicentred observational Canadian cohort study will enrol...

Significance HIV-1 infects CD4 T cells, and, among these, T helper 17 (Th17) cells are known to be particularly permissive for virus replication. The infection of Th17 cells is critical for AIDS pathogenesis and viral persistence. It is, however, not clear why these cells are highly permissive to HIV-1. We found that Th17 cell permissiveness depend...

(1→3)-β-D-Glucan (BDG) represents a potent pathogen-associated molecular pattern (PAMP) in triggering the host response to fungal and some bacterial infections. Monocytes play a key role in recognizing BDG and governing the acute host response to infections. However, the mechanisms regulating monocyte’s acute response to BDG are poorly understood....

The maintenance of a strong IL21 production in memory CD4 T cells, especially in HIV-1-specific cells, represents a major correlate of natural immune protection against the virus. However, the molecular mechanisms underlying IL21 production during HIV-1 infection, which is only elevated among the naturally protected elite controllers (EC), are stil...

The crosstalk between intestinal epithelial cells (IEC) and Th17-polarized CD4⁺ T-cells is critical for mucosal homeostasis, with HIV-1 causing significant alterations in people living with HIV (PLWH) despite antiretroviral therapy (ART). In a model of IEC and T-cell co-cultures we investigated the effects of IL-17A, the Th17 hallmark cytokine, on...

BACKGROUND:. Management of hematopoietic stem cell transplant complicated by respiratory failure has been facilitated by the use of extracorporeal membrane oxygenation as a bridge to curative chemotherapeutic options. This is the first report of hematopoietic stem cell transplantation on extracorporeal membrane oxygenation in the adult population....

Human herpesvirus-8 (HHV8)-associated multicentric Castleman disease (HHV8-MCD) is a rare nonmalignant lymphoproliferative disorder most commonly observed in PLWH. Herein, we describe an HIV-infected adult male from Cameroon with relapsing HHV8-MCD (HIV+MCD). The patient developed constitutional symptoms, diffuse lymphadenopathy, thrombocytopenia a...

People living with HIV (PLWH) develop both anti-Envelope-specific antibodies, which bind the closed trimeric HIV Envelope present on infected cells and anti-gp120-specific antibodies, which bind gp120 monomers shed by infected cells and taken up by CD4 on uninfected bystander cells. Both antibodies have an Fc portion that binds to Fc Receptors on s...

Background: Antigen-specific T cell impairment is observed in chronic infections. CD4+ T cells are diverse in phenotype and function; how their different lineages are impacted by inhibitory immune checkpoints (IC) is unknown. Methods: We examined IC expression and function in HIV-specific CD4+ T cells of viremic individuals prior to ART initiation...

People with human immunodeficiency virus (HIV) (PWH) have reduced gut barrier integrity (“leaky gut”) that permits diffusion of microbial antigens (microbial translocation) such as lipopolysaccharide (LPS) into the circulation, stimulating inflammation. A potential source of this disturbance, in addition to gut lymphoid tissue CD4+ T-cell depletion...

Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is often the result of recent infection with Mycobacterium tuberculosis (Mtb) followed by rapid progression to disease. Alveolar macrophages (AM) are the first cells of the innate immune system that engage Mtb, but how HIV and antiretroviral therapy (ART) i...

A case of a 67-year-old male with CLL, presented with prolonged pancytopenia after his first cycle of fludarabine, cyclophosphamide, and rituximab (FCR) chemotherapy. He was then treated with ibrutinib oral monotherapy. Shortly after ibrutinib treatment initiation, he developed a brain abscess and pulmonary disease as a part of an invasive aspergil...

Background HIV infection promotes the expansion of immunosuppressive regulatory T-cells (Tregs), contributing to immune dysfunction, tissue fibrosis and disease progression. Early antiretroviral treatment (ART) upon HIV infection improves CD4 count and decreases immune activation. However, Treg dynamics and their epigenetic regulation following ear...

Haemophagocytic lymphohistiocytosis (HLH) causing multiorgan failure has been reported as an acute clinical presentation of COVID-19. However, the literature surrounding HLH in the context of a postacute COVID-19 syndrome is limited. This report presents a case of a life-threatening HLH occurring 6 weeks after a pauci-symptomatic COVID-19 infection...

Phylogenetics has been advanced as a structural framework to infer evolving trends in the regional spread of HIV-1 and guide public health interventions. In Quebec, molecular network analyses tracked HIV transmission dynamics from 2002–2020 using MEGA10-Neighbour-joining, HIV-TRACE, and MicrobeTrace methodologies. Phylogenetics revealed three patte...

Although understanding the diversity of HIV-1 reservoirs is key to achieving a cure, their study at the single-cell level in primary samples remains challenging. We combine flow cytometric multiplexed fluorescent in situ RNA hybridization for different viral genes with HIV-1 p24 protein detection, cell phenotyping, and downstream near-full-length s...

In stark contrast to the rapid development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective human immunodeficiency virus (HIV) vaccine is still lacking. Furthermore, despite virologic suppression and CD4 T-cell count normalization with antiretroviral therapy (ART), people living with HIV (PLWH) still ex...

Background: Persistent inflammation in HIV infection is associated with elevated cardiovascular disease risk, even with viral suppression. Identification of novel surrogate biomarkers can enhance cardiovascular disease risk stratification and suggest novel therapies. We investigated the potential of IL-32, a proinflammatory multi-isoform cytokine,...

Objectives: Untreated HIV infection was previously associated with IL-32 overexpression in gut epithelial cells (IEC). Here, we explored IL-32 isoform expression in the colon of people living with HIV (PLWH) receiving antiretroviral therapy (ART) and IL-32 triggers/modulators in IEC. Design: Sigmoid colon biopsies (SCB) and blood were collected...

NKG2C is an activating NK cell receptor encoded by a gene having an unexpressed deletion variant. Cytomegalovirus (CMV) infection expands a population of NKG2C ⁺ NK cells with adaptive-like properties. Previous reports found that carriage of the deleted NKG2C ⁻ variant was more frequent in people living with HIV (PLWH) than in HIV ⁻ controls unexpo...

Persistent immune activation and inflammation in people living with HIV (PLWH) are associated with immunosenescence, premature aging and increased risk of non-AIDS comorbidities, with the underlying mechanisms not fully understood. In this study, we show that downregulation of the T-cell immunoglobulin receptor CD96 on CD8 ⁺ T cells from PLWH is as...

HIV reservoirs persist in gut-homing CD4+ T cells of people living with HIV and receiving antiretroviral therapy, but the antigenic specificity of such reservoirs remains poorly documented. The imprinting for gut homing is mediated by retinoic acid (RA), a vitamin A-derived metabolite produced by dendritic cells (DCs) exhibiting RA-synthesizing (RA...

Extracellular vesicles (EVs) and their contents (proteins, lipids, messenger RNA, microRNA, and DNA) are viewed as intercellular signals, cell-transforming agents, and shelters for viruses that allow both diagnostic and therapeutic interventions. EVs circulating in the blood of individuals infected with human immunodeficiency virus (HIV-1) may prov...

Background: Several types of extracellular vesicles (EVs) secreted by various immune and non-immune cells are present in the human plasma. We previously demonstrated that EV abundance and microRNA content change in pathological conditions, such as HIV infection. Here, we investigated daily variations of large and small EVs, in terms of abundance a...

Background: The newer generation NNRTIs, including doravirine and rilpivirine, were designed to show high potency and overcome K103N, Y181C and G190A resistance. Objectives: To assess emergent resistance to doravirine and rilpivirine, alone and paired with lamivudine or islatravir through in vitro drug selections. Methods: Subtype B (n = 3), n...

The intestinal epithelial layer serves as a physical and functional barrier between the microbiota in the lumen and immunologically active submucosa. Th17 T-cell function protects the gut epithelium from aggression from microbes and their by-products. Loss of barrier function has been associated with enhanced translocation of microbial products whi...