CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: Cannabis inhalation induces significant DNA methylation changes in PLHIV. Such modifications may lead to systematic changes in plasma (inflammatory) protein levels, and cytokine secretion of circulating immune cells. Downregulation of INF-y and INF-y induced protein CXCL10 may influence host response to HIV and co-pathogens. Our data indicate that cannabis use needs to be recorded and corrected for reporting inflammation in PLHIV.

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Impact of Hormone Therapy and HIV on the Immunometabolic Landscape in a Cohort of Transgender Women Erin Mihealsick 1 , Emilia Jalil 2 , Beatriz Grinsztejn 2 , Eileen Scully 1 1 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 Oswaldo Cruz Foundation - Fiocruz, Rio de Janeiro, Brazil Background: Studies of HIV-1 pathogenesis have found differences in set point viral load, immune activation, and latency reversal between cisgender men and women. Although mechanisms are unclear, sex steroid hormone 17-beta estradiol impacts HIV transcription, and sex chromosome genes including TLR7 impact HIV imunopathogenesis. Little is known about the relative influence of these factors in transfeminine individuals. We sought to investigate the impact of exogenous estrogens on markers of inflammation and metabolism in immune cells in a cohort of transgender women (TGW) living with HIV (TGWLWH) or HIV-negative. Methods: To parse the role of feminizing hormone therapy (FHT) versus a lived feminine gender identity in individuals with an XY chromosome complement, we recruited 120 TGW in Brazil through the Transcendendo cohort in 4 groups: HIV-negative on FHT(Group 1) HIV-negative not currently on FHT (Group 2), TGWLWH on FHT(Group 3), TGWLWH not currently on FHT (Group 4). We collected demographic data including depression, substance use, injected fillers, and biospecimens. Cryopreserved PBMCs were immunophenotyped with a 32 color panel using the Cytek Aurora and data were analyzed with FlowJo. Metabolic capacity was assessed using Single Cell ENergetIc metabolism by profiling Translation inhibition (SCENITH) to determine dependence on different metabolic pathways. T cells were isolated from individuals with HIV and qPCR was performed to determine mRNA expression levels of CPT1a. Results: Median age of participants was 37.5. Among TGWLWH, 99.17% had undetectable viral load. In TGWLWH, we saw expected decrease in CD4:CD8 T cell ratios and an increase in HLADR+CD38+ memory CD8 T cells, slightly attenuated by feminizing hormone therapy. Feminizing hormone therapy was linked to decreased expression of CPT1a (a metabolic marker associated with acetylation and fatty acid oxidation) in CD4 and CD8 T cells. Likewise, in PWH CPT1a gene expression levels were significantly lower in individuals on FHT. SCENITH assays performed on HIV- on hormone therapy (Group 1) indicated an increased glucose dependence after ex vivo T cell activation. Conclusion: The combined impact of HIV infection and FHT was associated with differences in mRNA and protein expression of CPT1a in T cells. Additionally, FHT leads to an increase in glucose dependence. These findings suggest that FHT directly impacts immunometabolic phenotypes and that HIV modulates these effects. IRF5 Mediates Persistent Inflammatory Responses in HIV-1–Infected Macrophages Sita Ramaswamy 1 , Jacob Berrigan 1 , Hisashi Akiyama 1 , Andrés Quiñones 1 , Alex Background: People living with HIV (PWH) experience chronic inflammation, which can contribute to HIV- associated co-morbidities. Long-lived HIV-1 infected macrophages are important mediators of chronic innate immune activation. Additive effects of aging and persistent HIV-1 infection can promote macrophage dysfunction, contributing to chronic inflammation, or "inflammaging". We previously reported that nuclear export and cytoplasmic expression of HIV-1 intron-containing RNA (icRNA) activates MAVS-dependent Olson 2 , Yunhan Chen 2 , Yan Mei Liang 2 , Rahm Gummuluru 1 1 Boston University, Boston, MA, USA, 2 Boston Medical Center, Boston, MA, USA

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Immunomodulatory Effects of Cannabis Use in PLHIV Elise M Meeder 1 , Jiang Xun 2 , Adriana Navas 1 , Louise E. van Eekeren 1 , Wilhelm A. Vos 3 , Marc Blaauw 4 , Albert L. Groenendijk 5 , Twan Otten 1 , Nadira Vadaq 1 , Mihai Netea 1 , Vasiliki Matzaraki 1 , Cheng-Jian Xu 2 , Andre J. van der Ven 1 , Arnt F. Schellekens 1 1 Radboud University Medical Center, Nijmegen, Netherlands, 2 Medizinische Hochschule Hannover, Hannover, Germany, 3 OLVG, Amsterdam, Netherlands, 4 Elisabeth-TweeSteden Ziekenhuis, Tilburg, Netherlands, 5 Erasmus University Medical Center, Rotterdam, Netherlands Background: Cannabis is one of the most commonly used psychoactive substances worldwide. Cannabinoids are known to have anti-inflammatory effects. However, cannabis is mainly used by smoking, which results in exposure to reactive particles, toxins and oxidants, inducing pro-inflammatory effects. The effect of cannabis inhalation on systemic inflammation and immune function has barely been studied in humans. Therefore, we assessed the effects of cannabis inhalation on systemic inflammation and immune function in a large cohort of people living with HIV (PLHIV), while taking into account the effects of tobacco inhalation. Methods: This cross-sectional study was performed in 1896 PLHIV using antiretroviral treatment. Cannabis and tobacco use were assessed by self questionnaire MATE-Q, and cannabis use was validated by metabolomic mass spectrometry. Systemic inflammation was assessed using targeted proteomics to assess a total of 2365 plasma proteins. Immune function was assessed by extensive phenotyping of circulating immune cells using flow cytometry, and assessing ex vivo cytokine production capacity of peripheral blood mononuclear upon bacterial, fungal and viral stimulation. The relation between these omics data and the use of cannabis was assessed correcting for age, sex, tobacco use and multiple hypothesis testing. Results: Cannabis use was associated with an upregulation of 15 and a downregulation of 50 proteins. Downregulated proteins in cannabis users were involved in leukocyte-mediated cytotoxicity and NK cell- mediated cytotoxicity. Regarding immune function, the production of monocyte- and lymphocyte derived cytokines did not differ between cannabis users and non-users, apart from increased MCP-1 production upon stimulation with IL1A. Extensive flow cytometry showed that cannabis use was associated with increased levels of CD27+CD21- B-cells only. In contrast, tobacco use was associated with an extensive upregulation of systemic immune-related proteins, increased ex vivo production of various cytokines, as well as extensive alternations in immune cell phenotypes. Conclusion: Our results suggest that cannabis has systemic anti-inflammatory effects, and little effect on immune function, even when used by inhalation. Based on our data, no conclusions can be drawn regarding local immunological effect of cannabis in the airways. Given the increasing legalization of cannabis use worldwide, future research on the health effects of cannabis inhalation is of crucial importance, especially for PLHIV.

Poster Abstracts

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CROI 2024 114