Anti-inflammatory effects of recreational marijuana in virally suppressed youth with HIV-1 are reversed by use of tobacco products in combination with marijuana

• Type of Material: Article
• Authors: Lin Yin, National Institute of Allergy and Infectious Diseases (NIAID); Ashok R. Dinasarapu, Emory University; Samiksha A. Borkar, National Institute of Allergy and Infectious Diseases (NIAID); Kai-Fen Chang, National Institute of Allergy and Infectious Diseases (NIAID); Kristina De Paris, The University of North Carolina at Chapel Hill; Julie J. Kim-Chang, Duke University School of Medicine; John W. Sleasman, Duke University School of Medicine; Maureen M. Goodenow, National Institute of Allergy and Infectious Diseases (NIAID)
• Language: English
• Date: 2022-12-01
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12977-022-00594-4
• Title of Journal or Parent Work: Retrovirology
• Volume: 19
• Issue: 1
• Start Page: 10
• End Page: 10
• Grant/Funding Information: Further support was provided by the Duke University Center for AIDS Research (CFAR) (NIH 5P30-AI064518).; This work was supported in part by funding from the Adolescent Trials Network for HIV/AIDS Interventions (ATN) from the NIH (U01-HD040533 and U01-HD040474) through the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), with supplemental funding from the National Institute on Drug Abuse (NIDA) and the National Institute for Mental Health (NIMH).; It was also supported by independent grants from the NIDA (R01-DA031017 and U01-DA044571). The study was co-endorsed by the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) which is supported by the NIAID, the Eunice Kennedy Shriver NICHD, and the NIMH (U01-A1068632).; Open Access funding provided by the National Institutes of Health (NIH). This work was supported by NIH Grants R01-DA031017 (MMG), U01-DA044571 (JWS), U01-HD040533 (JWS), U01-HD040474 (JWS), U01-A1068632 (JWS), 5P30-AI064518 (JWS, Duke University Center for AIDS Research), and the NIH Intramural Research Program, NIAID (MMG).
• Keywords: Biomarkers; Substance-Related Disorders; Inflammation; Δ9-Tetrahydrocannabinol; Tobacco; HIV-1; Youth with HIV-1; Tobacco Products; Marijuana; Humans; Bioprofiles; Transcriptome; HIV Infections; Cannabinoids; Adolescent; Cannabis
• Research Categories: Biology, Microbiology; Biology, Genetics; Health Sciences, Immunology

Abstract

Background Marijuana’s putative anti-inflammatory properties may benefit HIV-associated comorbidities. How recreational marijuana use affects gene expression in peripheral blood cells (PBC) among youth with HIV-1 (YWH) is unknown. Approach YWH with defined substance use (n = 54) receiving similar antiretroviral therapy (ART) were assigned to one of four analysis groups: YWH with detectable plasma HIV-1 (> 50 RNA copies/ml) who did not use substances (H+V+S−), and YWH with undetectable plasma HIV-1 who did not use substances (H+V−S−), or used marijuana alone (H+V−S+[M]), or marijuana in combination with tobacco (H+V−S+[M/T]). Non-substance using youth without HIV infection (H−S−, n = 25) provided a reference group. PBC mRNA was profiled by Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. Differentially expressed genes (DEG) within outcome groups were identified by Significance Analysis of Microarrays and used for Hierarchical Clustering, Principal Component Analysis, and Ingenuity Pathways Analysis. Results HIV-1 replication resulted in > 3000 DEG involving 27 perturbed pathways. Viral suppression reduced DEG to 313, normalized all 27 pathways, and down-regulated two additional pathways, while marijuana use among virally suppressed YWH resulted in 434 DEG and no perturbed pathways. Relative to H+V−S−, multiple DEG normalized in H+V−S+[M]. In contrast, H+V−S+[M/T] had 1140 DEG and 10 dysregulated pathways, including multiple proinflammatory genes and six pathways shared by H+V+S−. Conclusions YWH receiving ART display unique transcriptome bioprofiles based on viral replication and substance use. In the context of HIV suppression, marijuana use, alone or combined with tobacco, has opposing effects on inflammatory gene expression.