Dataset Information

Impact of Cannabis Use on Immune Cell Populations and the Viral Reservoir in People With HIV on Suppressive Antiretroviral Therapy.

ABSTRACT:

Background

Human immunodeficiency virus (HIV) infection remains incurable due to the persistence of a viral reservoir despite antiretroviral therapy (ART). Cannabis (CB) use is prevalent amongst people with HIV (PWH), but the impact of CB on the latent HIV reservoir has not been investigated.

Methods

Peripheral blood cells from a cohort of PWH who use CB and a matched cohort of PWH who do not use CB on ART were evaluated for expression of maturation/activation markers, HIV-specific T-cell responses, and intact proviral DNA.

Results

CB use was associated with increased abundance of naive T cells, reduced effector T cells, and reduced expression of activation markers. CB use was also associated with reduced levels of exhausted and senescent T cells compared to nonusing controls. HIV-specific T-cell responses were unaffected by CB use. CB use was not associated with intact or total HIV DNA frequency in CD4 T cells.

Conclusions

This analysis is consistent with the hypothesis that CB use reduces activation, exhaustion, and senescence in the T cells of PWH, and does not impair HIV-specific CD8 T-cell responses. Longitudinal and interventional studies with evaluation of CB exposure are needed to fully evaluate the impact of CB use on the HIV reservoir.

SUBMITTER: Falcinelli SD

PROVIDER: S-EPMC10681869 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impact of Cannabis Use on Immune Cell Populations and the Viral Reservoir in People With HIV on Suppressive Antiretroviral Therapy.

Falcinelli Shane D SD Cooper-Volkheimer Alicia D AD Semenova Lesia L Wu Ethan E Richardson Alexander A Ashokkumar Manickam M Margolis David M DM Archin Nancie M NM Rudin Cynthia D CD Murdoch David D Browne Edward P EP

The Journal of infectious diseases 20231101 11

<h4>Background</h4>Human immunodeficiency virus (HIV) infection remains incurable due to the persistence of a viral reservoir despite antiretroviral therapy (ART). Cannabis (CB) use is prevalent amongst people with HIV (PWH), but the impact of CB on the latent HIV reservoir has not been investigated.<h4>Methods</h4>Peripheral blood cells from a cohort of PWH who use CB and a matched cohort of PWH who do not use CB on ART were evaluated for expression of maturation/activation markers, HIV-specifi ...[more]

PMID: 37606598

Similar Datasets

Project description:HIV establishes a persistent viral reservoir in the brain despite viral suppression in blood to undetectable levels on antiretroviral therapy (ART). The brain viral reservoir in virally suppressed HIV+ individuals is not well-characterized. In this study, intact, defective, and total HIV proviral genomes were measured in frontal lobe white matter from 28 virally suppressed individuals on ART using the intact proviral DNA assay (IPDA). HIV gag DNA/RNA levels were measured using single-copy assays and expression of 78 genes related to inflammation and white matter integrity was measured using the NanoString platform. Intact proviral DNA was detected in brain tissues of 18 of 28 (64%) individuals on suppressive ART. The median proviral genome copy numbers in brain tissue as measured by the IPDA were: intact, 10 (IQR 1-92); 3' defective, 509 (225-858); 5' defective, 519 (273-906); and total proviruses, 1063 (501-2074) copies/106 cells. Intact proviral genomes accounted for less than 10% (median 8.3%) of total proviral genomes in the brain, while 3' and 5' defective genomes accounted for 44% and 49%, respectively. There was no significant difference in median copy number of intact, defective, or total proviruses between groups stratified by neurocognitive impairment (NCI) vs. no NCI. In contrast, there was an increasing trend in intact proviruses in brains with vs. without neuroinflammatory pathology (56 vs. 5 copies/106 cells, p = 0.1), but no significant differences in defective or total proviruses. Genes related to inflammation, stress responses, and white matter integrity were differentially expressed in brain tissues with >5 vs. +5 intact proviruses/106 cells. These findings suggest that intact HIV proviral genomes persist in the brain at levels comparable to those reported in blood and lymphoid tissues and increase CNS inflammation/immune activation despite suppressive ART, indicating the importance of targeting the CNS reservoir to achieve HIV cure.

Project description:Ear, nose, and throat (ENT) conditions are prevalent in people living with HIV (PLWH) and occur at all strata of CD4 counts and despite antiretroviral therapy (ART). ENT conditions are underreported in PLWH. Also, little is known about the adenotonsillar microbiota and its relation to resident adaptive and innate immune cells. To bridge this gap, we characterized immune cell populations and the bacterial microbiota of two anatomical sites (adenoids, tonsils) and the oral cavity. Adenoids and tonsils were obtained from PLWH (n = 23) and HIV-seronegative individuals (SN, n = 16) after nasal surgery and tonsillectomy and processed for flow cytometry. Nasopharyngeal, oropharyngeal swabs, and oral rinses were collected prior to surgery for 16S sequencing. Wilcoxon rank sum test, principal coordinate analysis, permutational multivariate analysis of variance, and linear discriminant analysis (LEfSe) were used to assess differences between PLWH and SN. Spearman's correlations were performed to explore interactions between the bacteriome and mucosal immune cells. Of the 39 individuals included, 30 (77%) were men; the median age was 32 years. All PLWH were on ART, with a median CD4 of 723 cells. ENT conditions were classified as inflammatory or obstructive, with no differences observed between PLWH and SN. PLWH had higher frequencies of activated CD4+ and CD8+ T cells, increased T helper (Th)1 and decreased Th2 cells; no differences were observed for B cells and innate immune cells. Alpha diversity was comparable between PLWH and SN at all 3 anatomical sites (adenoids, tonsils, and oral cavity). The impact of HIV infection on the bacterial community structure at each site, as determined by Permutational multivariate analysis of variance, was minor and not significant. Two discriminant genera were identified in adenoids using LEfSe: Staphylococcus for PLWH and Corynebacterium for SN. No discriminant genera were identified in the oropharynx and oral cavity. Niche-specific differences in microbial diversity and communities were observed. PLWH shared less of a core microbiota than SN. In the oropharynx, correlation analysis revealed that Th17 cells were inversely correlated with bacterial richness and diversity, Filifactor, Actinomyces and Treponema; and positively correlated with Streptococcus. Our study contributes toward understanding the role of the adenotonsillar microbiota in the pathophysiology of ENT conditions.

Dataset Information

Impact of Cannabis Use on Immune Cell Populations and the Viral Reservoir in People With HIV on Suppressive Antiretroviral Therapy.

Background

Methods

Results

Conclusions

Publications

Impact of Cannabis Use on Immune Cell Populations and the Viral Reservoir in People With HIV on Suppressive Antiretroviral Therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets