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Project description:Transgender women (TGW) are disproportionally affected by HIV infection, with a global estimated prevalence of 19.9%, often attributed to behavioral risk factors, with less known about biological factors. We evaluated potential biological risk factors for HIV acquisition in TGW at the sites of viral entry by assessing immune parameters of the neovaginal surface and gut mucosa. The neovagina in TGW, compared with the vagina in cisgender women (CW), shows distinct cell composition and may pose a more inflammatory environment, evidenced by increased CD4+ T cell activation and higher levels of soluble markers of inflammation (C-reactive protein, soluble CD30). Increased inflammation may be driven by microbiome composition, as shown by a greater abundance of Prevotella and a higher Shannon Diversity Index. In addition, we have observed higher frequency of CD4+CCR5+ target cells and decreased DNA methylation of the CCR5 gene in the gut mucosa of TGW compared with CW and men who have sex with men, which was inversely correlated with testosterone levels. The rectal microbiome composition in TGW appears to favor a proinflammatory milieu as well as mucosal barrier disruption. Thus, it is possible that increased inflammation and higher frequencies of CCR5-expressing target cells at sites of mucosal viral entry may contribute to increased risk of HIV acquisition in TGW, with further validation in larger studies warranted.
| S-EPMC10543719 | biostudies-literature
Project description:Distinct Mucosal and Systemic Immunological Characteristics in Transgender Women Potentially Relating to HIV Acquisition
| PRJNA983816 | ENA
Project description:A comparison of rectal mucosal RNA transcriptome findings between transgender women using feminizing hormone therapy, men who have sex with men engaging in receptive anal intercourse, and males who had never engaged in anal intercourse demonstrates differential gene expression involving pathways critical for mucosal inflammation, suggesting the urgent need for further exploration into the immunologic effects of cross-sex hormone therapy in the rectal mucosa and the potential impact on HIV transmission risk at this site.
2023-03-21 | GSE141785 | GEO
Project description:BackgroundWe previously reported association of increased cervical RANTES and decreased secretory leukocyte protease inhibitor (SLPI) with higher risk of HIV acquisition in reproductive-age women. We now examine the interaction of concomitantly altered systemic and cervical immunity on such risk.MethodsWe measured immune biomarkers in 4390 cervical and 2390 paired serum specimens at quarterly visits in 218 HIV seroconverters and 784 seronegative women. We assessed proinflammatory (IL-1β, IL-6, IL-8, MIP-3α, and RANTES), anti-inflammatory (IL-1RA and SLPI), vascular activation (vascular endothelial growth factor and Intercellular Adhesion Molecule-1) and defensin (BD2) cervical biomarkers and systemic (peripheral blood) C reactive protein (CRP), IL-6, IL-7, and sCD14 as indicators of immune dysregulation. Biomarker levels were Box-Cox transformed and odds ratios for HIV acquisition calculated based on top quartile or higher/lower than median levels for all HIV-negative visits.ResultsSubsequent HIV acquisition was associated with 5 of 14 individual biomarkers: low systemic CRP [odds ratio (OR) = 1.49, 1.21-1.83] and IL-6 (OR = 1.23, 1.00-1.51), high cervical BD-2 (OR = 1.33, 1.11-1.58) and RANTES (OR = 1.20, 1.01-1.43), and low cervical IL-1RA (OR = 0.65, 0.48-0.86). Low systemic CRP concomitant with altered cervical immunity, especially high BD2, conveyed highest HIV risk (1.63, 1.29-2.05). Additional markers of increased risk emerged when low systemic CRP coincided with: low systemic IL-6 and IL-7 (OR = 1.53, 1.18-1.97); high cervical IL-8 and MIP-3α (OR = 1.40, 1.07-1.83); high cervical IL-1β and IL-6 (OR = 1.43, 1.09-1.86); or low cervical SLPI (OR = 1.36, 1.08-1.71).ConclusionsChanges in both peripheral and mucosal immunity may precede and predispose women to HIV infection. Suppressed systemic immunity (ie, low CRP) alone or in combination with imbalanced cervical innate immunity (high proinflammatory and low anti-inflammatory mediators) indicated increased vulnerability to infection. Understanding these combined effects on HIV susceptibility is essential to preventing new infections.
| S-EPMC7948484 | biostudies-literature
Project description:HIV â??controllersâ?? are individuals infected with the human immunodeficiency virus, type I (HIV) who maintain long-term control of viremia without antiviral therapy and who usually do not develop the acquired immune deficiency syndrome (AIDS). In this study, we have used oligonucleotide expression arrays to characterize the mucosal immune responses of these subjects in relation to untreated HIV+ individuals with high viral loads and progressive disease (â??non-controllersâ??). Recto-sigmoid biopsies were analyzed from 9 controllers and 11 non-controllers. All of the genes identified to be significantly different were more highly expressed in the non-controllers. Many of these genes are involved in immunity and defence. These results underscore the importance of the sustained inflammatory response that attends progressive HIV disease. Keywords: Recto-sigmoid biopsy profiles from HIV infected individuals We analyzed a series of 20 HEEBO arrays on which were hybed RNA amplified from the recto-sigmoid biopsies of HIV infected individuals that either have progressive disease or can maintain long term control of viremia.
2010-10-08 | E-GEOD-20075 | biostudies-arrayexpress
Project description:Among transgender women (TGW), the effects of feminizing hormone therapy use on rectal mucosal (RM) HIV transmission are largely unknown. In this small pilot study, we compared the RM transcriptome in TGW utilizing feminizing hormone therapy with a group of cisgender men who have sex with men (MSM) engaging in condomless receptive anal intercourse (AI) and to a group of cisgender men who had never engaged in AI. There were 498 differentially expressed genes (DEGs) in TGW compared with men who had never engaged in AI, and 154 DEGs compared with the MSM. Among TGW, a unique RM transcriptome was identified that implicated pathways critical for mucosal immune responses, including upregulation of genes that mediate immune cell activation and the production of cytokines and other immune signaling molecules. Furthermore, gene set enrichment analyses identified immune signatures that implicated enrichment of proinflammatory immunological pathways in TGW, specifically involving interferon-α, interleukin-6, and tumor necrosis factor-α signaling, whereas metabolic pathways were shown to be enriched among the cisgender male groups. These findings suggest that TGW have a distinct RM immune environment influenced by the use of feminizing hormones, and consequently, there is an urgent need for further investigation into the immunological effects of gender-affirming hormone therapy and its potential impact on HIV mucosal transmission risk for transgender individuals.
| S-EPMC7482106 | biostudies-literature
Project description:PurposeLittle has been reported from population-based surveys on the characteristics of transgender persons living with HIV. Using Medical Monitoring Project (MMP) data, we describe the characteristics of HIV-infected transgender women and examine their care and treatment needs.MethodsWe used combined data from the 2009 to 2011 cycles of MMP, an HIV surveillance system designed to produce nationally representative estimates of the characteristics of HIV-infected adults receiving medical care in the United States, to compare demographic, behavioral, and clinical characteristics, and met and unmet needs for supportive services of transgender women with those of non-transgender persons using Rao-Scott chi-square tests.ResultsAn estimated 1.3% of HIV-infected persons receiving care in the United States self-identified as transgender women. Transgender women were socioeconomically more marginalized than non-transgender men and women. We found no differences between transgender women and non-transgender men and women in the percentages prescribed antiretroviral therapy (ART). However, a significantly lower percentage of transgender women compared to non-transgender men had 100% ART dose adherence (78.4% vs. 87.4%) and durable viral suppression (50.8% vs. 61.4%). Higher percentages of transgender women needed supportive services. No differences were observed in receipt of most of supportive services, but transgender women had higher unmet needs than non-transgender men for basic services such as food and housing.ConclusionWe found little difference between transgender women and non-transgender persons in regards to receipt of care, treatment, and most of supportive services. However, the noted disparities in durable viral suppression and unmet needs for basic services should be explored further.
| S-EPMC6711156 | biostudies-literature
Project description:BackgroundMucosal and systemic immune mediators have been independently associated with HIV acquisition risk, but the relationship between compartments remains unclear.MethodsTo address this, the concentrations of 12 cytokines were compared in matched plasma and cervicovaginal lavages (CVLs) from 57 HIV-positive women before their acquisition of HIV (cases) and 50 women who remained uninfected (controls) during the CAPRISA 004 trial.ResultsAlthough genital IP-10 concentrations were significantly higher in cases, plasma IP-10 concentrations were inversely associated with HIV risk. Comparing differences in mucosal and systemic cytokine concentrations between cases and controls, mucosa-biased gradients indicating higher cervicovaginal lavage relative to plasma concentrations were observed for all 5 chemokines in the panel. Four were significantly associated with HIV acquisition, including IP-10 (odds ratio [OR] 1.73, 95% confidence interval [CI]: 1.27 to 2.36), macrophage inflammatory protein-1? (OR 1.72, 95% CI: 1.23 to 2.40), interleukin (IL)-8 (OR 1.50, 95% CI: 1.09 to 2.05), and monocyte chemotactic protein-1 (OR 1.36, 95% CI: 1.01 to 1.83). None of the other 7 cytokines tested predicted HIV risk. Decision tree analyses confirmed this association, with gradients of IP-10, IL-8, and granulocyte-macrophage colony-stimulating factor concentrations correctly classifying 77% of HIV outcomes.ConclusionsOur findings suggest that mucosa-biased gradients of IP-10, macrophage inflammatory protein-1?, IL-8, and monocyte chemotactic protein-1 are associated with an increased risk of HIV infection.
| S-EPMC5305292 | biostudies-literature
Project description:The mechanisms behind acute mucosal injury responses in humans are poorly investigated.We thus examined the acute responses to mucosal barrier injury in humans with and without UC. A standardized mucosal wound extending to the muscularis mucosa layer was inflicted in the sigmoid colon of 6 patients with quiescent UC and 6 control subjects. Macroscopic, microscopic and molecular injury responses were assessed at 24 and 48 hours by repeated high resolution imaging and collection of biopsies across the wounds which were assessed by RNA sequencing.
2021-10-06 | GSE164918 | GEO
Project description: Not available
| S-EPMC6492192 | biostudies-literature