Positive Association between HIV RNA and IL-6 in the Genital Tract of Rwandan Women

Spear, Gregory T.; Zariffard, M. Reza; Chen, Hua Y.; Anzinger, Joshua J.; Anastos, Kathryn; Rusine, John; Gatabazi, John; French, Audrey L.; Cohen, Mardge H.; Landay, Alan

doi:10.1089/aid.2008.0004

Cited by 22 publications

(22 citation statements)

References 19 publications

(16 reference statements)

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“…[14][15][16] Vaginal hygiene practices 17 and cryotherapy for cervical neoplasia 18 have also been associated with genital HIV-1 shedding, which many hypothesize is related to inflammation resulting from trauma to vaginal epithelium. If inflammation is a risk factor for HIV-1 shedding and is present in the absence of infections, treating infections alone may not reduce genital HIV-1 concentrations and risk to sexual partners.…”

Section: Introductionmentioning

confidence: 99%

Cervicovaginal Shedding of HIV Type 1 Is Related to Genital Tract Inflammation Independent of Changes in Vaginal Microbiota

Mitchell

Hitti

Paul

et al. 2011

AIDS Research and Human Retroviruses

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We examined the relationship of proinflammatory vaginal cytokines and secretory leukocyte protease inhibitor (SLPI) with genital HIV-1 shedding after controlling for genital coinfections. Fifty-seven HIV-1-infected women in Seattle, WA (n = 38) and Rochester, NY (n = 19) were followed every 3-4 months for a total of 391 visits. At each visit, plasma and cervicovaginal lavage (CVL) were tested for HIV-1 RNA using qPCR. Vaginal samples were tested for bacterial vaginosis, yeast, hydrogen peroxide-producing Lactobacillus colonization, Trichomonas vaginalis, Neisseria gonorrhea, Chlamydia trachomatis, CMV, and HSV shedding. CVL interleukins (IL)-1β, IL-6, IL-8, and SLPI were measured using ELISA. Linear regression with generalized estimating equations examined effects of cytokine concentrations on CVL HIV-1 RNA, adjusted for plasma HIV RNA, and measured coinfections. CVL IL-1β and IL-8 were significantly associated with CVL HIV-1 RNA. This persisted after adjusting for plasma HIV-1 RNA. Higher levels of IL-1β were associated with higher concentrations of HIV-1 RNA in CVL (β = 0.25, 95% CI 0.09, 0.42), as were higher levels of IL-8 (β = 0.34, 95% CI 0.17, 0.50). Adjusting for the presence of the coinfections described, this relationship was attenuated for IL-1β (β = 0.16; 95% CI -0.01, 0.33) but still significant for IL-8 (β = 0.29; 95% CI 0.13, 0.45). The proinflammatory cytokines IL-1β and IL-8 are associated with higher cervicovaginal HIV-1 RNA concentrations, even after controlling for plasma viral load and vaginal microbial cofactors. This association suggests that there may be additional, noninfectious causes of inflammation that increase cervicovaginal HIV-1 shedding.

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Section: Introductionmentioning

confidence: 99%

Cervicovaginal Shedding of HIV Type 1 Is Related to Genital Tract Inflammation Independent of Changes in Vaginal Microbiota

Mitchell

Hitti

Paul

et al. 2011

AIDS Research and Human Retroviruses

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“…39-41 In this study 1/3 of the women reported a history of HPV, however the proportion of women with HPV was similar across categories. Other differences in study outcomes may include how cytokines at or below the LLQ are evaluated, 4,31,42,43 sensitivities between assay platforms at the LLQ (multiplexed Luminex assays vs. ELISA), 1,4,6,35,38 sample processing 1,32,35 and volumes used to assay for cytokines. 4,42 …”

Section: Discussionmentioning

confidence: 99%

HIV-1 Shedding From the Female Genital Tract is Associated With Increased Th1 Cytokines/Chemokines That Maintain Tissue Homeostasis and Proportions of CD8+FOXP3+ T Cells

Bull

Legard

Tapia

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background HIV-1 shedding from the female genital tract is associated with increased sexual and perinatal transmission, and has been broadly evaluated in cross-sectional studies. However, few longitudinal studies have evaluated how the immune microenvironment effects shedding. Methods Thirty-nine HIV-1–infected women had blood, cervicovaginal lavage (CVL), and biopsies of the uterine cervix taken quarterly for up to five years. Cytokines/chemokines were quantified by Luminex assay in CVL and cellular phenotypes were characterized using immunohistochemistry in cervical biopsies. Comparisons of cytokine/chemokine concentrations and the percent of tissue staining positive for T cells were compared using generalized estimating equations between non-shedding and shedding visits across all women, and within a subgroup of women who intermittently shed HIV-1. Results Genital HIV-1 shedding was more common when plasma HIV-1 was detected. Cytokines associated with cell growth (IL-7), Th1 cells/inflammation (IL-12p70), and fractalkine were significantly increased at shedding visits compared to non-shedding visits within intermittent shedders and across all subjects. Within intermittent shedders and across all subjects FOXP3+ T cells were significantly decreased at shedding visits. However, there were significant increases in CD8+ cells and proportions of CD8+FOXP3+ T cells associated with HIV-1 shedding. Conclusions Within intermittent HIV-1 shedders, decreases in FOXP3+ T cells at the shedding visit suggests that local HIV-1 replication leads to CD4 T cell depletion, with increases in the proportion of CD8+FOXP3+ cells. HIV-1–infected cell loss may promote a cytokine milieu that maintains cellular homeostasis and increases immune suppressor cells in response to HIV-1 replication in the cervical tissues.

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“…Studies have shown enhancement of HIV infection of target cells in the presence of mucosal fluids. 31,[93][94][95] Proinflammatory cytokines such as IL-6, tumor necrosis factor-a, and IL1b are known to directly stimulate viral replication. [96][97][98][99] Other mucosal innate immune factors that have been reported to have an enhancing effect on viral replication include mucosal factor MRP8/14 (calprotectin) 94,100 and scavenger receptor gp340.…”

Section: Hormonal Regulation Of Antimicrobialsmentioning

confidence: 99%

Secreted Mucosal Antimicrobials in the Female Reproductive Tract that are Important to Consider forHIVPrevention

Ghosh

2014

American J Rep Immunol

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The mucosal microenvironment of the female reproductive tract (FRT) is rich in secreted endogenous antimicrobials that provide the first line of defense against pathogens. This review focuses on the spectrum of secreted antimicrobials found in the FRT that have anti-HIV functions and are regulated by the natural hormonal changes in women's life cycle. Understanding the complex nature of FRT, mucosal microenvironment will enable us to better design therapeutic interventions for women against sexually transmitted pathogens.

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Positive Association between HIV RNA and IL-6 in the Genital Tract of Rwandan Women

Cited by 22 publications

References 19 publications

Cervicovaginal Shedding of HIV Type 1 Is Related to Genital Tract Inflammation Independent of Changes in Vaginal Microbiota

Cervicovaginal Shedding of HIV Type 1 Is Related to Genital Tract Inflammation Independent of Changes in Vaginal Microbiota

HIV-1 Shedding From the Female Genital Tract is Associated With Increased Th1 Cytokines/Chemokines That Maintain Tissue Homeostasis and Proportions of CD8+FOXP3+ T Cells

Secreted Mucosal Antimicrobials in the Female Reproductive Tract that are Important to Consider forHIVPrevention

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