Plasma and mucosal HIV viral loads are associated with genital tract inflammation in HIV-infected women

Betsy Herold, Marla J. Keller, Qiuhu Shi, Donald R. Hoover, Colleen A. Carpenter, Ashley Huber, Urvi M. Parikh, Kathy J. Agnew, Howard Minkoff, Christine Colie, Marek J. Nowicki, Gypsyamber D'Souza, D. Heather Watts, Kathryn Anastos

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background:: Systemic and mucosal inflammation may play a role in HIV control. A cross-sectional comparison was conducted among women in the Women's Interagency HIV Study to explore the hypothesis that compared with HIV-uninfected participants, women with HIV, and, in particular, those with high plasma viral load (PVL) have increased levels of mucosal and systemic inflammatory mediators and impaired mucosal endogenous antimicrobial activity. METHODS:: Nineteen HIV-uninfected, 40 HIV-infected on antiretroviral therapy (ART) with PVL ≤ 2600 copies/mL (low viral load) (HIV-LVL), and 19 HIV-infected on or off ART with PVL >10,000 (high viral load) (HIV-HVL) were evaluated. Immune mediators and viral RNA were quantified in plasma and cervicovaginal lavage (CVL). The CVL antimicrobial activity was also determined. RESULTS:: Compared to HIV-uninfected participants, HIV-HVL women had higher levels of mucosal but not systemic proinflammatory cytokines and chemokines, higher Nugent scores, and lower Escherichia coli bactericidal activity. In contrast, there were no significant differences between HIV-LVL and HIV-uninfected controls. After adjusting for PVL, HIV genital tract shedding was significantly associated with higher CVL concentrations of IL-6, IL-1β, MIP-1α, and CCL5 (RANTES) and higher plasma concentrations of MIP-1α. High PVL was associated with higher CVL levels of IL-1β and RANTES, as well as with higher Nugent scores, lower E. coli bactericidal activity, smoking, and lower CD4 counts; smoking and CD4 count retained statistical significance in a multivariate model. CONCLUSIONS:: Further study is needed to determine if the relationship between mucosal inflammation and PVL is causal and to determine if reducing mucosal inflammation is beneficial.

Original languageEnglish (US)
Pages (from-to)485-493
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume63
Issue number4
DOIs
StatePublished - Aug 1 2013

Fingerprint

Viral Load
HIV
Inflammation
Therapeutic Irrigation
Chemokine CCL5
CD4 Lymphocyte Count
Interleukin-1
Smoking
Escherichia coli
Viral RNA
Chemokines
Interleukin-6

Keywords

  • Female genital tract
  • HIV
  • HSV
  • Inflammation
  • Mucosal immunity
  • WIHS

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Plasma and mucosal HIV viral loads are associated with genital tract inflammation in HIV-infected women. / Herold, Betsy; Keller, Marla J.; Shi, Qiuhu; Hoover, Donald R.; Carpenter, Colleen A.; Huber, Ashley; Parikh, Urvi M.; Agnew, Kathy J.; Minkoff, Howard; Colie, Christine; Nowicki, Marek J.; D'Souza, Gypsyamber; Watts, D. Heather; Anastos, Kathryn.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 63, No. 4, 01.08.2013, p. 485-493.

Research output: Contribution to journalArticle

Herold, B, Keller, MJ, Shi, Q, Hoover, DR, Carpenter, CA, Huber, A, Parikh, UM, Agnew, KJ, Minkoff, H, Colie, C, Nowicki, MJ, D'Souza, G, Watts, DH & Anastos, K 2013, 'Plasma and mucosal HIV viral loads are associated with genital tract inflammation in HIV-infected women', Journal of Acquired Immune Deficiency Syndromes, vol. 63, no. 4, pp. 485-493. https://doi.org/10.1097/QAI.0b013e3182961cfc
Herold, Betsy ; Keller, Marla J. ; Shi, Qiuhu ; Hoover, Donald R. ; Carpenter, Colleen A. ; Huber, Ashley ; Parikh, Urvi M. ; Agnew, Kathy J. ; Minkoff, Howard ; Colie, Christine ; Nowicki, Marek J. ; D'Souza, Gypsyamber ; Watts, D. Heather ; Anastos, Kathryn. / Plasma and mucosal HIV viral loads are associated with genital tract inflammation in HIV-infected women. In: Journal of Acquired Immune Deficiency Syndromes. 2013 ; Vol. 63, No. 4. pp. 485-493.
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abstract = "Background:: Systemic and mucosal inflammation may play a role in HIV control. A cross-sectional comparison was conducted among women in the Women's Interagency HIV Study to explore the hypothesis that compared with HIV-uninfected participants, women with HIV, and, in particular, those with high plasma viral load (PVL) have increased levels of mucosal and systemic inflammatory mediators and impaired mucosal endogenous antimicrobial activity. METHODS:: Nineteen HIV-uninfected, 40 HIV-infected on antiretroviral therapy (ART) with PVL ≤ 2600 copies/mL (low viral load) (HIV-LVL), and 19 HIV-infected on or off ART with PVL >10,000 (high viral load) (HIV-HVL) were evaluated. Immune mediators and viral RNA were quantified in plasma and cervicovaginal lavage (CVL). The CVL antimicrobial activity was also determined. RESULTS:: Compared to HIV-uninfected participants, HIV-HVL women had higher levels of mucosal but not systemic proinflammatory cytokines and chemokines, higher Nugent scores, and lower Escherichia coli bactericidal activity. In contrast, there were no significant differences between HIV-LVL and HIV-uninfected controls. After adjusting for PVL, HIV genital tract shedding was significantly associated with higher CVL concentrations of IL-6, IL-1β, MIP-1α, and CCL5 (RANTES) and higher plasma concentrations of MIP-1α. High PVL was associated with higher CVL levels of IL-1β and RANTES, as well as with higher Nugent scores, lower E. coli bactericidal activity, smoking, and lower CD4 counts; smoking and CD4 count retained statistical significance in a multivariate model. CONCLUSIONS:: Further study is needed to determine if the relationship between mucosal inflammation and PVL is causal and to determine if reducing mucosal inflammation is beneficial.",
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AU - Keller, Marla J.

AU - Shi, Qiuhu

AU - Hoover, Donald R.

AU - Carpenter, Colleen A.

AU - Huber, Ashley

AU - Parikh, Urvi M.

AU - Agnew, Kathy J.

AU - Minkoff, Howard

AU - Colie, Christine

AU - Nowicki, Marek J.

AU - D'Souza, Gypsyamber

AU - Watts, D. Heather

AU - Anastos, Kathryn

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N2 - Background:: Systemic and mucosal inflammation may play a role in HIV control. A cross-sectional comparison was conducted among women in the Women's Interagency HIV Study to explore the hypothesis that compared with HIV-uninfected participants, women with HIV, and, in particular, those with high plasma viral load (PVL) have increased levels of mucosal and systemic inflammatory mediators and impaired mucosal endogenous antimicrobial activity. METHODS:: Nineteen HIV-uninfected, 40 HIV-infected on antiretroviral therapy (ART) with PVL ≤ 2600 copies/mL (low viral load) (HIV-LVL), and 19 HIV-infected on or off ART with PVL >10,000 (high viral load) (HIV-HVL) were evaluated. Immune mediators and viral RNA were quantified in plasma and cervicovaginal lavage (CVL). The CVL antimicrobial activity was also determined. RESULTS:: Compared to HIV-uninfected participants, HIV-HVL women had higher levels of mucosal but not systemic proinflammatory cytokines and chemokines, higher Nugent scores, and lower Escherichia coli bactericidal activity. In contrast, there were no significant differences between HIV-LVL and HIV-uninfected controls. After adjusting for PVL, HIV genital tract shedding was significantly associated with higher CVL concentrations of IL-6, IL-1β, MIP-1α, and CCL5 (RANTES) and higher plasma concentrations of MIP-1α. High PVL was associated with higher CVL levels of IL-1β and RANTES, as well as with higher Nugent scores, lower E. coli bactericidal activity, smoking, and lower CD4 counts; smoking and CD4 count retained statistical significance in a multivariate model. CONCLUSIONS:: Further study is needed to determine if the relationship between mucosal inflammation and PVL is causal and to determine if reducing mucosal inflammation is beneficial.

AB - Background:: Systemic and mucosal inflammation may play a role in HIV control. A cross-sectional comparison was conducted among women in the Women's Interagency HIV Study to explore the hypothesis that compared with HIV-uninfected participants, women with HIV, and, in particular, those with high plasma viral load (PVL) have increased levels of mucosal and systemic inflammatory mediators and impaired mucosal endogenous antimicrobial activity. METHODS:: Nineteen HIV-uninfected, 40 HIV-infected on antiretroviral therapy (ART) with PVL ≤ 2600 copies/mL (low viral load) (HIV-LVL), and 19 HIV-infected on or off ART with PVL >10,000 (high viral load) (HIV-HVL) were evaluated. Immune mediators and viral RNA were quantified in plasma and cervicovaginal lavage (CVL). The CVL antimicrobial activity was also determined. RESULTS:: Compared to HIV-uninfected participants, HIV-HVL women had higher levels of mucosal but not systemic proinflammatory cytokines and chemokines, higher Nugent scores, and lower Escherichia coli bactericidal activity. In contrast, there were no significant differences between HIV-LVL and HIV-uninfected controls. After adjusting for PVL, HIV genital tract shedding was significantly associated with higher CVL concentrations of IL-6, IL-1β, MIP-1α, and CCL5 (RANTES) and higher plasma concentrations of MIP-1α. High PVL was associated with higher CVL levels of IL-1β and RANTES, as well as with higher Nugent scores, lower E. coli bactericidal activity, smoking, and lower CD4 counts; smoking and CD4 count retained statistical significance in a multivariate model. CONCLUSIONS:: Further study is needed to determine if the relationship between mucosal inflammation and PVL is causal and to determine if reducing mucosal inflammation is beneficial.

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KW - HSV

KW - Inflammation

KW - Mucosal immunity

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