TY - JOUR
T1 - Plasma and mucosal HIV viral loads are associated with genital tract inflammation in HIV-infected women
AU - Herold, Betsy C.
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
PY - 2013/8/1
Y1 - 2013/8/1
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.
KW - Female genital tract
KW - HIV
KW - HSV
KW - Inflammation
KW - Mucosal immunity
KW - WIHS
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U2 - 10.1097/QAI.0b013e3182961cfc
DO - 10.1097/QAI.0b013e3182961cfc
M3 - Article
C2 - 23591635
SN - 1525-4135
VL - 63
SP - 485
EP - 493
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 4
ER -