Plasma and Mucosal HIV Viral Loads Are Associated With Genital Tract Inflammation in HIV-Infected Women

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 (WIHS) to explore the hypothesis that compared to 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 19 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). CVL antimicrobial activity was also determined. Results Compared to HIV-uninfected, HIV+-HVL women had higher levels of mucosal, but not systemic pro-inflammatory cytokines and chemokines, higher Nugent scores, and lower E. 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 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. Conclusion 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.

Influence of Common Mucosal Co‐Factors on HIV Infection in the Female Genital Tract

“…111 In another study, HIV genital tract shedding was significantly associated with higher cervico-vaginal lavage (CVL) concentrations of IL-6, IL-1b, MIP-1a, and RANTES. 112 Thus, a future exploration of using anti-inflammatory compounds for the purpose of protecting the epithelial barrier-disrupting function of HIV-1 gp120 as well as the inflammation associated with co-infecting microbes may therefore present a novel and valuable new modality for preventing HIV infection in the FGT or curbing the spread of the infection.…”

Biomarkers of Cervical Inflammation and Immunity Associated with Cervical Shedding of HIV-1

“…An association between cervical RANTES and HIV shedding has been seen in other studies. [16][17][18] The presence of higher levels of RANTES in women who become HIV infected and those who go on to shed, demonstrated in our studies, suggests that elevations in RANTES precede and may be causally related to increased HIV replication. Consistent with this notion is a study in which RANTES levels in the cervico-vaginal lavage (CVL) of highly exposed, but seronegative, women were lower than in HIV-negative (but not highly exposed) and HIV-positive women.…”

Protocolos y manejo práctico de pacientes con secreción uretral o vaginal patológica

“…Por si fuera poco, se ha comprobado que la liberació n de citocinas proinflamatorias por las cé lulas infectada por M. genitalium atrae y activa a linfocitos susceptibles al VIH, y ademá s aumenta la liberació n viral en cé rvix; por todo ello parece claro que la cervicitis porM. genitalium facilita tanto la adquisició n como la transmisió n de la infecció n por VIH 32,33 .…”