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Objective: Interleukin-8 (IL-8, CXCL8) plays important roles in immune responses at mucosal sites including in the lower genital tract. Since several types of bacteria produce proteases that cleave IL-8 and many types of bacteria can be present in lower genital tract microbiota, we assessed genital fluids for IL-8 cleavage/alteration. Study Design: Genital fluids collected by lavage from 200 women (23 HIV-seronegative and 177 HIV-seropositive) were tested for IL-8 cleavage/alteration by ELISA. Results: IL-8 cleaving/altering activity was observed in fluids from both HIV-positive (28%) and HIV-negative women (35%). There was no clear relationship between the activity and the types of bacteria present in the lower genital tract as determined by high-throughput sequencing of the 16S rRNA gene. Protease inhibitors specific for matrix metalloproteinases (MMPs) reduced the activity and a multiplex assay that detects both inactive and active MMPs showed the presence of multiple MMPs, including MMP-1, -3, -7, -8, -9, -10 and -12 in genital secretions from many of the women. The IL-8-cleaving/altering activity significantly correlated with active MMP-9 as well as with cleavage of a substrate that is acted on by several active MMPs. Conclusions: These studies show that multiple MMPs are present in the genital tract of women and strongly suggest that MMP-9 in genital secretions can cleave IL-8 at this mucosal site. These studies suggest that MMP-mediated cleavage of IL-8 can modulate inflammatory responses in the lower genital tract. [ABSTRACT FROM AUTHOR]

Background: Individuals with HIV infection exhibit high cytomegalovirus (CMV) IgG levels, but there are few data regarding the association of hepatitis C virus (HCV) with the immune response against CMV. Methods: Associations of HCV with CMV seropositivity and CMV IgG levels were studied in 635 HIV-infected women, 187 of whom were HCV-seropositive, with adjustment in multivariable models for age, race/ethnicity, and HIV disease characteristics. Eighty one percent of the women reported receipt of highly active antiretroviral therapy (HAART) prior to or at CMV testing. Results: In adjusted models women with chronic HCV had higher CMV IgG levels than those without HCV RNA (β = 2.86, 95% CI:0.89 – 4.83; P = 0.004). The association of HCV RNA with CMV IgG differed by age (Pinteraction = 0.0007), with a strong association observed among women in the low and middle age tertiles (≤45.3 years of age; β = 6.21, 95% CI:3.30 – 9.11, P<0.0001) but not among women in the high age tertile. CMV IgG levels were not associated with non-invasive measures of liver disease, APRI and FIB-4, or with HCV RNA level and adjustment for Epstein-Barr virus (EBV) IgG levels did not affect the association between HCV and CMV. Conclusions: CMV IgG levels are higher in HCV/HIV co-infected women than in HIV mono-infected women. Further research on the association of HCV with CMV IgG is indicated because prior studies have found CMV IgG to be associated with morbidity and mortality in the general population and subclinical carotid artery disease in HIV-infected patients. [ABSTRACT FROM AUTHOR]

Background. Cytomegalovirus (CMV) infection has been implicated in immune activation and accelerated progression of immunodeficiency from human immunodeficiency virus (HIV) coinfection. We hypothesized that CMV is associated with vascular disease in HIV-infected adults.Methods. In the Women's Interagency HIV Study, we studied 601 HIV-infected and 90 HIV-uninfected participants. We assessed the association of CMV immunoglobulin G (IgG) level with carotid artery intima-media thickness, carotid artery distensibility, Young's elastic modulus, and blood pressures. Multivariable models adjusted for age, race/ethnicity, smoking, diabetes, and body mass index.Results. Mean CMV IgG levels were higher in HIV-infected women compared with HIV-uninfected women (P < .01). Among HIV-infected women, higher CMV IgG level was associated with decreased carotid artery distensibility (P < .01) and increased Young's modulus (P = .02). Higher CMV IgG antibody level was associated with increased prevalence of carotid artery lesions among HIV-infected women who achieved HIV suppression on antiretroviral therapy, but not among viremic or untreated HIV-infected women. Adjustment for Epstein–Barr virus antibody levels and C-reactive protein levels had no effect on the associations between CMV IgG levels and vascular parameters.Conclusions. Cytomegalovirus antibody titers are increased in HIV-infected women and associated with subclinical cardiovascular disease. Host responses to CMV may be abnormal in HIV infection and associated with clinical disease. [ABSTRACT FROM AUTHOR]

Background. Individuals infected with human immunodeficiency virus (HIV) have increased risk of cardiovascular events. It is unknown whether T cell activation and senescence, 2 immunologic sequelae of HIV infection, are associated with vascular disease among HIV-infected adults. Methods. T cell phenotyping and carotid ultrasound were assessed among 115 HIV-infected women and 43 age- and race/ethnicity-matched HIV-uninfected controls participating in the Women's Interagency HIV Study. Multivariate analyses were used to assess the association of T cell activation (CD38+HLA-DR+) and senescence (CD28-CD57+) with subclinical carotid artery disease. Results. Compared with HIV-uninfected women, frequencies of CD4+CD38+HLA-DR+, CD8+CD38+HLA-DR+, and CD8+CD28-CD57+ T cells were higher among HIV-infected women, including those who achieved viral suppression while receiving antiretroviral treatment. Among HIV-infected women, adjusted for age, antiretroviral medications, and viral load, higher frequencies of activated CD4+ and CD8+ T cells and immunosenescent CD8+ T cells were associated with increased prevalence of carotid artery lesions (prevalence ratiolesions associated with activated CD4+ T cells, 1.6 per SD [95% confidence interval {CI}, 1.1-2.2]; P 5 .02; prevalence ratiolesions associated with activated CD8+ T cells, 2.0 per SD [95% CI, 1.2-3.3]; P < .01; prevalence ratiolesions associated with senescent CD8+ T cells, 1.9 per SD [95% CI, 1.1-3.1]; P = .01). Conclusions. HIV-associated T cell changes are associated with subclinical carotid artery abnormalities, which may be observed even among those patients achieving viral suppression with effective antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Background. Whether human immunodeficiency virus (HIV) infection is associated with a change in the diversity of genital microbiota in women was investigated. Methods. Amplicon length heterogeneity polymerase chain reaction (LH-PCR) analysis and pyrosequencing of the 16S ribosomal RNA gene were used to analyze the diversity of the microbiota in HIV-positive (HIV+) and HIV-negative (HIV-) women with or without bacterial vaginosis (BV). Results. LH-PCR analysis revealed significantly more microbiota diversity in BV-positive (BV+) women than in BV-negative (BV-) women, but no significant difference was noted between HIV+ women and HIV- women. Pyrosequencing revealed that Lactobacillus organisms constituted a median of 96% of the bacteria in BV- women. BV+ women had a significantly higher number of taxa found at ⩾1% of the total genital microbiota (median, 11 taxa). Commontaxa in BV+ women were Prevotella, Megasphaera, Gardnerella, Coriobacterineae, Lachnospira, and Sneathia. There was a trend (P = .07) toward the presence of a higher number of taxa in HIV+BV+ women than in HIV-BV+ women. Propionibacterineae, Citrobacter, and Anaerococcus were the taxa found only in HIV+ women (P <.05). Conclusions. The present study demonstrated that both LH-PCR analysis and pyrosequencing differentiated microbiota in BV+ women from that in BV- women and that pyrosequencing indicated a trend toward increased diversity in BV+HIV+ women, suggesting that HIV infection is associated with changes in the diversity of genital microbiota. [ABSTRACT FROM AUTHOR]

HIV is not usually transmitted by saliva from HIV-1-infected individuals. Antiviral substances in saliva responsible for this may include HIV-1-specific antibody-dependent cell-mediated cytotoxicity (ADCC). We evaluated saliva ADCC titers of 62 HIV-1-infected women from the Women's Interagency HIV Study (WIHS) and 55 uninfected individuals. HIV-1-infected women were less likely to have ADCC activity in saliva than in serum or cervical lavage fluid (CVL). 24% of HIV-1-positive women and a similar percentage of uninfected women had HIV-1-specific saliva ADCC activity. A significant amount of saliva ADCC activity in infected women was HIV-gp120-specific. These studies demonstrate that HIV-specific ADCC activity can be present in saliva. This activity may contribute to host defence against initial infection with HIV. [ABSTRACT FROM AUTHOR]

The short-term detection and variability of human immunodeficiency virus type 1 (HIV-1) RNA level was assessed in the blood plasma and genital tracts of 55 HIV-1-infected women. Specimens were collected weekly for 8 weeks from the endocervical canal with wicks and cytobrushes and from the ectocervix and vagina with cervicovaginal lavage. In all, 48 women (87.3%) had detectable genital tract HIV-1 RNA at ≥1 collection times. HIV-1 RNA levels varied least in specimens from endocervical canal wick and most in cervicovaginal lavage samples. The within-subject variation for genital-tract virus level was greater than that for blood. Overall, the odds for viral RNA detection in the genital tract approximately tripled for each 10-fold increase in plasma viral RNA concentration (P < .001) or with concomitant genital tract infection (P = .003). Endocervical canal wicks should be considered as an adjunct to cervicovaginal lavage, to improve the sensitivity and precision of HIV-1 RNA detection. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: HIV disease is associated with increased arterial stiffness, which may be related to inflammation provoked by HIV-related immune perturbation. We assessed the association of T cell markers of immune activation and immunosenescence with carotid artery stiffness among HIV-infected women. Methods: Among 114 HIV-infected and 43 HIV-uninfected women, we measured CD4+ and CD8+ T cell populations expressing activation (CD38+HLA-DR+) and senescence (CD28-CD57+) markers. We then related these measures of immune status with parameters of carotid artery stiffness, including decreased distensibility, and increased Young''s elastic modulus, as assessed by B-mode ultrasound. Results: HIV infection was associated with increased CD4+ T cell activation, CD8+ T cell activation and CD8+ T cell senescence. Among HIV-infected women, adjusted for age, HIV medications, and vascular risk factors, higher CD4+CD38+HLA-DR+ T cell frequency was associated with decreased carotid artery distensibility (β =−2.00, 95% confidence interval [CI]=−3.86, −0.14, P =0.04) and increased Young''s modulus (β =1.00, 95% CI=0.03, 1.97, P =0.04). These associations were affected little by further adjustment for CD4+ T cell count and viral load. Among HIV-infected women, higher frequencies of immunosenescent T cells, including CD4+CD28-CD57+ and CD8+CD28-CD57+ T cells, were also associated with decreased arterial distensibility. Among HIV-uninfected women, frequencies of activated or senescent T cells were not significantly associated with measures of carotid stiffness. Discussion: T cell activation and senescence are associated with arterial stiffness, suggesting that pro-inflammatory populations of T cells may produce functional or structural vascular changes in HIV-infected women. [Copyright &y& Elsevier]

The species of vaginal lactobacilli in HIV-seropositive and -seronegative women were determined by 16S gene pyrosequencing. Lactobacillus iners sequences were the predominant lactobacillus sequences in 66% of HIV+ women and 90% of HIV- women. This has implications for resistance of HIV+ and HIV- women to genital colonization by pathogenic organisms. [ABSTRACT FROM AUTHOR]

Examines the biomarkers of mitochondrial toxicity and genotoxicity in a well-characterized sample set consisting of infants born to HIV-uninfected mothers and HIV-infants born to HIV-infected mothers who received either no antiretroviral therapy during pregnancy. Loss of mitochondrial DNA; Telomere integrity; Use of polymerase chain reaction-based chemiluminescence detection method.