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1.  The insulin-like growth factor axis and risk of liver disease in hepatitis C virus/HIV-co-infected women 
AIDS (London, England)  2008;22(4):527-531.
Objective
Insulin-like growth factor (IGF) I stimulates the proliferation of hepatic stellate cells (HSC), the primary source of extracellular matrix accumulation in liver fibrosis. In contrast, insulin-like growth factor binding protein (IGFBP) 3, the most abundant IGFBP in circulation, negatively modulates HSC mitogenesis. To investigate the role of the IGF axis in hepatitis C virus (HCV)-related liver disease among high-risk patients, we prospectively evaluated HCV-viremic/HIV-positive women.
Design
A cohort investigation.
Methods
Total IGF-I and IGFBP-3 were measured in baseline serum specimens obtained from 472 HCV-viremic/HIV-positive subjects enrolled in the Women's Inter-agency HIV Study, a large multi-institutional cohort. The aspartate aminotransferase to platelet ratio index (APRI), a marker of liver fibrosis, was assessed annually.
Results
Normal APRI levels (< 1.0) at baseline were detected in 374 of the 472 HCV-viremic/HIV-positive subjects tested, of whom 302 had complete liver function test data and were studied. IGF-I was positively associated [adjusted odds ratio comparing the highest and lowest quartiles (AORq4–q1), 5.83; 95% confidence interval (CI) 1.17–29.1; Ptrend = 0.03], and IGFBP-3 was inversely associated (AORq4–q1, 0.13; 95% CI 0.02–0.76; Ptrend = 0.04), with subsequent (incident) detection of an elevated APRI level(> 1.5), after adjustment for the CD4 T-cell count, alcohol consumption, and other risk factors.
Conclusion
High IGF-I may be associated with increased risk and high IGFBP-3 with reduced risk of liver disease among HCV-viremic/HIV-positive women.
doi:10.1097/QAD.0b013e3282f22cdf
PMCID: PMC3507535  PMID: 18301066
aspartate aminotransferase to platelet ratio index; APRI; hepatitis C virus (HCV); HIV; IGFBP-3; IGF; liver disease
2.  Associations of Insulin-Like Growth Factor (IGF)–I and IGF-Binding Protein–3 with HIV Disease Progression in Women 
The Journal of infectious diseases  2008;197(2):319-327.
Background
The insulin-like growth factor (IGF) axis has been hypothesized to influence the rate of human immunodeficiency virus (HIV) disease progression. This premise is based largely on laboratory models showing that IGF-I stimulates thymic growth and increases lymphocyte numbers and that IGF-binding protein (IGFBP)–3 has an opposing effect, inhibiting hematopoietic stem cell development.
Methods
We studied 1422 HIV-infected women enrolled in a large cohort that entailed semiannual follow-up (initiated in 1994). Baseline serum samples were tested for IGF-I and IGFBP-3 to determine their associations with incident clinical acquired immunodeficiency syndrome (AIDS) and CD4+ T cell count decline prior to April 1996 (before the era of highly active antiretroviral therapy [HAART]).
Results
Low IGF-I levels (Ptrend = .02) and high IGFBP-3 levels (Ptrend = .02) were associated with rapid CD4+ T cell count decline. Only IGFBP-3, however, was significantly associated with AIDS incidence (hazard ratio for highest vs. lowest quartile, 2.65 [95% confidence interval, 1.30–5.42]; Ptrend = .02) in multivariable models.
Conclusions
These findings suggest that serum levels of IGFBP-3 (and possibly IGF-I) are associated with the rate of HIV disease progression in women and, more broadly, that interindividual heterogeneity in the IGF axis may influence HIV pathogenesis. If correct, the IGF axis could be a target for interventions to slow HIV disease progression and extend the time before use of HAART becomes necessary.
doi:10.1086/524848
PMCID: PMC3127259  PMID: 18177247
3.  Variations in Serum Mullerian Inhibiting Substance Between White, Black and Hispanic Women 
Fertility and sterility  2008;92(5):1674-1678.
Objective
To compare serum mullerian inhibiting substance (MIS) levels between white, black and Hispanic women to determine if ovarian aging occurs at a different time course for women of different racial groups.
Design
Longitudinal study of serum MIS levels in women of different race/ethnicity over two different time points.
Setting
Women’s Interagency HIV Study, a multicenter prospective cohort study.
Patient(s)
Serum samples obtained from 809 participants (122 white, 462 black and 225 Hispanic women).
Intervention(s)
Comparison of serum MIS between women of different race/ethnicity at two time points (median age 37.5 years and 43.3 years).
Main Outcome Measure(s)
Variation in MIS by race/ethnicity over time, controlling for age, BMI, HIV status and smoking.
Result(s)
Compared to white women, average MIS values were lower among black (25.2% lower, p=0.037) and Hispanic (24.6% lower, p=0.063) women, adjusting for age, BMI, smoking and HIV status.
Conclusion
There is an independent effect of race/ethnicity on the age-related decline in MIS over time.
doi:10.1016/j.fertnstert.2008.08.110
PMCID: PMC3037722  PMID: 18930217
Mullerian inhibiting substance; antiMullerian hormone; ovarian reserve; race; ethnicity
4.  Positive association between HIV RNA and IL-6 in the genital tract of Rwandan Women 
Infections and inflammation in the genital tract can influence HIV expression or HIV susceptibility. The goal of this study was to determine if significant relationships exist between cytokines and HIV in genital tract secretions from 57 HIV-seropositive Rwandan women. Genital tract secretions were obtained by cervicovaginal lavage (CVL). Ten different cytokines in CVL were measured by multiplex Cytometric Bead Arrays. HIV RNA in CVL and plasma were measured by quantitative PCR. In univariate analysis, genital tract HIV RNA was significantly associated with plasma HIV RNA and several of the cytokines, while in multivariate analysis, genital tract HIV RNA was only significantly associated with plasma HIV RNA and IL-6. This association of IL-6 with HIV RNA levels suggests that IL-6 is an indicator for conditions that induce HIV expression and that IL-6 may contribute to induction of HIV expression in the genital tract.
doi:10.1089/aid.2008.0004
PMCID: PMC2792594  PMID: 18671479
5.  Low CD4+ T cell count as a major atherosclerosis risk factor in HIV-infected women and men 
AIDS (London, England)  2008;22(13):1615-1624.
Objective
To assess the association of HIV infection, HIV disease parameters (including CD4+ T-cell counts, HIV viral load, and AIDS) and antiretroviral medication use with subclinical carotid artery atherosclerosis.
Design
Cross-sectional study nested within a prospective cohort study
Methods
Among participants in the Women's Interagency HIV Study (1,331 HIV-infected women, 534 HIV-uninfected women) and Multicenter AIDS Cohort Study (600 HIV-infected men, 325 HIV-uninfected men), we measured subclinical carotid artery lesions and common carotid artery intima-media thickness (CIMT) using B-mode ultrasound. We estimated adjusted mean CIMT differences and prevalence ratios (PRs) for carotid lesions associated with HIV-related disease and treatments, with multivariate adjustment to control for possible confounding variables.
Results
Among HIV-infected individuals, a low CD4+ T cell count was independently associated with an increased prevalence of carotid lesions. Compared to the reference group of HIV-uninfected individuals, the adjusted PR for lesions among HIV-infected individuals with CD4+ T-cell count <200 cells/mm3 was 2.00 (95% confidence interval 1.22, 3.28) in women and 1.74 (95% confidence interval 1.04, 2.93) in men. No consistent association of antiretroviral medications with carotid atherosclerosis was observed, except for a borderline significant association between protease inhibitor use and carotid lesions in men (with no association among women). History of clinical AIDS and HIV viral load were not significantly associated with carotid atherosclerosis.
Conclusions
Beyond traditional cardiovascular disease risk factors, low CD4+ T-cell count is the most robust risk factor for increased subclinical carotid atherosclerosis in HIV-infected women and men.
doi:10.1097/QAD.0b013e328300581d
PMCID: PMC2624572  PMID: 18670221
6.  Positive Association between HIV RNA and IL-6 in the Genital Tract of Rwandan Women 
Abstract
Infections and inflammation in the genital tract can influence HIV expression or HIV susceptibility. The goal of this study was to determine if significant relationships exist between cytokines and HIV in genital tract secretions from 57 HIV-seropositive Rwandan women. Genital tract secretions were obtained by cervicovaginal lavage (CVL). Ten different cytokines in CVL were measured by multiplex cytometric bead arrays. HIV RNA in CVL and plasma were measured by quantitative PCR. In univariate analysis, genital tract HIV RNA was significantly associated with plasma HIV RNA and several of the cytokines, while in multivariate analysis, genital tract HIV RNA was significantly associated only with plasma HIV RNA and IL-6. This association of IL-6 with HIV RNA levels suggests that IL-6 is an indicator for conditions that induce HIV expression and that IL-6 may contribute to induction of HIV expression in the genital tract.
doi:10.1089/aid.2008.0004
PMCID: PMC2792594  PMID: 18671479

Results 1-6 (6)