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The ability of virally suppressive antiretroviral therapy use to extend the life span of people with HIV (PWH) implies that the age of PWH will also increase. Among PWH, extended survival comes at a cost of earlier onset and increased rates of aging-associated comorbidities and geriatric syndromes, with persistent inflammation and immune dysregulation consequent to chronic HIV infection and to antiretroviral therapy use contributing to an overall decrease in health span. The geroscience hypothesis proposes that the root causes of most aging-related chronic diseases and conditions is the aging process itself. Hence, therapeutically targeting fundamental aging processes could have a greater impact on alleviating or delaying aging-associated comorbidities than addressing each disease individually. Extending the geroscience hypothesis to PWH, we speculate that targeting basic mechanisms of aging will improve overall health with age. Clinical features and pathophysiologic mechanisms of chronic diseases in PWH qualitatively resemble those seen in older adults without HIV. Therefore, drugs that target any of the pillars of aging, including metformin, rapamycin, and nicotinamide adenine dinucleotide precursors, may also slow the rate of onset of age-associated comorbidities and geriatric syndromes in PWH. Drugs that selectively induce apoptosis of senescent cells, termed senolytics, may also improve health span among PWH. Preliminary evidence suggests that senescent cell burden is increased in PWH, implying that senescent cells are an excellent therapeutic target for extending health span. Recently initiated clinical trials evaluating senolytics in age-related diseases offer insights into the design and potential implementation of similar trials for PWH. [ABSTRACT FROM AUTHOR]

Inflammation and hemostasis perturbation may be involved in vascular complications of HIV infection. We examined atherogenic biomarkers and subclinical atherosclerosis in HIV-infected adults before and after beginning highly active antiretroviral therapy (HAART).In the Women's Interagency HIV Study, 127 HIV-infected women studied pre and post HAART were matched to HIV-uninfected controls. Six semiannual measurements of soluble CD14, tumor necrosis factor (TNF) alfa, soluble interleukin (IL) 2 receptor, IL-6, IL-10, monocyte chemoattractant protein 1, D-dimer, and fibrinogen were obtained. Carotid artery intima-media thickness was measured by B-mode ultrasound.Relative to HIV-uninfected controls, HAART-naive HIV-infected women had elevated levels of soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank P < 0.0001), TNF-α (6.3 vs 3.4 pg/mL, P < 0.0001), soluble IL-2 receptor (1587 vs 949 pg/mL, P < 0.0001), IL-10 (3.3 vs 1.9 pg/mL, P < 0.0001), monocyte chemoattractant protein 1 (190 vs 163 pg/mL, P < 0.0001), and D-dimer (0.43 vs 0.31 μg/mL, P < 0.01). Elevated biomarker levels declined after HAART. Although most biomarkers normalized to HIV-uninfected levels, in women on effective HAART, TNF-α levels remained elevated compared with HIV-uninfected women (+0.8 pg/mL, P = 0.0002). Higher post-HAART levels of soluble IL-2 receptor (P = 0.02), IL-6 (P = 0.05), and D-dimer (P = 0.03) were associated with increased carotid artery intima-media thickness.Untreated HIV infection is associated with abnormal hemostasis (eg, D-dimer), proatherogenic (eg, TNF-α), and antiatherogenic (eg, IL-10) inflammatory markers. HAART reduces most inflammatory mediators to HIV-uninfected levels. Increased inflammation and hemostasis are associated with subclinical atherosclerosis in recently treated women. These findings have potential implications for long-term risk of cardiovascular disease in HIV-infected patients, even with effective therapy. [ABSTRACT FROM AUTHOR]

The article presents a study on the characterization of highly active antiretroviral therapy (HAART) in HIV-1 infected children. The study investigated 23 HIV 1-infected children, and 23 uninfected children, examined the frequency of their innate immunocells in blood which was fixed by flow cytometry, and evaluated the functional activity. The result shows that the HIV-1-infected children that are treated with HAART has displayed a decrease in plasmacytoid dendritic cell frequency.

Background: Persistent inflammation in HIV infection is associated with elevated cardiovascular disease (CVD) risk, even with viral suppression. Identification of novel surrogate biomarkers can enhance CVD risk stratification and suggest novel therapies. We investigated the potential of interleukin 32 (IL-32), a proinflammatory multi-isoform cytokine, as a biomarker for subclinical carotid artery atherosclerosis in virologically suppressed women living with HIV (WLWH). Methods and Results: Nested within the Women's Interagency HIV Study, we conducted a cross-sectional comparison of IL-32 between 399 WLWH and 100 women without HIV, followed by a case-control study of 72 WLWH (36 carotid artery plaque cases vs. 36 age-matched controls without plaque). Plasma IL-32 protein was measured by ELISA, and mRNA of IL-32 isoforms (IL-32α, β, γ, D, ε, and θ) was quantified by reverse transcription polymerase chain reaction from peripheral blood mononuclear cells. Plasma IL-32 protein levels were higher in WLWH compared with women without HIV (P = 0.02). Among WLWH, although plasma IL-32 levels did not differ significantly between plaque cases and controls, expression of IL-32 isoforms α, β, and ε mRNA was significantly higher in peripheral blood mononuclear cells from cases (P = 0.01, P = 0.005, and P = 0.018, respectively). Upregulation of IL-32β and IL-32ε among WLWH with carotid artery plaque persisted after adjustment for age, race/ethnicity, smoking, systolic blood pressure, body mass index, and history of hepatitis C virus (P = 0.04 and P = 0.045); the adjusted association for IL-32α was marginally significant (P = 0.07). Conclusions: IL-32 isoforms should be studied further as potential CVD biomarkers. This is of particular interest in WLWH by virtue of altered IL-32 levels in this population. [ABSTRACT FROM AUTHOR]

Background: Maladaptive immune responses contribute to the pathogenesis of many chronic lung diseases. Here, we tested hypotheses that CD4 and CD8 T-cell and monocyte phenotypes are associated with lung function in people living with HIV and those without HIV. Methods: Markers of T cell differentiation, activation, exhaustion and senescence, and markers of monocyte recruitment and migration were quantified in 142 HIV-positive and 73 HIV-negative participants of the Pittsburgh HIV Lung Cohort. All participants underwent lung function testing. Results: CD4 or CD8 T-cell phenotypes were not associated with measures of lung function in HIV-positive or HIV-negative participants after adjustment for multiple comparisons. In HIV-positive participants, however, the percentage of classical monocytes that were CD11b+ had positive associations at the Bonferroni-adjusted significance threshold of P = 0.05/63 with prebronchodilator and postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio (β = 0.36; P = 0.00003 and β = 0.31; P = 0.0003, respectively). In stratified analyses of n = 87 participants with CD4 ≥ 500 cells/µL, associations of percentage of classical monocytes that were CD11b+ with prebronchodilator and postbronchodilator FEV1/FVC ratio were stronger (β = 0.48 and β = 0.41, for pre- and post-, respectively) than in the entire HIV-positive study population. Significant associations of monocyte phenotypes were not observed in HIV-negative participants after adjustment for multiple comparisons. Conclusions: CD11b+ expression on classical monocytes is positively associated with FEV1/FVC ratio in people living with HIV including in those with CD4 T-cell recovery. Given the normal surveillance activity of monocytes, such association suggests this monocyte subset may play a role in preservation of pulmonary function in PLWH. [ABSTRACT FROM AUTHOR]

The article reports on genotyping of Urogenital Chlamydia trachomatis in Regional New South Wales, Australia. It is said that Chlamydia Trachomatis is the most common cause of bacterial sexually transmitted infections worldwide. Chlamydia also acts as a marker of increased risk for human immunodeficiency virus infection and may directly contribute to human immunodeficiency virus infection. C. trachomatis is seen rising rapidly in most developed countries, including Australia. It is stated that the population rate of C. trachomatis infection in New South Wales doubled between 1996 and 2000 and between 2001 and 2005.

Background: Expression of tissue factor (TF) on the surface of activated monocytes may trigger thrombosis, leading to clotting risk, inflammation, and atherosclerosis. TF-positive microparticles (MP-TF) represent a functionally active form of TF that may be promulgated by long-term HIV infection. We hypothesized that greater MP-TF activity is associated with carotid artery plaque in HIV+ women. Setting: In a case-control study nested within the Women's Interagency HIV Study (WIHS), eligible HIV+ participants underwent B-mode carotid artery ultrasound at 2 study visits occurring 7 years apart. Cases were defined by the presence of at least 1 carotid artery plaque assessed at either visit. Cases were matched 1:2 to controls who were found not to have carotid artery plaques. Methods: Conditional logistic regression estimated the association of MP-TF activity with the presence of carotid artery plaque, adjusting for demographic and behavioral characteristics, HIV-related factors, cardiometabolic risk factors, and serum inflammation biomarkers (high-sensitivity C-reactive protein, IL-6, sCD14, sCD163, Gal-3, and Gal-3BP). Results: Elevated MP-TF activity (>0.537 pg/mL) was found to be significantly associated with greater odds of plaque (adjusted odds ratio 3.86, 95% confidence interval: 1.06 to 14.07, P = 0.04). The association was attenuated after further adjustment for IL-6 but was unaffected by adjustment for other biomarkers including those denoting monocyte activation. Conclusions: Our findings suggest a link among HIV infection, innate immune system perturbation, coagulation, and atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Ceramides have been implicated in the pathophysiology of HIV infection and cardiovascular disease. However, no study, to our knowledge, has evaluated circulating ceramide levels in association with subclinical cardiovascular disease risk among HIV-infected individuals.Methods: Plasma levels of 4 ceramide species (C16:0, C22:0, C24:0, and C24:1) were measured among 398 women (73% HIV+) and 339 men (68% HIV+) without carotid artery plaques at baseline from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. We examined associations between baseline plasma ceramides and risk of carotid artery plaque formation, assessed by repeated B-mode carotid artery ultrasound imaging over a median 7-year follow-up.Results: Plasma levels of C16:0, C22:0, and C24:1 ceramides were significantly higher in HIV-infected individuals compared with those without HIV infection (all P<0.001), and further analysis indicated that elevated ceramide levels were associated with antiretroviral therapy use, particularly protease inhibitor use, in HIV-infected individuals (all P<0.001). All 4 ceramides were highly correlated with each other ( r=0.70-0.94; all P<0.001) and significantly correlated with total-cholesterol ( r=0.42-0.58; all P<0.001) and low-density lipoprotein cholesterol ( r=0.24-0.42; all P<0.001) levels. Of note, C16:0 and C24:1 ceramides, rather than C22:0 and C24:0 ceramides, were more closely correlated with specific monocyte activation and inflammation markers (eg, r=0.30 between C16:0 ceramide and soluble CD14; P<0.001) and surface markers of CD4+ T-cell activation. A total of 112 participants developed carotid artery plaques over 7 years, and higher levels of C16:0 and C24:1 ceramides were significantly associated with increased risk of carotid artery plaques (relative risk [95% CI]=1.55 [1.29, 1.86] and 1.51 [1.26, 1.82] per standard deviation increment, respectively; both P<0.001), after adjusting for demographic and behavioral factors. After further adjustment for cardiovascular disease risk factors and immune activation markers, these associations were attenuated but remained significant. The results were consistent between men and women and between HIV-infected and HIV-uninfected participants.Conclusions: In 2 HIV cohorts, elevated plasma levels of C16:0 and C24:1 ceramides, correlating with immune activation and inflammation, were associated with antiretroviral therapy use and progression of carotid artery atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: HIV-1 infection is associated with intestinal inflammation, changes in the enteric microbiota (dysbiosis), and intestinal epithelial cell damage. NKp44+ innate lymphoid cells (ILCs) play an important role in epithelial barrier maintenance through the production of interleukin (IL)-22 but also display functional plasticity and can produce inflammatory cytokines [eg, interferon gamma (IFNγ)] in response to cytokine milieu and stimulatory signals. The objective of this pilot study was to enumerate frequencies of IL-22 and IFNγ-expressing colonic NKp44+ ILCs during untreated, chronic HIV-1 infection. Setting: A cross-sectional study was performed to compare numbers of cytokine-expressing ILCs in colonic biopsies of untreated, chronic HIV-1 infected (n = 22), and uninfected (n = 10) study participants. Associations between cytokine+ ILC and previously established measures of virological, immunological, and microbiome indices were analyzed. Methods: Multicolor flow cytometry was used to measure the absolute number of colonic CD3-NKp±6CD56± ILCs expressing IL-22 or IFNγ after in vitro mitogenic stimulation. Results: Numbers of colonic NKp44+ ILCs that expressed IFNγ were significantly higher in HIV-1 infected versus uninfected persons and positively correlated with relative abundances of dysbiotic bacterial species in the Xanthomonadaceae and Prevotellaceae bacterial families and with colonic myeloid dendritic cell and T-cell activation. Conclusion: Higher numbers of inflammatory colonic ILCs during untreated chronic HIV-1 infection that associated with dysbiosis and colonic myeloid dendritic cell and T-cell activation suggest that inflammatory ILCs may contribute to gut mucosal inflammation and epithelial barrier breakdown, important features of HIV-1 mucosal pathogenesis. [ABSTRACT FROM AUTHOR]

Background: A low proportion of CD282CD8+ T cells that express CD57 is associated with increased mortality in HIV infection. The effect of increasing body mass index (BMI) changes in the proportion of CD57+CD282CD8+ T cells among HIV-infected individuals on antiretroviral therapy is unknown. Setting: In a US cohort of HIV-infected women, we evaluated associations of BMI and waist circumference with 3 distinct CD8+ T cell phenotypes: % CD282CD57+CD8+ T cells, % CD57+ of CD282CD8+ T cells, and % CD282 of all CD8+ T cells. Methods: Multivariable linear regression analysis was used to estimate beta coefficients for each of 3 T-cell phenotypes. Covariates included HIV parameters (current and nadir CD4, current viral load), demographics (age, race, income, and study site), and lifestyle (tobacco and alcohol use) factors. Results: Of 225 participants, the median age was 46 years and 50% were obese (BMI >30 m2/kg). Greater BMI and waist circumference were both associated with higher % CD282CD57+CD8+ T cells and % CD57+ of all CD282CD8+ T cells in multivariable analysis, including adjustment for HIV viral load (all P < 0.05). The association between greater BMI and the overall proportion of CD282 CD8+ cells in fully adjusted models (0.078, 95% confidence interval: 20.053 to 0.209) was not significant. Conclusions: In this analysis, greater BMI and waist circumference are associated with greater expression of CD57 on CD282CD8+ T cells and a greater proportion of CD57+CD282 CD8+ T cells. These findings may indicate that increasing BMI is immunologically protective in HIV-infected women. Future research is needed to understand the prognostic importance of these associations on clinical outcomes. [ABSTRACT FROM AUTHOR]

During HIV+ hepatitis C virus (HCV)+ coinfection CD14brightCD16- monocytes produce soluble immune-activation markers that predict disease progression and poor response to interferon (IFN)-α treatment. We evaluated relationships among immune activation, monocyte phenotype, CD4-memory T cells, and HCV-, cytomegalovirus-, and cytomegalovirus/Epstein-Barr virus/influenza-specific IFN-γ-response before and during IFN-α treatment. Effector-memory and central-memory CD4 T-cell frequencies were lower in HCV+ HIV+ donors than in uninfected donors and correlated negatively with HCV level, CD14brightCD16- monocytes, and plasma sCD14. sCD14 and CD14brightCD16- monocytes negatively correlated with IFN-α--dependent HCV decline. CD4 effector-memory T cells positively associated with cytomegalovirus/Epstein-Barr virus/influenza(CEF)-specific IFN-γ response, while sCD14 negatively associated with both CD4 effector-memory T cells and CEF-specific IFN-γ response. These data support a role for memory-CD4 T cells in HCV containment and link immune activation and CD14brightCD16--monocyte frequency to the failure of IFN-dependent HCV clearance. [ABSTRACT FROM AUTHOR]

Background: Therapeutic vaccination is being studied in eradication and "functional cure" strategies for HIV-1. The Profectus Biosciences multiantigen (MAG) HIV-1 DNA vaccine encodes HIV-1 Gag/Pol, Nef/Tat/Vif, and Envelope, and interleukin-12 (IL-12) and is delivered by electroporation combined with intramuscular injection (IM-EP). Methods: Sixty-two HIV-1-infected patients on antiretroviral therapy (plasma HIV-1 RNA levels ≤200 copies/mL; CD4+ T-cell counts ≥500 cells/mm3) were randomly allocated 5:1 to receive vaccine or placebo. At weeks 0, 4, and 12, 4 consecutive cohorts received 3000 μg HIV MAG pDNA with 0, 50, 250, or 1000 μg of IL-12 pDNA by IM-EP. A fifth cohort received HIV MAG pDNA and 1000 mg of IL-12 pDNA by standard IM injection. Results: CD4+ T cells expressing IL-2 in response to Gag and Pol and interferon-g responses to Gag, Pol, and Env increased from baseline to week 14 in the low-dose (50-μg) IL-12 arm vs. placebo (P < 0.05; intracellular cytokine staining). The total increase in the IL-2-expressing CD4+ T-cell responses to any antigen was also higher in the low-dose IL-12 arm vs. placebo (P = 0.04). Cytokine responses by CD8 T cells to HIV antigens were not increased in any vaccine arm relative to placebo. Conclusions: HIV-1 MAG/low-dose IL-12 DNA vaccine delivered by IM-EP augmented CD4+ but not CD8+ T-cell responses to multiple HIV-1 antigens. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) viremia is thought to have broad systemic effects on the cellular immune system that go beyond its impact on just those T cells that are HCV specific. However, previous studies of chronic HCV and circulating T-cell subsets (activation and differentiation phenotypes) in HIV negatives used general population controls, rather than a risk-appropriate comparison group. Studies in HIV positives did not address overall immune status (total CD4+ count).We used fresh blood from HIV-positive and at-risk HIV-negative women, with and without chronic HCV, to measure percentages of activated CD4+ and CD8+ T cells, Tregs, and T-cell differentiation phenotypes (naive, central memory, effector memory (EM), and terminally differentiated effector). This included 158 HIV negatives and 464 HIV positives, of whom 18 and 63, respectively, were HCV viremic.In multivariate models of HIV negatives, HCV viremia was associated with 25% fewer naive CD4+ (P = 0.03), 33% more EM CD4+ (P = 0.0002), and 37% fewer central memory CD8+ (P = 0.02) T cells. Among HIV positives, we observed only 1 of these 3 relationships: higher percentage of EM CD4+ among HCV viremic women. Furthermore, the association with EM CD4+ among HIV positives was limited to individuals with diminished immune status (total CD4+ count 500 cells/μL), as were associations of HCV viremia with higher percentages of activated CD4+ and Tregs. Among HIV positives with high CD4+ count, no significant associations were observed.These data suggest that HCV viremia in HIV negatives is associated with accelerated T-cell differentiation, but among HIV positives, the impact of HCV viremia is less straightforward and varies by total CD4+ count. [ABSTRACT FROM AUTHOR]

Poor CD4 lymphocyte recovery on antiretroviral therapy (ART) is associated with reduced function of the thymus. Palifermin (keratinocyte growth factor), by providing support to the thymic epithelium, promotes lymphopoiesis in animal models of bone marrow transplantation and graft-versus-host disease.In AIDS Clinical Trials Group A5212, a randomized, double-blind, placebo-controlled study, 99 HIV-infected patients on ART with plasma HIV-1 RNA levels 200 copies per milliliter for ≥6 months and CD4 lymphocyte counts <200 cells per cubic milliliter were randomized 1:1:1:1 to receive once daily intravenous administration of placebo or 20, 40, or 60 μg/kg of palifermin on 3 consecutive days.The median change in the CD4+ T-cell count from baseline to week 12 was not significantly different between the placebo arm [15 (-16, 23) cells/mm3] and the 20-μg/kg dose [11 (2, 32) cells/mm3], the 40-μg/kg dose [12 (-2, 25) cells/mm3], or the 60-μg/kg dose arm [8 (-13, 35) cells/mm3] of palifermin. No significant changes were observed in thymus size or in the number of naive T cells or recent thymic emigrants.Palifermin in the doses studied was not effective in improving thymic function and did not raise CD4 lymphocyte counts in HIV-infected patients with low CD4 cell counts despite virologically effective ART. [ABSTRACT FROM AUTHOR]

HIV/hepatitis C virus (HCV)-coinfected patients have accelerated liver disease compared with HCV monoinfection. In HIV-positive patients with viral suppression, data comparing inflammatory cytokines and immune activation between HIV/HCV coinfection with chronic hepatitis C (CHC) to HIV/HCV-seropositive patients with cleared HCV are limited.Fifty-nine age- and sex-matched patients were stratified: (1) HIV monoinfection (n = 15); (2) HCV monoinfection with CHC (n = 15); (3) HIV/HCV coinfection with CHC (n = 14); and (4) HIV/HCV seropositive with cleared HCV (n = 15). All HIV-positive patients had undetectable HIV viremia, and median CD4 was 420 cells per microliter. Liver fibrosis was assessed in each subject using transient elastography. Cells were collected for CD4 and CD8 immune activation (CD38/HLA-DR) markers via flow cytometry and plasma for luminex-multiplex cytokine assays.CD38+HLA-DR+ expression on CD4+ T cells was significantly increased in HIV/HCV coinfection with CHC (7%) versus HCV monoinfection (4%) (P = 0.012). CD4+ total HLA-DR+ expression was significantly increased in HIV/HCV coinfection with CHC (43%) versus HIV monoinfection (31%) (P = 0.010) and HIV/HCV seropositive with cleared HCV (38%) (P = 0.046). Total CD4+CD38+ and CD4+CD38+HLA-DR- expression was significantly higher in HIV monoinfection (23% and 18%) than HCV moninfection (13%, P = 0.002% and 9%, P = 0.001, respectively). Interleukin 10 levels were significantly lower in HIV monoinfection versus HIV/HCV coinfection with CHC (P = 0.0002). In multivariate analysis, severe fibrosis was associated with lower expression of CD4+CD38+HLA-DR+ and CD4+ total CD38+ than mild-moderate fibrosis (P = 0.03 and 0.03, respectively).CD4 immune activation with HLA-DR+ expression in HIV/HCV coinfection with well-controlled HIV may arise from chronic HCV viremia. Conversely, CD4+CD38+ expression may be driven by underlying HIV infection. CD4 immune activation was unexpectedly found to be associated with decreased liver fibrosis. [ABSTRACT FROM AUTHOR]

AIDS-related non-Hodgkin lymphoma (AIDS-NHL) is a common AIDS-defining cancer. Prior studies suggest that chronic B-cell activation precedes AIDS-NHL diagnosis. Activation of B cells by multiple factors, including Toll-like receptor (TLR) signaling, leads to the expression of activation-induced cytidine deaminase (AID), a DNA mutating molecule that can contribute to oncogene translocations/mutations, leading to NHL. The goal of this study was to determine whether surface markers expressed on activated and/or germinal center B cells, and AID expression, were elevated on circulating B cells preceding AIDS-NHL and to determine if TLR signaling contributes to this activated B-cell phenotype.Stored viable peripheral blood mononuclear cell specimens, obtained before AIDS-NHL diagnosis, were assessed by multicolor flow cytometry. Additionally, B cells isolated from peripheral blood mononuclear cell were exposed to TLR ligands in vitro, after which B-cell phenotype was assessed by flow cytometry.An elevated fraction of B cells expressing CD10, CD71, or CD86 was seen in those who went on to develop AIDS-NHL. AID expression was detected in some who developed AIDS-NHL, but not in HIV+ or HIV- controls. TLR2-stimulated purified B cells exhibited the activated B-cell phenotype observed in HIV+ subjects before AIDS-NHL diagnosis.These results indicate that an elevated fraction of B cells display an activated/germinal center phenotype in those HIV+ subjects who go on to develop AIDS-NHL and suggest that TLR2-mediated activation may play a role in HIV infection-associated B-cell activation, potentially contributing to the genesis of AIDS-NHL. [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.

Presents information relating to chemokines which are found in the genital tract of both human immunodeficiency virus (HIV)-seropositive and HIV-seronegative women. Important role which chemokines play; Collection of cervical cytology specimens; Performance of preliminary experiments.

A letter to the editor is presented which discusses a study on the expression of elevated Caspase-3 and activation of T-Cells in elite suppressors (ES).

Background: Atherosclerosis is characterized by infiltration of monocytes into the arterial wall, where they form atherosclerotic plaque. The inflammation pathways leading to cardiovascular disease through atherosclerosis may involve monocyte and macrophage activity in response to viral infection, including HIV and hepatitis C virus (HCV). We examined the association of three plasma markers of monocyte and macrophage activity, galectin-3 binding protein (Gal-3BP), soluble CD163 (sCD163), and soluble CD14 (sCD14), with subclinical atherosclerosis, in a subset of women participating in the Women's Interagency HIV Study (WIHS). We hypothesized that higher levels are associated with greater disease. Methods: The WIHS is a longitudinal study of HIV-infected and -uninfected women from 6 U.S. sites. We analyzed 4 groups of 66 women each: HIV+/HCV+, HIV+/HCV-, HIV-/HCV+, and HIV-/HCV-, matched by age, race/ethnicity, and smoking status. Carotid artery B-mode ultrasound assessed two measures of subclinical atherosclerosis: distensibility (in 10 *m /N) and presence of atherosclerotic plaque (IMT >1.5 mm). We created an inflammatory macrophage score (sum of the presence of plasma levels above the median for each marker, range 0-3) and assessed its independent cross-sectional association with subclinical CAD, using regression models with generalized estimating equations to take into account the matched design and controlling for known risk factors. We also assessed associations of Gal-3BP, sCD163, and sCD14 plasma levels individually with subclinical atherosclerosis. Results: 264 women were included (median age 46 [IQR 41-50], 62% black, 26% Hispanic, median distensibility 15.22 [IQR 11.05-21.76]). In models accounting for age, race/ethnicity, smoking, BMI, and CRP, higher macrophage scores were significantly associated with both a 1.5-fold greater odds of plaque (per elevated marker, 95% CI 1.06 to 2.09) and lower distensibility (β -1.40 units per marker, 95% CI -2.62 to -0.17). Gal-3BP alone was associated with both outcomes in adjusted analyses (ORplaque 1.51 per SD of Gal-3BP, 95% CI 1.01 to 2.26; βdistensibility -1.48 units per SD, 95% CI -2.37 to -0.58). sCD163 was associated with a greater odds of plaque only (OR 1.90 per SD, 95% CI 1.16 to 3.12), while sCD14 was associated with lower distensibility (β -1.09 units per SD, 95% CI -2.14 to -0.03). When we stratified by HIV and HCV status, Gal-3BP levels were higher among HCV+ women than HCV- women (mean 12.4 vs. 8.6 µg/mL, p<0.01), but did not differ by HIV status (mean 10.3 vs. 10.7 µg/mL, p=0.34). HIV+/HCV+ women had the highest levels of sCD163 and sCD14. Conclusions: Our data show that the macrophage inflammatory markers Gal-3BP, sCD163 and sCD14 are associated with subclinical carotid atherosclerosis in the setting of HIV and HCV infection. HCV infection may be more strongly associated with these markers than HIV infection. [ABSTRACT FROM AUTHOR]