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Significant sex differences in human immunodeficiency virus (HIV) ribonucleic acid (RNA) level and clusters of differentiation 4 (CD4) cell percentages were identified among 670 HIV-infected African children. Before puberty, these differences suggest that nonhormonal intrinsic biologic differences between the sexes influence HIV RNA level and CD4 cell percentages in HIV-infected individuals.

Background. HIV-infected women have lower HIV RNA levels and higher CD4-cell counts than do men. This observation has been attributed to the immunomodulatory effects of sex steroid hormones, such as estrogen and progesterone. Limited data exist regarding potential sex differences in HIV RNA level and CD4 parameters among prepubertal children with untreated HIV infection.

Methods. We examined the relationship of sex to HIV RNA level and CD4 parameters among 670 perinatally HIV-infected, antiretroviral therapy–naive African children aged <18 years (median age, 4.8 years) using multivariate linear regression. In a subset of 188 children, we used longitudinal data to compare changes in HIV RNA levels and CD4 percentage over time. Levels of CD4 and CD8 T-cell activation (CD38+HLA-DR+) were also compared between boys and girls.

Results. Female children had lower HIV RNA levels (P = .0004) and higher CD4 percentages (P < .0001), compared to male children. Multivariate linear regression demonstrated an independent association of sex with both HIV RNA level and CD4 percentages after controlling for other covariates. Multilevel mixed-effects linear regression analysis of longitudinal HIV RNA level and CD4 parameter data showed that sex differences persisted across all observed ages. Levels of T-cell activation did not differ between the sexes.

Conclusions. Significant sex differences in HIV RNA levels and CD4 parameters are present in HIV-infected children before the onset of puberty. These data suggest that intrinsic genetic differences between male and female individuals, unrelated to sex steroid hormone levels, influence HIV RNA level and CD4 parameters in HIV-infected individuals.

The majority of natural history studies of human immunodeficiency virus (HIV) infection have immune and viral parameters in men. Data demonstrating that women have lower HIV-1 RNA levels than men at the same CD4 cell counts have raised the question of immunologic differences in HIV-seropositive women. This study describes levels and changes in phenotypic markers of immune maturity, function, and activation in the CD4 and CD8 cell subsets in HIV-seropositive and high-risk HIV-seronegative women. Our primary hypothesis was that activation levels would be significantly higher among illicit drug users. However, results showed that HIV-1 RNA level was the strongest predictor of marker level and that both HIV-1 RNA level and CD4 cell count were independently associated with CD4 activation, but illicit drug use was not. In summary, this study demonstrated that immune activation was a significant pathogenic feature in women and that activation was driven by HIV infection and not illicit drug use.

Objectives

To assess the relationship between sex hormones and natriuretic peptide levels in community-based adults

Background

Women have higher circulating natriuretic peptide concentrations than men, but the mechanisms for these sex-related differences and the impact of hormone therapy are unclear. Experimental studies suggest that androgens may suppress natriuretic peptide secretion.

Methods

We measured plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP), total testosterone, and sex hormone binding globulin (SHBG) in 4,056 men and women (mean age 40±9 years) from the Framingham Heart Study Third Generation cohort. Sex/hormone status was grouped as: 1) men, 2) postmenopausal women not receiving hormone replacement therapy, 3) premenopausal women not receiving hormonal contraceptives, 4) postmenopausal women receiving hormone replacement therapy and 5) premenopausal women receiving hormonal contraceptives.

Results

Circulating NT-proBNP was associated with sex/hormone status (overall P<0.0001). Men had lower NT-proBNP than women of all menopause or hormone groups, and women receiving hormonal contraceptives had higher NT-proBNP than women who were not receiving hormone therapy (all P<0.0001). These relationships remained significant after adjusting for age, body mass index, and cardiovascular risk factors. Across sex/hormone status groups, FT decreased and SHBG increased in tandem with increasing NT-proBNP. In sex-specific analyses, NT-proBNP decreased across increasing quartiles of free testosterone in men (P for trend<0.01) and in women (P for trend<0.0001). Adjustment for FT markedly attenuated the association between sex/hormone status and NT-proBNP concentrations.

Conclusions

These findings suggest that lower circulating androgens and the potentiating effect of exogenous female hormone therapy contribute to the higher circulating NT-proBNP concentrations in women.

HIV persists in a reservoir of latently infected CD4+ T cells in individuals treated with highly active antiretroviral therapy (HAART). Here we identify central memory (TCM) and transitional memory (TTM) CD4+ T cells as the major cellular reservoirs for HIV and find that viral persistence is ensured by two different mechanisms. HIV primarily persists in TCM cells in subjects showing reconstitution of the CD4+ compartment upon HAART. This reservoir is maintained through T cell survival and low-level antigen-driven proliferation and is slowly depleted with time. In contrast, proviral DNA is preferentially detected in TTM cells from aviremic individuals with low CD4+ counts and higher amounts of interleukin-7–mediated homeostatic proliferation, a mechanism that ensures the persistence of these cells. Our results suggest that viral eradication might be achieved through the combined use of strategic interventions targeting viral replication and, as in cancer, drugs that interfere with the self renewal and persistence of proliferating memory T cells.

AIM/BACKGROUND: Previous studies have suggested that healthy subjects of African ancestry have lower total white cell counts, neutrophil counts and platelet counts than Caucasian subjects and that, at least among Caucasians, women have higher neutrophil and platelet counts than men. The primary aim of this study was to confirm and quantify the ethnic differences, confirm the sex difference in Caucasians and determine whether there was a similar sex difference in non-Caucasians. A secondary aim was to establish reference ranges for white cell and platelet counts for the different ethnic and sex groups. METHODS: The study population comprised 417 healthy volunteers (201 women and 216 men), of whom 200 were Caucasian, 102 were Afrocaribbean and 115 were African. Full blood counts, including a differential white cell count, were measured using a H.2 automated differential counter. White cell and platelet counts were compared between the three different ethnic groups and between men and women. Reference ranges were determined for each ethnic and sex group. RESULTS: Africans and Afrocaribbeans had lower total white cell, neutrophil and platelet counts than Caucasians and counts were lower in Africans than in Afrocaribbeans. Women had higher neutrophil and platelet counts than men in all ethnic groups. CONCLUSIONS: Sex and ethnic origin should be taken into consideration when assessing white cell and platelet counts.

Background

Sex differences in the natural history of HIV infection may vary between resource-rich and resource-limited settings.

Objective

Baseline characteristics from a randomized clinical trial of treatment naïve subjects conducted at sites in Africa, Asia, the Caribbean, and North and South America were analyzed to determine if there were significant differences by sex.

Results

Of the 1571 participants, 740 (47.1%) were women. Women had higher mean screening CD4 cell counts (average 15 cells higher, (p<0.001), lower mean hemoglobin and creatinine clearance, a lower mean baseline HIV-1 viral load (4.85 log10 vs. 5.05 log10 copies/mL (P<0.001)) and were less likely to have a prior AIDS diagnosis than men. The sex difference in viral load difference was related to CD4 cell count, however it was independent of country and persisted within the strata with CD4 < 200 cells/mm3.

Conclusion

Women in resource limited settings have lower levels of plasma HIV-1 RNA and appear to present for enrollment into a clinical trials at an earlier stage of disease than men. The biologic basis for lower viral in women compared to men remains unexplained. It will be important to determine if the sex differences observed at baseline impact clinical outcomes once the PEARLS clinical trial is completed.

Given the central role that interleukin 15 (IL-15) plays in human immunodeficiency virus (HIV) immunity, we hypothesized that IL-15 in breast milk may protect against postnatal HIV transmission. In a nested case-control study, we compared breast milk IL-15 levels in 22 HIV-infected women who transmitted HIV to their infants to those in 72 nontransmitters. Samples were collected in the first month of life, prior to HIV infection. IL-15 concentrations were associated with a decreased risk of HIV transmission in unadjusted analysis and after adjusting for milk viral load, CD4 cell count, and other cytokines in breast milk. IL-15–mediated immunity may protect against HIV transmission during breast-feeding.

Men have higher blood pressure than women through much of life regardless of race and ethnicity. This is a robust and highly conserved sex difference that it is also observed across species including dogs, rats, mice and chickens and it is found in induced, genetic and transgenic animal models of hypertension. Not only do the differences between the ovarian and testicular hormonal milieu contribute to this sexual dimorphism in blood pressure, the sex chromosomes also play a role in and of themselves. This review primarily focuses on epidemiological studies of blood pressure in men and women and experimental models of hypertension in both sexes. Gaps in current knowledge regarding what underlie male-female differences in blood pressure control are discussed. Elucidating the mechanisms underlying sex differences in hypertension may lead to the development of anti-hypertensives tailored to one's sex and ultimately to improved therapeutic strategies for treating this disease and preventing its devastating consequences.

This paper examined gender differences in Quality of Life (QOL) among people living with HIV/AIDS in South India using the locally validated version of the WHO Quality of Life Instrument for HIV (WHOQOL- HIV 120). Participants (N=109) were men and women with HIV1 Clade C infection participating in a cohort study. There was no gender difference in CD4 counts or use of antiretroviral therapy. Of the 29 facets of QOL, men reported significantly higher QOL in the following facets- positive feeling, sexual activity, financial resources and transport, while women reported significantly higher QOL on the forgiveness and blame facet. Of the six domains of QOL, men reported better quality of life in the environmental domain while women had higher scores on the spirituality/religion and personal beliefs domain. Understanding these gender differences may provide potentially useful information for tailoring interventions to enhance QOL among people infected with HIV/AIDS.

Human immunodeficiency virus type 1 (HIV-1) infection decreases the production of interleukin-2 (IL-2) from CD4+ and CD8+ T cells. Recombinant IL-2 (rIl-2) has been given to HIV-infected individuals to generate significant increases in CD4+ T-cell counts. There are limited data regarding the effects of pregnancy and HIV infection on IL-2 production in humans. To investigate the effects of human pregnancy, HIV infection, and HIV therapy on IL-2 production, we evaluated 61 women. Intracellular IL-2 production by CD4+ T cells from nonpregnant HIV-infected women was significantly lower than in that in uninfected women (45% ± 8% versus 52% ± 8%, P = 0.04). In contrast, there was no difference in levels of intracellular IL-2 production between HIV-infected and uninfected pregnant women. These observations suggest that pregnancy may down-regulate IL-2 production regardless of HIV infection status. Future studies should evaluate IL-2 production patterns in larger cohorts of women so that the physiological significance of IL-2 down-regulation in pregnancy can be further evaluated. This information is essential to assess the possible use of IL-2 supplementation therapy as a means of enhancing immune responses among HIV-infected pregnant women.

Manifestations of viral infections can differ between women and men1, and significant sex differences have been described in the course of HIV-1 disease. HIV-1-infected women tend to have lower viral load levels early in HIV-1 infection, but progress faster to AIDS for a given viral load than men2–7. Here we demonstrate substantial sex differences in the response of plasmacytoid dendritic cells (pDCs) to HIV-1. pDCs derived from women produce significantly more interferon-α (IFN-α) in response to HIV-1-encoded TLR7 ligands than pDCs derived from men, resulting in stronger secondary activation of CD8+ T cells. In line with these in vitro studies, treatment-naïve chronically HIV-1-infected women had significantly higher levels of CD8+ T cell activation than men after adjusting for viral load. These data show that sex differences in TLR-mediated activation of pDCs can account for higher immune activation in women compared to men at a given HIV-1 viral load, and provide a mechanism by which the same level of viral replication might result in faster HIV-1 disease progression in women compared to men. Modulation of the TLR7 pathway in pDCs may therefore represent a novel approach to reduce HIV-1-associated pathology.

The Duffy-null trait and ethnic neutropenia are highly prevalent in Africa. The authors found that the trait of Duffy-null–associated low neutrophil counts associated with increased HIV-1 susceptibility. The possible contribution of this trait to the high prevalence of HIV-1 in Africa requires further investigation

Background. The Duffy-null trait and ethnic netropenia are both highly prevalent in Africa. The influence of pre-seroconversion levels of peripheral blood cell counts (PBCs) on the risk of acquiring human immunodeficiency virus (HIV)–1 infection among Africans is unknown.

Methods. The triangular relationship among pre-seroconversion PBC counts, host genotypes, and risk of HIV acquisition was determined in a prospective cohort of black South African high-risk female sex workers. Twenty-seven women had seroconversion during follow-up, and 115 remained HIV negative for 2 years, despite engaging in high-risk activity.

Results. Pre-seroconversion neutrophil counts in women who subsequently had seroconversion were significantly lower, whereas platelet counts were higher, compared with those who remained HIV negative. Comprising 27% of the cohort, subjects with pre-seroconversion neutrophil counts of <2500 cells/mm3 had a ∼3-fold greater risk of acquiring HIV infection. In a genome-wide association analyses, an African-specific polymorphism (rs2814778) in the promoter of Duffy Antigen Receptor for Chemokines (DARC −46T > C) was significantly associated with neutrophil counts (P = 7.9 × 10−11). DARC −46C/C results in loss of DARC expression on erthyrocytes (Duffy-null) and resistance to Plasmodium vivax malaria, and in our cohort, only subjects with this genotype had pre-seroconversion neutrophil counts of <2500 cells/mm3. The risk of acquiring HIV infection was ∼3-fold greater in those with the trait of Duffy-null–associated low neutrophil counts, compared with all other study participants.

Conclusions. Pre-seroconversion neutrophil and platelet counts influence risk of HIV infection. The trait of Duffy-null–associated low neutrophil counts influences HIV susceptibility. Because of the high prevalence of this trait among persons of African ancestry, it may contribute to the dynamics of the HIV epidemic in Africa.

Women have a higher proportion of body fat compared to men. However, women consume fewer kilojoules per kilogram lean mass and burn fat more preferentially during exercise compared with men. During gestation, women store even greater amounts of fat that cannot be solely attributed to increased energy intake. These observations suggest that the relationship between kilojoules consumed and kilojoules utilised is different in men and women. The reason for these sex differences in energy metabolism is not known; however, it may relate to sex steroids, differences in insulin resistance, or metabolic effects of other hormones such as leptin. When considering lifestyle modifications, sex differences in energy metabolism should be considered. Moreover, elucidating the regulatory role of hormones in energy homeostasis is important for understanding the pathogenesis of obesity and perhaps in the future may lead to ways to reduce body fat with less energy restriction.

Background

Elevated perceptions of psychosocial stress and stressful life events are linked to faster disease progression in individuals living with HIV and these associations may be stronger for women from ethnic minority populations. Levels of neurohormones such as oxytocin (OT), cortisol, and norepinephrine (NE) have been shown to influence the effects of psychosocial stress in different populations. Understanding how intrinsic neuroendocrine substances moderate the effects of stressors in minority women living with HIV (WLWH) may pave the way for interventions to improve disease management.

Methods

We examined circulating levels of plasma OT as a moderator of the effects of stress on disease status (viral load, CD4+ cell count) in 71 low-income ethnic minority WLWH.

Results

At low levels of OT, there was an inverse association between stress and CD4+ cell counts. Counter-intuitively, at high levels of OT there was a positive association between stress and CD4+ cell counts. This pattern was unrelated to women’s viral load. Other neuroendocrine hormones known to down-regulate the immune system (cortisol, norepinephrine) did not mediate the effects of OT and stress on immune status.

Conclusions

OT may have stress buffering effects on some immune parameters and possibly health status in low income ethnic minority WLWH reporting elevated stress.

Objectives

Research on migration and HIV has largely focused on male migration, often failing to measure HIV risks associated with migration for women. We aimed to establish whether associations between migration and HIV infection differ for women and men, and identify possible mechanisms by which women's migration contributes to their high infection risk.

Design

Data on socio-demographic characteristics, patterns of migration, sexual behavior and HIV infection status were obtained for a population of 11,677 women aged 15–49 and men aged 15–54, resident members of households within a demographic surveillance area participating in HIV surveillance in 2003–04.

Methods

Logistic regression was conducted to examine whether sex and migration were independently associated with HIV infection in three additive effects models, using measures of recent migration, household presence and migration frequency. Multiplicative effects models were fitted to explore whether the risk of HIV associated with migration differed for males and females. Further modeling and simulations explored whether composition or behavioral differences accounted for observed associations.

Results

Relative to non-migrant males, non-migrant females had higher odds of being HIV-positive (adjusted odds ratio [aOR] = 1.72; 95% confidence interval [1.49–1.99]), but odds were higher for female migrants (aOR = 2.55 [2.07–3.13]). Female migrants also had higher odds of infection relative to female non-migrants (aOR = 1.48 [1.23–1.77]). The association between number of sexual partners over the lifetime and HIV infection was modified by both sex and migrant status: For male non-migrants, each additional partner was associated with 3% higher odds of HIV infection (aOR = 1.03 [1.02–1.05]); for male migrants the association between number of partners and HIV infection was non-significant. Each additional partner increased odds of HIV infection by 22% for female non-migrants (aOR = 1.22 [1.12–1.32]) and 46% for female migrants (aOR = 1.46 [1.25–1.69]).

Conclusions

Higher risk sexual behavior in the context of migration increased women's likelihood of HIV infection.

Background

The heterogeneity of CD4+ T-cell counts and HIV-1 RNA at 5-12 years after the initiation of highly active antiretroviral therapy (HAART) remains largely uncharacterized.

Methods

In the Multicenter AIDS Cohort Study, 614 men who initiated HAART contributed data 5-12 years subsequently. Multivariate regression was used to evaluate the predictors of CD4+ counts and HIV-1 RNA levels.

Results

At 5-12 years post-HAART, the median CD4+ T-cell count was 586 (inter quartile range (IQR): 421-791) cells/μl and 78% of the HIV-1 RNA measurements were undetectable. Higher CD4+ T-cell counts 5-12 years post-HAART were predicted by higher CD4+ T-cell counts and higher total lymphocyte count pre-HAART, lack of hepatitis B or C virus co-infections, and greater CD4+ T-cell change as well as suppressed HIV-1 RNA in the first 5 years after starting HAART. Older men (≥50 years) with 351-500 CD4+ cells/μl at HAART initiation had adjusted mean CD4+ T-cell count of 643 cells/μl at 10-12 years post-HAART, which was similar to the adjusted mean CD4+ T-cell count (670 cells/μl, p=0.45) in this period for younger men starting HAART with lower CD4+ T-cell counts. HIV-1 RNA suppression in the first 5 years post-HAART predicted subsequent viral suppression.

Conclusion

Immunological and virological responses in the first five years post-HAART predicted subsequent CD4+ T-cell counts and HIV-1 RNA levels. The association between age and subsequent CD4+ T-cell count supports incorporating age in guidelines for use of HAART.

Summary

A comparison of risks for the secondary transmission of HIV between young HIV-infected women-who-have-sex-with-men (WSM) and men-who-have-sex-with-men (MSM) found that recent partner-specific sexual risk behaviors are high among both populations. However, differences in the specific behaviors between WSM and MSM support population-specific interventions to reduce the secondary transmission of HIV.

Background

Secondary transmission remains a significant concern among HIV-infected youth. Little is known, however, about how partner-specific sexual risk behaviors for the secondary transmission of HIV may differ between the two largest subgroups of HIV positive youth, women-who-have-sex-with-men (WSM) and men-who-have-sex-with-men (MSM),

Methods

During 2003-2004, a convenience sample of HIV-infected youth, 13-24 years of age, were recruited from 15 Adolescent Medicine Trials Network clinical sites. Approximately 10-15 youth were recruited at each site. Participants completed an ACASI survey including questions about sex partners in the past year. Cross-sectional data analyses, including bivariate and multivariable regressions using generalized estimating equations, were conducted during 2008 to compare recent partner-specific sexual risk behaviors between WSM and MSM.

Results

Of 409 participants, 91% (371) were included in this analysis, including 176 WSM and 195 MSM. Ninety-two percent (163 WSM, 177 MSM) provided information on characteristics of their sexual partners. There were significant differences between the two groups in recent partner-specific sexual risk behaviors including: lower rates of condom use at last sex among WSM (61% WSM vs. 78% MSM; p=0.0011); a larger proportion of the sex partners of MSM reported as concurrent (56% MSM vs. 36% WSM; p=0.0001); and greater use of hard drugs at last sex by MSM and/or their partner (18% MSM vs. 4% WSM; p=0.0008). When measuring risk as a composite measure of sexual risk behaviors known to be associated with HIV transmission, both groups had high rates of risky behaviors, 74.7% among young MSM compared to 68.1% of WSM.

Conclusions

These data suggest that recent partner-specific sexual risk behaviors for HIV transmission are high among young infected MSM and WSM. These findings suggest the need to offer interventions to reduce the secondary transmission of HIV to all HIV-positive youth in care. However, differences in risk behaviors between young MSM and WSM supports population-specific interventions.

Borderline personality is diagnosed in clinical settings three times more often in women than in men, and symptom severity in women appears sensitive to circulating sex steroid levels. In non-human mammals, prenatal hormones contribute to the development of sex-linked behavior and their responsiveness to postnatal hormones. Therefore, this study examined the hypothesis that prenatal hormones may influence the development of borderline personality traits by measuring a marker of perinatal androgen action, the 2D:4D ratio, and salivary hormone levels in 58 men and 52 women. Participants completed the Borderline Features Subscales (BOR) of the Personality Assessment Inventory, gender role questionnaires, and four sex-linked cognitive tasks. Digit ratios were a significant predictor of the affective component of borderline personality, such that in both sexes 2D:4D ratios suggestive of weaker perinatal androgen action contributed to greater borderline personality features overall and greater affective instability. In addition, women reporting greater affective instability showed larger changes in estradiol across the session, consistent with the influence of stress and emotional reactivity on hormonal function. These findings are consistent with an increasing body of research suggesting that hormonal factors associated with the expression of typical gender-linked behavior may also contribute to the expression of gender-linked maladaptive behavior.

Ischemic stroke is emerging as a major health problem for elderly women. Women have lower stroke incidence than men until an advanced age, when the epidemiology of ischemic stroke shifts and incidence rises dramatically in women. Experimental models of rodent stroke have replicated this clinical epidemiology, with exacerbated injury in older compared with young female rodents Many of the detrimental effects of aging on ischemic stroke outcome in females can be replicated by ovariectomy, suggesting that hormones such as estrogen play a neuroprotective role. However, emerging data suggest that the molecular mechanisms leading to ischemic cell death differ in the two sexes, and these effects may be independent of circulating hormone levels. This article highlights recent clinical and experimental literature on sex differences in stroke outcomes and mechanisms.

Gay and bisexual men are often treated as a homogenous group; however, there may be important differences between them. In addition, behaviorally bisexual men are a potential source of HIV infection for heterosexual women. In this study, we compared 97 men who have sex with men only (MSM) to 175 men who have sex with men and women (MSMW). We also compared the 175 MSMW to 772 men who have sex with women only (MSW). Bivariate and multiple logistic regression analyses were performed to assess correlates of MSMW risk behaviors with men and with women as well as whether MSMW, compared with MSW, engaged in more risky behaviors with women. Compared with MSM, MSMW were less likely to be HIV-positive or to engage in unprotected receptive anal intercourse. In contrast, MSMW were more likely than MSW to be HIV-positive and to engage in anal intercourse with their female partners; however, rates of unprotected anal intercourse were similar. The study findings suggest that there may be important differences in HIV risk behaviors and HIV prevalence between MSM and MSMW as well as between MSMW and MSW.

Background

There is conflicting evidence regarding the effects of breast-feeding on maternal mortality from human immunodeficiency virus type 1 (HIV-1) infection, and little is known about the effects of breast-feeding on markers of HIV-1 disease progression.

Methods

HIV-1–seropositive women were enrolled during pregnancy and received short-course zidovudine. HIV-1 RNA levels and CD4 cell counts were determined at baseline and at months 1, 3, 6, 12, 18, and 24 postpartum and were compared between breast-feeding and formula-feeding mothers.

Results

Of 296 women, 98 formula fed and 198 breast-fed. At baseline, formula-feeding women had a higher education level and prevalence of HIV-1–related illness than did breast-feeding women; however, the groups did not differ with respect to CD4 cell counts and HIV-1 RNA levels. Between months 1 and 24 postpartum, CD4 cell counts decreased 3.9 cells/µL/month (P< .001), HIV-1 RNA levels increased 0.005 log10 copies/mL/month (P = .03), and body mass index (BMI) decreased 0.03 kg/m2/month (P< .001). The rate of CD4 cell count decline was higher in breast-feeding mothers (7.2 cells/µL/month) than in mothers who never breast-fed (4.0 cells/µL/month) (P = .01). BMI decreased more rapidly in breast-feeding women (P = .04), whereas HIV-1 RNA levels and mortality did not differ significantly between breast-feeding and formula-feeding women.

Conclusions

Breast-feeding was associated with significant decreases in CD4 cell counts and BMI. HIV-1 RNA levels and mortality were not increased, suggesting a limited adverse impact of breast-feeding in mothers receiving extended care for HIV-1 infection.

BACKGROUND--The role of cytokines in the pathogenesis of pneumonia is still poorly understood. In a previous study the diagnostic value of measuring blood concentrations of interleukin 6 and interferon gamma was established. In the present study the value of blood concentrations of interleukin 8, granulocyte-colony stimulating factor, and lactoferrin as markers of bacteraemic pneumonia is evaluated. METHODS--The circulating concentrations of interleukin 8 (IL-8), granulocyte-colony stimulating factor (G-CSF), and lactoferrin were measured in 14 patients with bacteraemic pneumococcal pneumonia and 49 patients with atypical pneumonia or influenza A infection using enzyme immunoassays. RESULTS--Serum G-CSF concentrations were higher in the group with bacteraemic pneumococcal pneumonia, and G-CSF values correlated with the white blood cell count and levels of C-reactive protein (CRP). The levels of IL-8 were higher in the group with bacteraemic pneumococcal pneumonia than the groups with Chlamydia pneumonia, Legionella pneumonia, or influenza A infection, but there was no difference when compared with the group with Mycoplasma pneumonia. A white blood cell count of > 15 x 10(9)/l was highly suggestive of bacteraemic pneumonia. The concentrations of lactoferrin were raised in all groups except those with influenza A infection, but no difference was found between the different aetiological groups. A correlation was found between lactoferrin and white blood cell counts. CONCLUSIONS--Serum G-CSF and IL-8 concentrations are potential markers of bacteraemic pneumonia.

Human immunodeficiency virus type 2 (HIV-2) infection leads to a lifelong asymptomatic period in the majority of patients. Even in patients with progressive disease, a slow CD4 count decline characterizes the chronic phase of HIV-2 infection, suggesting that peripheral T-cell homeostasis is controlled better following HIV-2 infection than following HIV-1 infection. Herein we showed that, in contrast to HIV-1-infected patients, HIV-2-infected patients demonstrate enhanced thymic function compared to age-matched healthy individuals. The correlation between higher thymic production and lower CD4 T-cell loss in these patients suggests that efficient thymopoiesis is implicated in the long-lasting maintenance of CD4 T-cell counts in HIV-2 disease.

Background

Between the ages of 45 and 65 years, the prevalence of cardiovascular disease is significantly lower in women compared with men. Circulating bone marrow-derived endothelial progenitor cells (EPCs) play an important role in vascular repair. Reduced EPC number is predictive of more cardiovascular events. It is currently unknown whether there is a sex-difference in EPC number in middle-aged adults.

Objective

We tested the hypothesis that circulating EPC number is higher in middle-aged women than men.

Methods

Peripheral blood samples were collected from 58 sedentary adults, 29 men (57 ± 1 yr) and 29 women (58 ± 1 yr). Mononuclear cells were isolated and fluorescence-activated cell sorting (FACS) analysis of cells negative for CD45 was performed for those positive for CD34, and triple positive for CD34, VEGFR-2, and CD133 according to the recommendations of the International Society for Hematotherapy and Graft Engineering.

Results

The number of CD45-/CD34+ and CD45-/CD34+/ VEGFR-2+/CD133+ were not significantly different between women and men (0.055 ± 0.006% vs 0.069 ± 0.008% and 0.0013 ± 0.0003% vs 0.0018 ± 0.0004%, respectively).

Conclusions

These results demonstrate no sex-difference in EPC number in middle-age adults. Therefore, it is unlikely that differences in EPC number contribute to the gender-related differences in the prevalence of cardiovascular events in this population.

Objective

Lower life expectancy in men is generally attributed to higher likelihood of risky behavior and because men develop chronic conditions earlier. If sex-related differences in survival are independent of pre-infection chronic health and health behavior, it would suggest that survival differences may occur due to sex differences in quality of care and biologic response to infection and these differences may contribute to sex differences in life expectancy. We assessed if sex-related survival difference following community-acquired pneumonia (CAP) is due to differences in clinical characteristics, quality of care, or immune response.

Design, setting, and subjects

Prospective observational cohort of 2183 subjects with CAP.

Measurements and main results

Mean age was 64.9 years. Compared to women, men were more likely to smoke and had more comorbidity. At emergency department presentation, men had different biomarker patterns, as evidenced by higher inflammation (tumor necrosis factor (TNF), interleukin (IL)-6, and IL-10) and fibrinolysis (D-dimer), and lower coagulation biomarkers (antithrombin-III and Factor IX) (P<0.05). Small differences in favor of men were seen in care quality, including antibiotic timing and compliance with American Thoracic Society guidelines. Men had lower survival at 30, 90, 365 days. The higher one-year mortality was not attenuated when adjusted for differences in demographics, smoking, resuscitation, insurance, and vaccination status, comorbidity, hospital characteristics, and illness severity (unadjusted hazard ratio (HR)=1.35, p=0.003 and adjusted HR=1.29, p=0.004). HR were no longer statistically significant when additionally adjusted for differences in ED concentrations of TNF, IL-6, IL-10, D-dimer, antithrombin-III, and Factor IX (adjusted HR=1.27, p=0.17). Patterns of biomarkers observed in men were associated with worse survival over one year.

Conclusions

Lower survival among men following CAP was not explained by differences in chronic diseases, health behaviors, and quality of care. Patterns of inflammatory, coagulation, and fibrinolysis biomarkers among men may explain reduced short and long-term survival.