Correlates of human herpesvirus 8 seropositivity among heterosexual men in Kenya

BACKGROUND: Several studies have suggested that sexual transmission of human herpesvirus 8 (HHV-8) occurs among homosexual men in developed countries. However, few studies have examined heterosexual HHV-8 transmission, especially among African populations in which HHV-8 is endemic. OBJECTIVES: To determine the seroprevalence and correlates of HHV-8 infection among heterosexual African men. DESIGN: Cross-sectional study. METHODS: Participants were 1061 men enrolled in a prospective cohort study of risk factors for HIV-1 acquisition among trucking company employees in Mombasa, Kenya. Stored frozen sera from the study baseline visit were tested for antibodies to HHV-8 by whole-virus lysate ELISA. RESULTS: HHV-8 seroprevalence was 43%. In multivariate logistic regression analysis, HHV-8 infection was independently associated with older age [for men aged 30-39 years: odds ratio (OR), 1.5; 95% confidence interval (CI), 1.1-2.0; for men aged > or = 40 years: OR, 1.7; 95% CI, 1.1-2.7, compared with men aged < 30 years], Christian religion (OR, 1.6; 95% CI, 1.2-2.1), being uncircumcised (OR, 1.5; 95% CI, 1.0-2.2), and ever having syphilis (OR, 2.2; 95% CI, 1.4-3.5). Ever having used condoms was associated with decreased likelihood of infection (OR, 0.7; 95% CI, 0.6-1.0). Seropositivity was not significantly related to other sexual behaviors characterized or to HIV-1 status. CONCLUSIONS: HHV-8 seropositivity is common in this population and increases with age, suggesting on-going transmission during adulthood. Infection was more common among men who were uncircumcised or who had ever had syphilis and was less common among those who had ever used condoms, suggesting that sexual factors may play a role in HHV-8 transmission. Prospective studies of HHV-8 acquisition in heterosexual African populations are needed to demonstrate whether safer sexual practices can reduce transmission.     

The rotator interval and long head biceps tendon: anatomy, function, pathology, and magnetic resonance imaging

The rotator interval is an anatomically defined triangular area located between the coracoid process, the superior aspect of the subscapularis, and the anterior aspect of the supraspinatus. It is widely accepted that the rotator interval structures fulfill a role in biomechanics and pathology of the glenohumeral joint and long head biceps tendon. However, there is ongoing debate regarding the biomechanical details and the indications for treatment. A better understanding of rotator interval anatomy and function will lead to improved treatment of rotator interval abnormalities, and guide the indications for imaging and surgical intervention.     

High PR3 or ELA2 expression by CD34+ cells in advanced-phase chronic myeloid leukemia is associated with improved outcome following allogeneic stem cell transplantation and may improve PR1 peptide-driven graft-versus-leukemia effects

The primary granule proteins elastase (ELA2) and proteinase 3 (PR3) both contain the nonapeptide PR1, which can induce cytotoxic T lymphocyte (CTL) responses against chronic myeloid leukemia (CML) cells. To investigate whether eradication of CML after allogeneic stem cell transplantation (SCT) was influenced by PR3 and ELA2 gene expression or PR1-specific CTL responses, we studied cells from 87 CML patients and 27 HLA-A*0201(+) donors collected prior to T-cell-depleted HLA-identical sibling SCT. For patients in advanced phase (AdP), a higher expression of both PR3 and ELA2 in CD34(+) progenitors before SCT was associated with a lower incidence of relapse-related death, improved leukemia-free survival (LFS), and overall survival (OS); in chronic phase patients, no differences were observed. PR1-CTL responses were detected in 7 of 27 HLA-identical sibling donors, and associated with improved LFS and OS after SCT on follow-up. PR1-CTL responses detected in 7 of 28 CML patients before transplantation were not predictive of outcome and correlated inversely with PR3 and ELA2 expression. These findings suggest that assessment of PR3 and ELA2 expression in leukemic progenitors is useful for predicting posttransplantation outcome in AdP patients undergoing SCT. The presence of a donor immune response against PR1 may be advantageous and could be exploited therapeutically.     

Herpes simplex virus type 2 infection as a risk factor for human immunodeficiency virus acquisition in men who have sex with men

The association of human immunodeficiency virus (HIV) acquisition with herpes simplex virus type 2 (HSV-2) was assessed among men who have sex with men (MSM) in a nested case-control study of 116 case subjects who seroconverted to HIV during follow-up and 342 control subjects who remained HIV seronegative, frequency-matched by follow-up duration and report of HIV-infected sex partner and unprotected anal sex. The baseline HSV-2 seroprevalence was higher among case (46%) than control (34%) subjects (P=.03); the HSV-2 seroincidence was 7% versus 4% (P=.3). Only 15% of HSV-2-infected MSM reported herpes outbreaks in the past year. HIV acquisition was associated with prior HSV-2 infection (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.9), reporting >12 sex partners (OR, 2.9; 95% CI, 1.4-6.3), and reporting fewer herpes outbreaks in the past year (OR, 0.3; 95% CI, 0.1-0.8). HSV-2 increases the risk of HIV acquisition, independent of recognized herpes lesions and behaviors reflecting potential HIV exposure. HSV-2 suppression with antiviral therapy should be evaluated as an HIV prevention strategy among MSM.     

Repeated PR1 and WT1 peptide vaccination in Montanide-adjuvant fails to induce sustained high-avidity, epitope-specific CD8+ T cells in myeloid malignancies

Background

We previously showed that vaccination with one dose of PR1 and WT1 peptides induces transient anti-leukemia immunity. We hypothesized that maintenance of a sustained anti-leukemia response may require frequent boost injections.

Design and Methods

Eight patients with myeloid malignancies were enrolled in this phase II study, and 6 completed 6 injections of PR1 and WT1 peptides in Montanide-adjuvant with GM-CSF, every two weeks.

Results

Both high- and low-avidity PR1 or WT1-specific CD8⁺ T cells were detected in all evaluable patients after the first vaccine dose. Repeated vaccination led to selective deletion of high avidity PR1- and WT1-specific CD8⁺ T cells and was not associated with significant reduction in WT1-expression. Additional boosting failed to increase vaccine-induced CD8⁺ T-cell frequencies further and in all patients the response was lost before the 6^th dose. PR1- or WT1-specific CD8⁺ T cells were not detected in bone marrow samples, excluding their preferential localization to this site. Following a booster injection three months after the 6^th vaccine dose, no high-avidity PR1 or WT1-specific CD8⁺ T cells could be detected, whereas low-avidity T cells were readily expanded.

Conclusions

These data support the immunogenicity of PR1 and WT1 peptide vaccines. However, repeated delivery of peptides with Montanide-adjuvant and GM-CSF leads to rapid loss of high-avidity peptide-specific CD8⁺ T cells. These results may offer an explanation for the lack of correlation between immune and clinical responses observed in a number of clinical trials of peptide vaccination. New approaches are needed to induce long-term high-avidity memory responses against leukemia antigens. (ClinicalTrials.gov Identifier: NCT00499772)     

Use of "<Emphasis Type="Italic">biokit</Emphasis>HSV-2 Rapid Assay" to improve the positive predictive value of Focus HerpeSelect HSV-2 ELISA

Background  

Commercially available assays to detect antibodies to the herpes simplex virus type 2 (HSV-2)-specific glycoprotein gG-2 have markedly improved serologic diagnosis of HSV-2 infection. However, even tests with high specificity can have low positive predictive values in low prevalence populations. HSV-2 is a chronic, life-long viral infection that requires both medical attention and potential alterations in health care strategy. As such, the concern for false positive diagnoses is high confirmatory testing is routine for other viral serologies such as HIV and hepatitis C. We evaluated such a strategy for HSV-2 serology by using an easily performed commercial test, biokitHSV-2 rapid test ("Biokit"; Biokit USA, Lexington MA) as a confirmatory test for the widely used gG-2 specific serology ("Focus;" HerpeSelect HSV-2 ELISA; Focus Diagnostics, Cypress CA).     

Polycystic ovarian syndrome and insulin resistance: implications for estrogen use in premenopausal and postmenopausal women

Polycystic ovarian syndrome (PCOS) is the most frequent endocrine disorder of reproductive age women, affecting an estimated 8-10% of all women in this age group or approximately six million women. Further, women with PCOS continue to manifest the metabolic alterations inherent in the insulin resistance syndrome after menopause, rendering them more susceptible to type 2 diabetes and cardiovascular disease. Aging and obesity further contribute to these risks. Since estrogen-containing therapy is commonly used for menstrual regulation in premenopausal women with PCOS, it is important to evaluate the possible consequences of hormonal therapy on subsequent metabolic and cardiovascular risk. In postmenopausal women, a consensus regarding the appropriate role of estrogen replacement therapy is currently in evolution. By examining the effects of estrogen with or without progesterone on insulin resistance, insight may be gained about the risk/benefit ratio of this therapy in the subset of women with insulin resistance, PCOS, and type 2 diabetes. The goal of this review, then, is to examine the known effects of estrogen on insulin sensitivity and its implications for cardiovascular and metabolic risk.     

A qualitative study on alcohol consumption and HIV treatment adherence among men living with HIV in Ugandan fishing communities

Ugandan fishing communities are dually burdened with high rates of HIV and alcohol use. This qualitative study explores context and motivation of alcohol consumption, and alcohol's effect on antiretroviral treatment (ART) adherence, among male fisherfolk living with HIV in Wakiso District, Uganda. We conducted in-depth semi-structured interviews with 30 men in HIV care and on ART, and used a thematic analysis approach for analysis. Alcohol use was identified as a major barrier to ART adherence through cognitive impairment and the intentional skipping of doses when drinking. Men reportedly reduced their drinking since HIV diagnosis – motivated by counseling received from providers and a newfound desire to live a healthy lifestyle. However, social, occupational, and stress-related influences that make alcohol reduction difficult were identified. Our findings suggest alcohol use may pose a challenge to ART adherence for fishermen living with HIV – and has implications for the tailoring of screening and brief intervention for alcohol reduction in HIV care for this population.