HIV infection among ethnic minority and migrant men who have sex with men in Britain

To examine human immunodeficiency virus (HIV) infection among men who have sex with men (MSM) from different ethnic and migrant groups living in Britain.

Unsafe sex and increased incidence of hepatitis C virus infection among HIV-infected men who have sex with men: the Swiss HIV Cohort Study

BACKGROUND: Data on the incidence of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected persons are sparse. It is controversial whether and how frequently HCV is transmitted by unprotected sexual intercourse. METHODS: We assessed the HCV seroprevalence and incidence of HCV infection in the Swiss HIV Cohort Study between 1988 and 2004. We investigated the association of HCV seroconversion with mode of HIV acquisition, sex, injection drug use (IDU), and constancy of condom use. Data on condom use or unsafe sexual behavior were prospectively collected between 2000 and 2004. RESULTS: The overall seroprevalence of HCV infection was 33% among a total of 7899 eligible participants and 90% among persons reporting IDU. We observed 104 HCV seroconversions among 3327 participants during a total follow-up time of 16,305 person-years, corresponding to an incidence of 0.64 cases per 100 person-years. The incidence among participants with a history of IDU was 7.4 cases per 100 person-years, compared with 0.23 cases per 100 person-years in patients without such a history (P<.001). In men who had sex with men (MSM) without a history of IDU who reported unsafe sex, the incidence was 0.7 cases per 100 person-years, compared with 0.2 cases per 100 person-years in those not reporting unsafe sex (P=.02), corresponding to an incidence rate ratio of 3.5 (95% confidence interval, 1.2-10.0). The hazard of acquiring HCV infection was elevated among younger participants who were MSM. CONCLUSIONS: HCV infection incidence in the Swiss HIV Cohort Study was mainly associated with IDU. In HIV-infected MSM, HCV infection was associated with unsafe sex.

Circumcision and HIV infection among men who have sex with men in Britain: the insertive sexual role

The objective was to examine the association between circumcision status and self-reported HIV infection among men who have sex with men (MSM) in Britain who predominantly or exclusively engaged in insertive anal intercourse. In 2007-2008, a convenience sample of MSM living in Britain was recruited through websites, in sexual health clinics, bars, clubs, and other venues. Men completed an online survey which included questions on circumcision status, HIV testing, HIV status, sexual risk behavior, and sexual role for anal sex. The analysis was restricted to 1,521 white British MSM who reported unprotected anal intercourse in the previous 3 months and who said they only or mostly took the insertive role during anal sex. Of these men, 254 (16.7 %) were circumcised. Among men who had had a previous HIV test (n = 1,097), self-reported HIV seropositivity was 8.6 % for circumcised men (17/197) and 8.9 % for uncircumcised men (80/900) (unadjusted odds ratio [OR], 0.97; 95 % confidence interval [95 % CI], 0.56, 1.67). In a multivariable logistic model adjusted for known risk factors for HIV infection, there was no evidence of an association between HIV seropositivity and circumcision status (adjusted OR, 0.79; 95 % CI, 0.43, 1.44), even among the 400 MSM who engaged exclusively in insertive anal sex (adjusted OR, 0.84; 95 % CI, 0.25, 2.81). Our study provides further evidence that circumcision is unlikely to be an effective strategy for HIV prevention among MSM in Britain.

Resurgence of HIV infection among men who have sex with men in Switzerland: mathematical modelling study

Background New HIV infections in men who have sex with men (MSM) have increased in Switzerland since 2000 despite combination antiretroviral therapy (cART). The objectives of this mathematical modelling study were: to describe the dynamics of the HIV epidemic in MSM in Switzerland using national data; to explore the effects of hypothetical prevention scenarios; and to conduct a multivariate sensitivity analysis. Methodology/Principal Findings The model describes HIV transmission, progression and the effects of cART using differential equations. The model was fitted to Swiss HIV and AIDS surveillance data and twelve unknown parameters were estimated. Predicted numbers of diagnosed HIV infections and AIDS cases fitted the observed data well. By the end of 2010, an estimated 13.5% (95% CI 12.5, 14.6%) of all HIV-infected MSM were undiagnosed and accounted for 81.8% (95% CI 81.1, 82.4%) of new HIV infections. The transmission rate was at its lowest from 1995–1999, with a nadir of 46 incident HIV infections in 1999, but increased from 2000. The estimated number of new infections continued to increase to more than 250 in 2010, although the reproduction number was still below the epidemic threshold. Prevention scenarios included temporary reductions in risk behaviour, annual test and treat, and reduction in risk behaviour to levels observed earlier in the epidemic. These led to predicted reductions in new infections from 2 to 26% by 2020. Parameters related to disease progression and relative infectiousness at different HIV stages had the greatest influence on estimates of the net transmission rate. Conclusions/Significance The model outputs suggest that the increase in HIV transmission amongst MSM in Switzerland is the result of continuing risky sexual behaviour, particularly by those unaware of their infection status. Long term reductions in the incidence of HIV infection in MSM in Switzerland will require increased and sustained uptake of effective interventions.

High prevalence of anorectal chlamydial infection in HIV-infected men who have sex with men in Switzerland

Human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) were enrolled in an anorectal Chlamydia trachomatis screening study. Anorectal Chlamydia DNA was detected in 16 (10.9%) of 147 men, mainly among asymptomatic patients and patients having >20 sexual partners. These results support routine anorectal Chlamydia screening in HIV-infected MSM who report unprotected anal intercourse.

Treatment-naive individuals are the major source of transmitted HIV-1 drug resistance in men who have sex with men in the Swiss HIV Cohort Study

BACKGROUND Human immunodeficiency virus type 1 (HIV-1) transmitted drug resistance (TDR) can compromise antiretroviral therapy (ART) and thus represents an important public health concern. Typically, sources of TDR remain unknown, but they can be characterized with molecular epidemiologic approaches. We used the highly representative Swiss HIV Cohort Study (SHCS) and linked drug resistance database (SHCS-DRDB) to analyze sources of TDR. METHODS ART-naive men who have sex with men with infection date estimates between 1996 and 2009 were chosen for surveillance of TDR in HIV-1 subtype B (N = 1674), as the SHCS-DRDB contains pre-ART genotypic resistance tests for >69% of this surveillance population. A phylogeny was inferred using pol sequences from surveillance patients and all subtype B sequences from the SHCS-DRDB (6934 additional patients). Potential sources of TDR were identified based on phylogenetic clustering, shared resistance mutations, genetic distance, and estimated infection dates. RESULTS One hundred forty of 1674 (8.4%) surveillance patients carried virus with TDR; 86 of 140 (61.4%) were assigned to clusters. Potential sources of TDR were found for 50 of 86 (58.1%) of these patients. ART-naive patients constitute 56 of 66 (84.8%) potential sources and were significantly overrepresented among sources (odds ratio, 6.43 [95% confidence interval, 3.22-12.82]; P < .001). Particularly large transmission clusters were observed for the L90M mutation, and the spread of L90M continued even after the near cessation of antiretroviral use selecting for that mutation. Three clusters showed evidence of reversion of K103N or T215Y/F. CONCLUSIONS Many individuals harboring viral TDR belonged to transmission clusters with other Swiss patients, indicating substantial domestic transmission of TDR in Switzerland. Most TDR in clusters could be linked to sources, indicating good surveillance of TDR in the SHCS-DRDB. Most TDR sources were ART naive. This, and the presence of long TDR transmission chains, suggests that resistance mutations are frequently transmitted among untreated individuals, highlighting the importance of early diagnosis and treatment.

Modelling the impact of deferring HCV treatment on liver-related complications in HIV coinfected men who have sex with men

BACKGROUND AND AIMS Hepatitis C (HCV) is a leading cause of morbidity and mortality in people who live with HIV. In many countries, access to direct acting antiviral agents to treat HCV is restricted to individuals with advanced liver disease (METAVIR stage F3 or F4). Our goal was to estimate the long term impact of deferring HCV treatment for men who have sex with men (MSM) who are coinfected with HIV and often have multiple risk factors for liver disease progression. METHODS We developed an individual-based model of liver disease progression in HIV/HCV coinfected men who have sex with men. We estimated liver-related morbidity and mortality as well as the median time spent with replicating HCV infection when individuals were treated in liver fibrosis stages F0, F1, F2, F3 or F4 on the METAVIR scale. RESULTS The percentage of individuals who died of liver-related complications was 2% if treatment was initiated in F0 or F1. It increased to 3% if treatment was deferred until F2, 7% if it was deferred until F3 and 22% if deferred until F4. The median time individuals spent with replicating HCV increased from 5 years if treatment was initiated in F2 to almost 15 years if it was deferred until F4. CONCLUSIONS Deferring HCV therapy until advanced liver fibrosis is established could increase liver-related morbidity and mortality in HIV/HCV coinfected individuals, and substantially prolong the time individuals spend with replicating HCV infection.

Different molecular and structural adaptations with eccentric and conventional strength training in elderly men and women

Reprogramming of gene expression contributes to structural and functional adaptation of muscle tissue in response to altered use. The aim of this study was to investigate mechanisms for observed improvements in leg extension strength, gain in relative thigh muscle mass and loss of body and thigh fat content in response to eccentric and conventional strength training in elderly men (n = 14) and women (n = 14; average age of the men and women: 80.1 ± 3.7 years) by means of structural and molecular analyses. Biopsies were collected from m. vastus lateralis in the resting state before and after 12 weeks of training with two weekly resistance exercise sessions (RET) or eccentric ergometer sessions (EET). Gene expression was analyzed using custom-designed low-density PCR arrays. Muscle ultrastructure was evaluated using EM morphometry. Gain in thigh muscle mass was paralleled by an increase in muscle fiber cross-sectional area (hypertrophy) with RET but not with EET, where muscle growth is likely occurring by the addition of sarcomeres in series or by hyperplasia. The expression of transcripts encoding factors involved in muscle growth, repair and remodeling (e.g., IGF-1, HGF, MYOG, MYH3) was increased to a larger extent after EET than RET. MicroRNA 1 expression was decreased independent of the training modality, and was paralleled by an increased expression of IGF-1 representing a potential target. IGF-1 is a potent promoter of muscle growth, and its regulation by microRNA 1 may have contributed to the gain of muscle mass observed in our subjects. EET depressed genes encoding mitochondrial and metabolic transcripts. The changes of several metabolic and mitochondrial transcripts correlated significantly with changes in mitochondrial volume density. Intramyocellular lipid content was decreased after EET concomitantly with total body fat. Changes in intramyocellular lipid content correlated with changes in body fat content with both RET and EET. In the elderly, RET and EET lead to distinct molecular and structural adaptations which might contribute to the observed small quantitative differences in functional tests and body composition parameters. EET seems to be particularly convenient for the elderly with regard to improvements in body composition and strength but at the expense of reducing muscular oxidative capacity.

Real-time quantitative PCR to determine chlamydial load in men and women in a community setting

We used a PCR method to quantify the loads of Chlamydia trachomatis organisms in self-collected urine and vulvovaginal swab (VVS) samples from 93 women and 30 men participating in the Chlamydia Screening Studies Project, a community-based study of individuals not seeking health care. For women, self-collected VVS had a higher mean chlamydial load (10,405 organisms/ml; 95% confidence interval [95% CI], 5,167 to 21,163 organisms/ml) than did first-void urines (FVU) (503 organisms/ml; 95% CI, 250 to 1,022 organisms/ml; P < 0.001). Chlamydial loads in female and male self-collected FVU specimens were similar (P = 0.634). The mean chlamydial load in FVU specimens decreased with increasing age in females and males. There was no strong statistical evidence of differences in chlamydial load in repeat male and female FVU specimens taken when patients attended for treatment a median of 23.5 (range, 14 to 62) and 28 (range, 13 to 132) days later, respectively, or in VVS taken a median of 35 (range, 14 to 217) days later. In this study, chlamydial load values for infected persons in the community who were not seeking treatment were lower than those published in other studies involving symptomatic patients attending clinical settings. This might have implications for estimates of the infectiousness of chlamydia. The results of this study provide a scientific rationale for preferring VVS to FVU specimens from women.

[Manifestation and course of coronary heart disease in men and women--consequences for diagnosis and treatment]

Gender related issues in manifestation, diagnosis and treatment of coronary artery disease are important but still not well recognized. Women are more likely to present late after first symptoms of myocardial infarction. Myocardial infarction is more often unrecognized. In regard to complications after myocardial infarctions ventricular tachycardia and cardiac arrest are more frequent and women are also more likely to develop heart failure or cardiogenic shock. The reason for this is most probably the fact that women presenting with myocardial infarction are of older age and have a higher incidence of co-morbidities. Thrombolysis and coronary angioplasty are less often performed in women in the setting of myocardial infarction. However there is a clear trend toward improvement of this situation during the last years. The reopening rate of occluded coronary arteries with thrombolysis and with coronary angioplasty is similar in women compared to men. Perioperative risk with aorto-coronary bypass surgery is higher in women, which can not be fully explained by higher age and co-morbidities. However 10 years survival rate after aorto-coronary bypass-surgery is similar for men and women, although occlusion of venous grafts is seen more often in women. The benefit of structured cardiac rehabilitation after an acute event is similar for younger and older women and as good as in men. Positive effects of cardiac rehabilitation include increased physical performance, reduction of body fat, improvement of lipid-profiles and an improvement of the psychosocial situation and quality of life.

Different response to eccentric and concentric training in older men and women

Sarcopenia is the age-related loss of muscle mass and strength and has been associated with an increased risk of falling and the development of metabolic diseases. Various training protocols, nutritional and hormonal interventions have been proposed to prevent sarcopenia. This study explores the potential of continuous eccentric exercise to retard age-related loss of muscle mass and function. Elderly men and women (80.6 +/- 3.5 years) were randomized to one of three training interventions demanding a training effort of two sessions weekly for 12 weeks: cognitive training (CT; n = 16), conventional resistance training (RET; n = 23) and eccentric ergometer training (EET; n = 23). Subjects were tested for functional parameters and body composition. Biopsies were collected from M. vastus lateralis before and after the intervention for the assessment of fiber size and composition. Maximal isometric leg extension strength (MEL: +8.4 +/- 1.7%) and eccentric muscle coordination (COORD: -43 +/- 4%) were significantly improved with EET but not with RET (MEL: +2.3 +/- 2.0%; COORD: -13 +/- 3%) and CT (MEL: -2.3 +/- 2.5%; COORD: -12 +/- 5%), respectively. We observed a loss of body fat (-5.0 +/- 1.1%) and thigh fat (-6.9 +/- 1.5%) in EET subjects only. Relative thigh lean mass increased with EET (+2.5 +/- 0.6%) and RET (+2.0 +/- 0.3%) and correlated negatively with type IIX/type II muscle fiber ratios. It was concluded that both RET and EET are beneficial for the elderly with regard to muscle functional and structural improvements but differ in their spectrum of effects. A training frequency of only two sessions per week seems to be the lower limit for a training stimulus to reveal measurable benefits.

Nighttime vagal cardiac control and plasma fibrinogen levels in a population of working men and women

BACKGROUND: Elevated plasma fibrinogen levels have prospectively been associated with an increased risk of coronary artery disease in different populations. Plasma fibrinogen is a measure of systemic inflammation crucially involved in atherosclerosis. The vagus nerve curtails inflammation via a cholinergic antiinflammatory pathway. We hypothesized that lower vagal control of the heart relates to higher plasma fibrinogen levels. METHODS: Study participants were 559 employees (age 17-63 years; 89% men) of an airplane manufacturing plant in southern Germany. All subjects underwent medical examination, blood sampling, and 24-hour ambulatory heart rate recording while kept on their work routine. The root mean square of successive differences in RR intervals during the night period (nighttime RMSSD) was computed as the heart rate variability index of vagal function. RESULTS: After controlling for demographic, lifestyle, and medical factors, nighttime RMSSD explained 1.7% (P = 0.001), 0.8% (P = 0.033), and 7.8% (P = 0.007), respectively, of the variance in fibrinogen levels in all subjects, men, and women. Nighttime RMSSD and fibrinogen levels were stronger correlated in women than in men. In all workers, men, and women, respectively, there was a mean +/- SEM increase of 0.41 +/- 0.13 mg/dL, 0.28 +/- 0.13 mg/dL, and 1.16 +/- 0.41 mg/dL fibrinogen for each millisecond decrease in nighttime RMSSD. CONCLUSIONS: Reduced vagal outflow to the heart correlated with elevated plasma fibrinogen levels independent of the established cardiovascular risk factors. This relationship seemed comparably stronger in women than men. Such an autonomic mechanism might contribute to the atherosclerotic process and its thrombotic complications.

Longitudinal platelet reactivity to acute psychological stress among older men and women

Platelet reactivity to acute stress is associated with increased cardiovascular disease risk; however, little research exists to provide systematic methodological foundations needed to generate strong longitudinal research designs. Study objectives were: 1) to evaluate whether markers of platelet function increase in response to an acute psychological stress test among older adults, 2) to establish whether reactivity remains robust upon repeated administration (i.e. three occasions approximately 1 year apart), and 3) to evaluate whether two different acute speech stress tasks elicit similar platelet responses. The 149 subjects (mean age 71 years) gave a brief impromptu speech on one of two randomly assigned topics involving interpersonal conflict. Blood samples drawn at baseline and post-speech were assayed using flow cytometry for platelet responses on three outcomes (% aggregates, % P-selectin expression, and % fibrinogen receptor expression). Three-level hierarchical linear modeling analyses revealed significant stress-induced increases in platelet activation on all outcomes (p < 0.001). No significant habituation on any measure was found. Additional reactivity differences were associated with male gender, history of myocardial infarction, and use of aspirin, statins, and antidepressants. The results demonstrate that laboratory acute stress tests continued to produce robust platelet reactivity on three activation markers among older adults over 3 years.

Remaining lifetime and absolute 10-year probabilities of osteoporotic fracture in Swiss men and women

SUMMARY: Remaining lifetime and absolute 10-year probabilities for osteoporotic fractures were determined by gender, age, and BMD values. Remaining lifetime probability at age 50 years was 20.2% in men and 51.3% in women and increased with advancing age and decreasing BMD. The study validates the elements required to populate a Swiss-specific FRAX model. INTRODUCTION: Switzerland belongs to high-risk countries for osteoporosis. Based on demographic projections, burden will still increase. We assessed remaining lifetime and absolute 10-year probabilities for osteoporotic fractures by gender, age and BMD in order to populate FRAX algorithm for Switzerland. METHODS: Osteoporotic fracture incidence was determined from national epidemiological data for hospitalised fractured patients from the Swiss Federal Office of Statistics in 2000 and results of a prospective Swiss cohort with almost 5,000 fractured patients in 2006. Validated BMD-associated fracture risk was used together with national death incidence and risk tables to determine remaining lifetime and absolute 10-year fracture probabilities for hip and major osteoporotic (hip, spine, distal radius, proximal humerus) fractures. RESULTS: Major osteoporotic fractures incidence was 773 and 2,078 per 100,000 men and women aged 50 and older. Corresponding remaining lifetime probabilities at age 50 were 20.2% and 51.3%. Hospitalisation for clinical spine, distal radius, and proximal humerus fractures reached 25%, 30% and 50%, respectively. Absolute 10-year probability of osteoporotic fracture increased with advancing age and decreasing BMD and was higher in women than in men. CONCLUSION: This study validates the elements required to populate a Swiss-specific FRAX model, a country at highest risk for osteoporotic fractures.

Epidemiology and direct medical costs of osteoporotic fractures in men and women in Switzerland

The aim of this study was to estimate the hospitalization incidence and the total number of hospital days related to all fractures and osteoporotic fractures in the year 2000 in Switzerland and to compare these with data from other frequent disorders in men and women. The official administrative and medical statistics database of the Swiss Federal Office of Statistics (SFOS) from the year 2000 was used. It covered 81.2% of all registered patient admissions and was considered to be representative of the entire population. We included the ICD-10 codes of 84 diagnoses that were compatible with an underlying osteoporosis and applied the best matching age-specific osteoporosis attribution rates published for the ICD-9 diagnosis codes to the individual ICD-10 codes. To preserve comparability with previously published data from 1992, we grouped the data related to the ICD-10 fracture codes into seven diagnosis pools (fractures of the axial skeleton, fractures of the proximal upper limbs, fractures of the distal upper limbs, fractures of the proximal lower limbs, fractures of the distal lower limbs, multiple fractures, and osteoporosis) and analyzed them separately for women and men by age group. Incidences of hospitalization due to fractures were calculated, and the direct medical costs related to hospitalization were estimated. In addition, we compared the results with those from chronic pulmonary obstructive disease (COPD), stroke, acute myocardial infarction, heart failure, diabetes and breast carcinoma from the same database. In Switzerland during 2000, 62,535 hospitalizations for fractures (35,586 women and 26,949 men) were registered. Fifty-one percent of all fractures in women and 24% in men were considered as osteoporotic. The overall incidences of hospitalization due to fractures were 969 and 768 per 100,000 in women and men, respectively. The hospitalization incidences for fractures of the proximal lower limbs and the axial skeleton increased exponentially after the age of 65 years. The direct medical cost of hospitalization of patients with osteoporosis and/or related fractures was 357 million CHF. Hip fractures accounted for approximately half of these costs in women and men. Among other common diseases in women and men, osteoporosis ranked number 1 in women and number 2 (behind COPD) in men. When compared with data from 1992, the average length of stay had shortened by 8.4 days for women and 4.7 days for men, leading to a decrease of almost 40% in direct medical costs related to acute hospitalizations. This apparent decrease in cost might result from a shift into the ambulatory cost segment, for which the assessment and management tools need to be developed. We conclude that, in 2000, osteoporosis continued to be a heavy burden on the Swiss healthcare system. Lack of awareness of the disease and its consequences prevents widespread use of drugs with anti-fracture efficacy. This limits their potential to reduce costs.