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We previously showed that anticholinergic (ACH) medications contribute to self-reported neurocognitive impairment (NCI) in elderly people with human immunodeficiency virus (PWH). The current cross-sectional study further evaluated the effect of ACH and sedative drugs on neurocognitive function in PWH who underwent comprehensive neuropsychological evaluation.A medication review was performed in PWH enrolled in the prospective Neurocognitive Assessment in Metabolic and Aging Cohort within the Swiss HIV Cohort Study. Neurocognitive functions were analyzed in 5 domains (motor skills, speed of information, attention/working memory, executive functions, and verbal learning memory). The effect of ACH and sedative medications on neurocognitive functioning was evaluated using linear regression models for the continuous (mean z-score) outcome and multivariable logistic regression models for the binary (presence/absence) outcome.A total of 963 PWH (80% male, 92% Caucasian, 96% virologically suppressed, median age 52) were included. Fourteen percent of participants were prescribed ≥1 ACH medication and 9% were prescribed ≥1 sedative medication. Overall, 40% of participants had NCI. Sedative medication use was associated with impaired attention/verbal learning and ACH medication use with motor skills deficits both in the continuous (mean z-score difference -0.26 to -0.14,Anticholinergic and sedative medications contribute to NCI. Clinicians need to consider these drugs when assessing NCI in PWH.

OBJECTIVES We aimed to assess prevalence and age at menopause, identify factors associated with early menopause and explore the provision and utilization of healthcare in women living with HIV in Switzerland. METHODS This was a retrospective Swiss HIV Cohort Study analysis from January 2010 to December 2018. Descriptive statistics to characterise the population and menopause onset. Logistic regression analysis to identify risk factors for early menopause. RESULTS Of all women in the SHCS, the proportion of postmenopausal women tripled from 11.5% (n��=��274) in 2010 to 36.1% (n��=��961) in 2018. The median age at menopause was 50��years. Early menopause (

Objectives Chronic hepatitis C virus (HCV) infection affects the immune system. Whether elimination of HCV with direct-acting antivirals (DAA) restores immunity is unclear. We used mass cytometry to get a broad and in-depth assessment of blood cell populations of patients with chronic HCV before and after DAA therapy. Methods Before and 12 weeks after sustained virological response (SVR12) to DAA therapy, 22 cell populations were analysed by mass cytometry in blood collected from ten healthy control individuals and 20 HCV-infected patients with (ten patients) or without (ten patients) human immunodeficiency virus (HIV) infection. Results HCV infection altered the frequency of 14/22 (64%) blood cell populations. At baseline, the frequencies (median, interquartile range (IQR); control, HCV, HCV/HIV) of intermediate monocytes (1.2, IQR 0.47–1.46; 1.76, IQR 0.83–2.66; 0.78, IQR 0.28–1.77), non-classical monocytes (1.11, IQR 0.49–1.26; 0.9, IQR 0.18–0.99; 0.54, IQR 0.28–1.77), conventional dendritic cells type 2 (0.55, IQR 0.35–0.59; 0.31, IQR 0.16–0.38; 0.19, IQR 0.11–0.36) and CD56dim natural killer cells (8.08, IQR 5.34–9.79; 4.72, IQR 2.59–6.05) 3.61, IQR 2.98–5.07) were reduced by 35% to 65%, particularly in HCV/HIV co-infected patients. In contrast, activated double-negative T cells (0.07, IQR 0.06–0.10; 0.10, IQR 0.09–0.19; 0.19, IQR 0.12–0.25), activated CD4 T cells (0.28, IQR 0.21–0.36; 0.56, IQR 0.33–0.77; 0.40, IQR 0.22–0.53) and activated CD8 T cells (0.23, IQR 0.14–0.42; 0.74, IQR 0.30–1.65; 0.80, IQR 0.58–1.16) were increased 1.4 to 3.5 times. Upon stimulation with Toll-like receptor ligands, the expression of cytokines was up-regulated in 7/9 (78%) and 17/19 (89%) of the conditions in HCV- and HCV/HIV-infected patients, respectively. Most alterations persisted at SVR12. Conclusions Chronic HCV and HCV/HIV infections induce profound and durable perturbations of innate and adaptive immune homeostasis.

Abstract. We describe the case of a 23-year old woman with a newly diagnosed thrombosis of the inferior vena cava associated with a Brucella melitensis infection. We suggest possible mechanisms leading to brucellosis-associated venous thrombosis and review 14 previously reported cases.

BackgroundHIV-infected individuals have an increased risk of avascular bone necrosis (AVN). Antiretroviral therapy (ART) and particularly protease inhibitors (PI) have been implicated as a risk factor. We aimed to study the associations of ART with the occurrence of AVN among Swiss HIV Cohort Study participants (SHCS).MethodsWe used incidence density sampling to perform a case control study within the Swiss HIV Cohort Study (SHCS) comparing prospectively collected AVN cases and controls by conditional logistic regression analysis. To evaluate the effect of ART, multivariable models were adjusted for HIV transmission risk group, age, alcohol consumption, use of corticosteroids, CD4 nadir, maximum viral load, and pancreatitis.ResultsWe compared 74 AVN cases and 145 controls. Associations with AVN were shown for heterosexual HIV acquisition (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.1–10), alcohol consumption (OR, 2.7; 95% CI, 1.3–5.7), and hyperlipidemia (OR, 3.6; 95% CI, 1.4–9.6). After adding ART substances to the multivariable base model, there was evidence of an association for treatment with tenofovir (TDF) >1 year (OR, 4.4; 95% CI, 1.4–14) with AVN. Neither exposure to specific frequently prescribed ART combinations or ART drug classes nor cumulative ART exposure showed any associations with AVN.ConclusionsIn the HIV-infected population, a combination of risk factors such as heterosexual HIV acquisition, moderate to severe alcohol intake, and hyperlipidemia seem to contribute to AVN. ART does not seem to be a relevant risk factor for AVN. The association of prolonged TDF exposure with AVN needs to be confirmed.

BACKGROUND AND STUDY AIMS Animal data and limited clinical evidence suggest a low incidence of infection following transvaginal natural orifice transluminal endoscopic surgery (NOTES). However, a systematic microbiological evaluation has not yet been carried out. The aim of this prospective cohort study was to evaluate the extent of microbiological contamination of the peritoneal cavity caused by the transvaginal access for NOTES and the impact of preoperative vaginal disinfection on vaginal colonization. PATIENTS AND METHODS Consecutive female patients with symptomatic cholecystolithiasis were offered either transvaginal rigid-hybrid cholecystectomy (tvCCE) or conventional laparoscopic cholecystectomy. Patients who opted for tvCCE were prospectively evaluated between February and June 2010. Disinfection in patients undergoing tvCCE included hexetidine tablets and octenidine applied vaginally. All patients received a single dose of perioperative cefuroxime. Swabs were obtained from the posterior fornix and the peritoneal cavity at different intervals. RESULTS Of 32 patients, 27 (84 %) opted to undergo tvCCE. One patient (4 %; 95 % confidence interval [CI] 0.7 % - 18.3 %) had a positive bacterial culture in the Douglas pouch prior to transvaginal access compared with two patients (7 %; 95 %CI 2.1 % - 23.4 %) following colpotomy closure (P = 1.000). Vaginal disinfection significantly decreased vaginal bacterial load (P = 0.001) and bacterial growth in routine cultures (P < 0.001); in 16 patients (59 %; 95 %CI 40.7 % - 75.5 %) vaginal swabs were sterile after disinfection. No postoperative surgical site infections occurred (95 %CI 0 % - 12.5 %). CONCLUSIONS In selected patients and following vaginal antisepsis, transvaginal access for NOTES is associated with microbiological contamination of the peritoneal cavity in a minority of patients, indicating a low risk of peritoneal contamination caused by the transvaginal access.

Die Einführung von Polymerase-Kettenreaktion (PCR)-basierter DNA-Amplifikation zu Beginn der 90er-Jahre hat die Diagnostik von Infektionskrankheiten revolutioniert und fundamentale Erkenntnisse über deren Epidemiologie und Klinik erlaubt. Verglichen mit der Serologie zeichnet sich die PCR-Diagnostik durch erhöhte Sensibilität und Spezifität aus und kann eine frühere Diagnose erlauben. Sie kann, je nach klinischer Situation, im Blut, anderen klinischen Untersuchungsmaterialien oder direkt ab histopathologischen Proben durchgeführt werden. Die PCR Amplifikation von Erreger-DNA wird zur Bestätigung von serologischen Suchtests und zur Diagnose von Keimen, die schwierig zu kultivieren sind, verwendet. Bei chronisch persistierenden Erregern kann sie die Unterscheidung zwischen klinisch unbedeutender und relevanter Infektion erlauben. Die quantitative Bestimmung von viraler DNA oder RNA wird routinemäßig zur Verlaufskontrolle bei der Behandlung von chronischer Hepatitis B, C, oder HIV-Infektion eingesetzt. Wichtig sind adäquate Patientenproben und für die Resultatinterpretation kann sich der Beizug eines Infektiologen lohnen. Genetische Tests werden zunehmend zur antimikrobiellen Sensibilitätstestung eingesetzt (TB, MRSA) und könnten in Zukunft zur Vorhersage der Immunantwort auf Infektionserreger und der antiretroviralen Toxizität beitragen. Vollautomatische Geräte und Multiplex-Technik werden in Zukunft die Attraktivität der PCR-Diagnostik weiter steigern und deren Kosten senken.

AA-amyloidosis in the setting of chronic visceral leishmaniasis (VL) has been reported in animal models but documentation in humans is unavailable. Here, we report on a Portuguese man who in 1996 was diagnosed with both human immunodeficiency virus (HIV)-infection and VL. Antiretroviral treatment led to sustained suppression of HIV viremia but CD4+ lymphocytes rose from 8 to only 160 cells/mL. Several courses of antimony treatment did not prevent VL relapses. Renal failure developed in 2006 and renal biopsy revealed AA-amyloidosis. The patient had cryoglobulinemia and serum immune complexes containing antibodies directed against seven leishmanial antigens. Antimony plus amphotericin B, followed by oral miltefosine resulted in a sustained VL treatment response with elimination of circulating Leishmania infantum DNA and CD4+ recovery. The concomitant reduction of serum AA levels and disappearance of circulating leishmanial immune complexes suggests that prolonged VL may lead to AA-amyloidosis in immunocompromised humans.

BACKGROUND: Atherosclerosis has been assessed in human immunodeficiency virus (HIV)-infected persons by using various methods. Peripheral arterial disease (PAD) has not been evaluated, however. We studied the cross-sectional prevalence of lower limb PAD in an HIV-infected population. METHODS: PAD was assessed using the Edinburgh Claudication Questionnaire and by measuring the systolic ankle-brachial blood pressure index (ABI) at rest and after exercise. Patients with PAD were further evaluated by duplex scan of lower limb arteries. RESULTS: Ninety-two consecutive HIV-infected patients were evaluated (23.9% women; mean age, 49.5 years; 61.9% current smokers). Claudication was reported by 15.2% of the patients. PAD was found in 20.7% of the patients: 9.8% had an abnormal ABI (25% decrease after exercise. Of the patients with PAD, 84.2% were investigated with duplex scan, all of whom had atherosclerotic occlusions or stenoses of the iliac or femoral arteries. Age, diabetes, smoking, and low CD4+ T lymphocyte counts were identified as independent predictors of PAD. CONCLUSIONS: The prevalence of symptomatic and asymptomatic PAD is high in the HIV-infected population and is much higher than expected (prevalence in the general population, approximately 3% at 60 years). This study suggests the presence of an epidemic of PAD approximately 20 years earlier in the HIV-infected than in the general population. Larger epidemiological studies are needed to better define risk factors and to evaluate whether PAD is associated with increased mortality, as it is in the general population.

Purpose of review To summarize current knowledge and provide perspective on relationships between human genetic variants, antiretroviral medications, and aging-related complications of HIV-1 infection. Recent findings Human genetic variants have been convincingly associated with interindividual variability in antiretroviral toxicities, drug disposition, and aging-associated complications in HIV-1 infection. Screening for HLA-B5701 to avoid abacavir hypersensitivity reactions has become a routine part of clinical care, and has markedly improved drug safety. There are well established pharmacogenetic associations with other agents (efavirenz, nevirapine, atazanavir, dolutegravir, and others), but this knowledge has yet to have substantial impact on HIV-1 clinical care. As metabolic complications including diabetes mellitus, dyslipidemia, osteoporosis, and cardiovascular disease are becoming an increasing concern among individuals who are aging with well controlled HIV-1 infection, human genetic variants that predispose to these complications also become more relevant in this population. Summary Pharmacogenetic knowledge has already had considerable impact on antiretroviral prescribing. With continued advances in the field of human genomics, the impact of pharmacogenomics on HIV-1 clinical care and research is likely to continue to grow in importance and scope.

Vaccine adjuvants are expected to play an important role in enhancing the immunogenicity of existing and new-generation vaccines against infectious diseases. In particular, adjuvants should direct the immune response in the most appropriate manner--furthering, for example, an expanded B-cell response, a cytotoxic T-cell response, or a T-helper 1 or 2 subset response. While some noncytokine adjuvants have exerted potent effects, their modes of action are most likely mediated by cytokines. Several cytokines have already been shown to be efficient adjuvants in animal models and/or in clinical trials. The mechanisms of cytokine function must be better understood and the techniques for the use of cytokines improved if the full potential of these substances as vaccine adjuvants is to be realized. When used to best advantage, such adjuvants enhance the immunity induced by viral, bacterial, and parasitic vaccines and thereby promote efficient protection or even cure.

BACKGROUND/AIMS: Alveolar echinococcosis (AE) is a serious liver disease. The aim of this study was to explore the long-term prognosis of AE patients, the burden of this disease in Switzerland and the cost-effectiveness of treatment. METHODS: Relative survival analysis was undertaken using a national database with 329 patient records. 155 representative cases had sufficient details regarding treatment costs and patient outcome to estimate the financial implications and treatment costs of AE. RESULTS: For an average 54-year-old patient diagnosed with AE in 1970 the life expectancy was estimated to be reduced by 18.2 and 21.3 years for men and women, respectively. By 2005 this was reduced to approximately 3.5 and 2.6 years, respectively. Patients undergoing radical surgery had a better outcome, whereas the older patients had a poorer prognosis than the younger patients. Costs amount to approximately Euro108,762 per patient. Assuming the improved life expectancy of AE patients is due to modern treatment the cost per disability-adjusted life years (DALY) saved is approximately Euro6,032. CONCLUSIONS: Current treatments have substantially improved the prognosis of AE patients compared to the 1970s. The cost per DALY saved is low compared to the average national annual income. Hence, AE treatment is highly cost-effective in Switzerland.

To the Editor: Increased risk for reactivation of tuberculosis (TB) after treatment with tumor necrosis factor (TNF) antagonists, particularly infliximab, is well documented (1). We describe a case of peritoneal TB, probably resulting from reactivation of Mycobacterium bovis infection after infliximab treatment. In retrospect, reactivation might have been preventable had physicians been aware of the patient’s history of regularly drinking fresh cow’s milk from a local farm in Switzerland during 1944–45, when bovine TB was prevalent. The patient was a 69-year-old Swiss woman who was examined for weakness, abdominal pain, increasing abdominal girth, and weight loss in April 2008. Her history included a diagnosis of Crohn disease in 1978 and treatment with glucocorticoids, cyclosporine, and mercaptopurine. In November 2007, during a recurrence of Crohn disease and while receiving treatment with azathioprine, the patient had a negative interferon gamma release assay (IGRA) result (QuantiFERON-TB in Tube test; Cellestis International, Carnegie, Victoria, Australia) and an unremarkable chest radiograph. On November 30, 2007, she was given prednisone (40 mg/d for 2 weeks, then tapered) and prescribed 3 doses of infliximab because of severe inflammation seen during colonoscopy (5 mg/kg on November 30, 2007, January 4, 2008, and February 15, 2008). She was hospitalized on April 25, 2008, at which time she had ascites; the fluid contained 1.4 × 109/L leukocytes (79.5% lymphocytes) but was negative for acid-fast bacilli on direct examination and PCR testing for Mycobacterium tuberculosis complex. Laparoscopy on May 2, 2008, showed extensive peritoneal inflammation. Peritoneal biopsy samples contained acid-fast bacilli and caseating granulomas; PCR for M. tuberculosis complex was positive. At this time, results of a repeat QuantiFERON-TB in Tube test and a tuberculin skin test (TST) were negative, but a T-SPOT.TB (Oxford Immunotec, Abingdon, UK) test was positive (6-kDa early secretory antigenic target [ESAT-6], >20 spots; 10-kDa culture filtrate protein [CFP-10], 11 spots). M. bovis ssp. bovis was grown in cultures of peritoneal biopsy samples. For culture, the MGIT 960 automated culture system (Becton Dickinson, Sparks, MD, USA) was used. The isolate was identified by use of a multiplex PCR-based, solid-phase, reverse-hybridization assay (GenoType MTBC, Hain Lifescience GmbH, Nehren, Germany), excluding M. bovis BCG (2). The patient was discharged May 30, 2008. In January 2009, she was much improved after treatment with isoniazid/rifampin/ethambutol for 3 months and moxifloxacin/rifampin for 5 months. This case of presumed reactivation of peritoneal TB caused by M. bovis in a patient treated with infliximab highlights the need to be aware of local epidemiology with regard to transmissible infectious diseases. It particularly emphasizes the value of careful history taking regarding consumption of unpasteurized dairy products in assessing risk for latent TB infection (LTBI) before starting anti-TNF treatment. Some infectious diseases experts (3) recommend considering LTBI treatment before prescribing anti-TNF therapy even when TST is negative or only minimally positive (