Trends in mortality in people with HIV from 1999 to 2020: a multi-cohort collaboration.

BACKGROUND: Mortality among people with HIV declined with the introduction of combination antiretroviral therapy. We investigated trends over time in all-cause and cause-specific mortality in people with HIV from 1999-2020. METHODS: Data were collected from the D:A:D cohort from 1999 through January 2015 and RESPOND from October 2017 through 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV (CoDe), were calculated. Poisson regression models were used to assess mortality trends over time. RESULTS: Among 55716 participants followed for a median of 6 years (IQR 3-11), 5263 participants died (crude mortality rate [MR] 13.7/1000 PYFU; 95%CI 13.4-14.1). Changing patterns of mortality were observed with AIDS as the most common cause of death between 1999- 2009 (n = 952, MR 4.2/1000 PYFU; 95%CI 4.0-4.5) and non-AIDS defining malignancy (NADM) from 2010 -2020 (n = 444, MR 2.8/1000 PYFU; 95%CI 2.5-3.1). In multivariable analysis, all-cause mortality declined over time (adjusted mortality rate ratio [aMRR] 0.97 per year; 95%CI 0.96, 0.98), mostly from 1999 through 2010 (aMRR 0.96 per year; 95%CI 0.95-0.97), and with no decline shown from 2011 through 2020 (aMRR 1·00 per year; 95%CI 0·96-1·05). Mortality due all known causes except NADM also declined over the entire follow-up period. CONCLUSION: Mortality among people with HIV in the D:A:D and/or RESPOND cohorts decreased between 1999 and 2009 and was stable over the period from 2010 through 2020. The decline in mortality rates was not fully explained by improvements in immunologic-virologic status or other risk factors.

Immune response to the recombinant herpes zoster vaccine in people living with HIV over 50 years of age compared to non-HIV age-/gender-matched controls (SHINGR'HIV): a multicenter, international, non-randomized clinical trial study protocol.

BACKGROUND: The burden of herpes zoster (shingles) virus and associated complications, such as post-herpetic neuralgia, is higher in older adults and has a significant impact on quality of life. The incidence of herpes zoster and post-herpetic neuralgia is increased in people living with HIV (PLWH) compared to an age-matched general population, including PLWH on long-term antiretroviral therapy (ART) with no detectable viremia and normal CD4 counts. PLWH - even on effective ART may- exhibit sustained immune dysfunction, as well as defects in cells involved in the response to vaccines. In the context of herpes zoster, it is therefore important to assess the immune response to varicella zoster virus vaccination in older PLWH and to determine whether it significantly differs to that of HIV-uninfected healthy adults or younger PLWH. We aim at bridging these knowledge gaps by conducting a multicentric, international, non-randomised clinical study (SHINGR'HIV) with prospective data collection after vaccination with an adjuvant recombinant zoster vaccine (RZV) in two distinct populations: in PLWH on long-term ART (> 10 years) over 50 years of and age/gender matched controls. METHODS: We will recruit participants from two large established HIV cohorts in Switzerland and in France in addition to age-/gender-matched HIV-uninfected controls. Participants will receive two doses of RZV two months apart. In depth-evaluation of the humoral, cellular, and innate immune responses and safety profile of the RZV will be performed to address the combined effect of aging and potential immune deficiencies due to chronic HIV infection. The primary study outcome will compare the geometric mean titer (GMT) of gE-specific total IgG measured 1 month after the second dose of RZV between different age groups of PLWH and between PLWH and age-/gender-matched HIV-uninfected controls. DISCUSSION: The SHINGR'HIV trial will provide robust data on the immunogenicity and safety profile of RZV in older PLWH to support vaccination guidelines in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05575830. Registered on 12 October 2022. Eu Clinical Trial Register (EUCT number 2023-504482-23-00).

Presence and Persistence of Andes Virus RNA in Human Semen.

When infecting humans, Andes orthohantavirus (ANDV) may cause a severe disease called hantavirus cardiopulmonary syndrome (HCPS). Following non-specific symptoms, the infection may progress to a syndrome of hemorrhagic fever combined with hyper-acute cardiopulmonary failure. The case fatality rate ranges between 25-40%, depending on the outbreak. In this study, we present the follow-up of a male patient who recovered from HCPS six years ago. We demonstrate that the ANDV genome persists within the reproductive tract for at least 71 months. Genome sequence analysis early and late after infection reveals a low number of mutations (two single nucleotide variants and one deletion), suggesting limited replication activity. We can exclude the integration of the viral genome into the host genome, since the treatment of the specimen with RNAse led to a loss of signal. We demonstrate a long-lasting, strong neutralizing antibody response using pseudovirions expressing the ANDV glycoprotein. Taken together, our results show that ANDV has the potential for sexual transmission.

[HealthyTravel.ch - The reference website for traveler's health advice]. / HealthyTravel.ch ­ Le site internet de référence pour les conseils de santé aux voyageurs.

The Swiss Expert Committee on Travel Medicine (ECTM) - a body of the Swiss Society of Tropical Medicine and Travel Medicine (FMH) - publishes recommendations and information on travel medicine on the website www.healthytravel.ch in four languages (German, French, Italian, English). HealthyTravel.ch, which has replaced Safetravel.ch, is the reference website for travelers' health advice in Switzerland supported by the Federal Office of Public Health (FOPH). It consists of a free version with basic travel medicine recommendations for the public, and a fee-based PRO version for professionals, containing more detailed information and recommendations. This article provides an overview of the available content and tips on how to make the best use of www.healthytravel.ch.

Le Comité suisse d'experts en médecine des voyages (CFMV), un organe de la Société suisse de médecine tropicale et de médecine des voyages (FMH), publie sur le site internet www.healthytravel.ch des recommandations et des informations sur la médecine des voyages en quatre langues (allemand, français, italien et anglais). HealthyTravel.ch, qui a remplacé le site Safetravel.ch, est le site internet de référence pour les conseils de santé aux voyageurs soutenu par l'Office fédéral de la santé publique (OFSP). Il est composé d'une version gratuite, avec des recommandations de base en matière de médecine des voyages pour le public, et d'une version PRO, payante, pour les professionnels, contenant des informations et des recommandations plus détaillées. Cet article donne un aperçu des contenus disponibles et des conseils d'utilisation optimale du site www.healthytravel.ch.

Ongoing toxin-positive diphtheria outbreaks in a federal asylum centre in Switzerland, analysis July to September 2022.

Two diphtheria outbreaks occurred in a Swiss asylum center from July to October 2022, one is still ongoing. Outbreaks mainly involved minors and included six symptomatic respiratory diphtheria cases requiring antitoxin. Phylogenomic analyses showed evidence of imported and local transmissions of toxigenic strains in respiratory and skin lesion samples. Given the number of cases (n = 20) and the large genetic diversity accumulating in one centre, increased awareness and changes in public health measures are required to prevent and control diphtheria outbreaks.

Humoral Responses to Repetitive Doses of COVID-19 mRNA Vaccines in Patients with CAR-T-Cell Therapy.

Background: Due to B-cell aplasia following CAR-T-cell therapy, patients are at risk of severe SARS-CoV-2 course. Methods: COVID-19 vaccines were assessed by IgG antibody tests against SARS-CoV-2 spike protein (anti-S1/S2). Vaccination procedures: group (1): CAR-T-cells followed by two to four vaccine doses; group (2): Two vaccine doses prior to CAR-T-cells, followed by doses 3 or 4. Results: In group 1 (n = 32), 7/30 patients (23.2%) had positive antibody tests after a second dose, 9/23 (39.1%) after a third dose, and 3/3 patients after a fourth dose. A third dose led to seroconversion in 5 of 21 patients (23.8%) with available data, while a fourth dose did so in 2/3 patients. Higher B-cells (AUC: 96.2%, CI: 89-100, p = 0.0006) and lower CAR-T-cell copies (AUC: 77.3%, CI: 57-97, p = 0.0438) were predictive of positive humoral vaccine response. In group 2 (n = 14), 6/14 patients (42.9%) had a positive antibody test after a second dose, 3/8 patients (37.5%) after a third dose, and 3/4 patients after a fourth dose. A third dose led to seroconversion in 1/8 patients (12.5%), while a fourth dose did so in 3/4 patients. Conclusion: Additional vaccine doses increased seroconversion rates whilst high B-cell counts and low CAR-T-cell copy numbers were associated with positive antibody response.

Humoral response to mRNA vaccines against SARS-CoV-2 in patients with humoral immunodeficiency disease.

OBJECTIVES: Although mRNA-based vaccines against SARS-CoV-2 induce a robust immune response and prevent infections and hospitalizations, there are limited data on the antibody response in individuals with humoral immunodeficiency. The aim of this study was to evaluate the humoral immune response after two vaccine doses with BNT162b2 or mRNA-1273 in patients with humoral immunodeficiency disease. METHODS: This cross-sectional study assessed 39 individuals with hypogammaglobulinemia under immunoglobulin replacement therapy. IgG anti-SARS-CoV-2 spike protein antibodies (anti-S) were measured 4 weeks to 4 months after two doses of an mRNA vaccine against SARS-CoV-2. The proportion of patients, who developed a humoral immune response to the spike protein were evaluated and compared to 19 healthy controls. RESULTS: After vaccination with two vaccine doses, 26/39 patients (66.7%) with humoral immunodeficiency disease and all healthy controls developed anti-S. In subjects with baseline IgG <3 g/l, only 1/5 (20%) showed a humoral immune response. 10 out of 26 with CVID (38.5%) and 7/9 under immunosuppressive drugs (77.8%) developed no immune response (13 subjects with no response) compared to 0/19 in healthy controls. Subgroup analysis in patients without immunosuppressive drugs revealed lower anti-S in patients with moderate to severe humoral immunodeficiency disease: baseline IgG <3 g/l: 12.0 AU/ml (95%CI 12.0-125.0), baseline IgG 3-5 g/l: 99.9 AU/ml (95%CI 14.4-400.0), baseline IgG >5 g/l: 151.5 AU/ml (95%CI 109.0-400.0), healthy controls 250.0 AU/ml (95%CI 209.0-358.0), p = 0.007. CONCLUSION: In most patients with mild to moderate humoral immunodeficiency we found only slightly lower anti-S antibodies compared with healthy controls after two vaccine doses with BNT162b2 and mRNA-1273. However, in patients with a decreased baseline IgG below 3 g/l and/or under immunosuppressive drugs, we found severely impaired humoral immune responses.

Trajectories of humoral and cellular immunity and responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy.

BACKGROUND: The majority of patients with B-cell-depleting therapies show compromised vaccination-induced immune responses. Herein, we report on the trajectories of anti-SARS-CoV-2 immune responses in patients of the RituxiVac study compared with healthy volunteers and investigate the immunogenicity of a third vaccination in previously humoral non-responding patients. METHODS: We investigated the humoral and cell-mediated immune response after SARS-CoV-2 messanger RNA vaccination in patients with a history with anti-CD20 therapies. Coprimary outcomes were antispike and SARS-CoV-2-stimulated interferon-γ concentrations in vaccine responders 4.3 months (median; IQR: 3.6-4.8 months) after first evaluation, and humoral and cell-mediated immunity (CMI) after a third vaccine dose in previous humoral non-responders. Immunity decay rates were compared using analysis of covariance in linear regression. RESULTS: 5.6 months (IQR: 5.1-6.7) after the second vaccination, we detected antispike IgG in 88% (29/33) and CMI in 44% (14/32) of patients with a humoral response after two-dose vaccination compared with 92% (24/26) healthy volunteers with antispike IgG and 69% (11/16) with CMI 6.8 months after the second vaccination (IQR: 6.0-7.1). Decay rates of antibody concentrations were comparable between patients and controls (p=0.70). In two-dose non-responders, a third SARS-CoV-2 vaccine elicited humoral responses in 19% (6/32) and CMI in 32% (10/31) participants. CONCLUSION: This study reveals comparable immunity decay rates between patients with anti-CD20 treatments and healthy volunteers, but inefficient humoral or CMI after a third SARS-CoV-2 vaccine in most two-dose humoral non-responders calling for individually tailored vaccination strategies in this population.Trial registration numberNCT04877496; ClinicalTrials.gov number.

Rate of treatment success and associated factors in the program for drug-susceptible tuberculosis in the Forest Region, Republic of Guinea, 2010-2017: A real-world retrospective observational cohort study.

OBJECTIVES: To analyze the treatment success rate (TSR = sum of cured or treatment completed) in the tuberculosis (TB) program for drug-susceptible TB (DS-TB) at the "Centre Hospitalier Régional Spécialisé" in Macenta, Forest Region, Republic of Guinea. METHODS: This cohort study included patients who started treatment for DS-TB between 2010 and 2017. Data collection was part of the documentation for the national TB program. Descriptive analysis was applied to determine the TSR in various patient groups. Further, logistic regression was performed to determine factors influencing the TSR in new and relapsed cases versus all other previously treated cases. A subgroup analysis for only microbiologically confirmed pulmonary TB was added. RESULTS: The study included 3969 patients. The TSR increased from 68.3% in 2010 to 80.8% in 2017 (p < 0.001). Mortality (11.2%) mainly occurred in early treatment months, while loss to follow-up (5.9%) increased towards later treatment months. Risk factors for low TSR were advanced age, positive HIV status, long travel distances (>100 km) to the clinic, and late treatment refill. CONCLUSION: The TSR in the Forest Region of Guinea remained below the WHO goal of 90%. Reaching this target remains a challenge in rural areas with high early mortality and increased risk of loss to follow-up.

Impact of rosuvastatin on atherosclerosis in people with HIV at moderate cardiovascular risk: a randomised, controlled trial.

BACKGROUND: People living with HIV-1 (PLHIV) are at increased risk for cardiovascular disease. OBJECTIVE: This study aimed to determine if PLHIV would benefit from starting statins at a lower threshold than currently recommended in the general population. DESIGN: A double-blind multicentre, randomised, placebo-controlled trial was performed. METHODS: Participants (n = 88) with well controlled HIV, at moderate cardiovascular risk (Framingham score of 10-15%), and not recommended for statins were recruited from Australia and Switzerland. They were randomized 1 : 1 to rosuvastatin (n = 44) 20 mg daily, 10 mg if co-administered with ritonavir/cobicistat-boosted antiretroviral therapy, or placebo (n = 40) for 96 weeks. Assessments including fasting blood collection and carotid--intima media thickness (CIMT) were performed at baseline, and weeks 48 and 96. The primary outcome was the change from baseline to week 96 in CIMT (clinicaltrials.gov: NCT01813357). RESULTS: Participants were predominantly men [82 (97.6%); mean age 54 years (SD 6.0)]. At 96 weeks, there was no difference in the progression of CIMT between the rosuvastatin (mean 0.004 mm, SE 0.0036) and placebo (0.0062 mm, SE 0.0039) arms (P = 0.684), leading to no difference in CIMT levels between groups at week 96 [rosuvastatin arm, 0.7232 mm (SE 0.030); placebo arm 0.7785 mm (SE 0.032), P = 0.075].Adverse events were common (n = 146) and predominantly in the rosuvastatin arm [108 (73.9%)]. Participants on rosuvastatin were more likely to cease study medication because of an adverse event [7 (15.9%) vs. 2 (5.0%), P = 0.011]. CONCLUSION: In PLHIV, statins prescribed at a lower threshold than guidelines did not lead to improvements in CIMT but was associated with significant adverse events.

Safety and immunogenicity of a primary yellow fever vaccination under low-dose methotrexate therapy-a prospective multi-centre pilot study1.

BACKGROUND: More people on immunosuppression live in or wish to travel to yellow fever virus (YFV)-endemic areas. Data on the safety and immunogenicity of yellow fever vaccination (YFVV) during immunosuppression are scarce. The aim of this study was to compare the safety and immunogenicity of a primary YFVV between travellers on methotrexate and controls. METHODS: We conducted a prospective multi-centre controlled observational study from 2015 to 2017 in six Swiss travel clinics. 15 adults (nine with rheumatic diseases, five with dermatologic conditions and one with a gastroenterological disease) on low-dose methotrexate (≤20 mg/week) requiring a primary YFVV and 15 age and sex-matched controls received a YFVV. Solicited/unsolicited adverse reactions were recorded, YFV-RNA was measured in serum samples on Days 3, 7, 10, 14, 28 and neutralizing antibodies on Days 0, 7, 10, 14, 28. RESULTS: Patients´ and controls' median ages were 53 and 52 years; 9 patients and 10 controls were female. 43% of patients and 33% of controls showed local side effects (P = 0.71); 86% of patients and 66% of controls reported systemic reactions (P = 0.39). YFV-RNA was detected in patients and controls on Day 3-10 post-vaccination and was never of clinical significance. Slightly more patients developed YFV-RNAaemia (Day 3: n = 5 vs n = 2, Day 7: n = 9 vs n = 7, Day 10: n = 3 vs n = 2, all P > 0.39). No serious reactions occurred. On Day 10, a minority of vaccinees was seroprotected (patients: n = 2, controls: n = 6). On Day 28, all vaccinees were seroprotected. CONCLUSIONS: First-time YFVV was safe and immunogenic in travellers on low-dose methotrexate. Larger studies are needed to confirm these promising results.

Seroprotection rates of vaccine-preventable diseases among newly arrived Eritrean asylum seekers in Switzerland: a cross-sectional study.

BACKGROUND: According to 2016 World Health Organization and United Nations Children's Fund country estimates, Eritrea has overall high vaccination coverage with immunization rates for three doses of diphtheria/tetanus/pertussis and polio vaccine of 95%, for two doses measles vaccine of 85% and for three doses hepatitis B vaccine of 85%. If confirmed, this could imply that routine basic vaccination of newly arrived Eritreans could be safely omitted. METHODS: We used stored serum samples from two cross-sectional studies that screened newly arrived Eritrean refugees for infectious diseases. Consenting refugees aged 16 years and older who registered in one of three neighbouring cantons in northwestern Switzerland were enrolled between January 2016 and December 2017. Antibody titers against the following vaccine-preventable diseases were measured (applied thresholds for seroprotection in brackets): diphtheria (>0.1 IU/ml), tetanus (>0.1 IU/ml), measles (>150 mIU/ml), rubella (only for women, >11 IU/ml), varicella (>50 mIU/ml), hepatitis B [hepatitis B surface antigen (HBsAg) Index >0.9, Hepatitis B core antibody (anti-HBc) Index >0.9 and antibodies to HBsAg (anti-HBs) >10 IE/L]. Differences between sex and age groups (≤25 and >25 years) were measured by Fisher's exact test. RESULTS: We analysed samples of 133 study participants (20 women, 15%) with a median age of 25 years (range 16-61). Rates of seropositivity were as follows for women/men, respectively: diphtheria 57.9%/74.8% (difference non-significant), tetanus 94.8%/41.1% (P < 0.001), measles 73.7%/76.6% (non-significant), rubella in women 78.9%, varicella 89.5%/95.3% (non-significant), anti-HBc 15.8%/26.2% (non-significant) and anti-HBs 15.8%/17.8% (non-significant). CONCLUSION: Seroprevalence for vaccine-preventable infections did not meet levels required to confer herd immunity in any of the human-to-human transmissible diseases that were studied. In general, the strategy proposed by the Federal Office of Public Health to offer basic immunization to all newly arrived refugees, including newly arriving Eritrean refugees, is justified.

Cost Estimates for Human Immunodeficiency Virus (HIV) Care and Patient Characteristics for Health Resource Use From Linkage of Claims Data With the Swiss HIV Cohort Study.

BACKGROUND: Comprehensive and representative data on resource use are critical for health policy decision making but often lacking for human immunodeficiency virus (HIV) infection. Privacy-preserving probabilistic record linkage of claim and cohort study data may overcome these limitations. METHODS: Encrypted dates of birth, sex, study center, and antiretroviral therapy (ART) from the Swiss HIV Cohort Study (SHCS) records for 2012 and 2013 were linked by privacy-preserving probabilistic record linkage with claim data from the largest health insurer covering 15% of the Swiss residential population. We modeled predictors for mean annual costs adjusting for censoring and grouped patients by cluster analysis into 3 risk groups for resource use. RESULTS: The matched subsample of 1196 patients from 9326 SHCS and 2355 claim records was representative for all SHCS patients receiving ART. The corrected mean (standard error) total costs in 2012 and 2013 were $30462 ($582) and $30965 ($629) and mainly accrued in ambulatory care for ART (70% of mean costs). The low-risk group for resource use had mean (standard error) annual costs of $26772 ($536) and $26132 ($589) in 2012 and 2013. In the moderate- and high-risk groups, annual costs for 2012 and 2013 were higher by $3526 (95% confidence interval, $1907-$5144) (13%) and $4327 ($2662-$5992) (17%) and $14026 ($8763-$19289) (52%) and $13567 ($8844-$18288) (52%), respectively. CONCLUSIONS: In a representative subsample of patients from linkage of SHCS and claim data, ART was the major cost factor, but patient profiling enabled identification of factors related to higher resource use.

Lipodystrophy Increases the Risk of CKD Development in HIV-Positive Patients in Switzerland: The LIPOKID Study.

INTRODUCTION: Antiretroviral therapy has improved the life expectancy of patients living with HIV. However, lipodystrophy syndrome (LD) remains prevalent, affecting mostly patients treated with first-generation antiretroviral drugs. This syndrome is characterized by changes in body fat distribution with or without associated metabolic changes. Here, we studied whether clinically evaluated LD is independently associated with chronic kidney disease (CKD) development (sustained estimated glomerular filtration rate [eGFR] < 60 ml/min per 1.73 m2) in HIV-positive patients. METHODS: We conducted a prospective cohort study (the LIPOKID Study) among all the patients from the Swiss HIV Cohort Study (SHCS) with an eGFR >60 ml/min per 1.73 m2 upon their entry into the cohort with more than 3 months of follow-up from January 2002 to August 2016. Cox regression models were used to estimate the association between LD and CKD development. RESULTS: Among the 5384 patients included, 1341 (24.9%) developed LD during the follow-up. The mean follow-up time was 72.3 months (SD ±48.4). In total, 252 patients (4.7%) reached the primary endpoint after a median time of 51.3 months (±SD 39.9 months) from inclusion. A diagnosis of LD significantly increased the risk of an eGFR on univariate analysis (hazard ratio [HR] = 2.72; 95% confidence interval [95% CI] = 2.07-3.58; P < 0.001) and remained significantly higher after adjustment for known HIV and non-HIV risk factors for CKD (HR = 2.37; 95% CI = 1.67-3.36; P < 0.001). The effect of LD on CKD was not mediated through the use of nephrotoxic antiretroviral drugs. CONCLUSION: Lipodystrophy syndrome is independently associated with CKD after adjustment for previously reported risk factors.

Population-based outcome analysis of diffuse large B-cell lymphoma in people living with HIV infection and competent individuals.

The prognostic factors and outcome of 58 acquired immunodeficiency syndrome-related diffuse large B-cell lymphoma (AR-DLBCL) patients from the Swiss HIV Cohort Study, diagnosed from 2004 to 2011, were compared with those of 326 immunocompetent (IC)-DLBCL from the Hematology Division of the Amedeo Avogadro University (Italy) and the Oncology Institute of Southern Switzerland. Median follow-up was 6 years; 5-year overall survival (OS) was 68% (95% CI: 63%-73%) in IC-DLBCL and 63% (95% CI: 49%-75%) in AR-DLBCL (P = .220). The acquired immunodeficiency syndrome-related lymphoma international prognostic index predicted OS in AR-DLBCL. Among 148 patients younger than 61 years (40 AR-DLBCL and 108 IC-DLBCL) treated with RCHOP/RCHOP-like regimens, 20 IC-DLBCL and 9 AR-DLBCL patients died and OS was not significantly different. A higher proportion of early deaths occurred in the AR-DLBCL: indeed, 1-year OS was 94% (95% CI: 87%-97%) in IC-DLBCL and 82% (95% CI: 66%-91%) in AR-DLBCL patients. After rituximab and active antiretroviral therapy introduction, AR-DLBCL and IC-DLBCL patients treated with curative intent have similar long-term survival.

Hantavirus Cardiopulmonary Syndrome Due to Imported Andes Hantavirus Infection in Switzerland: A Multidisciplinary Challenge, Two Cases and a Literature Review.

Two travellers returning from South America were diagnosed with Andes hantavirus infection, the only member of the Hantaviridae family known to be transmitted from person to person. We describe the clinical course and therapeutic and infection control measures. While both patients showed high viral load (VL) and shedding over several months, 1 patient recovered within 1 week from severe respiratory illness that required noninvasive ventilation, whereas the second patient developed severe hantavirus cardiopulmonary syndrome that required extracorporeal membrane oxygenation for 27 days. The clinical course in the latter patient was complicated by severe disseminated intravascular coagulopathy with diffuse hemorrhage that necessitated mass transfusions, as well as by multiple organ failure, including the need for renal replacement therapy. Results of VL in blood, respiratory secretions, and semen for the first 9 months of follow-up are reported. To our knowledge, these are the first cases of Andes hantavirus infection detected in Europe.

Is breastfeeding an equipoise option in effectively treated HIV-infected mothers in a high-income setting?

Combined antiretroviral treatment (cART) has reduced mother-to-child transmission (MTCT) of the human immunodeficiency virus (HIV) to virtually zero in industrialised countries, where strictly bottle feeding is recommended for HIV-infected mothers, and to as low as 0.7% after 12 months in low-resource settings, where breastfeeding is strongly encouraged. Given the theoretically very low risk of transmission by breastfeeding with cART, and the advantages and benefits of breastfeeding, also in industrialised countries, the strong recommendation to HIV-infected mothers to refrain from breastfeeding in this setting may no longer be justified. We have evaluated risks of breastfeeding for HIV MTCT in the light of accessible cART, the general benefits of breastfeeding, and the women's autonomy to consent to any intervention. As we found no evidence in the literature of HIV MTCT via breastfeeding whilst on effective cART, we identified a situation of clinical equipoise. We propose how to proceed in Switzerland when HIV-infected women consider breastfeeding. We advocate a shared decision-making process and suggest a list of topics on which to provide unbiased information for the HIV-infected mother to enable her comprehensive understanding of one or the other decision. Although breastfeeding still should not be actively recommended in Switzerland, any HIV-infected mother, regardless of her geographical and cultural background, who decides to breastfeed should be supported by the best strategy to achieve optimal medical care for both herself and her child. This includes continuous support of cART adherence and regular maternal HIV plasma viral load monitoring.

Dietary Patterns and Physical Activity Correlate With Total Cholesterol Independently of Lipid-Lowering Drugs and Antiretroviral Therapy in Aging People Living With Human Immunodeficiency Virus.

BACKGROUND: Hypercholesterolemia is a well established risk factor for coronary heart disease and is highly prevalent among human immunodeficiency virus (HIV)-positive persons. Antiretroviral therapy (ART) can both directly modify total cholesterol and have drug-drug interactions with statins. This makes investigating modifiable behavioral predictors of total cholesterol a pertinent task. METHODS: To explore the association between diet and physical activity with cross-sectionally measured total cholesterol, we administered a validated Food-Frequency-Questionnaire to participants of the Swiss HIV Cohort Study ≥45 years old. Linear mixed-effects models were applied to explore the associations between dietary patterns and physical activity with total cholesterol, after adjustment for clinical and demographic covariates. RESULTS: In total, 395 patients were included. Forty percent (158 of 395) had elevated total cholesterol (>5.2 mmol/L), and 41% (164 of 395) were not regularly physically active. In multivariable analysis, 2 factors were positively associated with total cholesterol; female sex (ß = 0.562; 95% confidence interval [CI], 0.229-0.896) and the combined consumption of meat, refined/milled grains, carbonated beverages, and coffee (ß = 0.243; 95% CI, 0.047-0.439). On the other hand, regular physical activity (ß = -0.381; 95% CI, -0.626 to -0.136), lipid-lowering drugs (ß = -0.443; 95% CI -0.691 to -0.196), ART containing tenofovir (ß = -0.336; 95% CI -0.554 to -0.118), and black ethnicity (ß = -0.967; 95% CI -1.524 to -0.410) exhibited a negative association. CONCLUSIONS: We found independent associations between certain dietary patterns and physical activity with total cholesterol. Increasing physical activity might achieve cardiovascular and other health benefits in HIV-positive individuals. The clinical relevance of the identified dietary patterns requires further investigation in prospective cohort studies and randomized controlled trials.

Long-term Immune Response to Yellow Fever Vaccination in Human Immunodeficiency Virus (HIV)-Infected Individuals Depends on HIV RNA Suppression Status: Implications for Vaccination Schedule.

Background: In human immunodeficiency virus (HIV)-infected individuals, the immune response over time to yellow fever vaccination (YFV) and the necessity for booster vaccination are not well understood. Methods: We studied 247 participants of the Swiss HIV Cohort Study (SHCS) with a first YFV after HIV diagnosis and determined their immune responses at 1 year, 5 years, and 10 years postvaccination by yellow fever plaque reduction neutralization titers (PRNTs) in stored blood samples. A PRNT of 1:≥10 was regarded as reactive and protective. Predictors of vaccination response were analyzed with Poisson regression. Results: At vaccination, 82% of the vaccinees were taking combination antiretroviral therapy (cART), 83% had suppressed HIV RNA levels (<400 copies/mL), and their median CD4 T-cell count was 536 cells/µL. PRNT was reactive in 46% (95% confidence interval [CI], 38%-53%) before, 95% (95% CI, 91%-98%) within 1 year, 86% (95% CI, 79%-92%) at 5 years, and 75% (95% CI, 62%-85%) at 10 years postvaccination. In those with suppressed plasma HIV RNA at YFV, the proportion with reactive PRNTs remained high: 99% (95% CI, 95%-99.8%) within 1 year, 99% (95% CI, 92%-100%) at 5 years, and 100% (95% CI, 86%-100%) at 10 years. Conclusions: HIV-infected patients' long-term immune response up to 10 years to YFV is primarily dependent on the control of HIV replication at the time of vaccination. For those on successful cART, immune response up to 10 years is comparable to that of non-HIV-infected adults. We recommend a single YFV booster after 10 years for patients vaccinated on successful cART, whereas those vaccinated with uncontrolled HIV RNA may need an early booster.

Associations Between Antiretroviral Treatment and Avascular Bone Necrosis: The Swiss HIV Cohort Study.

BACKGROUND: HIV-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). METHODS: We 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. RESULTS: We 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. CONCLUSIONS: In 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.