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Background Despite effective prevention approaches, ongoing human immunodeficiency virus 1 (HIV-1) transmission remains a public health concern indicating a need for identifying its drivers. Methods We combined a network-based clustering method using evolutionary distances between viral sequences with statistical learning approaches to investigate the dynamics of HIV transmission in the Swiss HIV Cohort Study and to predict the drivers of ongoing transmission. Results We found that only a minority of clusters and patients acquired links to new infections between 2007 and 2020. While the growth of clusters and the probability of individual patients acquiring new links in the transmission network was associated with epidemiological, behavioral, and virological predictors, the strength of these associations decreased substantially when adjusting for network characteristics. Thus, these network characteristics can capture major heterogeneities beyond classical epidemiological parameters. When modeling the probability of a newly diagnosed patient being linked with future infections, we found that the best predictive performance (median area under the curve receiver operating characteristic AUCROC = 0.77) was achieved by models including characteristics of the network as predictors and that models excluding them performed substantially worse (median AUCROC = 0.54). Conclusions These results highlight the utility of molecular epidemiology-based network approaches for analyzing and predicting ongoing HIV transmission dynamics. This approach may serve for real-time prospective assessment of HIV transmission.

SummaryBackgroundThe widespread use of the integrase strand transfer inhibitor (INSTI) dolutegravir (DTG) in first- and second-line antiretroviral therapy (ART) may facilitate emerging resistance. We combined data from HIV cohorts to examine patterns of drug resistance mutations (DRMs) and identify risk factors for DTG resistance.MethodsEight cohorts from Canada, Europe, and South Africa contributed data on individuals with genotypic resistance testing on DTG-based ART. Resistance levels were categorised using the Stanford algorithm. We identified risk factors for resistance using mixed-effects ordinal logistic regression models.ResultsWe included 750 people with genotypic resistance testing on DTG-based ART between 2013 and 2022. Most had HIV subtype B (N=444, 59·2%) and were treatment-experienced; 134 (17.9%) were on DTG dual and 19 (2.5%) on DTG monotherapy. INSTI DRMs were detected in 100 (13·3%) individuals; 21 (2·8%) had more than one mutation. Most (N=713, 95·1%) were susceptible to DTG, 8 (1·1%) had potential-low, 5 (0·7%) low, 18 (2·4%) intermediate and 6 (0·8%) high-level DTG resistance. The risk of DTG resistance was higher on DTG monotherapy (adjusted odds ratio (aOR) 37·25, 95% CI 11·17 to 124·2) and DTG lamivudine dual therapy (aOR 6·59, 95% CI 1·70 to 25·55) compared to combination ART, and higher in the presence of potential-low/low (aOR 4.62, 95% CI 1.24 to 17.2) or intermediate/high-level (aOR 7·01, 95% CI 2·52 to 19·48) nucleoside reverse transcriptase inhibitors (NRTI) resistance. Viral load on DTG showed a trend towards increased DTG resistance (aOR 1·42, 95% CI 0·92 to 2·19 per standard deviation of log10area under the viral load curve).InterpretationAmong people experiencing virological failure on DTG-based ART, INSTI DRMs were uncommon, and DTG resistance was rare. DTG monotherapy and NRTI resistance substantially increased the risk for DTG resistance, which is of concern, notably in resource-limited settings.FundingUS National Institutes of Health, Swiss National Science Foundation.Research in contextEvidence before this studyWe searched SCOPUS on 20 March 2023 for all publications from inception using the terms “dolutegravir” or “DTG”, “resistant” or “resistance”, and “HIV”. The available evidence on resistance evolution in people living with HIV (PLHIV) with virological failure on DTG-based ART is limited. Most studies assessed the efficacy of DTG-based regimens in clinical studies and reported drug resistance in individuals experiencing virological failure as a secondary objective or reported single or multiple cases of patients developing resistance on DTG-based ART. Clinical trials such as the NADIA trial showed a high degree of viral suppression even in people with NRTI resistance. Consequently, previous analyses included only a small number of people experiencing failure on DTG; the SINGLE trial with 39 people with virologic failure on DTG was the largest. The highest number of individuals with DTG resistance was nine study participants in the NADIA trial. There is evidence that DTG resistance in PLHIV on a DTG monotherapy may be more likely. Other studies suggest that HIV subtype and mutations acquired during a first-generation INSTI-based regimen might affect the risk of DTG resistance.Added value of this studyTo our knowledge, this is the first study systematically investigating resistance in PLHIV experiencing virologic failure on DTG-based ART using a multi-cohort collaboration design reflecting real-world routine care. We collected genotypic resistance tests and clinical data from eight observational HIV cohorts. This resulted in a large dataset of PLHIV experiencing virologic failure on a DTG regimen (over 700 individuals). It allowed a robust assessment of drug resistance mutations and risk factors for DTG resistance. Cross-resistance of first-generation INSTIs does not appear to explain the mutation patterns in HIV-infected individuals who experience virological failure on DTG-based ART regimens. PLHIV who received DTG monotherapy or DTG lamivudine dual therapy and those infected with non-B subtypes were more likely to develop resistance. Resistance to NRTIs was a major risk factor for DTG resistance, indicating that PLHIV receiving functional monotherapy are more likely to develop DTG resistance.Implications of all the available evidenceHIV drug resistance is a significant threat to the sustainability of current and future antiretroviral therapy for combating the ongoing HIV pandemic. Our collaborative analysis shows that cases of DTG resistance are so far rare but not negligible. Given the global DTG roll-out, this might lead to increased frequencies and transmission of DTG resistance, particularly in PLHIV with resistance to NRTIs. While the evidence regarding subtype differences is tentative, it indicates that non-B subtypes, which are most relevant for the global roll-out of DTG, might be associated with an increased risk of resistance.

Background Studying human immunodeficiency virus type 1 (HIV-1) superinfection is important to understand virus transmission, disease progression, and vaccine design. But detection remains challenging, with low sampling frequencies and insufficient longitudinal samples. Methods Using the Swiss HIV Cohort Study (SHCS), we developed a molecular epidemiology screening for superinfections. A phylogeny built from 22 243 HIV-1 partial polymerase sequences was used to identify potential superinfections among 4575 SHCS participants with longitudinal sequences. A subset of potential superinfections was tested by near-full-length viral genome sequencing (NFVGS) of biobanked plasma samples. Results Based on phylogenetic and distance criteria, 325 potential HIV-1 superinfections were identified and categorized by their likelihood of being detected as superinfections due to sample misidentification. NFVGS was performed for 128 potential superinfections; of these, 52 were confirmed by NFVGS, 15 were not confirmed, and for 61 sampling did not allow confirming or rejecting superinfection because the sequenced samples did not include the relevant time points causing the superinfection signal in the original screen. Thus, NFVGS could support 52 of 67 adequately sampled potential superinfections. Conclusions This cohort-based molecular approach identified, to our knowledge, the largest population of confirmed superinfections, showing that, while rare with a prevalence of 1%–7%, superinfections are not negligible events.

SHCS#879 is an ongoing Switzerland-wide multicenter observational study conducted within the Swiss HIV Cohort Study (SHCS) for the prospective follow-up of people living with HIV (PLWH) receiving long-acting injectable cabotegravir-rilpivirine (LAI-CAB/RPV). All adults under LAI-CAB/RPV and part of SHCS are enrolled in the project. The study addresses an integrated strategy of treatment monitoring outside the stringent frame of controlled clinical trials, based on relevant patient characteristics, clinical factors, potential drug-drug interactions, and measurement of circulating blood concentrations. So far, 91 blood samples from 46 PLWH have been collected. Most individuals are less than 50 years old, with relatively few comorbidities and comedications. The observed concentrations are globally in accordance with the available values reported in the randomized clinical trials. Yet, low RPV concentrations not exceeding twice the reported protein-adjusted 90% inhibitory concentration have been observed. Data available at present confirm a considerable between-patient variability overall. Based on the growing amount of PK data accumulated during this ongoing study, population pharmacokinetic analysis will characterize individual concentration-time profiles of LAI-CAB/RPV along with their variability in a real-life setting and their association with treatment response and tolerability, thus bringing key data for therapeutic monitoring and precision dosage adjustment of this novel long-acting therapy.

BACKGROUND The rapid course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic calls for fast implementation of clinical trials to assess the effects of new treatment and prophylactic interventions. Building trial platforms embedded in existing data infrastructures is an ideal way to address such questions within well-defined subpopulations. METHODS We developed a trial platform building on the infrastructure of two established national cohort studies: the Swiss human immunodeficiency virus (HIV) Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS). In a pilot trial, termed Corona VaccinE tRiAL pLatform (COVERALL), we assessed the vaccine efficacy of the first two licensed SARS-CoV-2 vaccines in Switzerland and the functionality of the trial platform. RESULTS Using Research Electronic Data Capture (REDCap), we developed a trial platform integrating the infrastructure of the SHCS and STCS. An algorithm identifying eligible patients, as well as baseline data transfer ensured a fast inclusion procedure for eligible patients. We implemented convenient re-directions between the different data entry systems to ensure intuitive data entry for the participating study personnel. The trial platform, including a randomization algorithm ensuring balance among different subgroups, was continuously adapted to changing guidelines concerning vaccination policies. We were able to randomize and vaccinate the first trial participant the same day we received ethics approval. Time to enroll and randomize our target sample size of 380 patients was 22 days. CONCLUSION Taking the best of each system, we were able to flag eligible patients, transfer patient information automatically, randomize and enroll the patients in an easy workflow, decreasing the administrative burden usually associated with a trial of this size.

We hypothesize that patterns of sexual behavior play a role in the conformation of transmission networks, i.e., the way you behave might influence whom you have sex with. If that was the case, behavioral grouping might in turn correlate with, and potentially predict transmission networking, e.g., proximity in a viral phylogeny. We rigorously present an intuitive approach to address this hypothesis by quantifying mapped interactions between groups defined by similarities in sexual behavior along a virus phylogeny while discussing power and sample size considerations. Data from the Swiss HIV Cohort Study on condom use and hepatitis C virus (HCV) sequences served as proof-of-concept. In this case, a strict inclusion criteria contrasting with low HCV prevalence hindered our possibilities to identify significant relationships. This manuscript serves as guide for studies aimed at characterizing interactions between behavioral patterns and transmission networks. Large transmission networks such as those of HIV or COVID-19 are prime candidates for applying this methodological approach.

Background Hospital acquired pneumonia (HAP) is divided in two distinct groups, ventilator-associated pneumonia (VAP) and non-ventilator-associated HAP (nvHAP). Although nvHAP occurs more frequently than VAP and results in similar mortality and costs, prevention guidelines and prevention focus almost exclusively on VAP. Scientific evidence about nvHAP prevention and its implementation is scarce. Therefore, we designed a mixed-methods hybrid type 2 effectiveness-implementation study to investigate both the effectiveness and implementation of a newly developed nvHAP prevention bundle. Methods This single-centre project at the 950-bed University Hospital Zurich (UHZ) will engage the wards of nine departments with substantial nvHAP rates. The nvHAP bundle consists of five primary prevention measures: 1) oral care, 2) prevention of dysphagia-related aspiration, 3) mobilization, 4) stopping unnecessary proton pump inhibitors, and, 5) respiratory therapy. Implementation includes the engagement of department-level implementation teams, who sustain the ‘core’ intervention components of education, training, and environmental restructuring and tailor the implementation strategy to local needs. Both effectiveness and implementation outcomes will be assessed using mixed-methods. As a primary outcome, nvHAP incidence rates will be analysed by Poisson regression models to compare incidence rates before, during, and after the implementation phases (on the hospital and department level). Additionally, the association between process indicators and nvHAP incidence rates will be analysed using longitudinal Poisson regression models. A longitudinal, qualitative study and formative evaluation based on interviews, focus groups, and observations identifies supporting or hindering factors for implementation success in participating departments dynamically over time. This accumulating implementation experience will be constantly fed back to the implementation teams and thus, represents an active implementation element. Discussion This comprehensive hybrid mixed-methods study is designed to both, measure the effectiveness of a new nvHAP prevention bundle and multifaceted implementation strategy, while also providing insights into how and why it worked or failed. The results of this study may contribute substantially to advancing knowledge and patient safety in the area of a rediscovered healthcare-associated infection - nvHAP. Trial registration ClinicalTrials.gov: NCT03361085. Registered December 2017.

Background Identifying local outbreaks and their drivers is a key step toward curbing human immunodeficiency virus (HIV) transmission and potentially achieving HIV elimination. Such outbreaks can be identified as transmission clusters extracted from phylogenetic trees constructed of densely sampled viral sequences. In this study, we combined phylogenetic transmission clusters with extensive data on virological suppression and behavioral risk of cluster members to quantify the drivers of ongoing transmission over 10 years. Methods Using the comprehensive Swiss HIV Cohort Study and its drug-resistance database, we reconstructed phylogenetic trees for each year between 2007 and 2017. We identified HIV transmission clusters dominated by men who have sex with men (MSM) and determined their annual growth. We used Poisson regression to assess if cluster growth was associated with a per-cluster infectivity and behavioral risk score. Results Both infectivity and behavioral risk scores were significantly higher in growing MSM transmission clusters compared to nongrowing clusters (P ≤ .01). The fraction of transmission clusters without infectious members acquiring new infections increased significantly over the study period. The infectivity score was significantly associated with per-capita incidence of MSM transmission clusters in 8 years, while the behavioral risk score was significantly associated with per-capita incidence of MSM transmission clusters in 3 years. Conclusions We present a phylogenetic method to identify hotspots of ongoing transmission among MSM. Our results demonstrate the effectiveness of treatment as prevention at the population level. However, the significantly increasing number of new infections among transmission clusters without infectious members highlights a relative shift from diagnosed to undiagnosed individuals as drivers of HIV transmission in Swiss MSM.

UNSTRUCTURED Multi-cohort projects in medicine provide an opportunity to investigate scientific questions beyond the boundaries of a single institution, and to increase sample size for more reliable results. However, the complications of these kinds of collaborations arise during management, with many administrative hurdles. Hands-on approaches and lessons learned from previous collaborations provide solutions for optimized collaboration models. Here, we use our experience in running the Swiss multi-cohort project PGX-link to show the strategy we used to tackle different challenges from project set up to getting the relevant permits, including ethic approval. We put PGX-link into an international context, since our struggles were to some extent similar to those encountered during the SYNCHROS project. We provide ad-hoc solutions for each cohort, general project management strategies, and suggestions for unified protocols between cohorts that would ease current management hurdles. Project managers are not necessarily familiar with medical projects, and even if they are, they are not aware of the intricacies behind decision making, and consequently of the time needed to set up multi-cohort collaborations. This paper is meant to be a brief overview of what we went through with our multi-cohort project and provides the necessary practices for future managers.

Background HIV-1 replication capacity (RC) of transmitted/founder viruses may influence the further course of HIV-1 infection. Methods RCs of 355 whole-genome primary HIV-1 isolates derived from samples acquired during acute and recent primary HIV-1 infection (PHI) were determined using a novel high-throughput infection assay in primary cells. The RCs were used to elucidate potential factors that could be associated with RC during PHI. Results Increased RC was found to be associated with increased set point viral load (VL), and significant differences in RCs among 13 different HIV-1 subtypes were discerned. Notably, we observed an increase in RCs for primary HIV-1 isolates of HIV-1 subtype B over a 17-year period. Associations were not observed between RC and CD4 count at sample date of RC measurement, CD4 recovery after initiation of antiretroviral treatment, CD4 decline in untreated individuals, and acute retroviral syndrome severity scores. Conclusions These findings highlight that RCs of primary HIV-1 isolates acquired during the acute and recent phase of infection are more associated with viral factors, that is set point VL, than with host factors. Furthermore, we observed a temporal increase in RC for HIV-1 subtype B viruses over a period of 17 years. Clinical Trials Registration NCT00537966.

We identified determinants of SARS-CoV-2 mRNA vaccine antibody response in people with HIV (PWH). Antibody response was higher among PWH less than 60 years, with CD4+ cell count superior to 350 cells/μl and vaccinated with mRNA-1273 by Moderna compared with BNT162b2 by Pfizer-BioNTech. Preinfection with SARS-CoV-2 boosted the antibody response and smokers had an overall lower antibody response. Elderly PWH and those with low CD4+ cell count should be prioritized for booster vaccinations.

Background Limited data exist examining the association between incident cancer and cumulative integrase inhibitor (INSTI) exposure. Methods Participants were followed from baseline (latest of local cohort enrollment or January 1, 2012) until the earliest of first cancer, final follow-up, or December 31, 2019. Negative binomial regression was used to assess associations between cancer incidence and time-updated cumulative INSTI exposure, lagged by 6 months. Results Of 29 340 individuals, 74% were male, 24% were antiretroviral treatment (ART)-naive, and median baseline age was 44 years (interquartile range [IQR], 36–51). Overall, 13 950 (48%) individuals started an INSTI during follow-up. During 160 657 person-years of follow-up ([PYFU] median 6.2; IQR, 3.9–7.5), there were 1078 cancers (incidence rate [IR] 6.7/1000 PYFU; 95% confidence interval [CI], 6.3–7.1). The commonest cancers were non-Hodgkin lymphoma (n = 113), lung cancer (112), Kaposi’s sarcoma (106), and anal cancer (103). After adjusting for potential confounders, there was no association between cancer risk and INSTI exposure (≤6 months vs no exposure IR ratio: 1.15 [95% CI, 0.89–1.49], >6–12 months; 0.97 [95% CI, 0.71–1.32], >12–24 months; 0.84 [95% CI, 0.64–1.11], >24–36 months; 1.10 [95% CI, 0.82–1.47], >36 months; 0.90 [95% CI, 0.65–1.26] [P = .60]). In ART-naive participants, cancer incidence decreased with increasing INSTI exposure, mainly driven by a decreasing incidence of acquired immune deficiency syndrome cancers; however, there was no association between INSTI exposure and cancer for those ART-experienced (interaction P Conclusions Cancer incidence in each INSTI exposure group was similar, despite relatively wide CIs, providing reassuring early findings that increasing INSTI exposure is unlikely to be associated with an increased cancer risk, although longer follow-up is needed to confirm this finding.

Background The Swiss HCVree Trial (NCT 02785666) was conducted in 2015–2017 with the goal of implementing a population-based systematic hepatitis C virus (HCV) micro-elimination program among men who have sex with men (MSM) with human immunodeficiency virus (HIV) enrolled in the Swiss HIV Cohort Study (SHCS). The trial led to a 91% and 77% decline of HCV prevalence and incidence, respectively. The long-term effect of this HCV micro-elimination program is yet to be explored. Methods All MSM enrolled in the SHCS were screened for HCV RNA using stored plasma samples obtained in 2019, termed “Swiss HCVree Post” screen. The incidence of HCV infection over time was assessed using additional information on HCV testing routinely collected in the SHCS. Characteristics of participants with replicating HCV infection were analyzed. Results The point-prevalence of “Swiss HCVree Post” (N = 4641) was 0.6%, reflecting a decline of 48% compared to the end of the Swiss HCVree Trial where the prevalence was 1.2%. Further, the incidence of HCV among MSM in the SHCS declined from 0.31/100 person-years (py) (95% confidence interval [CI] [.17, .55]) in 2017 to 0.19/100 py (95% CI [.09, .39]) in 2019. Conclusions A systematic HCV RNA-based screening among MSM with HIV conducted 2 years after the Swiss HCVree Trial revealed a sustained effect and further decline of the prevalence and incidence of replicating HCV infection. This indicates that the Swiss HCVree Trial was successful in curbing the HCV epidemic among MSM with HIV in Switzerland. Clinical Trials Registration NCT02785666.

Background BNT162b2 by Pfizer-BioNTech and mRNA-1273 by Moderna are the most commonly used vaccines to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Head-to-head comparison of the efficacy of these vaccines in immunocompromised patients is lacking. Methods Parallel, 2-arm (allocation 1:1), open-label, noninferiority randomized clinical trial nested into the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study. People living with human immunodeficiency virus (PLWH) or solid organ transplant recipients (SOTR; ie, lung and kidney) from these cohorts were randomized to mRNA-1273 or BNT162b2. The primary endpoint was antibody response to SARS-CoV-2 spike (S1) protein receptor binding domain (Elecsys Anti-SARS-CoV-2 immunoassay, Roche; cutoff ≥0.8 units/mL) 12 weeks after first vaccination (ie, 8 weeks after second vaccination). In addition, antibody response was measured with the Antibody Coronavirus Assay 2 (ABCORA 2). Results A total of 430 patients were randomized and 412 were included in the intention-to-treat analysis (341 PLWH and 71 SOTR). The percentage of patients showing an immune response was 92.1% (95% confidence interval [CI]: 88.4–95.8; 186/202) for mRNA-1273 and 94.3% (95% CI: 91.2–97.4; 198/210) for BNT162b2 (difference: -2.2%; 95% CI: -7.1 to 2.7), fulfilling noninferiority of mRNA-1273. With the ABCORA 2 test, 89.1% had an immune response to mRNA-1273 (95% CI: 84.8–93.4; 180/202) and 89.5% to BNT162b2 (95% CI: 85.4–93.7; 188/210). Based on the Elecsys test, all PLWH had an antibody response (100.0%; 341/341), whereas for SOTR, only 60.6% (95% CI: 49.2–71.9; 43/71) had titers above the cutoff level. Conclusions In immunocompromised patients, the antibody response of mRNA-1273 was noninferior to BNT162b2. PLWH had in general an antibody response, whereas a high proportion of SOTR had no antibody response.

While an increased risk of active and latent tuberculosis infection (LTBI) in people with type-2 diabetes (DM) has been demonstrated, it is less well characterized whether LTBI is associated with an increased risk of developing DM. We investigated the link between LTBI and DM in people living with HIV in the Swiss HIV Cohort Study via time-dependent Cox proportional hazards models. We found that LTBI significantly increased the risk of developing DM (HR = 1.47), which was robust across different adjustment and censoring techniques. Our results thus suggest that LTBI may be associated with an increased risk of developing DM.

We hypothesize that patterns of sexual behaviour play a role in the conformation of transmission networks. If that was the case, behavioural grouping might in turn correlate with transmission networks and have the potential to predict proximity in viral phylogenies. To address this hypothesis, we present an intuitive approach for quantifying interactions between clusters of sexual behaviour along a virus phylogeny. Data from the Swiss HIV Cohort Study on condom use and incident Hepatitis C virus (HCV) sequences served as proof-of-concept. A strict inclusion criteria contrasting with relatively low HCV prevalence hindered our ability to identify significant relationships. This manuscript intends to serve as guide for studies aimed at characterizing interactions between behavioural patterns and transmission networks. Large transmission networks such as those of HIV or COVID-19 are prime candidates for applying this methodological approach.

We investigated healthcare worker (HCW) behavior with regard to a voluntary methicillin-resistant Staphylococcus aureus (MRSA) staff screening during a MRSA outbreak in a neonatal ward. Avoiding MRSA transmission from HCWs to patients was the most important reason for participation. Inconvenient screening time was the most frequently cited reason for nonparticipation.

Background Cutibacterium species are common pathogens in periprosthetic joint infections (PJI). These infections are often treated with β-lactams or clindamycin as monotherapy, or in combination with rifampin. Clinical evidence supporting the value of adding rifampin for treatment of Cutibacterium PJI is lacking. Methods In this multicenter retrospective study, we evaluated patients with Cutibacterium PJI and a minimal follow-up of 12 months. The primary endpoint was clinical success, defined by the absence of infection relapse or new infection. We used Fisher’s exact tests and Cox proportional hazards models to analyze the effect of rifampin and other factors on clinical success after PJI. Results We included 187 patients (72.2% male, median age 67 years) with a median follow-up of 36 months. The surgical intervention was a 2-stage exchange in 95 (50.8%), 1-stage exchange in 51 (27.3%), debridement and implant retention (DAIR) in 34 (18.2%), and explantation without reimplantation in 7 (3.7%) patients. Rifampin was included in the antibiotic regimen in 81 (43.3%) cases. Infection relapse occurred in 28 (15.0%), and new infection in 13 (7.0%) cases. In the time-to-event analysis, DAIR (adjusted hazard ratio [HR] = 2.15, P = .03) and antibiotic treatment over 6 weeks (adjusted HR = 0.29, P = .0002) significantly influenced treatment failure. We observed a tentative evidence for a beneficial effect of adding rifampin to the antibiotic treatment—though not statistically significant for treatment failure (adjusted HR = 0.5, P = .07) and not for relapses (adjusted HR = 0.5, P = .10). Conclusions We conclude that a rifampin combination is not markedly superior in Cutibacterium PJI, but a dedicated prospective multicenter study is needed.

BACKGROUND HIV's capacity to escape immune recognition by Human Leukocyte Antigen (HLA) is a core component of HIV pathogenesis. A better understanding of the distribution of HLA Class I in HIV-infected patients would improve our knowledge of pathogenesis in relation to host HLA type, and could better improve therapeutic strategies against HIV. MATERIALS AND METHODS 301-325 transmission pairs and 469-496 clusters were identified for analysis among Swiss HIV Cohort Study (SHCS) participants using HIV pol sequences from the drug resistance database. HLA Class I data was compiled at three specificity levels: four-digit, two-digit alleles, and HLA-B supertype. The analysis tabulated HLA-I homogeneity as two measures: the proportion of transmission pairs which are HLA-concordant as well as the average percentage of allele matches within all clusters. These measures were compared to the mean value across randomizations with randomly assorted individuals. RESULTS We repeated the analysis for different HLA classification levels and separately for HLA-A, -B, and -C. Subanalyses by risk group were performed for HLA-B. HLA-B showed significantly greater homogeneity in the transmission chains (2-digit clusters: 0.291 vs.0.251, p-value=0.009; supertype clusters: 0.659 vs. 0.611, p-value=0.002; supertype pairs: 0.655 vs. 0.608, p-value=0.014). Risk group restriction caused the effect to disappear for men-who-have-sex-with-men (MSM) but not other risk groups. We also examined if protective HLA alleles B27 and B57 were under- or overrepresented in the transmission chains, though this yielded no significant pattern. CONCLUSIONS The HLA-B alleles of patients within HIV-1 transmission chains segregate in homogenous clusters/pairs, potentially indicating preferential transmission among HLA-B concordant individuals.

BackgroundOver the last decade, syphilis diagnoses among men-who-have-sex-with-men (MSM) have strongly increased in Europe. Understanding the drivers of the ongoing epidemic may aid to curb transmissions.Methods and FindingsWe set up an epidemiological model to assess the drivers of syphilis in MSM in Switzerland between 2006 and 2017. We stratified the model by syphilis stage, HIV-diagnosis, and behavioral factors to account for syphilis infectiousness and risk for transmission. In the main model, we used ‘reported non-steady partners’ (nsP) as the main proxy for sexual risk. We parameterized the model using data from the Swiss HIV Cohort Study, Swiss Voluntary Counselling and Testing center, cross-sectional surveys among the Swiss MSM population, and published syphilis notifications from the Federal Office of Public Health.The main model reproduced the increase in syphilis diagnoses from 168 cases in 2006 to 418 cases in 2017. It estimated that between 2006 and 2017, MSM with HIV diagnosis had 45.9 times the median syphilis incidence of MSM without HIV diagnosis. Defining risk as condomless anal intercourse with nsP decreased model accuracy (sum of squared weighted residuals, 378.8 vs 148.3). Counterfactual scenarios suggested that increasing screening of MSM without HIV diagnosis and with nsP from once every two-years to twice per year may reduce syphilis incidence (at most 12.8% reduction by 2017). Whereas, increasing screening among MSM with HIV diagnosis and with nsP from once per year to twice per year may substantially reduce syphilis incidence over time (at least 63.5% reduction by 2017).ConclusionsThe model suggests that reporting nsP regardless of condom use is suitable for risk stratification when modelling syphilis transmission. More frequent screening of MSM with HIV diagnosis, particularly those with nsP may aid to curb syphilis transmission.

We investigated healthcare worker (HCW) behavior with regard to a voluntary methicillin-resistant Staphylococcus aureus (MRSA) staff screening during a MRSA outbreak in a neonatal ward. Avoiding MRSA transmission from HCWs to patients was the most important reason for participation. Inconvenient screening time was the most frequently cited reason for nonparticipation.

BACKGROUND Separately addressing specific groups of people who share patterns of behavioural change might increase the impact of behavioural interventions to prevent transmission of sexually transmitted infections. We propose a method based on machine learning to assist the identification of such groups among men who have sex with men (MSM). METHODS By means of unsupervised learning, we inferred "behavioural clusters" based on the recognition of similarities and differences in longitudinal patterns of condomless anal intercourse with non-steady partners (nsCAI) in the Swiss HIV cohort study over the last 18 years. We then used supervised learning to investigate whether sociodemographic variables could predict cluster membership. RESULTS We identified four behavioural clusters. The largest behavioural cluster (Cluster 1) contained 53% of the study population and displayed the most stable behaviour. Cluster 3 (17% of the study population) displayed consistently increasing nsCAI. Sociodemographic variables were predictive for both of these clusters. The other two clusters displayed more drastic changes: nsCAI frequency in Cluster 2 (20% of the study population) was initially similar to that in Cluster 3, but accelerated in 2010. Cluster 4 (10% of the study population) had significantly lower estimates of nsCAI than all other clusters until 2017, when it increased drastically, reaching 85% by the end of the study period. CONCLUSIONS We identified highly dissimilar behavioural patterns across behavioural clusters, including drastic, atypical changes. These patterns suggest that the overall increase in the frequency of nsCAI is largely attributable to two clusters, accounting for a third of the population.

We study Poncelet's Theorem in finite projective planes over the field GF(q), q = pm for p an odd prime and m > 0, for a particular pencil of conics. We investigate whether we can find polygons with n sides which are inscribed in one conic and circumscribed around the other, so-called Poncelet Polygons. By using suitable elements of the dihedral group for these pairs, we prove that the length n of such Poncelet Polygons is independent of the starting point. In this sense Poncelet's Theorem is valid. By using Euler's divisor sum formula for the totient function, we can make a statement about the number of different conic pairs, which carry Poncelet Polygons of length n. Moreover, we will introduce polynomials whose zeros in GF(q) yield information about the relation of a given pair of conics. In particular, we can decide for a given integer n, whether and how we can find Poncelet Polygonsfor pairs of conics in the plane PG(2,q)., International Electronic Journal of Geometry, 13 (1), ISSN:1307-5624

Background People living with HIV who were diagnosed before highly active antiretroviral therapy became available in 1996 and who survived at least 15 years after HIV diagnosis, termed long-term survivors (LTS), form a particularly vulnerable population. We study social, clinical and mental factors of LTS in the Swiss HIV Cohort Study, with a particular focus on people who inject drugs (PWID). Methods We quantified differences between PWID LTS, and men who have sex with men (MSM) and heterosexual (HET) LTS. Using phylogenetic methods, we distinguished between heterosexual LTS who most likely shared a social network with PWID at the time of infection, termed clusteredHET, and those who did not, termed HET not clustered (HETnc). The analysis was performed using data collected at least 15 years post diagnosis. Results Overall, 1,663 of 5,686 (29.2%) PWID were LTS. We found significant differences between PWID LTS and MSM/HETnc LTS regarding self-reported depression (59.4% versus 43.3%; odds ratio [OR]=1.8; PConclusions Even more than 15 years post HIV diagnosis, special care for HIV-positive PWID is needed, with emphasis on mental health and social integration of PWID LTS.