Population-Based Severe Acute Respiratory Syndrome Coronavirus 2 Whole-Genome Sequencing and Contact Tracing During the Coronavirus Disease 2019 Pandemic in Switzerland.

BACKGROUND: Testing and contact tracing (CT) can interrupt transmission chains of SARS-CoV-2. Whole-genome sequencing (WGS) can potentially strengthen these investigations and provide insights on transmission. METHODS: We included all laboratory-confirmed COVID-19 cases diagnosed between 4 June and 26 July 2021, in a Swiss canton. We defined CT clusters based on epidemiological links reported in the CT data and genomic clusters as sequences with no single-nucleotide polymorphism (SNP) differences between any 2 pairs of sequences being compared. We assessed the agreement between CT clusters and genomic clusters. RESULTS: Of 359 COVID-19 cases, 213 were sequenced. Overall, agreement between CT and genomic clusters was low (Cohen's κ = 0.13). Of 24 CT clusters with ≥2 sequenced samples, 9 (37.5%) were also linked based on genomic sequencing but in 4 of these, WGS found additional cases in other CT clusters. Household was most often reported source of infection (n = 101 [28.1%]) and home addresses coincided well with CT clusters: In 44 of 54 CT clusters containing ≥2 cases (81.5%), all cases in the cluster had the same reported home address. However, only a quarter of household transmission was confirmed by WGS (6 of 26 genomic clusters [23.1%]). A sensitivity analysis using ≤1-SNP differences to define genomic clusters resulted in similar results. CONCLUSIONS: WGS data supplemented epidemiological CT data, supported the detection of potential additional clusters missed by CT, and identified misclassified transmissions and sources of infection. Household transmission was overestimated by CT.

Alpha Variant Coronavirus Outbreak in a Nursing Home Despite High Vaccination Coverage: Molecular, Epidemiological, and Immunological Studies.

BACKGROUND: Vaccination may control the coronavirus disease 2019 (COVID-19) pandemic, including in nursing homes where many high-risk people live. We conducted extensive outbreak investigations. METHODS: We studied an outbreak at a nursing home in Switzerland, where the uptake of messenger RNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was 82% among residents as of 21 January 2021. After diagnosis of COVID-19 in a vaccinated symptomatic healthcare worker (HCW) on 22 February, we performed outbreak investigations in house A (47 residents; 37 HCWs), using SARS-CoV-2-specific polymerase chain reaction testing of nasopharyngeal swab samples. We performed whole-genome sequencing of SARS-CoV-2 and serological analyses. RESULTS: We identified 17 individuals with positive polymerase chain reaction results, 10 residents (5 vaccinated) and 7 HCWs (3 vaccinated). The median age (interquartile range) was 86 (70-90) years among residents and 49 (29-59) years among HCWs. Of the 5 vaccinated residents, 3 had mild disease and 2 had no symptoms, whereas all 5 unvaccinated residents had mild to severe disease, and 2 died. Vaccine effectiveness for the prevention of infection among residents was 73.0% (95% confidence interval, 24.7%-90.1%). The 12 available genomes were all alpha variants. Neutralizing titers were significantly higher in vaccinated individuals on reexposure (>1 week after diagnosis) than in vaccinated, unexposed HCWs (P = .01). Transmission networks indicated 4 likely or possible transmissions from vaccinated to other individuals and 12 transmission events from unvaccinated individuals. CONCLUSIONS: COVID-19 outbreaks can occur in nursing homes, including transmission from vaccinated persons to others. Outbreaks might occur silently, underlining the need for continued testing and basic infection control measures in these high-risk settings.

Unsupervised machine learning predicts future sexual behaviour and sexually transmitted infections among HIV-positive men who have sex with men.

Machine learning is increasingly introduced into medical fields, yet there is limited evidence for its benefit over more commonly used statistical methods in epidemiological studies. We introduce an unsupervised machine learning framework for longitudinal features and evaluate it using sexual behaviour data from the last 20 years from over 3'700 participants in the Swiss HIV Cohort Study (SHCS). We use hierarchical clustering to find subgroups of men who have sex with men in the SHCS with similar sexual behaviour up to May 2017, and apply regression to test whether these clusters enhance predictions of sexual behaviour or sexually transmitted diseases (STIs) after May 2017 beyond what can be predicted with conventional parameters. We find that behavioural clusters enhance model performance according to likelihood ratio test, Akaike information criterion and area under the receiver operator characteristic curve for all outcomes studied, and according to Bayesian information criterion for five out of ten outcomes, with particularly good performance for predicting future sexual behaviour and recurrent STIs. We thus assess a methodology that can be used as an alternative means for creating exposure categories from longitudinal data in epidemiological models, and can contribute to the understanding of time-varying risk factors.

Weight and Metabolic Changes After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People Living With HIV : A Cohort Study.

BACKGROUND: Tenofovir-based antiretroviral therapy (ART) has become first-line in all major HIV treatment guidelines. Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has a favorable renal and bone safety profile, but concerns about metabolic complications remain. OBJECTIVE: To assess weight changes, the development of overweight/obesity, and changes in lipid levels 18 months after replacing TDF with TAF. DESIGN: Cohort study. SETTING: 5 university hospitals, affiliated hospitals, and private physicians in Switzerland. PARTICIPANTS: 4375 adults living with HIV who received TDF-containing ART for 6 months or longer. MEASUREMENTS: Changes in weight and lipid levels were assessed using mixed-effect models. Differences in proportions of newly overweight/obese participants were calculated using 2-proportions Z tests. RESULTS: 4375 individuals were included, with follow-up between 1 January 2016 and 31 July 2019. Median age was 50 years (interquartile range, 43 to 56 years), 25.9% were female, and 51.7% had a normal body mass index (BMI); 3484 (79.6%) switched to TAF and 891 (20.4%) continued TDF. After 18 months, switching to TAF was associated with an adjusted mean weight increase of 1.7 kg (95% CI, 1.5 to 2.0 kg), compared with 0.7 kg (CI, 0.4 to 1.0 kg) with the continued use of TDF (between-group difference, 1.1 kg [CI, 0.7 to 1.4 kg]). Among individuals with a normal BMI, 13.8% who switched to TAF became overweight/obese, compared with 8.4% of those continuing TDF (difference, 5.4 percentage points [CI, 2.1 to 8.8 percentage points]). Switching to TAF led to increases in adjusted mean total cholesterol (0.25 mmol/L [9.5 mg/dL]), high-density lipoprotein cholesterol (0.05 mmol/L [1.9 mg/dL]), low-density lipoprotein cholesterol (0.12 mmol/L [4.7 mg/dL]), and triglyceride (0.18 mmol/L [16.1 mg/dL]) levels after 18 months. LIMITATION: Short follow-up, small subgroup analyses, and potential residual confounding. CONCLUSION: Replacing TDF with TAF is associated with adverse metabolic changes, including weight increase, development of obesity, and worsening serum lipid levels. PRIMARY FUNDING SOURCE: Swiss National Science Foundation.

Association of antiviral prophylaxis and rituximab use with posttransplant lymphoproliferative disorders (PTLDs): A nationwide cohort study.

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation (SOT). Most PTLD cases are associated with Epstein-Barr virus (EBV) infection. The role of antiviral prophylaxis or rituximab therapy for prevention of PTLD in SOT recipients is controversial. In a nationwide cohort, we assessed the incidence, presentation, and outcome of histologically proven PTLD. We included 4765 patients with a follow-up duration of 23 807 person-years (py). Fifty-seven PTLD cases were identified; 39 (68%) were EBV positive (EBV+ PTLD). Incidence rates for EBV+ PTLD at 1, 2, and 3 years posttransplant were 3.51, 2.24, and 1.75/1000 py and 0.44, 0.25, and 0.29/1000 py for EBV- PTLD. We did not find an effect of antiviral prophylaxis on early and late EBV+ PTLD occurrence (early EBV+ PTLD: SHR 0.535 [95% CI 0.199-1.436], p = .264; late EBV+ PTLD: SHR 2.213, [95% CI 0.751-6.521], p = .150). However, none of the patients (0/191) who received a rituximab-containing induction treatment experienced PTLD, but 57 of 4574 patients without rituximab induction developed PTLD. In an adjusted restricted mean survival time model, PTLD-free survival was significantly longer (0.104 years [95% CI 0.077-0.131]) in patients receiving rituximab as induction treatment. This study provides novel data on the association of rituximab induction and reduced risk for PTLD.

Methods to systematically review and meta-analyse observational studies: a systematic scoping review of recommendations.

BACKGROUND: Systematic reviews and meta-analyses of observational studies are frequently performed, but no widely accepted guidance is available at present. We performed a systematic scoping review of published methodological recommendations on how to systematically review and meta-analyse observational studies. METHODS: We searched online databases and websites and contacted experts in the field to locate potentially eligible articles. We included articles that provided any type of recommendation on how to conduct systematic reviews and meta-analyses of observational studies. We extracted and summarised recommendations on pre-defined key items: protocol development, research question, search strategy, study eligibility, data extraction, dealing with different study designs, risk of bias assessment, publication bias, heterogeneity, statistical analysis. We summarised recommendations by key item, identifying areas of agreement and disagreement as well as areas where recommendations were missing or scarce. RESULTS: The searches identified 2461 articles of which 93 were eligible. Many recommendations for reviews and meta-analyses of observational studies were transferred from guidance developed for reviews and meta-analyses of RCTs. Although there was substantial agreement in some methodological areas there was also considerable disagreement on how evidence synthesis of observational studies should be conducted. Conflicting recommendations were seen on topics such as the inclusion of different study designs in systematic reviews and meta-analyses, the use of quality scales to assess the risk of bias, and the choice of model (e.g. fixed vs. random effects) for meta-analysis. CONCLUSION: There is a need for sound methodological guidance on how to conduct systematic reviews and meta-analyses of observational studies, which critically considers areas in which there are conflicting recommendations.

New-onset type 2 diabetes mellitus among patients receiving HIV care at Newlands Clinic, Harare, Zimbabwe: retrospective cohort analysis.

OBJECTIVE: To assess the incidence and associated factors of Type 2 Diabetes Mellitus (T2DM) among people living with HIV (PLHIV) in Zimbabwe. METHODS: We analysed data of all HIV-infected patients older than 16 years who attended Newlands Clinic between March 1, 2004 and April 29, 2015. The clinic considers patients whose random blood sugar is higher than 11.1 mmol/l and which is confirmed by a fasting blood sugar higher than 7.0 mmol/l to have T2DM. T2DM is also diagnosed in symptomatic patients who have a RBS >11.0 mmol/l. Risk factors for developing T2DM were identified using Cox proportional hazard models adjusted for confounding. Missing baseline BMI data were multiply imputed. Results are presented as adjusted hazard ratios (aHR) with 95% confidence intervals (95% CI). RESULTS: Data for 4,110 participants were included: 67.2% were women; median age was 37 (IQR: 31-43) years. Median baseline CD4 count was 197 (IQR: 95-337) cells/mm3 . The proportion of participants with hypertension at baseline was 15.5% (n=638). Over a median follow-up time of 4.7 (IQR: 2.1-7.2) years, 57 patients developed T2DM; the overall incidence rate was 2.8 (95% CI: 2.1-3.6) per 1000 person-years of follow-up. Exposure to PIs was associated with T2DM (HR: 1.80, 95% CI: 1.04-3.09). In the multivariable analysis, obesity (BMI>30 kg/m2 ) (aHR=2.26, 95% CI: 1.17-4.36), age >40 years (aHR=2.16, 95% CI: 1.22-3.83) and male gender, (aHR=2.13, 95% CI: 1.22-3.72) were independently associated with the risk of T2DM. HIV-related factors (baseline CD4 cell count and baseline WHO clinical stage) were not independent risk factors for developing T2DM. CONCLUSION: Although the incidence of T2DM in this HIV cohort was lower than that has been observed in others, our results show that risk factors for developing T2DM among HIV-infected people are similar to those of the general population. HIV-infected patients in sub-Saharan Africa need a comprehensive approach to care that includes better health services for prevention, early detection and treatment of chronic diseases especially among the elderly and obese.

Changes in incidence of hepatitis C virus reinfection and access to direct-acting antiviral therapies in people with HIV from six countries, 2010-19: an analysis of data from a consortium of prospective cohort studies.

BACKGROUND: Reinfection after successful treatment with direct-acting antivirals is hypothesised to undermine efforts to eliminate hepatitis C virus (HCV) infection among people with HIV. We aimed to assess changes in incidence of HCV reinfection among people with HIV following the introduction of direct-acting antivirals, and the proportion of all incident cases attributable to reinfection. METHODS: We pooled individual-level data on HCV reinfection in people with HIV after spontaneous or treatment-induced clearance of HCV from six cohorts contributing data to the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC) in Australia, Canada, France, the Netherlands, Spain, and Switzerland between Jan 1, 2010, and Dec 31, 2019. Participants were eligible if they had evidence of an HCV infection (HCV antibody or RNA positive test) followed by spontaneous clearance or treatment-induced clearance, with at least one HCV RNA test after clearance enabling measurement of reinfection. We assessed differences in first reinfection incidence between direct-acting antiviral access periods (pre-direct-acting antiviral, limited access [access restricted to people with moderate or severe liver disease and other priority groups], and broad access [access for all patients with chronic HCV]) using Poisson regression. We estimated changes in combined HCV incidence (primary and reinfection) and the relative contribution of infection type by calendar year. FINDINGS: Overall, 6144 people with HIV who were at risk of HCV reinfection (median age 49 years [IQR 42-54]; 4989 [81%] male; 2836 [46%] men who have sex with men; 2360 [38%] people who inject drugs) were followed up for 17 303 person-years and were included in this analysis. The incidence of first HCV reinfection was stable during the period before the introduction of direct-acting antivirals (pre-introduction period; 4·1 cases per 100 person-years, 95% CI 2·8-6·0). Compared with the pre-introduction period, the average incidence of reinfection was 4% lower during the period of limited access (incidence rate ratio [IRR] 0·96, 95% CI 0·78-1·19), and 28% lower during the period of broad access (0·72, 0·60-0·86). Between 2015 and 2019, the proportion of incident HCV infections due to reinfection increased, but combined incidence declined by 34%, from 1·02 cases per 100 person-years (95% CI 0·96-1·07) in 2015 to 0·67 cases per 100 person-years (95% CI 0·59-0·75) in 2019. INTERPRETATION: HCV reinfection incidence and combined incidence declined in people with HIV following direct-acting antiviral introduction, suggesting reinfection has not affected elimination efforts among people with HIV in InCHEHC countries. The proportion of incident HCV cases due to reinfection was highest during periods of broad access to direct-acting antivirals, highlighting the importance of reducing ongoing risks and continuing testing in people at risk. FUNDING: Australian National Health and Medical Research Council.

Contact tracing for COVID-19 in a Swiss canton: analysis of key performance indicators.

BACKGROUND: Contact tracing (CT) has played an important role in strategies to control COVID-19. However, there is limited evidence on the performance of digital tools for CT and no consensus on which indicators to use to monitor their performance. We aimed to describe the system and analyse outcomes of CT with a partially automated workflow in the Swiss canton of Solothurn, using key performance indicators (KPIs). METHODS: We describe the process of CT used in the canton of Solothurn between November 2020 and February 2022, including forward and backward CT. We developed 16 KPIs representing CT structure (S1-2), process (P1-11) and outcome (O1-3) based on previous literature to analyse the relative performance of CT. We report the changes in the indicators over waves of SARS-CoV-2 infections caused by several viral variants. RESULTS: The CT team in Solothurn processed 57,363 index cases and 71,809 contacts over a 15-month period. The CT team successfully contacted 99% of positive cases within 24 hours (KPI P7) throughout the pandemic and returned almost all test results on the same or next day (KPI P6), before the delta variant emerged. Three-quarters of contacts were notified within 24 hours of the CT interview with the index (KPI P8) before the emergence of the alpha, delta and omicron variants, when the proportions decreased to 64%, 36% and 54%, respectively. The percentage of new symptomatic cases tested and interviewed within 3 days of symptom onset was high at >70% (KPI P10) and contacts started quarantine within a median of 3 days of index case symptom onset (KPI P3). About a fifth of new index cases had already been in quarantine by the time of their positive test (KPI O1), before the delta variant emerged. The percentage of index cases in isolation by day of testing remained at almost 100% throughout the period of analysis (KPI O2). CONCLUSIONS: The CT in Solothurn used a partially automated workflow and continued to perform well throughout the pandemic, although the relative performance of the CT system declined at higher caseloads. CT remains an important tool for controlling the spread of infectious diseases, but clearer standards should improve the performance, comparability and monitoring of infection in real time as part of pandemic preparedness efforts.

Long-term course of neutralising antibodies against SARS-CoV-2 in vaccinated and unvaccinated staff and residents in a Swiss nursing home: a cohort study 2021-2022.

BACKGROUND: Given their high-risk resident population, nursing homes were critical institutions in the COVID-19 pandemic, calling for continued monitoring and vaccine administration to healthcare workers and residents. Here, we studied long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity in vaccinated and unvaccinated healthcare workers and residents of a nursing home in Switzerland between February 2021 and June 2022. METHODS: Our study comprised 45 participants, of which 39 were healthcare workers and six were residents. All participants were offered a maximum of three mRNA vaccine doses (Pfizer/BioNTech, BNT162b2) in December 2020, January 2021, and November/December 2021. Thirty-five participants received three vaccinations, seven either one or two, and three remained unvaccinated. We collected four blood samples: one in March 2021 and three during follow-ups in November 2021, February 2022, and June 2022. We performed a multifactorial serological SARS-CoV-2 assay (ABCORA) for immunoglobulin G, A, and M responses to spike (receptor-binding domain, S1, and S2) and nucleocapsid (N) proteins. Furthermore, we assessed predicted neutralisation activity based on signal over cutoff in ABCORA. We collected epidemiological data from participants via a standardised questionnaire. RESULTS: Thirty-two (71%) of the 45 participants showed hybrid immunity from combined vaccination and previous infection; 10 (22%) had only vaccine-induced immunity; and three (7%) had only post-infection immunity. Participants with hybrid immunity showed the highest predicted neutralisation activity at the end of the study period (median Sum S1 = 273), and unvaccinated participants showed the lowest (median Sum S1 = 41). Amongst participants who reported a SARS-CoV-2 infection, median Sum S1 levels increased with the number of vaccinations (p = 0.077). The healthcare worker group showed a significant time-dependent decrease in median Sum S1 after base immunisation (93% decrease, p = 0.0005) and the booster dose (26% decrease, p = 0.010). Predicted neutralisation activity was lower amongst residents (adjusted ratio of means [AM] = 0.7, 95% confidence interval [CI] = 0.3-1.0) and amongst smokers (AM = 0.5, 95% CI 0.3-0.8). Activity increased with the number of vaccinations (booster: AM = 3.6, 95% CI 1.5-8.8; no booster: AM = 2.3, 95% CI 0.9-2.5). Positive SARS-CoV-2 infection status tended to confer higher predicted neutralisation levels (AM = 1.5, 95% CI 0.9-2.5). CONCLUSIONS: Our study of the long-term serological course of SARS-CoV-2 in a nursing home showed that the first SARS-CoV-2 booster vaccine was essential for maintaining antiviral antibody levels. Hybrid immunity sustained SARS-CoV-2 immunity at the highest level. In critical settings such as nursing homes, monitoring the SARS-CoV-2 immune status may guide booster vaccinations.

Sexual Behaviour and STI Incidence in Sexually Active MSM Living With HIV in Times of COVID-19.

Despite decreased numbers of sexual partners, the COVID-19 pandemic had limited impact on the prevalence of attending private sex parties, traveling for sex within Switzerland, and practicing chemsex in men with HIV who have sex with men. COVID-19 risk perception was low, and STI-diagnosis incidence rates remained stable over time.

Vaccine-Preventable Infections Among Solid Organ Transplant Recipients in Switzerland.

Importance: Vaccine responses are decreased in solid organ transplant (SOT) recipients, and given the complexity of implementation, vaccination programs may be suboptimal. The actual burden of vaccine-preventable infections (VPIs) among SOT recipients remains unclear. Objectives: To assess the incidence rate of VPIs among SOT recipients and to evaluate whether SOT recipients are at increased risk for specific VPIs compared with the general population. Design, Setting, and Participants: This nationwide cohort study used data from the Swiss Transplant Cohort Study on VPIs in individuals who underwent SOT from May 2008 to June 2019 (follow-up until December 2019) and data from the Swiss Federal Office of Public Health on notifiable VPIs in the general population in the same period. Data were analyzed from January 2021 to June 2022. Exposures: Solid organ transplant. Main Outcomes and Measures: The main outcomes were the incidence rate of the following VPIs in SOT recipients: hepatitis A and B, diphtheria, Haemophilus influenzae infection, influenza, measles, mumps, pertussis, pneumococcal disease, poliomyelitis, meningococcal disease, rubella, tetanus, tick-borne encephalitis, and varicella zoster virus infection. Age-adjusted standardized incidence ratios were used to assess whether VPIs occurred more frequently in SOT recipients compared with the general population. For SOT recipients, factors associated with occurrence of VPIs were explored and the associated morbidity and mortality assessed. Results: Of 4967 SOT recipients enrolled (median age, 54 years [IQR, 42-62 years]; 3191 [64.2%] male), 593 (11.9%) experienced at least 1 VPI. The overall VPI incidence rate was higher in the population that underwent SOT (30.57 per 1000 person-years [PY]; 95% CI, 28.24-33.10 per 1000 PY) compared with the general population (0.71 per 1000 PY). The standardized age-adjusted incidence ratio for notifiable VPIs in SOT recipients was higher compared with the general population (27.84; 95% CI, 25.00-31.00). In SOT recipients, influenza and varicella zoster virus infection accounted for most VPI episodes (16.55 per 1000 PY [95% CI, 14.85-18.46 per 1000 PY] and 12.83 per 1000 PY [95% CI, 11.40-14.44 per 1000 PY], respectively). A total of 198 of 575 VPI episodes in the population that underwent SOT (34.4%) led to hospital admission, and the occurrence of a VPI was associated with an increased risk for death and/or graft loss (hazard ratio, 2.44; 95% CI, 1.50-3.99; P = .002). In multivariable analysis, age 65 years or older at the time of transplant (incidence rate ratio [IRR], 1.29; 95% CI, 1.02-1.62) and receipt of a lung (IRR, 1.77; 95% CI, 1.38-2.26) or a heart (IRR, 1.40; 95% CI, 1.05-1.88) transplant were associated with an increased risk of VPI occurrence. Conclusions and Relevance: In this study, 11.9% of SOT recipients experienced VPIs, and the incidence rate was higher than in the general population. There was significant morbidity and mortality associated with these infections in the population that underwent SOT, which highlights the need for optimizing immunization strategies.

Loss to programme between HIV diagnosis and initiation of antiretroviral therapy in sub-Saharan Africa: systematic review and meta-analysis.

OBJECTIVES: To assess the proportion of patients lost to programme (died, lost to follow-up, transferred out) between HIV diagnosis and start of antiretroviral therapy (ART) in sub-Saharan Africa, and determine factors associated with loss to programme. METHODS: Systematic review and meta-analysis. We searched PubMed and EMBASE databases for studies in adults. Outcomes were the percentage of patients dying before starting ART, the percentage lost to follow-up, the percentage with a CD4 cell count, the distribution of first CD4 counts and the percentage of eligible patients starting ART. Data were combined using random-effects meta-analysis. RESULTS: Twenty-nine studies from sub-Saharan Africa including 148,912 patients were analysed. Six studies covered the whole period from HIV diagnosis to ART start. Meta-analysis of these studies showed that of the 100 patients with a positive HIV test, 72 (95% CI 60-84) had a CD4 cell count measured, 40 (95% CI 26-55) were eligible for ART and 25 (95% CI 13-37) started ART. There was substantial heterogeneity between studies (P < 0.0001). Median CD4 cell count at presentation ranged from 154 to 274 cells/µl. Patients eligible for ART were less likely to become lost to programme (25%vs. 54%, P < 0.0001), but eligible patients were more likely to die (11%vs. 5%, P < 0.0001) than ineligible patients. Loss to programme was higher in men, in patients with low CD4 cell counts and low socio-economic status and in recent time periods. CONCLUSIONS: Monitoring and care in the pre-ART time period need improvement, with greater emphasis on patients not yet eligible for ART.

Risk Factors and Incidence of Sexually Transmitted Infections in the Swiss HIV Cohort Study.

Background: Sexually transmitted infections (STIs) are common among people with human immunodeficiency virus (PWH), but there are limited data about risk factors and incidence of STIs in large, representative cohort studies. Methods: We assessed incidence and risk factors of STIs reported by treating physicians within the Swiss HIV Cohort Study (SHCS). Sexually transmitted infections and demographic, clinical, and behavioral characteristics were prospectively collected at 6-month follow-up visits between October 2017 and November 2019. We used multilevel Poisson regression to assess incidence rate ratios of different STIs. Results: Among 10 140 study participants, a total of 1634 STIs in 1029 SHCS participants were reported over 17 766 person-years of follow up (PYFUP). The overall incidence of any reported STI was 91.9 per 1000 PYFU (95% confidence interval [CI], 85.8 -98.5). Among the 1634 STI episodes, there were 573 (35.1%) incident cases of syphilis, 497 gonorrhea (30.4%), and 418 chlamydia (25.6%). Men who have sex with men (MSM) younger than 50 years represented 21% of the study population, but accounted for 61% of reported STIs. Male sex (adjusted incidence rate ratio [aIRR], 2.03; 95% CI, 1.36-3.02), MSM (aIRR, 3.62; 95% CI, 2.88-4.55), age group 18-34 years (aIRR, 1.78; 95% CI, 1.51-2.10), history of sexual relationships with occasional partners (aIRR, 6.87; 95% CI, 5.40-8.73), and reporting injecting drug use (aIRR, 2.48; 95% CI, 1.91-3.23) were associated with a higher risk of incident STIs. Conclusions: Sexually transmitted infections were frequent among PWH and varied considerably between age and risk groups. Screening programs and recommendations for STI testing need to be adapted according to risk factors and demographic characteristics.

The HIV care cascade in sub-Saharan Africa: systematic review of published criteria and definitions.

INTRODUCTION: The HIV care cascade examines the attrition of people living with HIV from diagnosis to the use of antiretroviral therapy (ART) and suppression of viral replication. We reviewed the literature from sub-Saharan Africa to assess the definitions used for the different steps in the HIV care cascade. METHODS: We searched PubMed, Embase and CINAHL for articles published from January 2004 to December 2020. Longitudinal and cross-sectional studies were included if they reported on at least one step of the UNAIDS 90-90-90 cascade or two steps of an extended 7-step cascade. A step was clearly defined if authors reported definitions for numerator and denominator, including the description of the eligible population and methods of assessment or measurement. The review protocol has been published and registered in Prospero. RESULTS AND DISCUSSION: Overall, 3364 articles were screened, and 82 studies from 19 countries met the inclusion criteria. Most studies were from Southern (38 studies, 34 from South Africa) and East Africa (29 studies). Fifty-eight studies (71.6%) were longitudinal, with a median follow-up of three years. The medium number of steps covered out of 7 steps was 3 (interquartile range [IQR] 2 to 4); the median year of publication was 2015 (IQR 2013 to 2019). The number of different definitions for the numerators ranged from four definitions (for step "People living with HIV") to 21 (step "Viral suppression"). For the denominators, it ranged from three definitions ("Diagnosed and aware of HIV status") to 14 ("Viral suppression"). Only 12 studies assessed all three of the 90-90-90 steps. Most studies used longitudinal data, but denominator-denominator or denominator-numerator linkages over several steps were rare. Also, cascade data are lacking for many countries. Our review covers the academic literature but did not consider other data, such as government reports on the HIV care cascade. Also, it did not examine disengagement and reengagement in care. CONCLUSIONS: The proportions of patients retained at each step of the HIV care cascade cannot be compared between studies, countries and time periods, nor meta-analysed, due to the many different definitions used for numerators and denominators. There is a need for standardization of methods and definitions.

Vaccination willingness for COVID-19 among healthcare workers: a cross-sectional survey in a Swiss canton.

AIMS OF THE STUDY: Vaccination is regarded as the most promising response to the COVID-19 pandemic. We assessed opinions about COVID-19 vaccination, willingness to be vaccinated, and reasons for vaccination hesitancy among healthcare workers. METHODS: We conducted a cross-sectional, web-based survey among 3,793 healthcare workers in December 2020 in the Canton of Solothurn, Switzerland, before the start of the national COVID-19 vaccination campaign. RESULTS: Median age was 43 years (interquartile range [IQR] 31-53), 2,841 were female (74.9%). A total of 1,511 healthcare workers (39.8%) reported willingness to accept vaccination, whereas 1,114 (29.4%) were unsure and 1,168 (30.8%) would decline vaccination. Among medical doctors, 76.1% were willing, whereas only 27.8% of nurses expressed willingness. Among the 1,168 healthcare workers who would decline vaccination, 1,073 (91.9%) expressed concerns about vaccine safety and side effects. The willingness of healthcare workers to be vaccinated was associated with older age (adjusted odds ratio [aOR] 1.97, 95% confidence interval [Cl] 1.71-2.27) and having been vaccinated for influenza this year (aOR 2.70, 95% Cl 2.20-3.31). Healthcare workers who reported a lack of confidence in government were less likely to be willing to be vaccinated (aOR 0.58, 95% Cl 0.40-0.84), and women were less willing to be vaccinated than men (OR 0.33, 95% CI 0.28-0.38). CONCLUSION: Less than half of healthcare workers reported willingness to be vaccinated before the campaign start, but proportions varied greatly depending on profession and workplace. Strategies with clear and objective messages that particularly address the concerns of healthcare workers are needed if their willingness to be vaccinated against COVID-19 is to be further increased.

Seroprevalence of SARS-CoV-2 in healthcare workers from outpatient facilities and retirement or nursing homes in a Swiss canton.

BACKGROUND: Healthcare workers are more frequently exposed to SARS-CoV-2 than the general population. Little is known about healthcare settings outside of hospitals. We studied the seroprevalence of SARS-CoV-2 among healthcare workers in outpatient facilities and retirement or nursing homes in the Canton of Solothurn, Switzerland in the first wave of the COVID-19 pandemic. METHODS: Longitudinal seroprevalence study among healthcare workers with examinations at baseline and 2 months between June and September 2020. The Abbott SARS-CoV-2 IgG and Liaison/Diasorin SARS-CoV-2 S1/S2 IgG assay were used to detect antibodies against SARS-CoV-2. All participants provided demographic information. We report descriptive statistics and calculated the seroprevalence with 95% confidence intervals. RESULTS: We included 357 healthcare workers; their median age was 43 years (interquartile range 29-54), and 315 (88.2%) were female. Forty-nine (13.7%) were physicians, 87 (24.4%) practice assistants and 221 (61.9%) nurses. Overall seroprevalence among healthcare workers in outpatient facilities and retirement or nursing homes was 3.4% (12/357). The 12 seropositive healthcare workers were all nurses (12/221, 5.5%); 11 worked at retirement or nursing homes and one at the hospital's outpatient clinic. Symptoms such as loss of smell or taste, shortness of breath, and fever were more prevalent among seropositive healthcare workers than seronegative healthcare workers. No close contact had detectable antibodies against SARS-CoV-2. CONCLUSIONS: Seroprevalence among healthcare workers was low, but higher among nursing staff of retirement or nursing homes. Healthcare workers at private practices were able to protect themselves well during the first wave of the COVID-19 pandemic.

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.

Long-term retention on antiretroviral therapy among infants, children, adolescents and adults in Malawi: A cohort study.

OBJECTIVES: We examine long-term retention of adults, adolescents and children on antiretroviral therapy under different HIV treatment guidelines in Malawi. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Adults and children starting ART between 2005 and 2015 in 21 health facilities in southern Malawi. METHODS: We used survival analysis to assess retention at clinic level, Cox regression to examine risk factors for loss to follow up, and competing risk analysis to assess long-term outcomes of people on antiretroviral therapy (ART). RESULTS: We included 132,274 individuals in our analysis, totalling 270,256 person years of follow up (PYFU; median per patient 1.3, interquartile range (IQR) 0.26-3.1), 62% were female and the median age was 32 years. Retention on ART was lower in the first year on ART compared to subsequent years for all guideline periods and age groups. Infants (0-3 years), adolescents and young adults (15-24 years) were at highest risk of LTFU. Comparing the different calendar periods of ART initiation we found that retention improved initially, but remained stable thereafter. CONCLUSION: Even though the number of patients and the burden on health care system increased substantially during the study period of rapid ART expansion, retention on ART improved in the early years of ART provision, but gains in retention were not maintained over 5 years on ART. Reducing high attrition in the first year of ART should remain a priority for ART programs, and so should addressing poor retention among adolescents, young adults and men.

Implementation of "Treat-all" at adult HIV care and treatment sites in the Global IeDEA Consortium: results from the Site Assessment Survey.

INTRODUCTION: Since 2015, the World Health Organization (WHO) has recommended that all people living with HIV (PLHIV) initiate antiretroviral treatment (ART), irrespective of CD4+ count or clinical stage. National adoption of universal treatment has accelerated since WHO's 2015 "Treat All" recommendation; however, little is known about the translation of this guidance into practice. This study aimed to assess the status of Treat All implementation across regions, countries, and levels of the health care delivery system. METHODS: Between June and December 2017, 201/221 (91%) adult HIV treatment sites that participate in the global IeDEA research consortium completed a survey on capacity and practices related to HIV care. Located in 41 countries across seven geographic regions, sites provided information on the status and timing of site-level introduction of Treat All, as well as site-level practices related to ART initiation. RESULTS: Almost all sites (93%) reported that they had begun implementing Treat All, and there were no statistically significant differences in site-level Treat All introduction by health facility type, urban/rural location, sector (public/private) or country income level. The median time between national policy adoption and site-level introduction was one month. In countries where Treat All was not yet adopted in national guidelines, 69% of sites reported initiating all patients on ART, regardless of clinical criteria, and these sites had been implementing Treat All for a median period of seven months at the time of the survey. The majority of sites (77%) reported typically initiating patients on ART within 14 days of confirming diagnosis, with 60% to 62% of sites implementing Treat All in East, Southern and West Africa reporting same-day ART initiation for most patients. CONCLUSIONS: By mid- to late-2017, the Treat All strategy was the standard of care at almost all IeDEA sites, including rural, primary-level health facilities in low-resource settings. While further assessments of site-level capacity to provide high-quality HIV care under Treat All and to support sustained viral suppression after ART initiation are needed, the widespread introduction of Treat All at the service delivery level is a critical step towards global targets for ending the HIV epidemic as a public health threat.