Long-term trajectories of densely reported depressive symptoms during an extended period of the COVID-19 pandemic in Switzerland: Social worries matter.

Previous mental health trajectory studies were mostly limited to the months before access to vaccination. They are not informing on whether public mental health has adapted to the pandemic. The aim of this analysis was to 1) investigate trajectories of monthly reported depressive symptoms from July 2020 to December 2021 in Switzerland, 2) compare average growth trajectories across regions with different stringency phases, and 3) explore the relative impact of self-reported worries related to health, economic and social domains as well as socio-economic indicators on growth trajectories. As part of the population-based Corona Immunitas program of regional, but harmonized, adult cohorts studying the pandemic course and impact, participants repeatedly reported online to the DASS-21 instrument on depressive symptomatology. Trajectories of depressive symptoms were estimated using a latent growth model, specified as a generalised linear mixed model. The time effect was modelled parametrically through a polynomial allowing to estimate trajectories for participants' missing time points. In all regions level and shape of the trajectories mirrored those of the KOF Stringency-Plus Index, which quantifies regional Covid-19 policy stringency. The higher level of average depression in trajectories of those expressing specific worries was most noticeable for the social domain. Younger age, female gender, and low household income went along with higher mean depression score trajectories throughout follow-up. Interventions to promote long-term resilience are an important part of pandemic preparedness, given the observed lack of an adaptation in mental health response to the pandemic even after the availability of vaccines in this high-income context.

Participation, retention and uptake in a multicentre pre-exposure prophylaxis cohort using online, smartphone-compatible data collection.

OBJECTIVES: The aim of the study was to assess the feasibility of a national pre-exposure prophylaxis (PrEP) programme using smartphone-compatible data collection. METHODS: This was a multicentre cohort study (NCT03893188) enrolling individuals interested in PrEP in Switzerland. All centres participate in the SwissPrEPared programme, which uses smartphone-compatible data collection. Feasibility was assessed after centres had enrolled at least one participant. Participants were HIV-negative individuals presenting for PrEP counselling. Outcomes were participation (number enrolled/number eligible), enrolment rates (number enrolled per month), retention at first follow-up (number with first follow-up/number enrolled), and uptake (proportion attending first visit as scheduled). Participant characteristics were compared between those retained after baseline assessment and those who dropped out. RESULTS: Between April 2019 and January 2020, 987 individuals were assessed for eligibility, of whom 969 were enrolled (participation: 98.2%). The median enrolment rate was 86 per month [interquartile range (IQR) 52-137]. Retention at first follow-up and uptake were both 80.7% (782/969 and 532/659, respectively). At enrolment, the median age was 40 (IQR 33-47) years, 95% were men who have sex with men, 47% had a university degree, and 75.5% were already taking PrEP. Most reported multiple casual partners (89.2%), previous sexually transmitted infections (74%) and sexualized drug use (73.1%). At baseline, 25.5% tested positive for either syphilis, gonorrhoea or chlamydia. Participants who dropped out were at lower risk of HIV infection than those retained after baseline assessment. CONCLUSIONS: In a national PrEP programme using smartphone-compatible data collection, participation, retention and uptake were high. Participants retained after baseline assessment were at considerable risk of HIV infection. Younger, less educated individuals were underrepresented in the SwissPrEPared cohort.

Evaluation of a measles vaccination campaign at the universities in the city of Zurich, 2019.

OBJECTIVES: In 2019, there were 29 reported cases of measles in the Canton of Zurich, with two cases occurring among university students. In collaboration with the University of Zurich Travel Clinic, the Health Department of the Canton of Zurich offered free measles vaccination to all employees and students at the University of Zurich (UZH) and the Swiss Federal Institute of Technology (ETH). This short communication shares the results of this large measles vaccination campaign. STUDY DESIGN: Vaccination intervention campaign. METHODS: All employees and students at the UZH and ETH were informed via an email distribution list that they were eligible for cost-free consultation and measles vaccination (when indicated). Consultations and immunizations took place over the course of 3 days in June 2019 at the UZH Travel Clinic. All those who were missing one or two doses of measles vaccination, and had no contraindications, were vaccinated. Booster immunizations were offered until December 2019. RESULTS: A total of 411 individuals participated in the campaign. Thirty-five individuals (8.5%) were found to have sufficient measles vaccination on consultation and received no additional vaccination. A total of 376 individuals (91.5%) met the eligibility criteria and were vaccinated; 83 individuals (20.2% of all participants and 22.1% of those vaccinated) returned for a second vaccination. In total, the campaign saw 494 visits (including consultations without immunization and visits for second immunization). Demographic data were collected for 439 visits where measles vaccination was administered. From these, 51.7% were for an individual's first measles vaccine dose, 27.3% for a second dose, 18.9% for a booster immunization and 2.1% were unknown. 54.7% of campaign visits were made by females; and 45.0% of visits were made by those aged 18-29 years, 27.9% by those 30-39 years, 14.6% by those 40-49 years, and 12.6% by those 50+ years. 49.8% of visits were made by students and 48.5% by employees. More students needed the first dose (54.2% of first-dose visits), whereas more employees received booster immunization (57.8% of booster visits). CONCLUSIONS: The measles vaccination campaign was well attended, particularly by the younger age group 18-29 years and females. Coupled with intense media attention, such a campaign immediately following an outbreak may be an effective method to increase vaccination coverage.

Hyperglycaemia and pharmacokinetics of rifampicin/isoniazid among TB-HIV co-infected patients in Kampala, Uganda.

OBJECTIVE: 1) To determine the prevalence of diabetes mellitus and impaired fasting glucose (IFG) in patients with TB and HIV co-infection, and 2) to investigate the effect of fasting plasma glucose (FPG) on rifampicin (RIF) and isoniazid (INH) serum concentrations.DESIGN: Retrospective data analysis of a cohort of HIV-infected adults with newly diagnosed pulmonary TB. Plasma glucose and TB drug levels were obtained at Week 0, 2, 8 and 24 of TB treatment.RESULTS: A total of 107 patients were included in this analysis. Random plasma glucose ≥200 mg/dL was found in 1/53 (2%) participant at Week 0. The prevalence of FPG ≥ 126 mg/dL decreased from 8/41 (20%) at Week 2 to 3/89 (3%) at Week 24. IFG (100-125 mg/dL) was observed in 23/41 (56%) participants at Week 2, and 39/89 (44%) at Week 24. FPG was inversely correlated with lower area under the curve (AUC0-24h) for RIF (c = -0.52; 95%CI -0.84 to -0.21; P = 0.001). FPG was not associated with lower INH AUC0-24h.CONCLUSION: We found a high prevalence of FPG ≥ 126 mg/dL, which decreased significantly during treatment, and a high proportion of IFG at the end of TB treatment. Higher FPG was associated with lower AUC for RIF.

A systematic review and meta-analysis of first-line tuberculosis drug concentrations and treatment outcomes.

Low serum concentrations of first-line tuberculosis (TB) drugs have been widely reported. However, the impact of low serum concentrations on treatment outcome is less well studied. A systematic search of MEDLINE/Pubmed and the Cochrane Central Register of Controlled Trials up to 31 March 2018 was conducted for articles describing drug concentrations of first-line TB drugs and treatment outcome in adult patients with drug-susceptible TB. The search identified 3073 unique publication abstracts, which were reviewed for suitability: 21 articles were acceptable for inclusion in the qualitative analysis comprising 13 prospective observational cohorts, 4 retrospective observational cohorts, 1 case-control study and 3 randomised controlled trials. Data for meta-analysis were available for 15 studies, 13 studies of rifampicin (RMP), 10 of isoniazid (INH), 8 of pyrazinamide (PZA) and 4 of ethambutol (EMB). This meta-analysis revealed that low PZA concentration appears to increase the risk of poor outcomes (8 studies, n = 2727; RR 1.73, 95%CI 1.10-2.72), low RMP concentrations may slightly increase the risk of poor outcomes (13 studies, n = 2753; RR 1.40, 95%CI 0.91-2.16), whereas low concentrations of INH (10 studies, n = 2640; RR 1.32, 95%CI 0.66-2.63) and EMB (4 studies, n = 551; RR 1.12, 95%CI 0.41-3.05) appear to make no difference to treatment outcome. There was no significant publication bias or between-study heterogeneity in any of the analyses. The potential clinical impact of low concentrations of PZA and RMP warrants further evaluation. Also, comprehensive assessments of the complex pharmacokinetic-pharmacodynamic relationships in the treatment of TB are urgently needed.

Long-term immunogenicity after yellow fever vaccination in immunosuppressed and healthy individuals.

BACKGROUND: The live-attenuated yellow fever vaccine (YFV) is generally contraindicated in immunosuppressed patients. Our aim was to investigate if immunosuppressive therapy impairs the long-term protection against yellow fever virus in patients who had received YFV prior to the start of their immunosuppressive therapy. METHODS: Our study examined 35 healthy individuals and 40 immunosuppressed patients with autoimmune diseases or organ transplants. All individuals had received YFV prior to the onset of their immunosuppression. We analysed the long-term influence of the immunosuppressive therapy on the YFV protective immunity by measuring neutralising antibodies (NA) with the Plaque Reduction Neutralisation Test (PRNT). We assessed risk factors for a negative PRNT result (titre below 1: 10) and their influence on the magnitude of the NA. RESULTS: A median time interval of 21.1 years (interquartile range 14.4-31.3 years) after the YFV in all patients, a total of 35 immunosuppressed patients (88%) were seropositive (PRNT ≥ 1:10) compared to 31 patients (89%) in the control group. The geometric mean titres of NA did not differ between the groups. The duration of an underlying rheumatic disease was the only risk factor found for a lower magnitude of NA. An insufficient level of NA was found in nine subjects (12%) who had received a single dose of YFV (in one subject, the number of YFV doses was unknown). CONCLUSION: The use of an immunosuppressive drug started after the administration of the YFV did not affect long-term persistence of NA. A second dose of YFV may be necessary to secure long-term immunity.

Chemsex drugs on the rise: a longitudinal analysis of the Swiss HIV Cohort Study from 2007 to 2017.

OBJECTIVES: Chemsex refers to the use of sex-enhancing drugs among men who have sex with men (MSM) in combination with specific sexual and social behaviours. Longitudinal data on this development and the associated health risks are scarce. METHODS: Data on all recreational drugs reported in the Swiss HIV Cohort Study (SHCS) from 2007 to 2017 were collected. Drug use was analysed longitudinally for all drug classes. In addition, potential associations between patient characteristics and the consumption of methamphetamine, γ-hydroxybutric acid/γ-butyrolactone (GHB/GBL), 3,4-methylenedioxymethamphetamine (MDMA/XTC), cocaine and amphetamine were analysed. RESULTS: We analysed 166 167 follow-up entries for 12 527 SHCS participants, including 7101 free text field entries containing information about recreational drugs other than cannabis, cocaine and heroin. Overall, we observed a stable percentage (9.0%) of recreational drug use (excluding cannabis, amyl nitrite and prescription drugs). For MSM, however, there was an increase in overall drug use from 8.8% in 2007 to 13.8% in 2017, with particularly large increases for methamphetamine (from 0.2 to 2.4%; P < 0.001) and GHB/GBL (from 1.0 to 3.4%; P < 0.001). The use of each of the potentially sex-enhancing drugs methamphetamine, GHB/GBL, cocaine, XTC/MDMA and amphetamine was significantly associated with condomless sex with nonsteady partners, and higher prevalences of depression, syphilis and hepatitis C. CONCLUSIONS: The significant increase in the use of chemsex drugs among MSM in the SHCS and the strong association with coinfections and depression highlights the need for harm reduction programmes tailored to MSM. According to our results, improving knowledge about recreational drugs is important for all health care professionals working with people living with HIV.

Comparison of Löwenstein-Jensen and BACTEC MGIT 960 culture for Mycobacterium tuberculosis in people living with HIV.

OBJECTIVES: The aim of the study was to clarify how HIV infection affects tuberculosis liquid and solid culture results in a resource-limited setting. METHODS: We used baseline data from the Study on Outcomes Related to Tuberculosis and HIV Drug Concentrations in Uganda (SOUTH), which included 268 HIV/tuberculosis (TB)-coinfected individuals. Culture results from Löwenstein-Jensen (LJ) solid culture and mycobacteria growth indicator tube (MGIT) liquid culture systems and culture-based correlates for bacillary density from the sputum of HIV/TB-coinfected individuals at baseline were analysed. RESULTS: Of 268 participants, 243 had a CD4 cell count available and were included in this analysis; 72.2% of cultures showed growth on solid culture and 82.2% in liquid culture systems (P < 0.015). A higher CD4 cell count was predictive of LJ positivity [adjusted odds ratio (OR) 1.14; 95% confidence interval (CI) 1.03-1.25 per 50 cells/µL increase; P = 0.008]. The same, but insignificant trend was observed for MGIT positivity (adjusted OR 1.09; 95% CI 0.99-1.211 per 50 cells/µL increase; P = 0.094). A higher CD4 cell count was associated with a higher LJ colony-forming unit grade (adjusted OR 1.14; 95% CI 1.05-1.25 per 50 cells/µL increase; P = 0.011) and a shorter time to MGIT positivity [adjusted hazard ratio (HR) 1.08; 95% CI 1.04-1.12 per 50 cells/µL increase; P < 0.001]. CONCLUSIONS: In a resource-limited setting, the MGIT liquid culture system outperformed LJ solid culture in terms of culture yield and dependence on CD4 cell counts in HIV/TB-coinfected individuals. We therefore suggest considering an adaptation of diagnostic algorithms: when resources allow only one culture method to be performed, we recommend that MGIT liquid culture should be used exclusively in HIV-positive individuals as a first-line culture method, to reduce costs and make TB culture results accessible to more patients in resource-limited settings.

Quantifying the drivers of HIV transmission and prevention in men who have sex with men: a population model-based analysis in Switzerland.

OBJECTIVES: Despite the huge success of antiretroviral therapy (ART), there is an ongoing HIV epidemic among men who have sex with men (MSM) in resource-rich countries. Understanding the driving factors underlying this process is important for curbing the epidemic. METHODS: We simulated the HIV epidemic in MSM in Switzerland by stratifying a mathematical model by CD4 count, the care cascade and condom use. The model was parametrised with clinical, epidemiological and behavioural data from the Swiss HIV Cohort Study and surveys in the HIV-negative population. RESULTS: According to our model, 3.4% of the cases that would otherwise have occurred in 2008-2015 were prevented by early initiation of ART. Only 0.6% of the cases were attributable to a change in condom use in the HIV-positive population, as less usage is mainly seen in virally suppressed MSM. Most new infections were attributable to transmission from recently infected undiagnosed individuals. It was estimated that doubling the diagnosis rate would have resulted in 11.8% fewer cases in 2001-2015. Moreover, it was estimated that introducing pre-exposure prophylaxis (PrEP) for 50% of those MSM not using condoms with occasional partners would have resulted in 22.6% fewer cases in 2012-2015. CONCLUSIONS: By combining observational data on the relevant epidemiological and clinical processes with a mathematical model, we showed that the 'test and treat' approach is most effective in reducing the number of new cases. Only a moderate population-level effect was estimated for early initiation of ART and a weak effect for the change in condom use of diagnosed MSM. Protecting HIV-negative individuals who are not using condoms with PrEP was shown to have a major impact.

Rapid decline of anti-hepatitis C virus (HCV) antibodies following early treatment of incident HCV infections in HIV-infected men who have sex with men.

OBJECTIVES: Following clearance of incident hepatitis C virus (HCV) infections, HCV antibody levels may decline, resulting in seroreversion. It is unclear to what extent HCV antibody level trajectories differ between patients with treatment-induced sustained virological response (SVR), those with spontaneous clearance and those with untreated replicating HCV infection. We investigated HCV antibody level dynamics in HIV-infected MSM with different clinical outcomes. METHODS: We investigated anti-HCV antibody level dynamics following an incident HCV infection in 67 HIV-infected men who have sex with men (MSM) with different clinical outcomes: SVR (n = 33), spontaneous clearance (n = 12), and untreated replicating infection (n = 22). Antibody levels were measured at the time of HCV diagnosis, and at yearly intervals for 3 years thereafter. RESULTS: At baseline, median HCV antibody levels were similar in the three groups: 13.4, 13.8 and 13.5 sample to cut-off (S/CO) for SVR, spontaneous clearance and untreated infection, respectively. Over 3 years of follow-up, SVR was associated with a more pronounced decrease in anti-HCV levels compared with spontaneous clearance and untreated infection [median decline 71% [interquartile range (IQR: 43-87%), 38% (IQR: 29-60%) and 12% (IQR: 9-22%), respectively; P < 0.001]. Seroreversions occurred in five of 33 (15%) patients with SVR and in one of 12 (8%) with spontaneous clearance. A shorter delay between time of infection and treatment start correlated with higher rates of decline in antibody levels. Seven patients experienced a reinfection. CONCLUSIONS: Treatment-induced HCV clearance was associated with a more pronounced decline in anti-HCV antibody levels and with higher rates of seroreversion compared with spontaneous clearance or untreated replicating HCV infection among HIV-infected MSM with incident HCV infections. Rapid clearance of HCV RNA following early HCV treatment might impair the development of persistent antibody titres.

Detection of tuberculosis patterns in digital photographs of chest X-ray images using Deep Learning: feasibility study.

OBJECTIVE: To evaluate the feasibility of Deep Learning-based detection and classification of pathological patterns in a set of digital photographs of chest X-ray (CXR) images of tuberculosis (TB) patients. MATERIALS AND METHODS: In this prospective, observational study, patients with previously diagnosed TB were enrolled. Photographs of their CXRs were taken using a consumer-grade digital still camera. The images were stratified by pathological patterns into classes: cavity, consolidation, effusion, interstitial changes, miliary pattern or normal examination. Image analysis was performed with commercially available Deep Learning software in two steps. Pathological areas were first localised; detected areas were then classified. Detection was assessed using receiver operating characteristics (ROC) analysis, and classification using a confusion matrix. RESULTS: The study cohort was 138 patients with human immunodeficiency virus (HIV) and TB co-infection (median age 34 years, IQR 28-40); 54 patients were female. Localisation of pathological areas was excellent (area under the ROC curve 0.82). The software could perfectly distinguish pleural effusions from intraparenchymal changes. The most frequent misclassifications were consolidations as cavitations, and miliary patterns as interstitial patterns (and vice versa). CONCLUSION: Deep Learning analysis of CXR photographs is a promising tool. Further efforts are needed to build larger, high-quality data sets to achieve better diagnostic performance.

On the potential of a short-term intensive intervention to interrupt HCV transmission in HIV-positive men who have sex with men: A mathematical modelling study.

Increasing access to direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection and decelerating the rise in high-risk behaviour over the next decade could curb the HCV epidemic among HIV-positive men who have sex with men (MSM). We investigated if similar outcomes would be achieved by short-term intensive interventions like the Swiss-HCVree-trial. We used a HCV transmission model emulating two 12-months intensive interventions combining risk counselling with (i) universal DAA treatment (pangenotypic intervention) and (ii) DAA treatment for HCV genotypes 1 and 4 (replicating the Swiss-HCVree-trial). To capture potential changes outside intensive interventions, we varied time from HCV infection to treatment in clinical routine and overall high-risk behaviour among HIV-positive MSM. Simulated prevalence dropped from 5.5% in 2016 to ≤2.0% over the intervention period (June/2016-May/2017) with the pangenotypic intervention, and to ≤3.6% with the Swiss-HCVree-trial. Assuming time to treatment in clinical routine reflected reimbursement restrictions (METAVIR ≥F2, 16.9 years) and stable high-risk behaviour in the overall MSM population, prevalence in 2025 reached 13.1% without intensive intervention, 11.1% with the pangenotypic intervention and 11.8% with the Swiss-HCVree-trial. If time to treatment in clinical routine was 2 years, prevalence in 2025 declined to 4.8% without intensive intervention, to 2.8% with the pangenotypic intervention, and to 3.5% with the Swiss-HCVree-trial. In this scenario, the pangenotypic intervention and the Swiss-HCVree-trial reduced cumulative (2016-2025) treatment episodes by 36% and 24%, respectively. Therefore, intensive interventions could reduce future HCV treatment costs and boost the benefits of long-term efforts to prevent high-risk behaviour and to reduce treatment delay. But if after intensive interventions treatment is deferred until F2, short-term benefits of intensive interventions would dissipate in the long term.

Assessing the need for a pre-exposure prophylaxis programme using the social media app Grindr®.

OBJECTIVES: HIV pre-exposure prophylaxis (PrEP) is not approved in Switzerland and therefore must be paid for by the users themselves. We conducted a survey to find out whether men who have sex with men (MSM) in Switzerland are already taking PrEP, or are considering using it, and whether it is being taken under medical supervision or not. METHODS: Grindr® is a geosocial networking app for MSM. Between 5 and 24 January 2017, users of the app who were located in Switzerland by a global positioning system (GPS) were asked to participate in a ten-question survey on PrEP use. RESULTS: Of the 2455 people who took part in the survey, 1893 were included in the analysis. Eighty-two participants (4.3%) reported that they were currently taking PrEP, 64 of whom (78%) said that they were under medical supervision. Seven PrEP users (9%) declared that they had not taken an HIV test within the previous 12 months. Nine hundred and forty-four (49.9%) were considering taking PrEP in the next 6 months, and 1474 (77.9%) were considering taking it at some point in the future. CONCLUSIONS: In an online survey carried out among sexually active MSM in Switzerland, only a minority of the individuals approached responded that they were currently using PrEP. However, the majority of participants were considering taking PrEP in the future. We identified a substantial proportion of PrEP users taking PrEP outside a medical setting. Hence, a national programme facilitating access to medical care and providing PrEP is urgently needed.

Ethnicity predicts viral rebound after travel to the tropics in HIV-infected travelers to the tropics in the Swiss HIV Cohort Study.

OBJECTIVES: The number of HIV-infected individuals from developed countries travelling to tropical and subtropical areas has increased as a result of the clinical and survival benefits of combination antiretroviral therapy. The aim of our study was to describe the traveler population in the SHCS and to determine the frequency of viral rebound in virologically suppressed individuals after a travel episode to the tropics compared to non-travelers. METHODS: Swiss HIV Cohort Study participants with at least one follow-up visit between 1 January 1989 and 28 February 2015 were eligible for inclusion in the study. The primary outcome was the occurrence of viral rebound (viral load > 200 HIV-1 RNA copies/mL) after a travel episode compared with a nontravel episode in previously suppressed individuals (≤ 200 copies/mL). All virologically suppressed patients contributed multiple travel or nontravel episodes to the analysis. Logistic regression was performed including factors associated with viral rebound. RESULTS: We included 16 635 patients in the study, of whom 6084 (36.5%) had ever travelled to the tropics. Travel frequency increased over time, with travellers showing better HIV parameters than nontravellers [less advanced Centers for Disease Control and Prevention (CDC) stage and higher CD4 count nadir]. Viral rebound was seen in 477 (3.9%) of 12 265 travel episodes and in 5121 (4.5%) of 114 884 nontravel episodes [unadjusted odds ratio (OR) 0.87; 95% confidence interval (CI) 0.78-0.97]. Among these 477 post-travel viral rebounds, 115 had a resistance test performed and 51 (44%) of these showed new resistance mutations. Compared with European and North American patients, the odds for viral rebound were significantly lower in Southeast Asian (OR 0.67; 95% CI 0.51-0.88) and higher in sub-Saharan African (SSA) patients (OR 1.41; 95% CI 1.22-1.62). Travel further increased the odds of viral rebound in SSA patients (OR 2.00; 95% CI 1.53-2.61). CONCLUSIONS: Region of origin is the main risk factor for viral rebound rather than travel per se. Pre-travel adherence counselling should focus on patients of SSA origin.

Ocular Toxoplasmosis: Therapy-Related Adverse Drug Reactions and Their Management.

Background There are different treatment options for ocular toxoplasmosis (OT). "Classic" therapy consists of pyrimethamine, sulfadiazine and folinic acid combined with systemic steroids and is still widely used. However, potentially severe side effects of this therapy have been reported. The aim of this retrospective study was to evaluate the incidence and types of adverse drug reactions in patients treated for OT. Clinical management of each adverse drug reaction was assessed. Patients and Methods In this retrospective analysis, we reviewed data of patients with OT, who were consecutively examined between December 2011 and December 2015 at the Department of Ophthalmology, University Hospital Zurich. Results In total, 49 patients had at least one episode of active OT. In 54 (83.0 %) of 65 treated episodes, the classic regimen was used. Of the 37 patients who received classic treatment, 9 (24.3 %) developed at least one adverse drug reaction which led to drug discontinuation, including elevated creatinine (5.4 %), elevated liver enzymes (5.4 %), vomiting (5.4 %), rash (5.4 %) and facial swelling (2.7 %). In 5 patients, treatment was switched to another drug, while in the other 4 patients, therapy was stopped. In these 9 patients, inflammation was well controlled 8 weeks after onset of therapy. No patient suffered from severe side effects, such as potentially life-threatening allergic reactions or pancytopenia. Conclusions In OT patients who were treated with classic therapy, adverse drug reactions are common. Therefore, clinical and laboratory monitoring is mandatory. Adverse drug reactions may require interdisciplinary management.

Anti-TB drug concentrations and drug-associated toxicities among TB/HIV-coinfected patients.

Background: Toxicities due to anti-TB treatment frequently occur among TB/HIV-coinfected patients. Objectives: To determine the association between anti-TB drug concentrations and the occurrence of hepatotoxicity and peripheral neuropathy among TB/HIV-coinfected patients. Methods: TB/HIV-coinfected patients were started on standard dose anti-TB treatment according to WHO guidelines. Anti-TB drug concentrations were measured using HPLC 1, 2 and 4 h after drug intake at 2, 8 and 24 weeks following initiation of TB treatment. Participants were assessed for hepatotoxicity using Division of AIDS toxicity tables and for peripheral neuropathy using clinical assessment of tendon reflexes, vibration sensation or symptoms. Cox regression was used to determine the association between toxicities and drug concentrations. Results: Of the 268 patients enrolled, 58% were male with a median age of 34 years. Participants with no hepatotoxicity or mild, moderate and severe hepatotoxicity had a median C max of 6.57 (IQR 4.83-9.41) µg/mL, 7.39 (IQR 5.10-10.20) µg/mL, 7.00 (IQR 6.05-10.95) µg/mL and 3.86 (IQR 2.81-14.24) µg/mL, respectively. There was no difference in the median C max of rifampicin among those who had hepatotoxicity and those who did not ( P = 0.322). There was no difference in the isoniazid median C max among those who had peripheral neuropathy 2.34 (1.52-3.23) µg/mL and those who did not 2.21 (1.45-3.11) µg/mL ( P = 0.49). Conclusions: There was no association between rifampicin concentrations and hepatotoxicity or isoniazid concentrations and peripheral neuropathy among TB/HIV-coinfected patients.

Challenges in achieving a target international normalized ratio for deep vein thrombosis among HIV-infected patients with tuberculosis: a case series.

BACKGROUND: Tuberculosis (TB) and HIV are among the risk factors for deep vein thrombosis (DVT). There are several challenges in the management of DVT patients with TB-HIV co-infection including drug-drug interactions and non-adherence due to pill burden. METHODS: HIV infected patients starting treatment for TB were identified and followed up two weekly. Cases of DVT were diagnosed with Doppler ultrasound and patients were initiated on oral anticoagulation with warfarin and followed up with repeated INR measurements and warfarin dose adjustment. RESULTS: We describe 7 cases of TB and HIV-infected patients in Uganda diagnosed with DVT and started on anticoagulation therapy. Their median age was 30 (IQR: 27-39) years and 86 % were male. All patients had co-medication with cotrimoxazole, tenofovir, lamivudine and efavirenz and some were on fluconazole. The therapeutic range of the International Normalization Ratio (INR) was difficult to attain and unpredictable with some patients being under-anticoagulated and others over-anticoagulated. The mean Time in Therapeutic Range (TTR) for patients who had all scheduled INR measurements in the first 12 weeks was 33.3 %. Only one patient among those with all the scheduled INR measurements had achieved a therapeutic INR by 2 weeks. Four out of seven (57 %) of the patients had at least one INR above the therapeutic range which required treatment interruption. None of the patients had major bleeding. CONCLUSION: We recommend more frequent monitoring and timely dose adjustment of the INR, as well as studies on alternative strategies for the treatment of DVT in TB-HIV co-infected patients.

Emergence of Acquired HIV-1 Drug Resistance Almost Stopped in Switzerland: A 15-Year Prospective Cohort Analysis.

BACKGROUND: Drug resistance is a major barrier to successful antiretroviral treatment (ART). Therefore, it is important to monitor time trends at a population level. METHODS: We included 11 084 ART-experienced patients from the Swiss HIV Cohort Study (SHCS) between 1999 and 2013. The SHCS is highly representative and includes 72% of patients receiving ART in Switzerland. Drug resistance was defined as the presence of ≥1 major mutation in a genotypic resistance test. To estimate the prevalence of drug resistance, data for patients with no resistance test was imputed based on the patient's risk of harboring drug-resistant viruses. RESULTS: The emergence of new drug resistance mutations declined dramatically from 401 to 23 patients between 1999 and 2013. The upper estimated prevalence limit of drug resistance among ART-experienced patients decreased from 57.0% in 1999 to 37.1% in 2013. The prevalence of 3-class resistance decreased from 9.0% to 4.4% and was always <0.4% for patients who initiated ART after 2006. Most patients actively participating in the SHCS in 2013 with drug-resistant viruses initiated ART before 1999 (59.8%). Nevertheless, in 2013, 94.5% of patients who initiated ART before 1999 had good remaining treatment options based on Stanford algorithm. CONCLUSIONS: Human immunodeficiency virus type 1 drug resistance among ART-experienced patients in Switzerland is a well-controlled relic from the era before combination ART. Emergence of drug resistance can be virtually stopped with new potent therapies and close monitoring.

HIV-1 Transmission During Recent Infection and During Treatment Interruptions as Major Drivers of New Infections in the Swiss HIV Cohort Study.

BACKGROUND: Reducing the fraction of transmissions during recent human immunodeficiency virus (HIV) infection is essential for the population-level success of "treatment as prevention". METHODS: A phylogenetic tree was constructed with 19 604 Swiss sequences and 90 994 non-Swiss background sequences. Swiss transmission pairs were identified using 104 combinations of genetic distance (1%-2.5%) and bootstrap (50%-100%) thresholds, to examine the effect of those criteria. Monophyletic pairs were classified as recent or chronic transmission based on the time interval between estimated seroconversion dates. Logistic regression with adjustment for clinical and demographic characteristics was used to identify risk factors associated with transmission during recent or chronic infection. FINDINGS: Seroconversion dates were estimated for 4079 patients on the phylogeny, and comprised between 71 (distance, 1%; bootstrap, 100%) to 378 transmission pairs (distance, 2.5%; bootstrap, 50%). We found that 43.7% (range, 41%-56%) of the transmissions occurred during the first year of infection. Stricter phylogenetic definition of transmission pairs was associated with higher recent-phase transmission fraction. Chronic-phase viral load area under the curve (adjusted odds ratio, 3; 95% confidence interval, 1.64-5.48) and time to antiretroviral therapy (ART) start (adjusted odds ratio 1.4/y; 1.11-1.77) were associated with chronic-phase transmission as opposed to recent transmission. Importantly, at least 14% of the chronic-phase transmission events occurred after the transmitter had interrupted ART. CONCLUSIONS: We demonstrate a high fraction of transmission during recent HIV infection but also chronic transmissions after interruption of ART in Switzerland. Both represent key issues for treatment as prevention and underline the importance of early diagnosis and of early and continuous treatment.