Cervical intraepithelial neoplasia in migrant women living with HIV

The aim of this thesis was to study high-grade cervical intraepithelial neoplasia (CIN) in women living with HIV (WLWH) in Sweden compared with HIV-negative women (HNW) of the same region of birth. In Paper I we assessed the cumulative incidence (CuI) and hazard ratio (HR) of CIN3, adenocarcinoma, and invasive cervical cancer (CIN3+) in a cohort of WLWH (n = 893) and HNW (n = 205 842) by linking the Swedish national HIV registry (InfCare HIV) with the Swedish Population Registry (SPR) and the Swedish National Cervical Screening Registry (NKCx). The CuI of CIN3+ was 13.1% (95% CI 8.9-17.2) and 2.1% (95% CI 2.0-2.2) for WLWH and HNW, respectively. WLWH had more than eight times higher risk of CIN3+ than HNW (HR 8.8: 95% CI 6.9–11.3), increasing with the level of immunosuppression. The highest risk was seen in WLWH born in the East region, dominated by Thai women. In Paper II we analysed if the prevalence of undiagnosed HIV in women diagnosed with CIN2+ (n = 62 874) in the counties of Stockholm and Gothenburg, Sweden, would reach the threshold of 0.1%, which has been suggested cost-effective for HIV-testing. The proportion of undiagnosed HIV was calculated by linking NKCx with InfCare HIV and did not exceed 0.1% in all women, indicating that HIV-testing all women with CIN2+ in Sweden may not be cost-effective. However the proportion of undiagnosed HIV exceeded 0.1% among migrant women diagnosed with CIN2+ suggesting that HIVtesting should routinely be performed in this population. In Paper III we assessed outcome after treatment of CIN2+ in 140 WLWH and 284 HNW, matched for country of birth, identified by linking NKCx with InfCare HIV and SPR. WLWH were three times more likely to have treatment failure (odds ratio (OR) 3.7 [95% CI 2.0-6.8]) and five times more likely to recur (hazard ratio 5.0: 95% CI 2.1-11.6) than HNW. Suppressive (HIV-RNA<50 copies/mL) antiretroviral therapy (ART) at time of treatment of CIN2+ was associated with reduced odds ratio of treatment failure (OR 0.3: 95% CI 0.1-0.8). In Paper IV we studied whether HPV genotypes in women with CIN2+, identified in paper III, differed depending on their HIV status. Cervical tissue blocks of included women were retrieved from bio banks and HPV type was identified using modified general primer PCR and Luminex genotyping. WLWH were less likely to be infected with HPV 16 (prevalence ratio [PR] 0.6: 95% CI 0.35-0.97), and more likely to be infected with multiple high-risk (HR) HPV (PR 2.1, 95% CI 1.17-3.79). Only 25% of WLWH vs. 47% of HNW had HR HPV types that are covered by the bivalent and quadrivalent HPV vaccines (HPV 16 and/or 18) (PR 0.6: 95% CI 0.38-0.97). In summary, my thesis showed that WLWH in Sweden are at higher risk of developing CIN3+, have poorer outcome after treatment of CIN2+, and less proportion of HPV 16 than HNW. We also found level of immunosuppression and, for the first time, suppressive ART to be associated with effective treatment of CIN2+. We recommend migrants diagnosed with CIN2+ to be HIV-tested. Early HIV diagnosis, access and adherence to ART, HPV vaccination of young people living with HIV and those at high-risk of HIV-infection, and finally access and adherence to cervical cancer screening are all crucial to minimize the incidence of CIN2+ and its progression to ICC in WLWH

The use of pediatric health care services in Switzerland : a claims data analysis (preliminary results)

Exposure to unfavorable circumstances in childhood has been shown to have negative implications on physical, cognitive and psychological health in adulthood. Health problems in childhood should, therefore, be detected and treated at an early stage. Adequate pediatric health care, and in particular, preventive pediatric health screenings, play a key role in this context. In Switzerland, children and adolescents from 0-14 years are recommended to go through ten preventive health screenings. These screenings are performed at the parents’ initiative by the pediatrician or family doctor, except for two to three compulsory screenings at around the age of 6, 10 and 14 years, which are typically performed by the school medical services. However, little is known about the extent to which these screenings are performed and about potential barriers limiting the utilization of health care services. The aim of our study is to evaluate children’s access to adequate health care in Switzerland. In particular, we aim to identify potential inequalities in the use of pediatric health care between socioeconomic groups. We employ two strategies: a) Using data from the school medical services in the city of Bern, we assess the extent of foregone pediatric health care in different socioeconomic groups by evaluating the incidence of untreated or inadequately treated health problems. b) Using claims data from a large Swiss health insurer, we assess the health care utilization patterns throughout childhood and the extent to which preventive health screenings are performed. The identification of groups at risk of inadequate health care and a better understanding of the underlying mechanisms can contribute to improving access to preventive health care services and, hence, to reducing health inequalities in childhood

CASCADE protocol: exploring current viral and host characteristics, measuring clinical and patient-reported outcomes, and understanding the lived experiences and needs of individuals with recently acquired HIV infection through a multicentre mixed-methods observational study in Europe and Canada

Introduction: Despite the availability of pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART), 21 793 people were newly diagnosed with HIV in Europe in 2019. The Concerted action on seroconversion to AIDS and death in Europe study aims to understand current drivers of the HIV epidemic; factors associated with access to, and uptake of prevention methods and ART initiation; and the experiences, needs and outcomes of people with recently acquired HIV. / Methods and analysis: This longitudinal observational study is recruiting participants aged ≥16 years with documented laboratory evidence of HIV seroconversion from clinics in Canada and six European countries. We will analyse data from medical records, self-administered questionnaires, semistructured interviews and participatory photography. We will assess temporal trends in transmitted drug resistance and viral subtype and examine outcomes following early ART initiation. We will investigate patient-reported outcomes, well-being, and experiences of, knowledge of, and attitudes to HIV preventions, including PrEP. We will analyse qualitative data thematically and triangulate quantitative and qualitative findings. As patient public involvement is central to this work, we have convened a community advisory board (CAB) comprising people living with HIV. / Ethics and dissemination: All respective research ethics committees have approval for data to contribute to international collaborations. Written informed consent is required to take part. A dissemination strategy will be developed in collaboration with CAB and the scientific committee. It will include peer-reviewed publications, conference presentations and accessible summaries of findings on the study’s website, social media and via community organisations

Adequate use of pediatric primary health care during the first three years of life in Switzerland : an analysis using claims data

Introduction: Adequate pediatric primary care, in particular health screenings, is important for the early detection and treatment of diseases or developmental disorders in early childhood. Therefore, pediatric associations recommend regular screenings for children. In Switzerland, there is little systematic knowledge about the uptake of pediatric primary care in early childhood. The aim of this study is to investigate the uptake of pediatric primary health care consultations in the first three years of life and to identify possible differences between socioeconomic subgroups. Methods: We used health care claims data from a large Swiss health insurer from 2012 to 2018. We identified medical consultations in the age of 0 to 7 months, 0 to 13 months, and 14 to 30 months and included pediatricians, general practitioners (GPs), and hospital in- and outpatient care. We analyzed associations with primary care supply accessibility, area of residence, nationality, as well as individual health insurance premium reduction and having a supplementary coverage, which serve as proxy measures for socioeconomic status. Prevalence estimates are based on logit regressions. Results: In the first seven months of life, 3.4% of children had never visited a primary care physician (pediatrician or GP), and 17% had had less than the four consultations recommended for screening purposes. In the first year (0 to 13 months) the non-uptake of any primary care consultations decreased to 2.1%. Taking hospital care into consideration, the share of children that did not have any contact with a care provider decreased to 1.1%. Foreign nationality, living in rural areas, low accessibility of primary care services, and not having a supplementary coverage are associated with lower uptake of pediatric consultations. Discussion: Most children seem to have an adequate number of health care consultations in early childhood. However, in rural areas, a substantial share of pediatric care is provided by GPs and not by specialized pediatricians. Also, there seem to be barriers to pediatric care for a few children who do not have any or not at least the number of consultations corresponding to the national screening recommendations

COVID-19 hospitalization outcomes in adults by HIV status; a nation-wide register-based study

Objectives: To assess the outcome of patients hospitalized with COVID-19 by HIV status and risk factors for severe COVID-19 in people living with HIV (PWH), we performed a nationwide cohort study using register data. Methods: All people aged ≥18 years hospitalized with a primary COVID-19 diagnosis (U07.1 or U07.2) in Sweden between February 2020 and October 2021 were included. The primary outcome was severe COVID-19 [intensive care unit (ICU) admission or 90-day mortality]. Secondary outcomes were days in hospital and ICU, complications in hospital, and risk factors for severe COVID-19 in PWH. Regression analyses were performed to assess severe COVID-19 by HIV status and risk factors. Results: Data from 64 815 hospitalized patients were collected, of whom 121 were PWH (0.18%). PWH were younger (p < 0.001), and larger proportions were men (p = 0.014) and migrants (p < 0.001). Almost all PWH had undetectable HIV-RNA (93%) and high CD4 T-cell counts (median = 560 cells/μL, interquartile range: 376–780). In an unadjusted model, PWH had statistically significant lower odds of severe COVID-19 compared with patients without HIV [odds ratio (OR) = 0.6, 95% confidence interval (CI): 0.34–0.94], but there was no significant difference after adjusting for age and comorbidity (adjusted OR = 0.7, 95% CI: 0.43–1.26). A statistically significant lower proportion of PWH (8%, 95% CI: 5–15%) died within 90 days compared with those without HIV (16%, 95% CI: 15–16%, p = 0.024). There was no statistically significant difference in days in hospital and complications during the hospital stay between PWH and patients without HIV. Conclusions: In this nationwide study including well-treated PWH, HIV was not a risk factor in hospitalized patients for developing severe COVID-19

The clinical impact of implementing GenMark ePlex blood culture panels for around-the-clock blood culture identification; a prospective observational study

Background:Implementing rapid molecular blood culture diagnostics in the clinical management of sepsis is essential for early pathogen identification and resistance gene testing. The GenMark ePlex blood culture panels offer a broad microbial spectrum with minimal hands-on time and approximately 1.5 h to result. Therefore, ePlex can be utilized at times when the clinical microbiology laboratory is unavailable. Methods:From 23 October 2019 to 30 December 2019, consecutive non-duplicate positive blood cultures signalling microbial growth at the 24 h/7 days-a-week available clinical chemistry laboratory between 9 pm and 7 am were analysed with ePlex. All blood cultures were transported to the microbiology laboratory the following day for conventional identification and antibiotic susceptibility testing. Results:We used ePlex to test 91 blood cultures, of which 86 had confirmed microbial growth. Eighty-one were positive for ePlex target pathogens. The ePlex results were in complete agreement with conventional methods in 72/81 (88.9%) of cases and available within a median of 10.9 h earlier. Resistance gene targets (11mecA and 1 CTX-M) were concordant with phenotypic susceptibility in all cases. In 18/86 (20.9%) of the patient cases, there was an opportunity to optimize antimicrobial therapy based on the ePlex result. The ePlex result affected clinical decision-making in 4/86 (4.7%) of the cases and reduced the average time to effective antimicrobial therapy by 8.9 h. Conclusions:Our implementation of ePlex is a feasible option to attain around-the-clock blood culture identification in many hospitals. It can significantly reduce time-to-pathogen identification and have an impact on clinical decision-making

Incidence and costs of hypoglycemia in insulin-treated diabetes in Switzerland: A health-economic analysis

AIMS We assess the incidence and economic burden of severe and non-severe hypoglycemia in insulin-treated diabetes type 1 and 2 patients in Switzerland. METHODS We developed a health economic model to assess the incidence of hypoglycemia, the subsequent medical costs, and the production losses in insulin-treated diabetes patients. The model distinguishes between severity of hypoglycemia, type of diabetes, and type of medical care. We used survey data, health statistics, and health care utilization data extracted from primary studies. RESULTS The number of hypoglycemic events in 2017 was estimated at 1.3 million in type 1 diabetes patients and at 0.7 million in insulin-treated type 2 diabetes patients. The subsequent medical costs amount to 38 million Swiss Francs (CHF), 61 % of which occur in type 2 diabetes. Outpatient visits dominate costs in both types of diabetes. Total production losses due to hypoglycemia amount to CHF 11 million. Almost 80 % of medical costs and 39 % of production losses are due to non-severe hypoglycemia. CONCLUSIONS Hypoglycemia leads to substantial socio-economic burden in Switzerland. Greater attention to non-severe hypoglycemic events and to severe hypoglycemia in type 2 diabetes could have a major impact on reducing this burden

Associations between HIV viremia during antiretroviral therapy and cardiovascular disease

OBJECTIVE: To investigate the association between HIV viremia exposure during antiretroviral therapy (ART) and cardiovascular disease (CVD) risk.DESIGN: Nationwide observational cohort.METHODS: Participants (age > 15 years) from the Swedish nationwide InfCareHIV register initiating ART 1996-2017 were categorized in a time-updated manner into four viremia categories, starting from 12 months after ART initiation: suppression (<50 copies/ml), low-level viremia (50-199 copies/ml and 200-999 copies/ml, respectively), and high-level viremia (≥1000 copies/ml). In addition, cumulative viremia was estimated as the area under the log viral load (VL) curve. Proportional subhazard models adjusted for sex, age, pre-ART CD4 and VL, injection drug use, and country of birth were used to analyze the association between viremia exposure and CVD risk (ischemic heart disease, stroke, and heart failure; data obtained by linkage to national registers), accounting for the competing risk of non-CVD death.RESULTS: In all, 337 cases of CVD were observed during 44 937 person-years of follow-up (n = 6562). Higher viremia exposure was associated with CVD, both when parameterized as cumulative viremia (adjusted subhazard ratio [aSHR] per 1 log10 copy × year/ml, 1.03; 95% confidence interval [CI], 1.01-1.05) and as viremia category (aSHR for high-level viremia versus suppression, 1.45; 95% CI, 1.03-2.05). We observed no association between CVD and low-level viremia compared with those with suppression.CONCLUSIONS: Higher exposure to HIV viremia was linked to CVD in ART recipients, whereas no increased risk was detected for people with low-level viremia compared with viral suppression. Causal inference is limited by the observational nature of this study

Cohort profile: InfCareHIV, a prospective registry-based cohort study of people with diagnosed HIV in Sweden

PURPOSE: The Swedish InfCareHIV cohort was established in 2003 to ensure equal and effective care of people living with HIV (PLHIV) and enable long-term follow-up. InfCareHIV functions equally as a decision support system as a quality registry, ensuring up-to-date data reported in real time.PARTICIPANTS: InfCareHIV includes data on >99% of all people with diagnosed HIV in Sweden and up to now 13 029 have been included in the cohort. InfCareHIV includes data on HIV-related biomarkers and antiretroviral therapies (ART) and also on demographics, patient-reported outcome measures and patient-reported experience measures.FINDINGS TO DATE: Sweden was in 2015 the first country to reach the UNAIDS (United Nations Programme on HIV/AIDS)/WHO's 90-90-90 goals. Late diagnosis of HIV infection was identified as a key problem in the Swedish HIV-epidemic, and low-level HIV viraemia while on ART associated with all-cause mortality. Increased HIV RNA load in the cerebrospinal fluid (CSF) despite suppression of the plasma viral load was found in 5% of PLHIV, a phenomenon referred to as 'CSF viral escape'. Dolutegravir-based treatment in PLHIV with pre-existing nucleoside reverse transcriptase inhibitor-mutations was non-inferior to protease inhibitor-based regimens. An increase of transmitted drug resistance was observed in the InfCareHIV cohort. Lower efficacy for protease inhibitors was not due to lower adherence to treatment. Incidence of type 2 diabetes and insulin resistance was high in the ageing HIV population. Despite ART, the risk of infection-related cancer as well as lung cancer was increased in PLHIV compared with HIV-negative. PLHIV were less likely successfully treated for cervical precancer and more likely to have human papillomavirus types not included in current HPV vaccines. Self-reported sexual satisfaction in PLHIV is improving and is higher in women than men.FUTURE PLANS: InfCareHIV provides a unique base to study and further improve long-term treatment outcomes, comorbidity management and health-related quality of life in people with HIV in Sweden