Questioning risk compensation: pre-exposure prophylaxis (PrEP) and sexually transmitted infections among men who have sex with men, capital region of Denmark, 2019 to 2022.

BackgroundPre-exposure prophylaxis (PrEP) effectively prevents HIV, but its association with sexually transmitted infections (STIs) has raised concerns about risk compensation, potentially impacting the expansion of PrEP programmes.AimWe examined the relationship between PrEP and the incidence of chlamydia, gonorrhoea and syphilis.MethodsIn this prospective cohort study, we compared STI rates before and after PrEP initiation among users in the capital region of Denmark (2019-2022), calculating incidence rate ratios adjusted for age and testing frequency (aIRR). To pinpoint when increases began, we plotted weekly STI rates, adjusting the timeline to correspond with PrEP initiation.ResultsThe study included 1,326 PrEP users with a median age of 35 years. The STI incidence rate per 100,000 person-years rose from 35.3 before to 81.2 after PrEP start, with an aIRR of 1.35 (95% CI: 1.18-1.56). Notably, this increase preceded PrEP initiation by 10-20 weeks. Specific aIRR for chlamydia, gonorrhoea and syphilis were 1.23 (95% CI: 1.03-1.48), 1.24 (95% CI: 1.04-1.47) and 1.15 (95% CI: 0.76-1.72), respectively. In subanalyses for anatomical sites aIRR was 1.26 (95% CI: 1.01-1.56) for rectal chlamydia and 0.66 (95% CI: 0.45-0.96) for genital gonorrhoea.ConclusionWe found a 35% increase in STI incidence associated with PrEP use. It started before PrEP initiation, challenging the assumption that PrEP leads to risk compensation. Instead, the data suggest that individuals seek PrEP during periods of heightened sexual risk-taking. Consequently, PrEP programmes should include sexual health consultations, STI testing, treatment and prevention strategies to prevent HIV and improve sexual health.

Mortality and cause of death in persons with chronic hepatitis B virus infection versus healthy persons from the general population in Denmark.

The study aimed to determine adjusted all-cause mortality and cause of death in persons with chronic hepatitis B virus (HBV) infection compared with age- and sex-matched persons from the general population. We used nationwide registers to identify persons aged ≥18 years with chronic HBV infection in 2002-2017 in Denmark and included 10 age- and sex-matched controls for each. Follow-up was from 6 months after diagnosis until death, emigration, or 31 December 2017. Mortality rate ratios (MRRs) adjusted for age, sex, employment, origin and comorbidity were calculated using Poisson regression. Unadjusted cause-specific mortality rate ratios with 95% confidence intervals were calculated assuming a Poisson distribution. A total of 6988 persons with chronic HBV infection and 69,847 controls were included. During a median follow-up of 7.7 years (range 0.0-15.5), 315 (5%) persons with-and 1525 (2%) without-chronic HBV infection died. The adjusted all-cause MRR was 1.5 (95% CI 1.2-2.0). Persons with chronic HBV infection had increased mortality due to liver disease including hepatocellular carcinoma (MRR 12.3 [8.6-17.7]), external causes (MRR 3.3 [2.5-4.7]), endocrine disease (MRR 3.2 [1.8-5.4]), genitourinary disease (MRR 3.2 [1.2-7.6]) and neoplasms (except hepatocellular carcinoma; MRR 1.6 [1.2-2.0]). In conclusion, this study showed an increased all-cause mortality in persons with chronic HBV infection in comparison with age- and sex-matched persons without chronic HBV infection which remained after adjustment for several confounding factors. Excess mortality was mainly associated with liver disease, but also external factors, endocrine disease, genitourinary disease and neoplasms (excluding hepatocellular carcinoma).

Evaluation of commercially available immuno-magnetic agglutination in comparison to enzyme-linked immunosorbent assays for rapid point-of-care diagnostics of COVID-19.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is caused by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Fast, accurate, and simple blood-based assays for quantification of anti-SARS-CoV-2 antibodies are urgently needed to identify infected individuals and keep track of the spread of disease. METHODS: The study included 33 plasma samples from 20 individuals with confirmed COVID-19 by real-time reverse-transcriptase polymerase chain reaction and 40 non-COVID-19 plasma samples. Anti-SARS-CoV-2 immunoglobulin M (IgM)/immunoglobulin A (IgA) or immunoglobulin G (IgG) antibodies were detected by a microfluidic quantitative immunomagnetic assay (IMA) (ViroTrack Sero COVID IgM + IgA/IgG Ab, Blusense Diagnostics) and compared to an enzyme-linked immunosorbent assay (ELISA) (EuroImmun Medizinische Labordiagnostika). RESULTS: Of the 33 plasma samples from the COVID-19 patients, 28 were positive for IgA/IgM or IgG by IMA and 29 samples were positive by ELISA. Sensitivity for only one sample per patient was 68% for IgA + IgM and 75% IgG by IMA and 80% by ELISA. For samples collected 14 days after symptom onset, the sensitivity of both IMA and ELISA was around 91%. The specificity of the IMA reached 100% compared to 95% for ELISA IgA and 97.5% for ELISA IgG. CONCLUSION: IMA for COVID-19 is a rapid simple-to-use point-of-care test with sensitivity and specificity similar to a commercial ELISA.

Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery.

BACKGROUND: Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality. METHODS: We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/µL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality. RESULTS: Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/µL. The increased mortality was seen across different patient groups and for all causes of death. CONCLUSIONS: Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality.

Pre-exposure prophylaxis against HIV infection.

Pre-exposure prophylaxis (PrEP) decreases the risk for HIV transmission in high-risk populations. PrEP has been available in Denmark since 2019 and consists of antiretroviral drugs in a combination tablet taken daily or on demand. The effect of this prophylaxis in Denmark is summarized in the review. PrEP is indicated in men and transgender persons with unprotected anal intercourse with multiple male partners in the latest 12 weeks or recent diagnoses of syphilis, chlamydia, or gonorrhoea. PrEP is provided by infectious disease specialists. Continued implementation could significantly reduce HIV transmission and potentially end the epidemic in Denmark.

Prospective screening for monkeypox infection among users of HIV pre-exposure prophylaxis in Denmark.

INTRODUCTION: During the 2022 outbreak of mpox (previously called monkeypox), which primarily affected Gay, Bisexual, and other Men who have Sex with Men (GBMSM), testing was mainly limited to individuals with symptoms of infection. Although sporadic cases of mpox continue to be diagnosed in Denmark, the feasibility of screening asymptomatic high-risk populations, such as those using HIV pre-exposure prophylaxis (PrEP), is still unknown. METHODS: During the autumn of 2022, a rectal swab test for mpox PCR was included in the routine sexually transmitted infections (STI) screening for PrEP users. RESULTS: The screening included 224 asymptomatic men with a median age of 36.5 years. One patient (0.4%) tested positive for mpox. Ten (4.5%) and nine (4.0%) had chlamydia and gonorrhea, respectively. DISCUSSION: Our study demonstrates that screening for mpox is feasible in two Danish PrEP clinics.

Existing Data Sources in Clinical Epidemiology: Database of Community Acquired Infections Requiring Hospital Referral in Eastern Denmark (DCAIED) 2018-2021.

Infectious diseases are major health care challenges globally and a prevalent cause of admission to emergency departments. Epidemiologic characteristics and outcomes based on population level data are limited. The Database of Community Acquired Infections in Eastern Denmark (DCAIED) 2018-2021 was established with the aim to explore and estimate the population characteristics, and outcomes of patients suffering from community acquired infections at the emergency departments in the Capital Region and the Zealand Region of Denmark using data from electronic medical records. Adult patients (≥18 years) presenting to the emergency department with suspected or confirmed infection are included in the cohort. Presence of sepsis and organ failure are assessed using modified criteria from the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). During the inclusion period from January 2018 to January 2022, 2,241,652 adult emergency department visits have been registered. Of these, 451,825 were unique encounters of which 60,316 fulfilled criteria of suspected infection and 28,472 fulfilled sepsis criteria and 8,027 were defined as septic shock. The database covers the entire Capital and Zealand Region of Denmark with an uptake area of 2.6 million inhabitants and includes demographic, laboratory and outcome indicators, with complete follow-up. The database is well-suited for epidemiological research for future national and international collaborations.

Renal function and incidence of chronic kidney disease in HIV patients: a Danish cohort study.

BACKGROUND: Impaired renal function is of major concern in human immunodeficiency virus (HIV)-infected patients. METHODS: We used a mixed effects linear regression model to determine estimated glomerular filtration rates (eGFRs) in a population-based cohort of incident Danish HIV patients and stratified on baseline eGFR (eGFR(B)) < 90 and ≥ 90 ml/min per 1.73 m(2). Incidence rate ratios (IRRs) for chronic kidney disease (CKD) - 2 consecutive eGFR values < 60 ml/min per 1.73 m(2) measured > 3 months apart - were estimated (time-updated Cox-regression model). RESULTS: The effect of time with HIV on eGFR was small in both strata (- 0.09 (95% confidence interval (CI) - 0.27, 0.09) and - 0.46 (95% CI - 0.64, - 0.27) ml/min per 1.73 m(2) per y). Treatment with tenofovir and indinavir was associated with lower eGFR in both strata: tenofovir - 2.00 (95% CI - 3.45, - 0.56) and - 1.94 (95% CI - 3.43, - 0.44) ml/min per 1.73 m(2) and indinavir - 2.14 (95% CI - 3.63, - 0.64) and - 3.29 (95% CI - 5.25, - 1.32) ml/min per 1.73 m(2). Nevirapine, atazanavir, and the combination of tenofovir and atazanavir were associated with lower eGFR in patients with eGFR(B) < 90 ml/min per 1.73 m(2). Highly active antiretroviral therapy (HAART) and exposure to tenofovir and atazanavir in combination were associated with CKD in patients with eGFR(B) < 90 ml/min per 1.73 m(2) (adjusted IRRs 6.08 (95% CI 2.76-13.41) and 26.75 (95% CI 9.54-75.05)). CONCLUSION: Tenofovir and indinavir reduce eGFR, while time with HIV only has a modest effect on this parameter. Low eGFR(B) is associated with an increased risk of CKD, especially when receiving HAART regimens containing the combination tenofovir/atazanavir.

Late presenters, repeated testing, and missed opportunities in a Danish nationwide HIV cohort.

BACKGROUND: We aimed to estimate the incidence and predictors of late presentation among human immunodeficiency virus (HIV)-infected individuals in Denmark. METHODS: Incidence rates (IR) of presentation with advanced HIV (CD4 < 200 cells/µl and/or acquired immune deficiency syndrome (AIDS)) and late presentation (CD4 < 350 cells/µl and/or AIDS) were calculated per 100,000 population aged 16-60 y. Mortality rate ratios (MRR) were estimated using Poisson regression analysis. RESULTS: Three thousand and twenty-seven individuals were diagnosed with HIV in 1995-2009; 34.7% presented with advanced HIV and 51.2% were late presenters. The IR of HIV was stable (6.2/100,000 population), but IR of presentation with advanced HIV declined during the study period from 2.2 (95% confidence interval (CI) 1.8-2.8) to 1.1 (95% CI 0.8-1.5). Age >50 y, heterosexuals of non-Danish origin, 'other' route of transmission, and diagnosis before 2002 were associated with an increased risk of presenting with advanced HIV, whereas a negative HIV test prior to diagnosis was associated with a significantly reduced risk. A total of 414 individuals (40.0%) had attended a hospital 1-3 y before presenting with advanced HIV. After 2002 the proportion of men who have sex with men with a negative HIV test prior to diagnosis increased (incidence rate ratio (IRR) 1.3, 95% CI 1.1-1.6), coinciding with a reduction in IR of presentation with advanced HIV. Mortality rates were increased the first 2 y following presentation with advanced HIV (MRR 5.9, 95% CI 3.6-9.4 and MRR 2.5, 95% CI 1.4-4.1, respectively). CONCLUSION: In a setting with a low HIV prevalence, the rate of presentation with advanced HIV can potentially be reduced by repeated HIV testing of individuals with a continuous high risk of transmission and by adhering to guidelines for targeted HIV testing.

Rapid Quantitative Point-Of-Care Diagnostic Test for Post COVID-19 Vaccination Antibody Monitoring.

Point-of-care (POC) quantification of antibody responses against SARS-CoV-2 spike protein can enable decentralized monitoring of immune responses after infection or vaccination. We evaluated a novel POC microfluidic cartridge-based device (ViroTrack Sero COVID-19 Total Ab) for quantitative detection of total antibodies against SARS-CoV-2 spike trimeric spike protein compared to standard laboratory chemiluminescence (CLIA)-based tests. Antibody responses of 101 individuals were measured on capillary blood, venous whole blood, plasma, and diluted plasma samples directly on the POC. Results were available within 7 min. As the reference, plasma samples were analyzed on DiaSorin LIAISON XL CLIA analyzer using LIAISON SARS-CoV-2 IgM, LIAISON SARS-CoV-2 S1/S2 IgG, and LIAISON SARS-CoV-2 TrimericS IgG assays. The Spearman rank's correlation coefficient between ViroTrack Sero COVID-19 Total Ab and LIAISON SARS-CoV-2 S1/S2 IgG and LIAISON SARS-CoV-2 TrimericS IgG assays was found to be 0.83 and 0.89, respectively. ViroTrack Sero COVID-19 Total Ab showed high correlation between the different matrixes. Agreement for determination of samples of >230 binding antibody units (BAU)/mL on POC and CLIA methods is estimated to be around 90%. ViroTrack Sero Covid Total Ab is a rapid and simple-to-use POC test with high sensitivity and correlation of numerical results expressed in BAU/mL compared to those of a commercial CLIA assay. IMPORTANCE Serological testing is an important diagnostic support tool in the fight against COVID-19. So far, serological testing has been performed on either lateral flow assays, which perform only qualitatively and can be difficult for the individual to read, or standard laboratory assays, which are time- and resource-consuming. The purpose of the study was to evaluate the performance of a new POC microfluidic cartridge-based device based on immunomagnetic agglutination assay that can provide an accurate numerical quantification of the total antibodies within only 7 min from a single drop of capillary blood. We demonstrated a high level of correlation between the POC and the two CLIA laboratory-based immunoassays from Diasorin, thus allowing a potentially wider use of quantitative serology tests in the COVID-19 pandemic.

Incidence of Hepatocellular Carcinoma and Decompensated Liver Cirrhosis and Prognostic Accuracy of the PAGE-B HCC Risk Score in a Low Endemic Hepatitis B Virus Infected Population.

Purpose: We aimed to determine incidence of hepatocellular carcinoma (HCC) and decompensated liver cirrhosis in persons with chronic hepatitis B virus (HBV) infection in Denmark stratified by disease phase, liver cirrhosis, and treatment status at baseline. Additionally, we aimed to assess the prognostic value of the PAGE-B HCC risk score in a mainly non-cirrhotic population. Patients and Methods: In this register-based cohort study, we included all individuals over the age of 18, with chronic HBV infection first registered between 2002 and 2016 in at least one of three nationwide registers. The study population was followed until HCC, decompensated liver cirrhosis, death, emigration, or December 31, 2017, which ever came first. Results: Among 6016 individuals included in the study, 10 individuals with and 23 without baseline liver cirrhosis developed HCC during a median follow up of 7.3 years (range 0.0-15.5). This corresponded to five-year cumulative incidences of 7.1% (95% confidence interval (CI) 2.0-12.3) and 0.2% (95% CI 0.1-0.4) in persons with and without baseline liver cirrhosis. The five-year cumulative incidence of decompensated liver cirrhosis was 0.7% (95% CI 0.5-1.0). Among 2038 evaluated for liver events stratified by disease phase, incidence of HCC was low in all who were non-cirrhotic and untreated for HBV at baseline. PAGE-B score was evaluated in 1529 persons. The 5-year cumulative incidence of HCC was 0, 0.8 (95% CI 0.5-1.8), and 8.7 (95% CI 1.0-16.4) in persons scoring <10, 10-17 and >17, respectively (c-statistic 0.91 (95% CI 0.84-0.98)). Conclusion: We found low incidence of HCC and decompensated liver cirrhosis in persons with chronic HBV infection in Denmark. Moreover, the PAGE-B score showed good accuracy for five-year risk of developing HCC in the population with chronic HBV infection in Denmark.

Ischemic Heart Disease in Chronic Hepatitis B: A Danish Nationwide Cohort Study.

Objective: Data on the risk of ischemic heart disease (IHD) in patients with chronic hepatitis B virus (CHB) are conflicting. Our objective was to address the rate of IHD in patients with CHB compared with individuals without CHB (control-persons) from the general population. Study Design and Setting: We conducted a cohort study of prospectively obtained data from Danish nationwide registries. We produced cumulative incidence curves and calculated the unadjusted incidence rate ratio (IRR) of IHD in persons with and without CHB. The adjusted association between having CHB and developing IHD was examined using a cause-specific Cox regression model. Results: In total, 6472 persons with CHB and 62,251 age- and sex-matched individuals from the general population were followed for 48,840 and 567,456 person-years, respectively, during which 103 (1,59%) with CHB and 1058 (1,70%) control-persons developed IHD. The crude IRR was 1.13 (95% CI: 0.91-1.39). CHB did not have a statistically significant effect on the rate of IHD after adjusting for several confounding factors (adjusted hazard ratio: 0.96, 95% CI: 0.76-1.21). Conclusion: In this nationwide cohort study, we did not find any difference between rate of IHD in persons with CHB in comparison with the general population.

Incidence and impact on mortality of severe neurocognitive disorders in persons with and without HIV infection: a Danish nationwide cohort study.

OBJECTIVE: The risk of neurocognitive disorders in human immunodeficiency virus (HIV)-infected patients in the era of highly active antiretroviral therapy (HAART) is controversial. We aimed to compare the incidence and impact on mortality of severe neurocognitive disorders (SNCDs) in HIV-infected patients with that of the background population. METHODS: The method used was a nationwide, population-based cohort study using Danish registries. We calculated incidence rates, incidence rate ratios, mortality rate ratios, and Kaplan-Meier tables to estimate the incidence of and survival after SNCD in HIV-infected patients, compared with a general population control cohort matched by age and sex. RESULTS: We observed 32 cases of SNCDs among 4452 HIV-infected patients and 120 cases of SNCDs among 62 328 population control subjects. The overall risk of SNCD among HIV-infected patients was 1.0 case per 1000 person-years (PYR), compared with 0.23 cases per 1000 PYR for population control subjects but became 0.35 cases/1000 PYR after 2004, compared with 0.27 cases/1000 PYR in population control subjects. The absence of HAART and a low CD4 lymphocyte count increased the risk of SNCD. The mortality among HIV-infected patients with SNCD was higher than that among population controls with SNCD (median survival, 4.3 years vs 9.7 years [P = .02]). CONCLUSION: HIV-infected patients have an increased risk of SNCD, but the risk is low and has, in recent years, become comparable to that seen in the background population. In contrast, the mortality remains high among HIV-infected patients diagnosed with SNCD.

Lung cancer in HIV patients and their parents: a Danish cohort study.

BACKGROUND: HIV patients are known to be at increased risk of lung cancer but the risk factors behind this are unclear. METHODS: We estimated the cumulative incidence and relative risk of lung cancer in 1) a population of all Danish HIV patients identified from the Danish HIV Cohort Study (n = 5,053) and a cohort of population controls matched on age and gender (n = 50,530) (study period; 1995 - 2009) and 2) their parents (study period; 1969 - 2009). Mortality and relative risk of death after a diagnosis of lung cancer was estimated in both populations. RESULTS: 29 (0.6%) HIV patients vs. 183 (0.4%) population controls were diagnosed with lung cancer in the observation period. HIV patients had an increased risk of lung cancer (adjusted incidence rate ratio (IRR); 2.38 (95% CI; 1.61 - 3.53)). The IRR was considerably increased in HIV patients who were smokers or former smokers (adjusted IRR; 4.06 (95% CI; 2.66 - 6.21)), male HIV patients with heterosexual route of infection (adjusted IRR; 4.19 (2.20 - 7.96)) and HIV patients with immunosuppression (adjusted IRR; 3.25 (2.01 - 5.24)). Both fathers and mothers of HIV patients had an increased risk of lung cancer (adjusted IRR for fathers; 1.31 (95% CI: 1.09 - 1.58), adjusted IRR for mothers 1.35 (95% CI: 1.07 - 1.70)). Mortality after lung cancer diagnose was increased in HIV patients (adjusted mortality rate ratio 2.33 (95%CI; 1.51 - 3.61), but not in the parents. All HIV patients diagnosed with lung cancer were smokers or former smokers. CONCLUSION: The risk was especially increased in HIV patients who were smokers or former smokers, heterosexually infected men or immunosuppressed. HIV appears to be a marker of behavioural or family related risk factors that affect the incidence of lung cancer in HIV patients.

Predictors of unsafe sex among HIV patients in Denmark: a population-based cohort study.

UNLABELLED: Abstract Background: Sexual transmission continues to be the primary mode of human immunodeficiency virus (HIV) infection in Western Europe. We aimed to describe predictors of unsafe sex and reasons given for such behaviour. METHODS: We performed a survey examining sexual risk behaviours and reasons for unsafe sex in a nationwide cohort of adult Danish HIV-1-positive patients. Differences in characteristics between those who practiced safe and unsafe sex were estimated by binary logistic regression. The fraction with detectable viral load was determined in the 2 groups, and reasons for unsafe sex were evaluated. RESULTS: Of 812 eligible patients, a total of 275 (34%) had engaged in unsafe sex with an HIV-negative partner or a partner with unknown HIV status in the previous year. On multivariate analysis, men who have sex with men (MSM) was the only statistically significant risk factor associated with unsafe sex (odds ratio 3.24, 95% confidence interval 1.72-6.12). The main reason for practicing unsafe sex was that the partner did not wish to use a condom (53%). CONCLUSIONS: A high proportion of HIV-positive patients engage in unsafe sex, especially MSM. The reasons for unsafe sex are primarily linked to negotiation issues concerning condom use, including assumptions about the sexual partner's intent.

Incidence, risk factors and mortality of tuberculosis in Danish HIV patients 1995-2007.

BACKGROUND: Human Immunodeficiency Virus (HIV) infection predisposes to tuberculosis (TB). We described incidence, risk factors and prognosis of TB in HIV-1 infected patients during pre (1995-1996), early (1997-1999), and late Highly Active Antiretroviral Therapy (HAART) (2000-2007) periods. METHODS: We included patients from a population-based, multicenter, nationwide cohort. We calculated incidence rates (IRs) and mortality rates (MRs). Cox's regression analysis was used to estimate risk factors for TB infection with HAART initiation included as time updated variable. Kaplan-Meier was used to estimate mortality after TB. RESULTS: Among 2,668 patients identified, 120 patients developed TB during the follow-up period. The overall IR was 8.2 cases of TB/1,000 person-years of follow-up (PYR). IRs decreased during the pre-, early and late-HAART periods (37.1/1000 PYR, 12.9/1000 PYR and 6.5/1000 PYR respectively). African and Asian origin, low CD4 cell count and heterosexual and injection drug user route of HIV transmission were risk factors for TB and start of HAART reduced the risk substantially. The overall MR in TB patients was 34.4 deaths per 1,000 PYR (95% Confidence Interval: 22.0-54.0) and was highest in the first two years after the diagnosis of TB. CONCLUSIONS: Incidence of TB still associated with conventional risk factors as country of birth, low CD4 count and route of HIV infection while HAART reduces the risk substantially. The mortality in this patient population is high in the first two years after TB diagnosis.

Risk Factors for Being Seronegative following SARS-CoV-2 Infection in a Large Cohort of Health Care Workers in Denmark.

Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but being seronegative is observed in 1 to 9%. We aimed to investigate the risk factors associated with being seronegative following PCR-confirmed SARS-CoV-2 infection. In a prospective cohort study, we screened health care workers (HCW) in the Capital Region of Denmark for SARS-CoV-2 antibodies. We performed three rounds of screening from April to October 2020 using an enzyme-linked immunosorbent assay (ELISA) method targeting SARS-CoV-2 total antibodies. Data on all participants' PCR for SARS-CoV-2 RNA were captured from national registries. The Kaplan-Meier method and Cox proportional hazards models were applied to investigate the probability of being seronegative and the related risk factors, respectively. Of 36,583 HCW, 866 (2.4%) had a positive PCR before or during the study period. The median (interquartile range [IQR]) age of 866 HCW was 42 (31 to 53) years, and 666 (77%) were female. After a median of 132 (range, 35 to 180) days, 21 (2.4%) of 866 were seronegative. In a multivariable model, independent risk factors for being seronegative were self-reported asymptomatic or mild infection hazard ratio (HR) of 6.6 (95% confidence interval [CI], 2.6 to 17; P < 0.001) and body mass index (BMI) of ≥30, HR 3.1 (95% CI, 1.1 to 8.8; P = 0.039). Only a few (2.4%) HCW were not seropositive. Asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges. IMPORTANCE Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but negative serology is observed in 1 to 9%. We found that asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges.

Long-term mortality in patients diagnosed with pneumococcal meningitis: a Danish nationwide cohort study.

The objective of the study was to determine the long-term mortality and the causes of death in patients diagnosed with pneumococcal meningitis. The authors performed a nationwide, population-based cohort study including all Danish patients diagnosed with pneumococcal meningitis from 1977 through 2006 and alive 1 year after diagnosis. Data were retrieved from medical databases in Denmark. The absolute and relative risks of all-cause and cause-specific death were analyzed by using Kaplan-Meier survival curves, Poisson regression analysis, Cox regression analysis, and cumulative incidence functions. The authors identified 2,131 pneumococcal meningitis patients and an age- and gender-matched, population-based cohort of 8,524 individuals. Compared with the background population, the pneumococcal meningitis patients had an increased long-term mortality varying from an 8-fold increased mortality in the age category 0-<20 years to a 1.5-fold increased mortality in those aged 60-<80 years. The increased risk of death stemmed from neoplasms, liver diseases, and nervous system diseases. The excess mortality due to neoplasms stemmed mainly from a 5-fold increased risk of death due to hematologic neoplasms. To improve survival in patients surviving the acute phase of pneumococcal meningitis, physicians should meticulously screen this patient population for neurologic sequelae and comorbidity predisposing to the disease.

Long-term mortality in HIV patients virally suppressed for more than three years with incomplete CD4 recovery: a cohort study.

BACKGROUND: The mortality in patients with persistent low CD4 count despite several years of HAART with sustained viral suppression is poorly documented. We aimed to identify predictors for inadequate CD4 cell recovery and estimate mortality in patients with low CD4 count but otherwise successful HAART. METHOD: In a nationwide cohort of HIV patients we identified all individuals who started HAART before 1 January 2005 with CD4 cell count ≤ 200 cells/µL and experienced three years with sustained viral suppression. Patients were categorized according to CD4 cell count after the three years suppressed period (≤ 200 cells/µL; immunological non-responders (INRs), >200 cells/µL; immunological responders (IRs)). We used logistic regression and Kaplan-Meier analysis to estimated risk factors and mortality for INRs compared to IRs. RESULTS: We identified 55 INRs and 236 IRs. In adjusted analysis age > 40 years and > one year from first CD4 cell count ≤ 200 cells/µL to start of the virologically suppressed period were associated with increased risk of INR. INRs had substantially higher mortality compared to IRs. The excess mortality was mainly seen in the INR group with > one year of immunological suppression prior to viral suppression and injection drug users (IDUs). CONCLUSION: Age and prolonged periods of immune deficiency prior to successful HAART are risk factors for incomplete CD4 cell recovery. INRs have substantially increased long-term mortality mainly associated with prolonged immunological suppression prior to viral suppression and IDU.

Retrivability in The Danish National Hospital Registry of HIV and hepatitis B and C coinfection diagnoses of patients managed in HIV centers 1995-2004.

BACKGROUND: Hospital-based discharge registries are used increasingly for longitudinal epidemiological studies of HIV. We examined completeness of registration of HIV infections and of chronic hepatitis B (HBV) and hepatitis C (HCV) coinfections in the Danish National Hospital Registry (DNHR) covering all Danish hospitals. METHODS: The Danish HIV Cohort Study (DHCS) encompasses all HIV-infected patients treated in Danish HIV clinics since 1 January 1995. All 2,033 Danish patients in DHCS diagnosed with HIV-1 during the 10-year period from 1 January 1995 to 31 December 2004 were included in the current analysis. We used the DHCS as a reference to examine the completeness of HIV and of HBV and HCV coinfections recorded in DNHR. Cox regression analysis was used to estimate hazard ratios of time to diagnosis of HIV in DNHR compared to DHCS. RESULTS: Of the 2,033 HIV patients in DHCS, a total of 2,006 (99%) were registered with HIV in DNHR. Of these, 1,888 (93%) were registered in DNHR within one year of their first positive HIV test. A CD4 < 200 cells/microl, a viral load > or = 100,000 copies/ml and being diagnosed after 1 January 2000, were associated with earlier registration in DNHR, both in crude and adjusted analyses. Thirty (23%) HIV patients registered with chronic HBV (n = 129) in DHCS and 126 (48%) of HIV patients with HCV (n = 264) in DHCS were registered with these diagnoses in the DNHR. Further 17 and 8 patients were registered with HBV and HCV respectively in DNHR, but not in DHCS. The positive predictive values of being registered with HBV and HCV in DHCS were thereby estimated to 0.88 and 0.97 and in DNHR to 0.32 and 0.54. CONCLUSION: The study demonstrates that secondary data from national hospital databases may be reliable for identification of patients diagnosed with HIV infection. However, the predictive value of co-morbidity data may be low.