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Objectives: To investigate receipt of antibiotics among patients with neuroborreliosis after initial antibiotic treatment, likely attributable to posttreatment symptoms., Methods: We performed a nationwide, matched, population-based cohort study in Denmark (2009-2021). We included all Danish patients with neuroborreliosis, i.e. a positive Borrelia burgdorferi intrathecal antibody index test and a cerebrospinal fluid leukocyte count ≥10 × 10 6 /l, and initially treated with doxycycline. To form a comparison cohort, we randomly extracted individuals from the general population matched 1:10 to patients with neuroborreliosis on date of birth and sex. The main outcome was receipt of doxycycline, and the secondary outcome was receipt of phenoxymethylpenicillin. We calculated short-term (<1 year) and long-term (≥1 year) hazard ratios (HR) with 95% confidence intervals (95%CI)., Results: We included 463 patients with neuroborreliosis and 2,315 comparison cohort members. Compared with the comparison cohort members, patients with neuroborreliosis initially treated with doxycycline had increased receipt of additional doxycycline within 1 year (HR: 38.6, 95%CI: 17.5-85.0) and ≥1 years (HR: 3.5, 95%CI: 1.9-6.3). Compared with comparison cohort members, patients with neuroborreliosis had no increased receipt of phenoxymethylpenicillin (<1 year HR 1.0, 95%CI: 0.7-1.3; ≥1 years HR 1.2, 95%CI: 0.9-1.5)., Conclusions: After initial antibiotic treatment, patients with neuroborreliosis have increased receipt of doxycycline particularly within one year after initial antibiotic therapy but also subsequently. The lack of increased receipt of phenoxymethylpenicillin suggests that the receipt of doxycycline was not merely due to differences in healthcare-seeking behaviour, increased risk of early Lyme borreliosis due to exposure, or differences in antibacterial usage in general.

Background: Few studies have investigated the risk of psychiatric neurodevelopmental disorders (PNDD) after childhood meningitis., Methods: Nationwide population-based cohort study (Denmark, 1995-2021) of children with positive cerebrospinal fluid for bacteria or enterovirus, stratified on age as young infants (0 to <90 days, n  = 637) or older children (≥90 days to <17 years, n  = 1,218). We constructed a comparison cohort from the general population ( n  = 18,550), and cohorts of siblings of participants. As risk estimates of PNDD we calculated age- and sex-adjusted hazard ratios (aHRs) with 95% confidence intervals (95%CI)., Results: Children with bacterial meningitis had increased risks of PNDD, especially learning and intellectual developmental disorders (young infants: aHR 4.2, 95%CI: 2.4-7.1; older children: aHR 1.5, 95%CI: 1.0-2.3), attention deficit disorder (ADHD) (young infants: aHR 2.8, 95%CI: 1.5-5.2; older children: 1.4, 95%CI: 0.9-2.2) and redemption of ADHD medication (young infants: aHR 2.2, 95%CI: 1.0-4.7; older children: 1.5, 95%CI: 1.0-2.3). Young infants with bacterial meningitis additionally had increased risks of autism spectrum disorders (aHR 1.9, 95%CI: 0.9-4.1) and behavioural and emotional disorders (aHR 2.0, 95%CI: 1.0-3.9). In young infants, the excess risk of PNDD was especially observed in premature children. Siblings of older children with bacterial meningitis also had increased risks of PNDD. Children with enteroviral meningitis at any age did not have increased risks of PNDD or redemption of ADHD medication., Conclusions: Bacterial meningitis in childhood is associated with subsequent diagnosis of PNDD, while enteroviral meningitis is not. The association appears to be partly explained by prematurity and familial and socioeconomic factors.

Background: It is important to understand current trends in cancer risk among people living with HIV (PLWH) to improve outcomes and to commission and delivery appropriate services., Methods: Nationwide, population-based, matched cohort study on all adult PLWH treated at Danish HIV health care centres since 1 January 1995 and a comparison cohort, randomly selected from the background population and matched on sex and date of birth., Results: We included 6327 PLWH and 63,270 individuals in the comparison cohort - 74% were men and median age was 37 (interquartile range: 30-46). For both smoking related cancers, virological cancers and other cancers, incidence was substantially higher in the first year of observation for PLWH than for the remaining observation period. The risk of smoking related cancer remained stably increased throughout the observation period, whereas the relative risk of virological cancers decreased, especially in the first year of follow up. Finally, the risk of other cancers for PLWH decreased to a level below that of the background population during the study period., Conclusion: The fact that the risk of other cancers was probably not higher among PLWH than in the comparison cohort is encouraging, as the excess risk of virological and smoking related cancers is potentially preventable by timely treatment of HIV and smoking cessation.

Objectives: It is unknown whether invasive procedures are associated with brain abscess., Methods: Nationwide, population-based, matched case-control study of patients with culture verified brain abscess in Denmark from 1989 to 2016. Exposure was invasive procedures 0-6 months before study inclusion., Results: We identified 435 patients and 3909 controls. The level of comorbidity was higher among patients with brain abscess than among controls. A total of 48 cases (11%) had one or more invasive procedures 0-6 months before study inclusion (adjusted odds ratios (aOR) of 3.6 (95% confidence interval (CI): 2.5-5.1), a population attributable fractions of 8% (95% CI: 7-9)). In primary care, ear, nose and throat (ENT) procedures were associated with brain abscess (aOR of 4.0 (95% CI: 2.0-8.0)), but gastrointestinal endoscopies were not (aOR of 1.0 (95% CI: 0.3-3.2)). No bronchoscopies were performed in primary care. In the hospital-based setting, ENT procedures, bronchoscopies and gastrointestinal endoscopies were associated with an increased risk of brain abscess (aOR of 14.5 (95% CI: 4.8-43.8), 20.3 (95% CI: 3.8-110.1) and 3.4 (95% CI: 2.0-5.6), respectively)., Conclusions: The association between invasive procedures and brain abscess was more pronounced in the hospital-based setting than in primary care.

Objectives : To evaluate the influence of low socioeconomic status (SES) on mortality among patients with granulomatosis with polyangiitis (GPA). Methods : Using nationwide registers, we established a cohort of 827 patients diagnosed with GPA in the public hospital system of Denmark. For each patient, information regarding educational level, civil status, employment status, and comorbidities at time of GPA diagnosis was collected. We used Cox regression analyses to calculate hazard ratios (HRs) adjusted for age, gender, calendar period of GPA diagnosis, and Charlson Comorbidity Index score for preceding illnesses as a measure of relative risk of death. We assessed the risk of death associated with three measures of low SES: basic schooling only, civil status as single, and being unemployed or recipient of disability pension. Results : The median age of patients at GPA diagnosis was 61 (interquartile range 51-69) years, and 508 were 18-64 years old. During a total of 4337 person-years, 237 patients died. Among patients aged 18-64 years at GPA diagnosis, all three measures of low SES were identified as risk factors for death [basic schooling only: HR = 2.04, 95% confidence interval (CI) 1.30-3.19; civil status as single: HR = 1.95, 95% CI 1.24-3.05; being unemployed or recipient of disability pension: HR = 2.96, 95% CI 1.72-5.08]. The association between low SES and mortality was less pronounced among patients aged ≥ 65 years. Conclusions : Our observations indicate that low SES is associated with increased mortality in GPA, especially among patients of working age.

Objective: To assess the long-term risk and outcome of infection-related hospitalization (IH) among patients with granulomatosis with polyangiitis (GPA)., Method: We used administrative databases to establish a GPA cohort (n = 398), construct a comparison cohort of population controls (n = 3980), and collect clinical data. Cox regression analyses were used to determine hazard ratios (HRs) as a measure of relative risk. Follow-up began at date of GPA diagnosis and continued for up to 10 years., Results: GPA patients had a markedly increased long-term risk of IH compared to controls [HR (95% confidence interval) year 1: 9.5 (7.0-12.8); years 2-5: 3.2 (2.4-4.3); years 6-10: 2.6 (1.8-3.9)]. Increased long-term risks were found for hospital-treated pneumonia, urinary tract infection, sepsis, and skin infection. We did not observe a lower risk of IH for people diagnosed with GPA during 2005-2014 than for those diagnosed during 1995-2004. Mortality at 3 and 6 months after IH did not differ significantly between patients diagnosed with vasculitis during 2005-2014 and those diagnosed during 1995-2004. Charlson Comorbidity Index score ≥1 was identified as a predictor of pneumonia and urinary tract infection in the GPA cohort, but not of sepsis or skin infection., Conclusion: Patients with GPA have a high risk of IH, even after prolonged follow-up. The long-term risk of IH and mortality after IH did not decline across recent calendar periods among Danish GPA patients. These observations underscore the need for clinical strategies to reduce the burden of infectious complications in GPA.

Aim: We investigated the use of non-antiretroviral drugs in the HIV-infected compared to the general population., Methods: From the Danish HIV Cohort Study, we identified all HIV-infected individuals older than 18 years at HIV diagnosis who received care in Denmark through 1995-2013 and reported no injection drug abuse or hepatitis C infection. Population controls were identified from The Danish Civil Registration System and matched on age and gender (5:1). We analyzed the proportion of individuals who redeemed 0-1, 2-4, 5-9, or 10 or more non-antiretroviral drugs. Data were analyzed according to calendar time, age, time from initiation of combination antiretroviral therapy (cART) and stratified by gender, geographical origin and route of HIV transmission. We further analyzed the use of the 25 most used non-antiretroviral drug classes., Results: We identified 4,928 HIV-infected individuals (median age: 37; 76.4% males). Overall, the HIV-infected population had a higher use of non-antiretroviral drugs compared to the background population. Whereas, the use of non-antiretroviral drugs in the HIV-infected population only changed marginally with time, the use in the background population increased considerably. Thus, use in the HIV-infected population only differed marginally from that of the background population in recent years. This difference was most pronounced in men who have sex with men (MSM)., Conclusion: Compared to the background population, HIV infected individuals have increased use of non-antiretroviral drugs. The excess use is mainly observed in MSM and has decreased with calendar time, why it in recent years only differs marginally from that observed in the background population.

Background: Data on long-term prognosis after spondylodiscitis are scarce. The purpose of this study was to determine long-term mortality and the causes of death after spondylodiscitis., Methods: A nationwide, population-based cohort study using national registries of patients diagnosed with non-post-operative pyogenic spondylodiscitis from 1994-2009, alive 1 year after diagnosis (n = 1505). A comparison cohort from the background population individually matched for sex and age was identified (n = 7525). Kaplan-Meier survival curves were constructed and Poisson regression analyses used to estimate mortality rate ratios (MRR)., Results: Three hundred and sixty-five patients (24%) and 1115 individuals from the comparison cohort (15%) died. Unadjusted MRR for spondylodiscitis patients was 1.76 (95% CI = 1.57-1.98) and 1.47 (95% CI = 1.30-1.66) after adjustment for comorbidity. No deaths were observed in 128 patients under the age of 16 years. Siblings of patients did not have increased long-term mortality compared with siblings of the individuals from the comparison cohort. This study observed increased mortality due to infections (MRR = 2.57), neoplasms (MRR = 1.40), endocrine (MRR = 3.72), cardiovascular (MRR = 1.62), respiratory (MRR = 1.71), gastrointestinal (MRR = 3.35), musculoskeletal (MRR = 5.39) and genitourinary diseases (MRR = 3.37), but also due to trauma, poisoning and external causes (MRR = 2.78), alcohol abuse-related diseases (MRR = 5.59) and drug abuse-related diseases (6 vs 0 deaths, MRR not calculable)., Conclusions: Patients diagnosed with spondylodiscitis have increased long-term mortality, mainly due to comorbidities, particularly substance abuse.

Background: Several studies have demonstrated an increased risk of non-AIDS cancers in HIV patients and, for some cancers, also in relatives of HIV patients. We aimed to estimate (1) the risk of anal carcinoma among HIV patients and their parents, and (2) the mortality after a diagnosis of anal carcinoma., Methods: We used Poisson regression to estimate the incidence rate ratios (IRR) of anal carcinoma in (1) a population of HIV patients identified from the Danish HIV Cohort Study (n = 4993) compared with a population control cohort matched on age and gender (n = 59,916) for the period 1995-2009, and (2) parents of HIV patients compared with parents of controls for the period 1978-2009. Cancer diagnoses were identified from The Danish Cancer Registry. We further estimated the mortality rate ratios (MRR) of HIV patients compared with controls after the diagnosis of anal carcinoma., Results: Thirty-six HIV patients versus 8 population controls were diagnosed with anal carcinoma. HIV patients had an increased risk of anal carcinoma (IRR 77.9, 95% CI 36.2-167.7), especially among men who have sex with men (MSM) (IRR 101.4, 95% CI 39.3-261.5). Fathers of HIV patients had an increased risk of anal carcinoma (IRR 7.4, 95% CI 1.4-38.3) compared to fathers of population controls. Mortality after diagnosis of anal carcinoma was increased in male HIV patients compared with the male control cohort (MRR 3.2, 95% CI 1.1-9.2)., Conclusions: Danish HIV patients, especially MSM, have a considerably increased risk of anal carcinoma. We cannot exclude that fathers of HIV patients have an increased risk of anal carcinoma.

Background: Gender differences in the risk of AIDS-defining illness (ADI) and mortality have been reported in the HIV-1-infected (HIV-positive) population, with conflicting findings. We aimed to assess the impact of gender on the risk of ADI and death in HIV-positive patients infected sexually., Methods: This was a population-based, nationwide cohort study of incident Danish HIV-positive individuals infected by sexual contact. Outcomes were progression to AIDS and death. We used Cox proportional hazards models and Poisson regression analyses to calculate the risk of progression to AIDS and mortality rate ratios (MRR) between risk groups and compared these with the general Danish population., Results: We identified 587 heterosexually infected women, 583 men who have sex with women (MSW), and 1089 men who have sex with men (MSM). The total follow-up time was 13,708 person-y. At the time of HIV diagnosis MSM had a lower prevalence of AIDS compared to MSW. Women and MSW presented more often with tuberculosis and less often with AIDS-defining cancers compared to MSM. In the adjusted analyses we observed no differences in progression to AIDS. In the adjusted analyses of risk of death, there were no differences between the 3 risk groups, although we saw a trend towards a higher risk of death in older MSW. MSM had a lower risk of death compared to the background population than women and MSW., Conclusions: In the Danish HIV population, gender has no major impact on progression to AIDS or mortality. Differences in these factors between women, MSW, and MSM are mainly due to confounding from race and CD4 + cell count at diagnosis.

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.

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.

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.

The objective of this study was to determine the effect of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected patients infected through injecting drug use (injecting drug users, IDUs) compared to patients infected via other routes (non-IDUs). We conducted a nationwide population-based cohort study of all HIV-infected patients who initiated HAART during the study period of 1 January 1995 to 31 December 2007. We compared changes in CD4(+) cell counts, percentage of full viral suppression (< 500 copies/ml) and mortality from start of HAART, as well as differences in initial HAART regimen. Three thousand six hundred and fifteen patients were included in the study, representing 22,804 person-y of observation. A total of 346 (9.6%) were categorized as IDUs. Of IDUs, 55% gained full viral control within the first y after HAART compared to 76% of non-IDUs (p = 0.0002). Absolute CD4(+) cell count and survival were lower for IDUs compared to non-IDUs (adjusted mortality rate ratio 3.6 (95% CI 2.9-4.3)). IDUs were more likely to receive a first regimen based on protease inhibitors (PIs) compared to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens for non-IDUs, and IDUs initiated HAART later than non-IDUs. In conclusion, more than half of the HIV-infected patients in Denmark infected through injecting drug use gained full viral suppression after initiating HAART. Absolute CD4(+) cell count was lower and mortality higher among IDUs than non-IDUs.

The long-term impact of highly active antiretroviral therapy (HAART) on HIV-1 infected children is not well known. The Danish Paediatric HIV Cohort Study includes all patients <16 y of age with HIV-1 infection in Denmark. We report the complete follow-up from 1996 to 2005 of 49 perinatally infected children treated with HAART. Initial HAART included 2 nucleoside reverse-transcriptase inhibitors in combination with either a protease inhibitor (n =38) or a non-nucleoside reverse-transcriptase inhibitor (n =12). 19 (39%) patients were previously treated with mono- or dual therapy. Baseline characteristics were median CD4 percentage 14% and HIV-RNA viral load 4.9 log(10). Within the first 12 weeks of therapy approximately 60% achieved HIV-RNA viral load <500 copies/ml, and this remained stable for up to 8 y, although many children changed the components of HAART. The proportion of children with CD4 percentage >25% increased to 60-70% over the y of treatment. For the total cohort, 245 patient-y of observation were available with only 1 death. During our observation period there were no signs of a waning impact. The challenge remains to maintain a high adherence to therapy as the children grow into adolescence and develop more independence from family and health care staff.

HIV-1 viral load falls rapidly on initiation of HAART. This phase of decreasing yet substantial viral production in the presence of antiretroviral drugs could generate resistant HIV-1. Whether switching a drug from a failing regime changes the demography of the mutations associated with it in the CD4+ T-cell compartment is not well-defined. We investigated the presence/absence and quantity of 184M and 184V in the CD4+ T-cell compartment of naïve patients initiated to HAART (group I), and patients who shifted to a non-lamivudine therapy (group II). We initiated a prospective 90 d follow-up study of 11 patients to detect and quantity proviral HIV-1 184M and 184V in the CD4+ T-cell compartment with a sensitive real time PCR assay. Results showed that the 184V was not detected in the CD4+ T-cell compartment of any of the 7 naïve patients who started on HAART. Three out of the 4 patients in group II experienced a fall in the percentage of 184V, with reduction to below detection limits in 2 patients. It can be concluded that initiation of HAART does not allow the archiving of the lamivudine associated mutation, 184V, in the CD4+ T-cell compartment. Reduction in the quantity of 184V when therapy is switched to an effective non-lamivudine regime indicates that the mutation in this compartment is dynamic.

We present the demographic data on HIV-infected children from the Danish Paediatric HIV Cohort Study, an observational database on HIV in Denmark. Up to 1 July 2003 a total of 89 children had been diagnosed with HIV infection before the age of 16 y, of which 12 (13.5%) had died, 2 (2.2%) had emigrated from Denmark, and 13 had reached the age of 16 y. Estimates of prevalence and incidence of HIV infection in the area were 5.77/100,000 and 0.39/100,000 respectively, which are lower than in the adult population. After 1993 the number of newly diagnosed HIV infected children remained quite constant with an average of 4.2 diagnoses per y. Of the enrolled patients only 15.7% had both their parents of Danish origin, while 58.5% had at least 1 of the parents from an African country. Of the entire cohort, 20% were Caucasians, 51% were males and 76% were infected perinatally. There has been a shift in the HIV epidemic in children over recent y, with a higher proportion of newly diagnosed HIV patients having contracted the infection perinatally, a higher proportion being of non-Caucasian race, and the newly diagnosed individuals being younger. Even since 1995, a major part of the newly diagnosed children was born in Denmark by mothers from high-endemic areas and we therefore suggest that HIV-testing should actively be offered to all pregnant women coming from these high-risk areas.

We used a population-based cohort study design to describe the demographic characteristics of the HIV-infected population in Denmark and their variation over time. HIV treatment in Denmark is restricted to 9 centres, and all 3941 HIV-1 infected patients more than 15 y old seen at these centres in 1995-2003 were included. We found an estimated HIV prevalence of 70 per 100,000, and a mean annual incidence rate of 5.1 per 100,000 persons. The number of newly infected individuals was stable with a median of 231 per y (period 1995-2002), whereas the number of deaths decreased from 166 in 1995 to 50 in 2000 (p=0.000) and remained stable thereafter. Of the enrolled patients, 75% were males, 80% were Caucasian, 13% were black African, and the primary risk behaviour was male-to-male sexual contact (44%), heterosexual contact (36%), and injection drug use (11%). During the y 1995-2003 we found an increase in age at diagnosis (p=0.000), and no major changes in gender, race, mode of infection, or baseline CD4+ cell count and viral load, neither overall not within subgroups of patients. In this period 14.5% had AIDS at the time of HIV diagnosis. Our data do not confirm concerns about unmonitored evolution in the HIV epidemic in Denmark.

Greenland is a high-income country with free access to human immunodeficiency virus (HIV) care, including highly active antiretroviral therapy (HAART). We aimed to examine the HIV prevalence, age and gender distribution, and the effectiveness of HAART on CD4 positive cell count, viral load (VL), and mortality in the Greenland HIV-infected population. In this population-based cohort study we collected demographic, clinical and biochemical data on all HIV-infected patients followed in health clinics since 1995. For each case, we identified 100 age- and gender-matched population controls. The HIV cohort included 103 patients of whom 91% were Inuit; 81% were infected heterosexually. Only 40% of the patients had a VL <400 copies/ml at 48 weeks after starting HAART, and patients on HAART had a substantial excess relative mortality compared with the general population (mortality rate ratio [MRR]: 10.6; 95% confidence interval [CI]: 6.9-16.4). After the introduction of HAART, the mortality decreased (MRR: 2.5; 95% CI 0.9-6.8), but remained high with a mortality rate of 62 per 1000 person-years (py) (95% CI 29-129). Our findings underline the difficulties of implementing successful HIV treatment even with unlimited economic resources and free access to health care.

The aim of the present study was to explore the treatment effect of tenofovir as implemented in clinical practice. Data are presented on 34 patients. 11 patients had tenofovir added to a stable anti-retroviral treatment (ART) and 23 patients had drugs other than tenofovir. CD4 counts, HIV-RNA levels and genotypic resistance were determined at baseline and after 3 and 6 months. After initiation of tenofovir treatment, a mean decrease in HIV-RNA for all 34 patients was observed (-0.43 log1o copies/ml (+/- 1.22) and -0.49 log10 copies/ml (+/- 1.36) after 3 and 6 months, respectively, (p = 0.045)). However, the effect of tenofovir on HIV-RNA in the group of patients who had tenofovir added to a stable ART was limited, and the decrease in HIV-RNA was significantly higher in patients who had drugs other than tenofovir changed as well (p = 0.004 and p = 0.03 after 3 and 6 months, respectively). After initiation of tenofovir treatment, no significant increases in CD4 count were observed. All new NRTI-associated mutations could be explained by the background treatment. In conclusion, we observed a significant decrease in HIV-RNA only when tenofovir was prescribed, in conjunction with other anti-retroviral drugs, to patients on a failing highly active antiretroviral drug regimen (HAART).

The aim of this study was to monitor the prevalence of drug resistance mutations in newly diagnosed HIV-1 positive individuals in Denmark. In addition we assessed the prevalence of non-B subtypes based on phylogenetic analysis of the pol gene. Plasma samples from 104 newly diagnosed HIV-1 positive patients were obtained in the year 2000. The entire protease gene and 320 amino acids of the reverse transcriptase gene were genotyped. Sequences were obtained from 97 patients. No subjects displayed primary resistance mutations in the protease gene, whereas all carried 1 or more secondary mutations. Resistance mutations in the RT-gene associated with NRTI-resistance were found in 1 patient, who was infected with zidovudine resistant HIV-1 harbouring the M41L mutation in combination with T215S and L210S. The T215S mutation has been showed to be associated with reversion of zidovudine resistance. The T215S mutation was found in 1 additional patient. The subtype distribution was subtype B 59%, C 18%, A 8%, CRF02&#95;AG 5%, CRF01&#95;AE 4%, D 3% and G 2%. We found 2 patients (2%) with mutations associated with resistance in the RT-gene and none in the protease gene indicating a low prevalence of resistant HIV-1 in Denmark in the year 2000.

The objective of this study was to describe the symptoms, diagnostic measures and outcomes of extrapulmonary tuberculosis (ex-TB) in a Danish university clinic from 1990 to 1999. 48 patients with ex-TB were identified retrospectively and clinical and laboratory data extracted from the patient files. The majority were immigrants from Africa (71%). A direct connection between symptoms on admission and anatomical localization of TB was found in 83%. The main localizations of ex-TB were peripheral lymph nodes (n = 15) and the abdomen (n = 19). In 73% Mycobacterium tuberculosis could be cultured. One culture was resistant to isoniazide and 1 had decreased sensitivity to isoniazide and etambutol. Two patients relapsed with TB. Some pitfalls in diagnosing TB were found, as 13% had a normal erythrocyte sedimentation rate at presentation, 9% had a negative tuberculin skin test and fever was absent in 31% of the cases. The patients' subjective complaints on admission should guide the diagnostic procedures.

Saquinavir hard gel capsule (hgc), the first human immunodeficiency virus (HIV) protease inhibitor (PI) used in clinical practice, has been shown to have insufficient effectiveness. A population-based cohort study assessed the long-term consequences of using saquinavir hgc as initial PI in HIV-infected patients pre-exposed to nucleoside reverse transcriptase inhibitors. 121 patients starting a regimen with saquinavir hgc were compared with 91 starting with non-boosted indinavir (n = 72) or ritonavir (n = 19). Median follow-up time was 4.6 and 4.7 y for the 2 groups. Starting with saquinavir hgc was associated with a lower overall probability of achieving an undetectable viral load [risk ratio (RR) = 0.41, 95%, confidence interval (95% CI) 0.30-0.56]. However, the lower probability of having undetectable viral load during follow-up declined over time with odds ratios (OR) = 0.27 (95%, CI 0.14-0.54), 0.35 (951% CI 0.19-0.66), 0.47 (95% CI 0.24-0.91) and 0.73 (95% CI 0.34-1.55) at 60, 120, 180 and 240 weeks, respectively, after starting HAART. Starting with saquinavir hgc was correlated with a higher risk of having the initial PI discontinued (RR = 1.89, 95% CI 1.39-2.58). The insufficient suppression of viral load in patients starting with saquinavir hgc subsided during follow-up, probably owing to the earlier discontinuation of saquinavir hcg in favour of newer and more potent HAART regimens.

YKL40 is secreted by activated macrophages and neutrophils. Elevated serum concentrations of YKL40 are found in patients with diseases characterized by inflammation or ongoing fibrosis. The aim of this study was to evaluate serum YKL-40 levels in patients with Streptococcus pneumoniae bacteremia and to correlate these levels with clinical findings and outcomes. YKL40 was determined by ELISA and 89 patients were included in the study. Serum YKL-40 levels were significantly higher in patients with S. pneumoniae bacteremia (median 342 microg/l; range 20-20,400 microg/l) than in age-matched healthy subjects (44 microg/l; 20-184; p < 0.001). Serum YKL-40 levels were related to the severity of the infection, with significantly higher serum YKL-40 levels being observed in patients who needed hemodialysis (p < 0.001), pharmacological treatment of hypotension (p < 0.001) and mechanical ventilation (p = 0.003) compared to those in patients who did not need this supportive treatment. Nineteen patients died and these patients had significantly higher serum YKL-40 levels (980 microg/l; 88-20,400 microg/l) than those of survivors (256 microg/l; 20-9,100 microg/l; p < 0.001). Serum YKL40 level was an independent prognostic factor of survival in logistic multivariate regression analysis (p = 0.002). In conclusion, high serum levels of YKL40 indicated a poorer prognosis for patients with S. pneumoniae bacteremia.

New antiretroviral drugs, expanding knowledge of their long-term toxic effects and the large number of patients with treatment failure have increased the demand for new strategies in the antiretroviral treatment of HIV-infected patients. The present study was conducted as part of the HIV Cohort Study in western Denmark to reveal trends in the use of antiretrovirals in the region. The cohort includes all patients attached to those centers treating HIV patients in western Denmark. A total of 537 patients who started highly active antiretroviral therapy (HAART) were included. The number of patients receiving HAART increased dramatically in 1996 and 1997 before leveling off, with 45-75 patients initiating treatment annually thereafter. Median follow-up time after initiation of HAART was 151 weeks. An estimated 45.1% of patients had the initial HAART regimen modified during the first year of follow-up. Side-effects and treatment failure were the main reasons for treatment modifications. Major new strategies implemented in the region in 1999 and 2000 included treatment with boosted protease inhibitors and non-nucleoside reverse transcriptase inhibitors.

The objective of this study was to investigate the presence of non-subtype B HIV-1 in Denmark. The C2-V3-C3 region of the env gene from proviral DNA obtained from patients suspected of being infected with non-subtype B virus was PCR-amplified and directly sequenced. The DNA sequences were aligned with full-length HIV-1 reference strains from each subtype and analysed using the phylogenetic package PHYLIP 3.1. The neighbour-joining method was used with 100 bootstraps. Of the 144 patients included in this study C2-V3-C3 sequences were obtained from 129 patients (90%). The phylogenetic analyses showed that virus from 49 patients (38%) was subtype A, 39 (30%) subtype C, 9 (7%) subtype D, 14 (11%) subtype CRF01&#95;AE, 16 (12%) subtype B, 1 (1%) subtype F and 1 (1%) subtype J. This study demonstrates that almost all subtypes can be detected in Denmark; all non-subtype B infections could be traced to countries with a high prevalence of non-subtype B virus.

We present demographic data from an observational database of HIV and AIDS in the Western part of Denmark, a region with a population of 2,935,156 individuals (55.1% of the population of Denmark). Five centers in the region treat HIV-positive adults; all patients attached to these centers since 1995 are included in this study. In total, 749 adult HIV-infected individuals were enrolled as of 31 December, 1999. Estimates of prevalence and incidence of HIV infection in the area were 25.9/100,000 and 2.6/100,000, respectively, which are lower than average for the country. The number of newly diagnosed HIV-infected patients remained constant during the period 1995-99, with an average of 62 diagnoses per year. The number of HIV-related deaths declined from 43 in 1995 to 15 in 1999. Of the enrolled patients, 70.9% were of Danish origin, 75% were Caucasians, 69.7% were male and 47.2% had heterosexual contact as their primary risk behavior. There seems to have been a shift in the HIV epidemic in recent years, with a higher proportion of newly diagnosed HIV patients having contracted the infection through heterosexual contact, a higher proportion being immigrants from less developed countries and newly diagnosed individuals getting older.

The diagnosis of familial Mediterranean fever (FMF) was, until recently, based on exclusion of diseases with related clinical signs. Now an exact diagnosis of FMF is possible by polymerase chain reaction (PCR). We report here a case with 2 different mutations in the gene responsible for FMF, thereby being a compound heterozygote (M694V/V726A).

Protease inhibitors are important components in anti-retroviral regimens. In this retrospective study 29 HIV-infected patients treated with a regimen of zidovudine, lamivudine and saquinavir hard gel in 1 centre in Denmark were compared with 58 patients treated with zidovudine, lamivudine and ritonavir or indinavir followed at 5 other centres in Scandinavia. All patients were naive to anti-retroviral therapy prior to institution of the actual anti-retroviral regimen and were followed for a median of 1.3 and 1.4 y respectively. The 2 groups did not differ significantly with respect to age, gender, route of infection, ethnic background, viral load, CD4 count, AIDS at baseline or frequency of clinical controls. Six and 12 months after initiating anti-retroviral therapy, 31% and 34% of the patients on the saquinavir regimen obtained HIV-RNA < or = 500 compared with 76% and 73% in the control group (p < 0.001). In contrast to viral load, the increase in CD4 count did not differ significantly between the 2 groups. In conclusion, we found that with respect to suppression of viral load a regimen of saquinavir, zidovudine and lamivudine seemed to be inferior to a regimen of zidovudine, lamivudine and ritonavir or indinavir.

The aim of the study was to evaluate the effects of treatment with methotrexate, sulphasalazine and aurothiomalate on polymorphonuclear leucocytes (PMN) in rheumatoid arthritis (RA). Circulating PMNs from 58 RA patients treated with either methotrexate (n = 27), sulphasalazine (n = 16) or aurothiomalate (n = 15) were assayed for their chemotactic capacity and generation of superoxide anions. The expression of CD18/CD11b was measured for 17 RA patients treated with methotrexate. Chemotaxis and generation of superoxide anions were not affected by any of the three drugs. We found no difference in the expression of CD18/CD11b in RA patients treated with methotrexate compared to healthy subjects. Further methotrexate and aurothiomalate did not in vitro alter chemotaxis, generation of superoxide anion or expression of CD18/CD11b on normal PMNs. In conclusion we found no evidence that the effect of methotrexate, aurothiomalate or sulphasalazine in RA can be explained by modulation of chemotactic ability or superoxide anion generation of peripheral circulating PMNs.

We describe a 28-year-old HIV-infected woman with AIDS, defined by cerebral toxoplasmosis and a CD4-count of less than 10 x 10(6) cells/I, who, after several eruptions of genital herpes and typical dermatomal herpes zoster, all successfully treated with acyclovir, developed chronic cutaneous ulcerating lesions on a finger and on the tibia. The lesions were found to contain varicella zoster virus antigen but repeated treatment courses with acyclovir were unsuccessful. After a course of intravenous foscarnet the lesions resolved. They recurred after discontinuation of foscarnet but finally responded to a second course of treatment.

Early diagnosis and treatment of Schistosoma haematobium infections is imperative to prevent chronic manifestations of the disease. Microscopical examination of urine and faeces, and rectal biopsy are widely used standard methods for the rapid diagnosis of schistosomiasis. We report a case in whom numerous Schistosoma haematobium eggs were demonstrated in sperm, even though repeated examination of urine and rectal biopsies had been futile. It is concluded that the case presented demonstrates the importance of using sperm as an alternative sample material when schistosoma eggs are not found in conventional sample materials from male patients suspected of being infected with Schistosoma haematobium.