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Gitte Kronborg

Publications and source records attributed to Gitte Kronborg.

At least 19 recordsLinked to original sources
PubMed2007

Survival of persons with and without HIV infection in Denmark, 1995-2005.

BACKGROUND: The expected survival of HIV-infected patients is of major public health interest. OBJECTIVE: To estimate survival time and age-specific mortality rates of an HIV-infected population compared with that of the general population. DESIGN: Population-based cohort study. SETTING: All HIV-infected persons receiving care in Denmark from 1995 to 2005. PATIENTS: Each member of the nationwide Danish HIV Cohort Study was matched with as many as 99 persons from the general population according to sex, date of birth, and municipality of residence. MEASUREMENTS: The authors computed Kaplan-Meier life tables with age as the time scale to estimate survival from age 25 years. Patients with HIV infection and corresponding persons from the general population were observed from the date of the patient's HIV diagnosis until death, emigration, or 1 May 2005. RESULTS: 3990 HIV-infected patients and 379,872 persons from the general population were included in the study, yielding 22,744 (median, 5.8 y/person) and 2,689,287 (median, 8.4 years/person) person-years of observation. Three percent of participants were lost to follow-up. From age 25 years, the median survival was 19.9 years (95% CI, 18.5 to 21.3) among patients with HIV infection and 51.1 years (CI, 50.9 to 51.5) among the general population. For HIV-infected patients, survival increased to 32.5 years (CI, 29.4 to 34.7) during the 2000 to 2005 period. In the subgroup that excluded persons with known hepatitis C coinfection (16%), median survival was 38.9 years (CI, 35.4 to 40.1) during this same period. The relative mortality rates for patients with HIV infection compared with those for the general population decreased with increasing age, whereas the excess mortality rate increased with increasing age. LIMITATIONS: The observed mortality rates are assumed to apply beyond the current maximum observation time of 10 years. CONCLUSIONS: The estimated median survival is more than 35 years for a young person diagnosed with HIV infection in the late highly active antiretroviral therapy era. However, an ongoing effort is still needed to further reduce mortality rates for these persons compared with the general population.

Adult↗
PubMed2006

Mortality in siblings of patients coinfected with HIV and hepatitis C virus.

BACKGROUND: Coinfection with hepatitis C virus (HCV) is a poor prognostic factor for human immunodeficiency virus (HIV)-infected patients. We examined whether the increased mortality in these patients is partly explained by a familial excess risk of death. METHODS: Danish HIV-infected patients who had had at least 1 HCV test were included (n=3531). In addition, 336,652 population control subjects matched for sex, age, and residency were identified from the Danish Civil Registration System. For both HIV-infected patients and population control subjects, we identified all siblings born after 1951, with dates of death or emigration. Siblings of HIV-infected patients were classified according to the patients' HCV serostatus. Survival after age 20 years was compared among the groups of siblings. RESULTS: We identified 437 siblings of HIV/HCV-coinfected patients, 1856 siblings of HIV-monoinfected patients, and 285,509 siblings of population control subjects. Mortality was substantially higher in siblings of HIV/HCV-coinfected patients than in either siblings of HIV-monoinfected patients (mortality rate ratio [MRR], 2.97 [95% confidence interval {CI}, 1.98-4.45]) or siblings of control subjects (MRR, 4.23 [95% CI, 3.09-5.79]). Siblings of HIV-monoinfected patients had slightly higher mortality (MRR, 1.43 [95% CI, 1.10-1.85]) than siblings of control subjects. CONCLUSIONS: HCV infection is a marker of familial factors that affect the survival of HIV-infected patients independently of the pathogenicity of HCV.

Adult↗
PubMed2006

Impact of hepatitis C virus coinfection on response to highly active antiretroviral therapy and outcome in HIV-infected individuals: a nationwide cohort study.

BACKGROUND: Coinfection with hepatitis C virus (HCV) in human immunodeficiency virus (HIV) type 1-infected patients may decrease the effectiveness of highly active antiretroviral therapy. We determined the impact of HCV infection on response to highly active antiretroviral therapy and outcome among Danish patients with HIV-1 infection. METHODS: This prospective cohort study included all adult Danish HIV-1-infected patients who started highly active antiretroviral therapy from 1 January 1995 to 1 January 2004. Patients were classified as HCV positive (positive HCV serological test and/or HCV PCR results [443 patients [16%]]), HCV negative (consistent negative HCV serological test results [2183 patients [80%]]) and HCV-U (never tested for HCV [108 patients [4%]]). The study end points were viral load, CD4+ cell count, and mortality. RESULTS: Compared with the HCV-negative group, overall mortality was significantly higher in the HCV-positive group (mortality rate ratio, 2.4; 95% confidence interval [CI], 1.9-3.0), as was liver disease-related mortality (mortality rate ratio, 16; 95% CI, 7.2-33). Furthermore, patients in the HCV-positive group had a higher risk of dying with a prothrombin time <0.3, from acquired immunodeficiency syndrome-related disease, and if they had a history of alcohol abuse. Although we observed no difference in viral load between the HCV-positive and HCV-negative groups, the HCV-positive group had a marginally lower absolute CD4+ cell count. CONCLUSIONS: HIV-HCV-coinfected patients are compromised in their response to highly active antiretroviral therapy. Overall mortality, as well as mortality from liver-related and acquired immunodeficiency syndrome-related causes, is significantly increased in this patient group.

AIDS-Related Opportunistic Infections↗
PubMed2006

Macrophage serum markers in pneumococcal bacteremia: Prediction of survival by soluble CD163.

OBJECTIVE: Soluble CD163 (sCD163) is a new macrophage-specific serum marker. This study investigated sCD163 and other markers of macrophage activation (neopterin, ferritin, transcobalamin, and soluble urokinase plasminogen activator receptor [suPAR]) as prognostic factors in patients with pneumococcal bacteremia. DESIGN: Observational cohort study. SETTING: Five university hospitals in Denmark. PATIENTS: A total of 133 patients with Streptococcus pneumoniae bacteremia (positive blood culture) and 133 age- and gender-matched controls. INTERVENTIONS: Samples were collected for biochemical analyses at the time of first positive blood culture. MEASUREMENTS AND MAIN RESULTS: sCD163 was highly correlated with other macrophage markers and was significantly elevated (median [25-75 percentiles], 4.6 mg/L [2.8-8.9]) compared with healthy controls (2.7 mg/L [2.1-3.3], p < .0001). Increased levels were observed in patients who needed intensive care (hemodialysis, p = .0011; hypotension, p = .0014; mechanical ventilation, p = .0019). Significantly lower levels of sCD163, ferritin, transcobalamin, and suPAR (but not C-reactive protein) were measured in patients > or =75 yrs. In patients <75 yrs, all macrophage markers were increased in patients who died from their infection compared with survivors, whereas no change was observed in any of the markers in the very old age. At cutoff levels of 9.5 mg/L (sCD163) and 1650 nmol/L (C-reactive protein), the relative risk for fatal outcome in patients <75 yrs was 10.1 (95% confidence interval 3.4-31.0) and 7.0 (95% confidence interval 2.4-21.6) for sCD163 and C-reactive protein, respectively. In a multivariate logistic regression model for patients <75 yrs, ferritin, transcobalamin, neopterin, and suPAR contained no significant information on the probability of survival when sCD163 and CRP were known (p = .25). CONCLUSIONS: Macrophage marker response in pneumococcal bacteremia was compromised in old age. In patients <75 yrs old, sCD163 was superior to other markers, including C-reactive protein, in predicting fatal disease outcome.

Adult↗
PubMed2006

Declining prevalence of HIV-infected individuals at risk of transmitting drug-resistant HIV in Denmark during 1997-2004.

BACKGROUND: Transmission of drug-resistant HIV is a potential threat to the substantial clinical benefit of highly active antiretroviral therapy (HAART). To explore the background for the low rates of drug resistance transmission (2.5%) in our population, we estimated acquisition of HIV drug resistance and examined temporal trends in the prevalence of patients at risk of transmitting drug-resistant HIV. METHODS: The study population included all 4,025 patients from The Danish HIV Cohort Study seen during the period 1995-2004. Virological failure to a given drug class was defined as a viral load (VL) > 1,000 copies/ml for 120 days while on a HAART regimen including that drug class. In addition, receiving nucleoside reverse transcriptase inhibitors (NRTIs) for 180 days before HAART counted as NRTI failure irrespective of VL. Having experienced failure was considered a proxy for harbouring drug-resistant virus in subsequent observation time. Patients with a current VL > 1,000 copies/ml were considered at risk of transmitting HIV. RESULTS: We found a decrease from 1997 to 2004 in the prevalence of potential transmitters of drug-resistant HIV. The number of these patients with previous NRTI failure decreased from 429 (24% of all patients) in 1998 to 213 (8.0% of all patients) in 2004. Previous protease inhibitor (PI) failure peaked at 279 (14%) in 1999, declining to 142 (5.3%) in 2004. Previous NNRTI failure peaked at 121 patients (4.7%) in 2002, and occurred in 113 patients (4.2%) in 2004. Of all 686 potential transmitters in 2004, 31% had previously experienced NRTI failure, 21% PI failure, and 16% non-NRTI failure. CONCLUSION: In the population of HIV-infected individuals in Denmark with complete follow-up, the number at risk of transmitting drug-resistant virus declined over time.

Antiretroviral Therapy, Highly Active↗
PubMed2005

Virological control during the first 6-18 months after initiating highly active antiretroviral therapy as a predictor for outcome in HIV-infected patients: a Danish, population-based, 6-year follow-up study.

BACKGROUND: Our objective was to examine whether virological control during the first 6-18 months after HAART initiation is a predictor for viral suppression, CD4+ cell count increase, and mortality in human immunodeficiency virus (HIV)-infected patients 18-90 months after initiation of highly active antiretroviral therapy (HAART). METHODS: We conducted a population-based observational cohort study in Denmark. Patients were divided into 3 groups, according to the proportion of time each patient had a detectable HIV RNA load (i.e., > or = 400 copies/mL) during the 6-18 months after HAART initiation: 0% of the time interval (group 1), 1%-99% of the time interval (group 2), and 100% of the time interval (group 3). The proportion of patients with undetectable HIV RNA, CD4+ cell count changes, and mortality were examined by logistic, linear, and Cox regression analyses, respectively. We constructed cumulative mortality curves. RESULTS: We observed 2046 patients, for a total of 8898 person-years of follow-up that started at 18 months after HAART initiation. Mean CD4+ cell count increase rates during 72 months of follow-up were as follows: group 1, 3.3 x 10(6) cells/L per month (95% confidence interval [CI], 2.9-3.7 x 10(6) cells/L); group 2, 2.9 x 10(6) (95% CI, 2.5-3.3 x 10(6) cells/L); and group 3, 2.6 x 10(6) (95% CI, 2.0-3.3 x 10(6) cells/L). Survival at 72 months were as follows: group 1, 92.7% (95% CI, 90.5%-94.4%); group 2, 85.6% (95% CI, 82.1%-88.5%); and group 3, 76.1% (95% CI, 70.6%-80.7%). At 72 months, 96% of group 1, 83% of group 2, and 57% of group 3 had an HIV RNA load of < 400 copies/mL (P < .01). Treatment interruption before baseline was a predictor of mortality in group 2 (adjusted rate ratio, 2.94; 95% CI, 1.75-4.92]). CONCLUSIONS: Viral suppression during the first 6-18 months after HAART initiation predicts viral suppression, CD4+ cell count progression, and survival at 72 months.

Adult↗
PubMed2005

Declining risk of triple-class antiretroviral drug failure in Danish HIV-infected individuals.

OBJECTIVES: To analyse the incidence, prevalence, and predictors for development of triple-class antiretroviral drug failure (TCF) in individuals infected with HIV. DESIGN: Population-based observational cohort study from 1 January 1995 to 31 December 2003, focusing on all 2722 recipients of highly active antiretroviral therapy (HAART) in Denmark. METHODS: We used person-years analysis, Kaplan-Meier survival curves and Cox regression analysis. TCF was defined as a minimum of 120 days with viral load > 1000 copies/ml on treatment with each of the three major drug classes. RESULTS: We observed 177 TCFs, yielding a crude incidence rate (IR) of 1.8 per 100 person-years [95% confidence interval (CI), 1.6-2.1]. Seven years after initiation of HAART, 17.2% (95% CI, 14.5-20.5) of antiretroviral (ART)-experienced patients, but only 7.0% (95% CI, 4.3-11.2) of ART-naive patients were estimated to have failed. After an initial rise, the IR from the third to the sixth year of HAART declined significantly for ART-experienced patients [incidence rate ratio (IRR), 0.80 per year (95% CI, 0.66-0.97); P = 0.022], and non-significantly for ART-naive patients [IRR, 0.79 per year (95% CI, 0.53-1.18); P = 0.255]. The IR for all patients being followed each year declined from 1997 to 2003 [IRR, 0.88 (95% CI, 0.81-0.96); P = 0.002]. The prevalence of TCF remained stable at less than 7% after 2000. Predictors of TCF at commencement of HAART were a CD4 cell count below 200, a previous AIDS-defining event, previous antiretroviral exposure, earlier year of HAART initiation, and young age. CONCLUSIONS: The risk of TCF is declining in Denmark and the prevalence remains stable.

Adult↗
PubMed2005

Demographics of HIV-1 infection in Denmark: results from the Danish HIV Cohort Study.

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.

Adult↗
PubMed2004

Effect of hyperglycemia and hyperinsulinemia on the response of IL-6, TNF-alpha, and FFAs to low-dose endotoxemia in humans.

Insulin therapy to maintain euglycemia increases survival in critically ill patients. To explore possible mechanisms of action, we investigated the effect of endotoxin on circulating cytokines, free fatty acids (FFA), and leukocytes during manipulated plasma glucose and insulin concentrations. Ten volunteers underwent three trials each, receiving an intravenous bolus of endotoxin (0.2 ng/kg) during normoglycemia (trial A, control), during a hyperglycemic clamp at 15 mM (trial B), and during a hyperinsulinemic euglycemic clamp (trial C). Endotoxin induced an increase in neutrophil count, a decrease in lymphocyte count, and an increase in serum levels of TNF-alpha, IL-6, and FFA. There was no difference in the TNF response between the three trials; the IL-6 levels were increased during the late phase of trials B and C compared with trial A. The endotoxin-induced elevation in FFA in trial A was suppressed during trials B and C. Clamping (trials B and C) caused a reduction in lymphocyte count that persisted after endotoxin injection. We conclude that low-dose endotoxemia triggers a subclinical inflammatory response and an elevation in FFA. The finding that high insulin serum concentrations induce a more prolonged increase in the anti-inflammatory cytokine IL-6 and suppress the levels of FFA suggests that insulin treatment of patients with sepsis may exert beneficial effects by inducing anti-inflammation and protection against FFA toxicity, and thereby inhibit FFA-induced insulin resistance.

Adult↗
PubMed2003

Acanthamoeba keratitis in a non-contact lens wearer with human immunodeficiency virus.

Acanthamoeba keratitis is potentially blinding and often associated with contact lens wearing. A human immunodeficiency virus (HIV)-positive patient, a non-contact lens wearer, presented with keratitis. She experienced a protracted course of disease, characterized by exacerbations and remissions, and was treated with various topical antibiotics and steroids. 13 months after symptom onset the eye was removed owing to serious scarring of cornea and unbearable pain. Microbiological and histopathological examination of the cornea showed Acanthamoeba. In non-contact lens wearers suffering from Acanthamoeba keratitis the diagnosis is delayed, pathognomonic features are often not seen and visual outcome is usually poor. There is no known relation between HIV infection and Acanthamoeba keratitis.

Acanthamoeba Keratitis↗
PubMed2003

Death from the Nile crosses the Atlantic: the West Nile Fever story.

The present paper reviews the American epidemic of West Nile Fever (WNF), which is the largest recorded outbreak ever. The epidemiological consequences of introducing a novel and immunologically unknown pathogen in a previously unexposed population and the possible evolution of a more pathogenic viral strain are discussed. In view of recent reports of imported cases in Denmark the issue of possible disease spread to Scandinavia is likewise addressed. However, the main scope of the article is to provide the clinician with an overview of the natural history, epidemiology and clinical characteristics of the disease.

Communicable Disease Control↗
PubMed2003

Optimization and immune recognition of multiple novel conserved HLA-A2, human immunodeficiency virus type 1-specific CTL epitopes.

MHC-I-restricted cytotoxic responses are considered a critical component of protective immunity against viruses, including human immunodeficiency virus type 1 (HIV-1). CTLs directed against accessory and early regulatory HIV-1 proteins might be particularly effective; however, CTL epitopes in these proteins are rarely found. Novel artificial neural networks (ANNs) were used to quantitatively predict HLA-A2-binding CTL epitope peptides from publicly available full-length HIV-1 protein sequences. Epitopes were selected based on their novelty, predicted HLA-A2-binding affinity and conservation among HIV-1 strains. HLA-A2 binding was validated experimentally and binders were tested for their ability to induce CTL and IFN-gamma responses. About 69 % were immunogenic in HLA-A2 transgenic mice and 61 % were recognized by CD8(+) T-cells from 17 HLA-A2 HIV-1-positive patients. Thus, 31 novel conserved CTL epitopes were identified in eight HIV-1 proteins, including the first HLA-A2 minimal epitopes ever reported in the accessory and regulatory proteins Vif, Vpu and Rev. Interestingly, intermediate-binding peptides of low or no immunogenicity (i.e. subdominant epitopes) were found to be antigenic and more conserved. Such epitope peptides were anchor-optimized to improve immunogenicity and further increase the number of potential vaccine epitopes. About 67 % of anchor-optimized vaccine epitopes induced immune responses against the corresponding non-immunogenic naturally occurring epitopes. This study demonstrates the potency of ANNs for identifying putative virus CTL epitopes, and the new HIV-1 CTL epitopes identified should have significant implications for HIV-1 vaccine development. As a novel vaccine approach, it is proposed to increase the coverage of HIV variants by including multiple anchor-optimized variants of the more conserved subdominant epitopes.

Adult↗
PubMed2002

Variant mannose-binding lectin alleles are not associated with susceptibility to or outcome of invasive pneumococcal infection in randomly included patients.

Invasive pneumococcal disease is a serious infection that primarily affects very young children and elderly or immunocompromised individuals but also affects previously healthy people. Variant mannose-binding lectin (MBL) alleles are associated with recurrent infections and may be a risk factor for pneumococcal infections. To assess the influence of MBL genotypes on the course and outcome of invasive pneumococcal disease, clinical data for 141 adult patients were collected prospectively and their genotypes were determined. All patients included had positive blood cultures for Streptococcus pneumoniae. The distribution of variant MBL alleles related to low MBL serum concentrations was similar among the patients and healthy individuals, and MBL genotype was not associated with infection outcome. Thus, in a random adult population with invasive pneumococcal infection, MBL does not seem to play a role in the pathophysiology, in contrast to earlier observations in patients with other concomitant immune abnormalities.

Adolescent↗