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Biomedical subjects

Niels Obel

Publications and source records attributed to Niels Obel.

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

HIV-1 reverse transcriptase gene 103K/N and 184M/V combinations in tandem: detection and quantification of HIV-1 populations in the CD45RO+ T-cell compartment by a double-ARMS real-time PCR assay.

BACKGROUND: The proviral HIV-1 reverse transcriptase gene for the 103K/N and 184M/V combinations were studied in tandem. The CD45RO T (memory) cell compartment was investigated. METHODS: A new double-ARMS (amplification refractory mutation system) real-time polymerase chain reaction assay was developed to detect and quantify 4 populations (103K-184M, 103K-184V, 103N-184M, and 103N-184V) in the CD45RO T-cell compartment. Twenty-one patients, 18 lamivudine and efavirenz/nevirapine experienced, were enrolled in a cross-sectional study. RESULTS: None of the mutation combinations were detected in patients on highly active antiretroviral therapy (HAART) (naive at start) with viremia suppression below detection limits. Conversely, all patients exposed to mono- or dual therapy (prior to HAART) carried at least 1 mutation combination regardless of viral load. In 9 patients, 17 mutations were detected in a mosaic of combinations. This study provides definite evidence of the existence of 103N and 184V mutation quasi-populations in tandem, and separately in combination with the wild-type codons, 184M and 103K, in the CD45RO T-cell compartment. CONCLUSIONS: The initiation and continuation of potent antiretroviral therapy effectively hinders the appearance of 103N and 184V mutations alone or in tandem in memory cells. When switching therapies because of failure, caution should be exercised with drugs associated with single-mutation threshold; they can appear in tandem with contemporary resistant virus populations, leading to multidrug resistance.

Adult↗
PubMed2006

Dynamics of proviral HIV-1 184M/V in circulating CD4+ T-cells: a 90 days follow-up study after initiation/switch of HAART.

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.

Anti-HIV Agents↗
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

[Mycoplasma genitalium--a new challenge in sexually transmitted diseases].

Although Mycoplasma genitalium was described 20 years ago, the knowledge concerning it is still limited. The publications in the area are surprisingly few in number, especially considering that the pathogen is rather common and has been connected with a number of different urogenital diseases. The PCR technique has made it possible to perform investigations on a large scale, which might elucidate the pathogenic role of M. genitalium in the urogenital tract. However, it seems well established that M. genitalium causes non-gonococcal urethritis (NGU). The mycoplasma behaves almost identically to Chlamydia trachomatis with respect to routes of infection and inflammatory response, but no further relationship between the two organisms seems obvious. M. genitalium is believed to produce urethritis with almost the same frequency as C. trachomatis. In the female genital tract, M. genitalium is strongly incriminated as a primary cause of cervicitis, endometritis and salpingitis, the latter complicated by tubal damage. The role of the organisms in epididymitis, prostatitis and neonatal infections is unclear. In the case of urethritis and upper genital tract infections in the female, it is recommended to test for M. genitalium using molecular biological assays and in the event of a positive result institute antimicrobial therapy.

Animals↗
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

Detection and quantification of proviral HIV-1 184 M/V in circulating CD4(+) T cells of patients on HAART with a viremia less than 1,000 copies/ml.

BACKGROUND: Highly active anti-retroviral therapy (HAART) effectively reduces HIV replication but does not completely hinder it. Sub-optimal therapy leads to HIV resistance to the drugs administered. However, the role of low-level viremia (viral-load less than 1,000 copies/ml) on mutation genesis and incorporation of resistant forms in the long-lived CD4(+) T cellular DNA compartment is not clear. OBJECTIVE: To investigate the relationship between lamivudine associated mutant-type 184 V and the wild-type 184 M proviral forms in the circulating CD4(+) T cells of patients and low-level viremia. STUDY DESIGN: Cross-sectional study of 50 patients on long-term HAART, with a viremia of less than 1 000 copies/ml. Patients were stratified into three groups; on lamivudine, group I (viral load <20 copies/ml), group II (viral load 20-1000 copies/ml) and as lamivudine experienced, group III (viral load <1000 copies/ml). 184 M and 184 V proviral HIV-1 was detected and quantified by a specific and sensitive assay combining a TaqMan real-time PCR analysis with the amplification-refractory mutation system (ARMS) principle. RESULTS: Fifty-six percent of patients with low-level viremia had 184 V in the CD4(+) T cellular DNA compartment as compared to only 8% in those with undetectable viremia. The presence of 184 V was significantly associated with a higher viral load (P=0.001). Patients with low-level viremia without 184 V in the CD4(+) T cellular DNA compartment, had a median plasma viral load of 135 copies/ml, while patients harbouring 184 V had a median viral load of 498 copies/ml (P=0.006). No significant differences between the groups were observed in proviral HIV-1 DNA load. CONCLUSIONS: The frequency of the 184 V mutation was significantly lower, in the CD4(+) T cellular compartment of patients with a viral load of less than 20 copies/ml as compared to patients with a viremia of 20-1,000 copies/ml. Viremia, sustained below 20 copies/ml may prevent the appearance of 184 V mutation in this reservoir and therefore should be the objective of treatment.

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↗
PubMed2005

Demographics in HIV-infected children in Denmark: results from the Danish Paediatric HIV Cohort Study.

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.

Adolescent↗
PubMed2005

Patients' answers to simple questions about treatment satisfaction and adherence and depression are associated with failure of HAART: a cross-sectional survey.

Psychosocial and behavioral factors have been shown to be associated with adherence to highly active antiretroviral therapy (HAART) and treatment effectiveness. These factors have often been identified in selected populations through complex or time-consuming questionnaires. In this study we aimed at asking all the patients of a large population-based cohort receiving HAART a few short, explicit, and direct questions about these factors, and to examine the associations between their answers and prevalent treatment failure. All patients receiving HAART in western Denmark and central Copenhagen were offered participation. Participants answered a short, self-administered, anonymous questionnaire assessing psychosocial and behavioral factors and treatment adherence. Findings were linked with data on demographics, disease history, and treatment effect. Treatment failure was defined as two consecutive measurements of HIV-RNA above 400 copies per milliliter taken at least 14 days apart. Prevalence odds ratios were estimated by logistic regression. We found that a total of 887 of 1126 patients returned a completed questionnaire (response rate 79%). The overall rate of treatment failure in participants was 20%. Adjusted odds ratio estimates for treatment failure were 2.3 (confidence interval [CI] 1.3-4.3) for patients who stated poor treatment satisfaction, 2.1 (CI 1.2-3.7) for patients not fully disagreeing that they were depressed, and 2.8 (CI 1.5-5.4) for patients who stated to have been nonadherent within the preceding 4 days. Because of the cross-sectional nature of the study, causality could not be determined. These questions, however, may be relevant screening tools in clinical practice and in follow-up studies.

Adult↗
PubMed2004

Low mortality in HIV-infected patients starting highly active antiretroviral therapy: a comparison with the general population.

OBJECTIVES: To assess the mortality in a cohort of HIV-infected patients starting highly active antiretroviral therapy (HAART) compared to the mortality of the general population, focusing on the influence of the CD4 cell count at the time of starting HAART. METHODS: Patients in the HIV Cohort Study in Western Denmark starting HAART before 1 January 2002 were identified. For each patient, 100 population controls matched on age and gender were extracted from the Danish Civil Registration System. Mortality rates were compared between the two cohorts overall, and in four groups defined by baseline CD4 cell counts. RESULTS: A total of 647 HIV-infected patients and 64 700 population controls were included, accounting for 53 and 815 deaths during follow-up. In the HIV group, mortality rates were 70.0 per 1000 person-years at risk in the lowest CD4 cell group (< 50 x 10 cells/l), and 3.2 in the highest (> or = 200 x 10 cells/l). Compared with population controls, mortality rate ratios declined with increasing CD4 cell counts, being 15.3 [95% confidence interval (CI), 9.8-23.8], 8.6 (95% CI, 4.3-16.8), 5.9 (95% CI, 3.0-11.4), and 3.6 (95% CI, 2.0-6.5) in the groups with CD4 cell count < 50, 50-99, 100-199, and > or = 200 x 10 cells/l. CONCLUSION: In comparison with the general population, HIV-infected patients starting HAART with a CD4 cell count above 200 x 10 cells/l had low mortality rates that were comparable with the rates found in other chronic medical diseases. The mortality rates increased considerably when treatment was started at lower baseline CD4 cell counts.

Adult↗
PubMed2004

The occurrence of Chlamydia pneumoniae, Mycoplasma pneumoniae, and herpesviruses in otitis media with effusion.

In a previous report we found Chlamydia (C.) pneumoniae to be present in middle ear fluids (MEE) from older children with otitis media with effusion (OME). However, OME is a disease of younger children the present study was conducted in toddlers. MEEs (n = 150) and nasopharynx samples (n = 83) from children with OME was analyzed by PCR for the presence of C. pneumoniae and Mycoplasma (M.) pneumoniae. C. pneumoniae was not present in any and M. pneumoniae only in one of the MEEs, and these pathogens could be demonstrated in one and two nasopharynx samples, respectively. Further, 133 MEEs were analyzed by PCR for the presence of the 8 human herpesviruses, and all samples were found to be negative. We conclude that neither C. pneumoniae or M. pneumoniae, or any of the 8 human herpesviruses seems to play a major role in the pathogenesis of OME in early childhood OME.

Child↗