Niels Obel

Impact of Hepatitis C Virus Coinfection on Response to Highly Active Antiretroviral Therapy and Outcome in HIV-Infected Individuals: A Nationwide Cohort Study

BACKGROUNDnCoinfection 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.nnnMETHODSnThis 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.nnnRESULTSnCompared 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.nnnCONCLUSIONSnHIV-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.

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 70u2005per 100,000, and a mean annual incidence rate of 5.1u2005per 100,000 persons. The number of newly infected individuals was stable with a median of 231u2005peru2005y (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.

Use of fluroquinolone and risk of Achilles tendon rupture: a population-based cohort study

ObjectiveSeveral case-control studies have reported that the use of fluoroquinolone increases the risk of rupture of the Achilles tendon. Our aim was to estimate this risk by means of a population-based cohort approach.SettingData on Achilles tendon ruptures and fluoroquinolone use were retrieved from three population-based databases that include information on residents of Funen County (population: 470,000) in primary and secondary care during the period 1991–1999. A study cohort of all 28,262 first-time users of fluoroquinolone and all incident cases of Achilles tendon ruptures were identified.Main outcome measuresThe incidence rate of Achilles tendon ruptures among users and non-users of fluoroquinolones and the standardised incidence rate ratio associating fluoroquinolon use with Achilles tendon rupture were the main outcome measures.ResultsBetween 1991 and 2002 the incidence of Achilles tendon rupture increased from 22.1 to 32.6/100,000 person-years. Between 1991 and 1999 the incidence of fluoroquinolone users was 722/100,000 person-years, with no apparent trend over time. Within 90xa0days of their first use of fluoroquinolone, five individuals had a rupture of the Achilles tendon; the expected number was 1.6, yielding an age- and sex-standardised incidence ratio of 3.1 [(95% confidence interval (95%CI): 1.0–7.3). The 90-day cumulative incidence of Achilles tendon ruptures among fluoroquinolone users was 17.7/100,000 (95%CI: 5.7–41.3), which is an increase of 12.0/100,000 (95%CI: 0.0–35.6) compared to the background population.ConclusionFluoroquinolone use triples the risk of Achilles tendon rupture, but the incidence among users is low.

'Simply forgot' is the most frequently stated reason for missed doses of HAART irrespective of degree of adherence.

Previous studies have reported that forgetfulness is the most frequently mentioned reason for missed doses among patients on highly active antiretroviral therapy (HAART). However, no previous study has compared the reasons given by highly nonadherent patients with the reasons given by patients with better adherence. The objective of this study was to examine further patients self‐reported reasons for missing doses of HAART and to compare the reasons given by patients with lower adherence with those given by patients with higher adherence.

Mortality in Siblings of Patients Coinfected with HIV and Hepatitis C Virus

BACKGROUNDnCoinfection 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.nnnMETHODSnDanish 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.nnnRESULTSnWe 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.nnnCONCLUSIONSnHCV infection is a marker of familial factors that affect the survival of HIV-infected patients independently of the pathogenicity of HCV.

Pronounced lipoatrophy in HIV-infected men receiving HAART for more than 6 years compared with the background population

To establish the prevalence and quantify the severity of body fat redistribution and dyslipidaemia in HIV‐infected men after long‐term highly active antiretroviral therapy (HAART) compared with the background population.

Mortality after discharge from the intensive care unit during the early weekend period: a population-based cohort study in Denmark.

Background:u2002 As a result of a shortage of intensive care capacity, patients may be discharged prematurely early during weekends which may lead to an increased mortality and risk of readmission to intensive care units (ICU). We examined whether discharge from the ICU during the first part of the weekend was associated with an increased mortality and readmission to the ICU.

Novel Mutation in the Interferon-γ-Receptor Gene and Susceptibility to Mycobacterial Infections

In 1981 we presented a patient with Mycobacterium intracellulare osteomyelitis and depressed monocyte cytotoxicity. It is now demonstrated that the molecular defect was a never‐before‐described nucleotide deletion at position 794 (794delT) in the interferon‐γ‐receptor alpha‐1 gene. The genetic defect was passed on to his daughter who was diagnosed with non‐tuberculous mycobacterial osteomyelitis at the age of 7u2003years.

Ten years of extrapulmonary tuberculosis in a Danish university clinic.

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.

Low body weight and type of protease inhibitor predict discontinuation and treatment‐limiting adverse drug reactions among HIV‐infected patients starting a protease inhibitor regimen: consistent results from a randomized trial and an observational cohort

Departments of Infectious Diseases, 1 Hvidovre Hospital, University of Copenhagen, Hvidovre, 2 Rigshospitalet, University of Copenhagen, Copenhagen, 3 Odense University Hospital, Odense, 4 Aalborg Hospital, Aalborg and 5 Marselisborg University Hospital, Aarhus, Denmark