Ann-Brit Eg Hansen

Incidence of low- and high-energy fractures in persons with and without HIV-infection: a Danish population-based cohort study

Objective:To compare fracture risk in persons with and without HIV infection and to examine the influence of highly active antiretroviral therapy (HAART) initiation on risk of fracture. Design:Population-based nationwide cohort study using Danish registries. Methods:Outcome measures were time to first fracture at any site, time to first low-energy and high-energy fracture in HIV-infected patients (n = 5306) compared with a general population control cohort (n = 26 530) matched by sex and age during the study period 1995–2009. Cox regression analyses were used to estimate incidence rate ratios (IRRs). Results:HIV-infected patients had increased risk of fracture [IRR 1.5, 95% confidence interval (CI) 1.4–1.7] compared with population controls. The relative risk was lower in HIV-monoinfected patients (IRR 1.3, 95% CI 1.2–1.4) than in HIV/hepatitis C virus (HCV)-coinfected patients (IRR 2.9, 95% CI 2.5–3.4).Both HIV-monoinfected and HIV/HCV-coinfected patients had increased risk of low-energy fracture, IRR of 1.6 (95% CI 1.4–1.8) and 3.8 (95% CI 3.0–4.9). However, only HIV/HCV-coinfected patients had increased risk of high-energy fracture, IRR of 2.4 (95% CI 2.0–2.9). Among HIV-monoinfected patients the risk of low-energy fracture was only significantly increased after HAART exposure, IRR of 1.8 (95% CI 1.5–2.1). The increased risk in HAART-exposed patients was not associated with CD4 cell count, prior AIDS, tenofovir or efavirenz exposure, but with comorbidity and smoking. Conclusion:HIV-infected patients had increased risk of fracture compared with population controls. Among HIV-monoinfected patients the increased risk was observed for low-energy but not for high-energy fractures, and the increased risk of low-energy fracture was only observed in HAART-exposed patients.

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.

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.

Rate of Accumulation of Thymidine Analogue Mutations in Patients Continuing to Receive Virologically Failing Regimens Containing Zidovudine or Stavudine: Implications for Antiretroviral Therapy Programs in Resource-Limited Settings

BACKGROUND Because changes in antiretroviral therapy in resource-limited settings (RLSs) are delayed until patients experience immunological or clinical failure, it is important to be able to estimate the consequences in terms of accumulation of thymidine analogue (TA) mutations (TAMs). METHODS The study included patients in EuroSIDA with 2 available genotypic resistance tests (GRTs) (human immunodeficiency virus [HIV] RNA level, >500 copies/mL in any measure between tests), provided that the first GRT was performed after the first virological failure of a TA and that the same TA was continued until the second GRT. RESULTS At the time of the first GRT in a pair (t0), 1 year after virological failure, a median of 3 TAMs were detected, mutations 41L and 215Y in 65% of pairs and 67N in 52%. Overall, 126 TAMs were accumulated during 548 person-years of follow-up (PYFUs) (1/4.3 years; 95% confidence interval, 3.7-5.0 years). Greater predicted activity of the TA at t0, TAM profile 2 (TAM2; vs TAM profile 1 [TAM1]) profiles at t0, use of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) at t0 (vs combined NNRTI and protease inhibitor), and acquisition of HIV infection through heterosexual (vs homosexual) contacts were associated with a faster rate of TAM accumulation. CONCLUSIONS Although the estimated rate of TAM accumulation was lower than anticipated, all possible efforts should be continued to increase the availability of drug options in RLSs.

High plasma level of interleukin-18 in HIV-infected subjects with lipodystrophy

Abstract:The level of interleukin-18 (IL-18) is elevated in patients with HIV infection as well as in people with insulin resistance (IR). As HIV-associated lipodystrophy (LD) shares metabolic characteristics with the metabolic syndrome, it was hypothesized that IL-18 would be elevated in patients with LD. Two groups of HIV-infected men with LD, one with fat accumulation (mixed group) (n = 12) and one without fat accumulation (lipoatrophic group) (n = 15) were included. Controls were HIV-positive men without LD (n = 15) and HIV-negative, age-matched men (n = 12). The levels of plasma IL-18 were elevated in all 3 HIV groups compared with HIV-negative controls (P <0.01). In the HIV groups the lipoatrophic group had the highest IL-18, followed by the mixed group and the HIV-positive controls. Only the differences between the lipoatrophic group and the HIV-positive controls were significant (P <0.01). Plasma IL-18 correlated with tumor necrosis factor-&agr; (P <0.05), but not IL-6, adiponectin, or HOMA-IR (homeostasis model of insulin resistance). In contrast to the HIV-negative controls, IL-18 did not correlate with total or low-density cholesterol in either of the HIV groups. An inverse correlation was observed between IL-18 and limb fat (P <0.05). In conclusion, the level of IL-18 is elevated in patients with LD and closely linked to limb atrophy, whereas it is not associated with cholesterol or IR.

Adipose tissue expression of IL-18 and HIV-associated lipodystrophy.

IL-18 is an inducer of apoptosis/tissue injury. IL-18 messenger RNA expression was examined in adipose tissue (AT) obtained from HIV patients with lipodystrophy, without lipodystrophy and healthy controls. IL-18 mRNA was expressed in AT at increased levels in lipodystrophy-positive compared with lipodystrophy-negative patients and healthy controls. Higher levels of IL-18 mRNA were found in femoral-gluteal AT compared with abdominal AT, and correlated with limb fat loss. These findings suggest that IL-18 is linked to HIV-associated lipodystrophy.

Severe Metabolic Acidosis and Renal Failure in an HIV-1 Patient Receiving Tenofovir

A 55-y-old male developed severe metabolic acidosis and renal failure during tenofovir therapy. Increased tenofovir exposure due to low body weight and chronic stable renal insufficiency could have enhanced the risk of nephrotoxicity, and creatinine clearance should be estimated before initiation of tenofovir.

Inpatient admissions and outpatient visits in persons with and without HIV infection in Denmark, 1995-2007.

Objective:HAART has changed morbidity and mortality in the HIV-infected population dramatically. We aimed to estimate the use of healthcare facilities in HIV-infected patients after the introduction of HAART. Design:This is a prospective nationwide cohort study. Methods:We identified all Danish HIV patients and a cohort of population controls matched on sex and date of birth. The study period was 1995–2007. We calculated inpatient admission rates and outpatient visit rates stratified by medical speciality and International Classification of Diseases-10 diagnose categories. Relative risks were computed. Results:Four thousand, seven hundred and sixty HIV-infected patients and 23 800 population controls were identified. Overall inpatient admission rates [95% confidence interval (CI)] for HIV-infected patients decreased from 90 (88–93) to 57 (56–58)/100 person-years in the study period. The risk ratio (95% CI) fell from 6.2 (6.0–6.5) to 3.1 (3.1–3.2) predominantly due to reduced inpatient admission rates to departments of infectious diseases. The overall outpatient visit rates (95% CI) for the HIV-infected patients increased from 744 (737–751) to 877 (872–882)/100 person-years, mainly due to visits at departments other than infectious diseases. A marked increase in outpatient visit rates (95% CI) in the background population decreased the risk ratio from 16.5 (16.2–16.8) to 7.1 (7.0–7.2). We observed a decreased relative risk of inpatient admissions and outpatient visits due to cancers and a small increase in relative risk due to cardiovascular disease. Conclusion:After the introduction of HAART, the inpatient treatment of HIV-infected patients has decreased, especially at departments of infectious disease. In contrast, this populations use of outpatient facilities has increased in noninfectious disease specialities.

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

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