Magnus Glindvad Ahlström

Long-term mortality in HIV-infected individuals 50 years or older: a nationwide, population-based cohort study

Background:Although the prevalence of HIV-infection among individuals ≥50 years of age has increased, the impact of HIV-infection on risk of death in this population remains to be established. Our aim was to estimate long-term mortality among HIV-infected individuals who were 50 years or older, when compared with an individually-matched cohort from the background population. Methods:Population-based cohort-study including HIV-infected individuals ≥50 years, who were alive 1 year after HIV-diagnosis (n = 2440) and a comparison cohort individually-matched by age and gender extracted from the background population (n = 14,588). Cumulative survival was evaluated using Kaplan–Meier method and Mortality Rate Ratios (MRRs) were estimated using Cox Regression Models. Study period 1996–2014. Results:Estimated median survival time from age 50 years for HIV-infected individuals increased from 11.8 years (95% CI: 10.2 to 14.5) during 1996–1999 to 22.8 years (20.0–24.2) in 2006–2014. MRR decreased with increasing age from 3.8 (3.1–4.7) for 50–55 years to 1.6 (1.0–2.6) for 75–80 years. In a cohort of well-treated HIV-infected individuals ≥50 years without AIDS-defining events or comorbidity at study inclusion (n = 517). MRR was 1.7 (1.2–2.3) compared with population controls without comorbidity. Conclusion:Among HIV-infected individuals estimated median survival time from age 50 years has increased by more than 10 years from 1996–1999 to 2006–2014, but is still substantially lower than in the background population. Even among well-treated HIV-infected individuals ≥50 years without comorbidity or AIDS-defining events the estimated median survival time remains lower than in the general population.

Cohort profile update: the Danish HIV Cohort Study (DHCS).

The DHCS is a cohort of all HIV-infected individuals seen in one of the eight Danish HIV centres after 31 December 1994. Here we update the 2009 cohort profile emphasizing the development of the cohort. Every 12-24 months, DHCS is linked with the Danish Civil Registration System (CRS) in order to extract an age- and sex-matched comparison cohort from the general population, as well as cohorts of family members of the HIV-infected patients and of the comparison cohort. The combined cohort is linked with CRS, the Danish Cancer Registry, the Danish National Hospital Registry, the Danish Registry of Causes of Death, the Danish National Prescription Registry, the Attainment Register and the Integrated Database for Labour Market Research to get information on vital status, migration, cancer, hospital contacts, causes of death, dispensed prescriptions, education and employment. Using this design, rates of a range of outcomes have been compared between HIV-infected patients and the comparison cohort, as well as between families of these two cohorts in order to disaggregate the effects of HIV infection and familial/environmental factors. Data can be shared with foreign institutions following approval from the Danish Data Protection Agency. Potential collaborators can contact the study director, Niels Obel (e-mail: niels.obel@regionh.dk).

Impact of pre-existing co-morbidities on mortality in granulomatosis with polyangiitis: a cohort study

OBJECTIVE To assess the impact of pre-existing co-morbidities on mortality among patients affected by granulomatosis with polyangiitis (GPA). METHODS By means of the Danish National Hospital Register, we identified a cohort of patients hospitalized for GPA during 1994-2010 (n = 308). The burden of pre-existing co-morbidities among the patients was quantified according to the Charlson Comorbidity Index (CCI). Each patient was matched with five age- and gender-matched population controls with no pre-existing co-morbidities captured by the CCI (CCI score = 0). The study subjects were followed throughout 2010. Cox regression analyses were used to calculate mortality rate ratios (MRRs). RESULTS The median duration of follow-up in the GPA cohort was 5.8 years (interquartile range 2.3-10.0). Compared with their matched population controls, the MRR for patients presenting with a CCI score of 0 (n = 246) was 3.9 (95% CI 2.0, 7.5) during years 0-2 and 1.4 (95% CI 0.9, 2.0) from the second year of follow-up onwards. The corresponding MRRs were 13.3 (95% CI 5.8, 31) and 1.9 (95% CI 1.1, 3.6) for patients with a CCI score ⩾1 (n = 62). In a direct comparison, GPA patients with a CCI score ⩾1 were found to have significantly higher mortality than GPA patients with a CCI score of 0 during years 0-2 [adjusted MRR 3.4 (95% CI 1.6, 7.0)] but not after >2 years of follow-up [adjusted MRR 1.3 (95% CI 0.7, 2.6)]. CONCLUSION During early follow-up periods, the mortality among GPA patients with pre-existing co-morbidities is markedly higher than that among GPA patients with no pre-existing illnesses. Our analyses identify an increased CCI score for pre-existing co-morbidities as an important risk factor for a fatal outcome in GPA.

Risk of Diabetes Mellitus among Patients Diagnosed with Giant Cell Arteritis or Granulomatosis with Polyangiitis: Comparison with the General Population

Objective. Patients with organ- or life-threatening vasculitis receive high cumulative glucocorticoid (GC) doses during their disease course. GC have diabetogenic effects, but the risk of diabetes mellitus (DM) related to vasculitis therapy is not well characterized. We assessed the DM risk among patients diagnosed with giant cell arteritis (GCA) or granulomatosis with polyangiitis (GPA), i.e., patients with relatively common forms of systemic vasculitis. Methods. We used Danish healthcare registries to identify 1682 patients diagnosed with GCA and 342 patients diagnosed with GPA from 1997 to 2015 and to obtain information regarding medication exposures. Each patient with vasculitis was matched with 9 population controls. Date of new-onset DM was defined as date of first claimed prescription for an antidiabetic drug. We used Cox regression analyses to calculate incidence rate ratios (IRR) for DM as a measure of the DM risk among patients relative to population controls. Logistic regression was used to study the association between prednisolone/prednisone (PRED) dose and DM. Results. Median duration of followup was 6.5 years [interquartile range (IQR) 2.6–10.4] in the GCA cohort and 5.8 years (IQR 1.7–10.6) in the GPA cohort. During the first year after diagnosis of vasculitis, the IRR for DM was 7.0 (95% CI 5.2–9.3) among patients with GCA and 10.4 (95% CI 4.4–24) among patients with GPA. IRR for DM were not significantly increased in either cohort during later followup periods. Within the first year, treatment with high cumulative prednisolone/PRED doses was associated with new-onset DM among the patients with vasculitis. Conclusion. Patients diagnosed with GCA or GPA have a markedly increased risk of new-onset DM during early treatment phases.

Incidence, presentation and outcome of toxoplasmosis in HIV infected in the combination antiretroviral therapy era

BACKGROUND HIV-associated incidence and prognosis of cerebral toxoplasmosis (CTX) is not well established during later years. METHODS From the Danish HIV Cohort Study, we identified 6325 HIV-infected individuals. We assessed incidence, mortality, predictive and prognostic factors of CTX during the pre-combination antiretroviral therapy (pre-cART; 1995-1996) and cART-era (1997-2014). Adjusted incidence rate ratios (aIRR), mortality rate ratios (aMRR) and 95% confidence intervals (CI) were assessed using Poisson regression analysis. RESULTS CTX IR was 1.17/1000 PYR (95% CI 0.93-1.47). We observed no change in CTX-risk in the first year after HIV-diagnosis, but a substantial reduction in mortality in the first 3 months after CTX diagnosis when comparing the cART-era to the pre-cART-era; {(aIRR: 0.79; 95% CI: 0.37-1.72) (aMRR: 0.15; 95% CI: 0.06-0.38)}. For individuals surviving the first year after HIV-diagnosis or the first 3 months after CTX-diagnosis, IRR and MRR had declined to minimal levels {(aIRR: 0.06; 95% CI: 0.03-0.10); (aMRR: 0.02; 95% CI: 0.01-0.05)}. Three years after CTX-diagnosis 30% of the patients still had neurological deficits. CONCLUSION Although, CTX remains an important cause of morbidity and mortality in the cART-era, with high prevalence of neurological sequelae, incidence and mortality has largely declined, especially among those surviving the first year after diagnosis.

Smoking and renal function in people living with human immunodeficiency virus: a Danish nationwide cohort study

Introduction Smoking is a main risk factor for morbidity and mortality in people living with human immunodeficiency virus (PLHIV), but its potential association with renal impairment remains to be established. Methods We did a nationwide population-based cohort study in Danish PLHIV to evaluate the association between smoking status and 1) overall renal function and risk of chronic kidney disease (CKD), 2) risk of any renal replacement therapy (aRRT), and 3) mortality following aRRT. We calculated estimated creatinine clearance using the Cockcroft–Gault equation (CG-CrCl), and evaluated renal function graphically. We calculated cumulative incidence of CKD (defined as two consecutive CG-CrCls of ≤60 mL/min, ≥3 months apart) and aRRT and used Cox regression models to calculate incidence rate ratios (IRRs) for risk of CKD, aRRT, and mortality rate ratios (MRRs) following aRRT. Results From the Danish HIV Cohort Study, we identified 1,475 never smokers, 768 previous smokers, and 2,272 current smokers. During study period, we observed no association of smoking status with overall renal function. Previous and current smoking was not associated with increased risk of CKD (adjusted IRR: 1.1, 95% confidence interval [CI]: 0.7–1.7; adjusted IRR: 1.3, 95% CI: 0.9–1.8) or aRRT (adjusted IRR: 0.8, 95% CI: 0.4–1.7; adjusted IRR: 0.9, 95% CI: 0.5–1.7). Mortality following aRRT was high in PLHIV and increased in smokers vs never smokers (adjusted MRR: 3.8, 95% CI: 1.3–11.2). Conclusion In Danish PLHIV, we observed no strong association between smoking status and renal function, risk of CKD, or risk of aRRT, but mortality was increased in smokers following aRRT.

Agreement between Estimated and Measured Renal Function in an Everyday Clinical Outpatient Setting of Human Immunodeficiency Virus-Infected Individuals

Introduction: Estimated renal function (eRF) has been widely implemented as a screening tool in handling human immunodeficiency virus (HIV)-infected individuals. Our primary objective was to investigate the agreement between measured renal function (mRF) and eRF in HIV-infected individuals in an everyday clinical setting. Methods: A single-center study at the HIV-outpatient clinic at Copenhagen University Hospital, Rigshospitalet. Study period from January 1, 2004-June 1, 2015. We included all HIV-infected individuals who had an mRF performed and compared this with eRF assessed with 9 different serum-creatinine-based equations and the eRF reported by the Department of Clinical Biochemistry. We evaluated performance characteristics of the different eRFs, with concordance correlation coefficient, total deviation index, coverage probability, relative accuracy, and Bland Altman plots. We also evaluated whether exposure to (1) rilpivirine, cobicistat, or dolutegravir (RLP/COB/DTG), (2) protease inhibitors (PIs), or (3) tenofovir disoproxil fumarate (TDF) had an impact on agreement. Furthermore, we compared inter- and intra-individual differences between mRF and eRF. Results: Ninety-eight individuals had an mRF performed during the study period. We found that the agreement between mRF and eRF was poor irrespective of the eRF equation. Exposure to RLP/COB/DTG and PIs was not associated with different agreement. Exposure to TDF was associated with statistically significant better agreement for 3 of the evaluated equations. Conclusion: Irrespective of calculation methods, the agreement between mRF and eRF is poor. Surprisingly TDF exposure was associated with a better agreement compared with TDF-unexposed individuals.

Incidence, clinical presentation, and outcome of hiv-1-associated cryptococcal meningitis during the highly active antiretroviral therapy era: A nationwide cohort study

Background Human immunodeficiency virus (HIV) infection with advanced immunosuppression predisposes to cryptococcal meningitis (CM). We describe the incidence, clinical presentation, and outcome of CM in HIV-infected individuals during the highly active antiretroviral therapy (HAART) era. Methods A nationwide, population-based cohort of HIV-infected individuals was used to estimate incidence and mortality of CM including risk factors. A description of neurological symptoms of CM at presentation and follow-up in the study period 1995–2014 was included in this study. Results Among 6,351 HIV-infected individuals, 40 were diagnosed with CM. The incidence rates were 3.7, 1.8, and 0.3 per 1000 person-years at risk in 1995–1996, 1997–1999, and 2000–2014, respectively. Initiation of HAART was associated with decreased risk of acquiring CM [incidence rate ratio (IRR), 0.1 (95% CI, 0.05–0.22)]. African origin was associated with increased risk of CM [IRR, 2.05 (95% CI, 1.00–4.20)]. The main signs and symptoms at presentation were headache, cognitive deficits, fever, neck stiffness, nausea, and vomiting. All individuals diagnosed with CM had a CD4+ cell count <200 cells/µl [median 26; interquartile range (IQR), 10–50)]. Overall, mortality following CM was high and mortality in the first 4 months has not changed substantially over time. However, individuals who survived generally had a favorable prognosis, with 86% (18/21) returning to the pre-CM level of activity. Conclusion The incidence of HIV-associated CM has decreased substantially after the introduction of HAART. To further decrease CM incidence and associated mortality, early HIV diagnosis and HAART initiation seems crucial.

Mortality and Risk of Cancer After Prophylactic Bilateral Oophorectomy in Women With a Family History of Cancer

Abstract Background Current international guidelines recommend systemic hormone therapy (HT) to oophorectomized women until the age of natural menopause. Despite an inherited predisposition to estrogen-dependent malignancies, the guidelines also apply to women oophorectomized because of a family history of cancer. The objective of this study was to investigate the impact of HT on mortality and risk of cancer in women oophorectomized because of a family history of cancer. Methods A nationwide, population-based cohort was used to study women oophorectomized because of a family history of cancer (n = 2002). Comparison cohorts included women from the background population individually matched on age (n = 18 018). Oophorectomized women were subdivided into three groups: oophorectomized at 1) age 45 years or younger not using HT, 2) age 45 years or younger using HT, 3) older than age 45 years, and their respective population comparison cohorts. Results Women oophorectomized at age 45 years or younger using HT had increased overall mortality (mortality rate ratio [MRR] = 3.45, 95% confidence interval [CI] = 1.53 to 7.79), mortality because of cancer (MRR = 5.67, 95% CI = 1.86 to 17.34), and risk of overall cancer (incidence rate ratio [IRR] = 3.68, 95% CI = 1.93 − 6.98), primarily reflected in an increased risk of breast cancer (IRR = 4.88, 95% CI = 2.19 − 10.68). Women oophorectomized at age 45 years or younger not using HT and women oophorectomized at older than age 45 years did not have increased mortality, mortality because of cancer, or risk of overall cancer, but they had increased risk of breast cancer (IRR = 2.64, 95% CI = 1.14 to 6.13, and IRR = 1.72, 95% CI = 1.14 to 2.59, respectively). Conclusions Use of HT in women oophorectomized at age 45 years or younger with a family history of cancer is associated with increased mortality and risk of overall cancer and breast cancer. Our study warrants further investigation to establish the impact of HT on mortality and cancer risk in oophorectomized women with a family history of cancer.

Association between smoking status assessed with plasma-cotinine and inflammatory and endothelial biomarkers in HIV-positive and HIV-negative individuals

Smoking is a major contributor to mortality and morbidity in HIV‐positive individuals. Our primary objective was to evaluate the association between smoking status determined by plasma cotinine (P‐cotinine) concentration and inflammatory and endothelial biomarkers in HIV‐positive versus HIV‐negative individuals.