Cancer risk and temporal trends in people with HIV during a quarter of a century - a nationwide population-based matched cohort study.

BACKGROUND: It is important to understand current trends in cancer risk among people living with HIV (PLWH) to improve outcomes and to commission and delivery appropriate services. METHODS: Nationwide, population-based, matched cohort study on all adult PLWH treated at Danish HIV health care centres since 1 January 1995 and a comparison cohort, randomly selected from the background population and matched on sex and date of birth. RESULTS: We included 6327 PLWH and 63,270 individuals in the comparison cohort - 74% were men and median age was 37 (interquartile range: 30-46). For both smoking related cancers, virological cancers and other cancers, incidence was substantially higher in the first year of observation for PLWH than for the remaining observation period. The risk of smoking related cancer remained stably increased throughout the observation period, whereas the relative risk of virological cancers decreased, especially in the first year of follow up. Finally, the risk of other cancers for PLWH decreased to a level below that of the background population during the study period. CONCLUSION: The fact that the risk of other cancers was probably not higher among PLWH than in the comparison cohort is encouraging, as the excess risk of virological and smoking related cancers is potentially preventable by timely treatment of HIV and smoking cessation.

Risk of Depression in People With Human Immunodeficiency Virus: A Nationwide Population-based Matched Cohort Study.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with depression. However, previous studies have not addressed familial factors. METHODS: Nationwide, population-based, matched cohort study of people with HIV (PWH) in Denmark between 1995 and 2021 who were matched on sex and date of birth with a comparison cohort randomly selected from the Danish population. Family-related factors were examined by inclusion of siblings of those in the cohorts. We calculated hazard ratios (HRs) for depression, receipt of antidepressants, electroconvulsive therapy (ECT), and suicide, as well as the yearly proportions of study cohorts with psychiatric hospital contact due to depression and receipt of antidepressants from 10 years before to 10 years after study inclusion. RESULTS: We included 5943 PWH and 59 430 comparison cohort members. Median age was 38 years, and 25% were women. We observed an increased risk of depression, receipt of antidepressants, ECT, and suicide among PWH in the 2 first years of observation (HR, 3.3; 95% confidence interval [CI]: 2.5-4.4), HR, 3.0 (95% CI: 2.7-3.4), HR, 2.8 (95% CI: .9-8.6), and HR, 10.7 (95% CI: 5.2-22.2), thereafter the risk subsided but remained increased. The proportions of PWH with psychiatric hospital contact due to depression and receipt of antidepressants were increased prior to and especially after HIV diagnosis. Risk of all outcomes was substantially lower among siblings of PWH than among PWH (HR for receipt of antidepressants, 1.1; 95% CI: 1.0-1.2). CONCLUSIONS: PWH have an increased risk of depression. Family-related factors are unlikely to explain this risk.

Incidence of Childbirth, Pregnancy, Spontaneous Abortion, and Induced Abortion Among Women With Human Immunodeficiency Virus in a Nationwide Matched Cohort Study.

BACKGROUND: Reproductive health in women with human immunodeficiency virus (HIV) (WWH) has improved in recent decades. We aimed to investigate incidences of childbirth, pregnancy, spontaneous abortion, and induced abortion among WWH in a nationwide, population-based, matched cohort study. METHODS: We included all WWH aged 20-40 years treated at an HIV healthcare center in Denmark from 1995 to 2021 and a matched comparison cohort of women from the general population (WGP). We calculated incidence rates per 1000 person-years and used Poisson regression to calculate adjusted incidence rate ratios (aIRRs) of childbirth, pregnancy, spontaneous abortion, and induced abortion stratified according to calendar periods (1995-2001, 2002-2008, and 2009-2021). RESULTS: We included 1288 WWH and 12 880 WGP; 46% of WWH were of African origin, compared with 1% of WGP. Compared with WGP, WWH had a decreased incidence of childbirth (aIRR, 0.6 [95% confidence interval, .6-.7]), no difference in the incidence of pregnancy (0.9 [.8-1.0]) or spontaneous abortion (0.9 [.8-1.0]), but an increased incidence of induced abortion (1.9 [1.6-2.1]) from 1995 to 2021. The aIRRs for childbirth, pregnancy, and spontaneous abortion increased from 1995-2000 to 2009-2021, while the aIRR for induced abortion remained increased across all time periods for WWH. CONCLUSIONS: From 1995 to 2008, the incidences of childbirth, pregnancy, and spontaneous abortion were decreased among WWH compared with WGP. From 2009 to 2021, the incidence of childbirth, pregnancy, and spontaneous abortion no longer differed among WWH compared with WGP. The incidence of induced abortions remains increased compared with WGP.

Risk of subarachnoid haemorrhages and aneurysms in Danish people with HIV.

OBJECTIVE: It remains unclear whether people with HIV (PWH) have increased risk of aneurysms. We aimed to investigate if the risk of subarachnoid haemorrhage, cerebral aneurysm, aortic aneurysm and other arterial aneurysms and dissections is increased in PWH compared with the general population. DESIGN: We performed a nationwide population-based matched cohort study. METHODS: We compared PWH with age-matched and sex-matched comparison cohort members to calculate incidence rate ratios (IRR) of subarachnoid haemorrhage, cerebral aneurysm, aortic aneurysm and other arterial aneurysms and dissections as well as surgery for these conditions. RESULTS: We included all PWH, who were Danish residents and treated at a HIV healthcare centre between January 1995 and February 2018 ( n  = 6935) and an age-matched and sex-matched comparison cohort ( n  = 55 480). PWH had increased risk of subarachnoid haemorrhage (IRR 1.7, 95% CI, 1.1-2.6), but no increased risk of surgery for this condition. PWH had no increased risk of cerebral aneurysm or aortic aneurysm or surgery for these conditions. The risk of other arterial aneurysms and dissections was increased in PWH (IRR 2.0, 95% CI, 1.4-2.9), but this only applied for PWH who reported intravenous substance use as a route of HIV transmission (IRR 18.4, 95% CI, 9.3-36.6), and not for PWH without reported injection drug use (IRR 1.2, 95% CI, 0.73-1.7). CONCLUSION: PWH were not at an increased risk of cerebral, aortic or other arterial aneurysms and dissections. Although PWH were at an increased risk of subarachnoid haemorrhage, subarachnoid haemorrhages were rare among PWH.

Incidence of Chronic Obstructive Pulmonary Disease in People With Human Immunodeficiency Virus and Their Parents and Siblings in Denmark.

BACKGROUND: People with human immunodeficiency virus (PWH) may be at increased risk of several respiratory syndromes including chronic obstructive pulmonary disease (COPD). In matched cohort studies, we examined risk factors for COPD in PWH and their parents and siblings compared with population controls. METHODS: Using data from national registries, competing risk regression models were constructed and used to calculate adjusted hazard ratios (aHRs) for COPD. We evaluated the effect of human immunodeficiency virus characteristics, smoking, and educational attainment on COPD incidence in PWH. RESULTS: A total of 226 PWH and 1029 population controls were diagnosed with COPD during 63 661 and 562 171 person-years of follow-up. PWH had increased risk of being diagnosed with COPD compared to controls (aHR, 2.02 [95% confidence interval, 1.75-2.33]). Parents and siblings of PWH were also more likely to be diagnosed with COPD compared to controls. CD4+ T-cell counts were not associated with COPD, but unsuppressed viral replication, smoking status, and educational attainment were associated with COPD in PWH. No COPD diagnoses were registered in PWH with high educational attainment and absence of smoking. CONCLUSIONS: PWH have an increased risk of being diagnosed with COPD, as have their parents and siblings. This seems to be driven primarily by smoking and low socioeconomic status.

Risk of Cancer Among Sarcoidosis Patients With Biopsy-verified Nonnecrotizing Granulomatous Inflammation: Population-based Cohort Study.

OBJECTIVE: To assess the long-term risk of hematologic cancers, invasive solid tumors, and nonmelanoma skin cancer (NMSC) among sarcoidosis patients with biopsy-verified nonnecrotizing granulomatous inflammation. METHODS: We used Danish administrative registers with nationwide coverage to construct a cohort of 3892 patients with sarcoidosis and an age- and sex-matched comparison cohort of 38,920 population controls. For all patients, a biopsy demonstrating nonnecrotizing granulomatous inflammation had been obtained from the lower respiratory tract at the time of diagnosis. Study outcome was time to diagnosis of cancer. Follow-up began at time of sarcoidosis diagnosis and continued for up to 10 years. We calculated hazard ratios (HRs) as estimates of the cancer risk among the patients with sarcoidosis relative to that among the population controls and used cumulative incidence functions to calculate absolute 10-year risk estimates. RESULTS: We observed an increased long-term risk of hematologic cancers (HR during the first 2 years of follow-up: 2.71 [95% CI 1.18-6.25]; HR after > 2 years of follow-up: 2.12 [95% CI 1.29-3.47]) and NMSC (HR after > 2 years of follow-up: 1.82 [95% CI 1.43-2.32]) among the patients with sarcoidosis. An increased risk of invasive solid tumors was only observed during the first 2 years (HR 1.55, 95% CI 1.18-2.04). Compared with the population controls, the patients with sarcoidosis had an increased absolute 10-year risk of hematologic cancers (risk difference 0.56%, 95% CI 0.11-1.01%) and NMSC (risk difference 1.58%, 95% CI 0.70-2.47%). CONCLUSION: Sarcoidosis patients with biopsy-verified nonnecrotizing granulomatous inflammation have an increased long-term risk of hematologic cancers and NMSC compared with the general population.

Real-world Treatment Patterns and Overall Survival in Locally Advanced and Metastatic Urothelial Tract Cancer Patients Treated with Chemotherapy in Denmark in the Preimmunotherapy Era: A Nationwide, Population-based Study.

BACKGROUND: Real-world treatment patterns and survival outcomes of locally advanced, unresectable, and metastatic urinary tract cancer (mUTC) patients have not previously been studied in a nationwide, population-based cohort. OBJECTIVE: To describe treatment patterns and survival outcomes in mUTC patients treated in the real-world clinical setting. DESIGN SETTING AND PARTICIPANTS: This nationwide, population-based study included all mUTC patients initiating first-line chemotherapy at Danish oncology departments from January 2010 to March 2016. Data were retrospectively obtained from electronic medical records. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcome measurements were descriptive. Kaplan-Meier was used for survival analysis. RESULTS AND LIMITATIONS: Of 952 patients included in the study, 46.2% initiated standard gemcitabine/cisplatin (GC) and 21.1% gemcitabine/carboplatin (CaG); the remaining patients initiated other treatment regimens. Median follow-up was 11.6 mo. The overall response rate and disease control rate were 43.0% and 61.7% in all patients, 51.4% and 69.1% in GC-treated patients, and 34.4% and 58.8% in CaG-treated patients, respectively. Median overall survival (OS) was 11.7 (95% confidence interval [CI]: 10.8-12.5) mo in all patients, 14.0 (95% CI: 12.5-15.5) mo in GC-treated patients, and 9.8 (95% CI: 8.7-10.9) mo in CaG-treated patients. Limitations include the retrospective study design. CONCLUSIONS: Real-world mUTC patients are older and less fit than patients enrolled in clinical trials; despite this, tumor responses and survival are comparable. Survival in our patient cohort is also comparable with that reported from other real-world studies in this patient group. PATIENT SUMMARY: We studied treatment patterns and survival in urinary tract cancer patients receiving chemotherapy in the real-world clinical practice. Survival in our patient cohort was comparable with that reported from clinical trials and other real-world studies in this patient group.

Long-Term Survival, Morbidity, Social Functioning and Risk of Disability in Patients with a Herpes Simplex Virus Type 1 or Type 2 Central Nervous System Infection, Denmark, 2000-2016.

BACKGROUND: The long-term prognosis following herpes simplex virus (HSV) central nervous system (CNS) infection is still debated. PATIENTS AND METHODS: We examined outcomes in all Danish residents who, during 2000-2016, tested PCR positive for HSV-1 (n=208) or HSV-2 (n=283) in the cerebrospinal fluid, compared to comparison cohorts from the general population (n=2080 and n=2830). RESULTS: One-year mortality was increased among HSV-1 patients (difference 19.3%; 95% CI: 13.6% to 25.0%) and HSV-2 patients (difference 5.3%; 95% CI: 2.5% to 8.1%), but thereafter mortality was not increased. After exclusion of persons diagnosed with cancer prior to study inclusion, one-year mortality difference for HSV-2 patients was 1.7% (-0.1% to 3.5%). After five years, HSV-1 patients had lower employment (difference -19.8%; 95% CI: -34.7% to -4.8%) and higher disability pension rates (difference 22.2%; 95% CI: 8.4% to 36.0%) than the comparison cohort, but similar number of inpatient days, outpatient visits, and sick leave. HSV-2 patients had employment and disability pension rates comparable to the comparison cohort, but more inpatient days (difference 1.5/year; 95% CI: -0.2 to 3.2), outpatient visits (difference 1.3/year; 95% CI: 0.3 to 3.2), and sick leave days (difference 9.1/year; 95% CI: 7.9 to 10.4). CONCLUSION: HSV-1 and HSV-2 CNS infections differ substantially with respect to prognosis. HSV-1 CNS infection is followed by increased short-term mortality and long-term risk of disability. HSV-2 CNS infection has no substantial impact on mortality or working capability but is associated with increased morbidity.

Long-Term Survival, Health, Social Functioning, and Education in Patients With an Enterovirus Central Nervous System Infection, Denmark, 1997-2016.

BACKGROUND: The long-term clinical course of patients with an enterovirus central nervous system infection (ECI) is poorly understood. METHODS: We performed a nationwide population-based cohort study of all Danish patients with ECI diagnosed 1997-2016 (n = 1745) and a comparison cohort from the general population individually matched on date of birth and sex (n = 17 450). Outcomes were categorized into mortality and risk of cancer and likely measures of neurological sequelae: neuropsychiatric morbidities, educational landmarks, use of hospital services, employment, receipt of disability pension, income, number of sick leave days, and nursing home residency. RESULTS: Mortality in the first year was higher among patients with ECI (mortality rate ratio [MRR] = 10.0; 95% confidence interval [CI], 4.17-24.1), but thereafter mortality was not higher (MMR = 0.94; 95% CI, 0.47-1.86). Long-term outcomes for patients with ECI were not inferior to those of the comparison cohort for risk of cancer, epilepsy, mental and behavioral disorders, dementia, depression, school start, school marks, high school education, use of hospital services, employment, receipt of disability pension, income, days of sick leave, or nursing home residency. CONCLUSIONS: Diagnosis of an ECI had no substantial impact on long-term survival, health, or social/educational functioning.

Long term survival, health, social functioning, and education in patients with European Lyme neuroborreliosis: nationwide population based cohort study.

OBJECTIVE: To estimate long term survival, health, and educational/social functioning in patients with Lyme neuroborreliosis compared with the general population. DESIGN: Nationwide population based cohort study using national registers. SETTING: Denmark. PARTICIPANTS: All Danish residents diagnosed during 1986-2016 as having Lyme neuroborreliosis (n=2067), defined as a positive Borrelia burgdorferi intrathecal antibody test and a clinical diagnosis of Lyme borreliosis, and a comparison cohort from the general population matched on sex and date of birth (n=20 670). MAIN OUTCOME MEASURES: Mortality rate ratios, incidence rate ratios of comorbidities, and differences in educational and social outcomes. RESULTS: Mortality among patients with Lyme neuroborreliosis was not higher than in the general population (mortality rate ratio 0.90, 95% confidence interval 0.79 to 1.03). Lyme neuroborreliosis patients had increased risk of haematological (incidence rate ratio 3.07, 2.03 to 4.66) and non-melanoma skin cancers (1.49, 1.18 to 1.88). At diagnosis, Lyme neuroborreliosis patients had slightly higher employment and lower disability pension rates. After five years, patients and comparison cohort members had similar numbers of hospital contacts (difference -0.22, 95% confidence interval -0.45 to 0.02, in-hospital days/year; 0.37, -0.10 to 0.83, outpatient visits/year), employment rates (difference 1.5%, -2.1% to 5.1%), income (difference -1000, -20 000 to 18 000, Danish kroner), days of sick leave (difference -0.3, -3.5 to 3.0, per year), rates of receipt of a disability pension (difference -0.9%, -3.2% to 1.3%), and number of children (difference -0.10, -0.27 to 0.08). More patients were married (difference 4.8%, 2.2% to 7.4%) and had completed high school education (difference 7%, 1% to 12%). CONCLUSION: A verified diagnosis of Lyme neuroborreliosis had no substantial effect on long term survival, health, or educational/social functioning. Nevertheless, the diagnosis decreased labour market involvement marginally and was associated with increased risk of haematological and non-melanoma skin cancers.

Association Between Educational Level and Risk of Cancer in HIV-infected Individuals and the Background Population: Population-based Cohort Study 1995-2011.

BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals have increased risk of cancer. To our knowledge, no previous study has examined the impact of socioeconomic position on risk and prognosis of cancer in HIV infection. METHODS: Population-based cohort-study, including HIV-infected individuals diagnosed (without intravenous drug abuse or hepatitis C infection) (n = 3205), and a background population cohort matched by age, gender, and country of birth (n = 22 435) were analyzed. Educational level (low or high) and cancer events were identified in Danish national registers. Cumulative incidences, incidence rate ratios (IRRs), and survival using Kaplan-Meier methods were estimated. RESULTS: Low educational level was associated with increased risk of cancer among HIV-infected individuals compared to population controls: all (adjusted-IRRs: 1.4 [95% confidence interval {CI}, 1.1-1.7] vs 1.1 [95% CI, .9-1.2]), tobacco- and alcohol-related (2.1 [95% CI, 1.3-3.4] vs 1.3 [95% CI, 1.1-1.6]), and other (1.7 [95% CI, 1.1-2.8] vs 0.9 [95% CI, .7-1.0]). Educational level was not associated with infection-related or ill-defined cancers. One-year-survival was not associated with educational level, but HIV-infected individuals with low educational level had lower 5-year-survival following infection-related and ill-defined cancers. CONCLUSIONS: Education is associated with risk and prognosis of some cancers in HIV infection, and diverges from what is observed in the background population.

Unexpected Diagnosis of Cerebral Toxoplasmosis by 16S and D2 Large-Subunit Ribosomal DNA PCR and Sequencing.

The protozoan parasite Toxoplasma gondii causes severe opportunistic infections. Here, we report an unexpected diagnosis of cerebral toxoplasmosis. T. gondii was diagnosed by 16S and D2 large-subunit (LSU) ribosomal DNA (rDNA) sequencing of a cerebral biopsy specimen and confirmed by T. gondii-specific PCR and immunohistochemistry. The patient was later diagnosed with HIV/AIDS.

Educational attainment and risk of HIV infection, response to antiretroviral treatment, and mortality in HIV-infected patients.

OBJECTIVE: To estimate association between educational attainment and risk of HIV diagnosis, response to HAART, all-cause, and cause-specific mortality in Denmark in 1998-2009. DESIGN: Prospective, population-based cohort study including 1277 incident HIV-infected patients without hepatitis C virus or intravenous drug abuse identified in the Danish HIV Cohort Study and 5108 individually matched population controls. METHODS: Data on educational attainment, categorized as low, medium, or high, were identified in The Danish Attainment Register. Logistic and Poisson regression were used to estimate odds ratios (ORs) and mortality rate ratios (MRRs). RESULTS: OR of HIV diagnosis was 1.7 (95% confidence interval, CI 1.3-2.3) among heterosexual individuals with low educational attainments, but no associations between educational attainment and time to HAART initiation, CD4 cell count, or viral suppression were identified. All-cause MRRs were 1.8 (95% CI 1.0-3.2) and 1.8 (1.1-2.8) for HIV-infected patients and population controls with low educational attainment compared with medium and high educational attainment. MRRs for smoking and alcohol-related deaths were 3.6 (95% CI 1.5-8.9) for HIV-infected patients and 2.0 (95% CI 1.2-3.4) for population controls with low educational attainment compared with medium and high educational attainment. CONCLUSION: With free and equal access to healthcare, low educational attainment might increase risk of HIV infection among heterosexual individuals, but was not associated with late/very late presentation of HIV, time to HAART initiation, or HAART response. However, low educational attainment substantially increased lifestyle-related mortality, which indicates that increased mortality in HIV-infected patients with low educational attainments stems from risk factors unrelated to HIV.