The Impact of HAART on the Respiratory Complications of HIV Infection: Longitudinal Trends in the MACS and WIHS Cohorts

Objective: To review the incidence of respiratory conditions and their effect on mortality in HIV-infected and uninfected individuals prior to and during the era of highly active antiretroviral therapy (HAART). Design: Two large observational cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study [MACS]) and women (Women's Interagency HIV Study [WIHS]), followed since 1984 and 1994, respectively. Methods: Adjusted odds or hazards ratios for incident respiratory infections or non-infectious respiratory diagnoses, respectively, in HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS only) and HAART eras; and adjusted Cox proportional hazard ratios for mortality in HIV-infected persons with lung disease during the HAART era. Results: Compared to HIV-uninfected participants, HIV-infected individuals had more incident respiratory infections both pre-HAART (MACS, odds ratio [adjusted-OR], 2.4; 95% confidence interval [CI], 2.2-2.7; p<0.001) and after HAART availability (MACS, adjusted-OR, 1.5; 95%CI 1.3-1.7; p<0.001; WIHS adjusted-OR, 2.2; 95%CI 1.8-2.7; p<0.001). Chronic obstructive pulmonary disease was more common in MACS HIV-infected vs. HIV-uninfected participants pre-HAART (hazard ratio [adjusted-HR] 2.9; 95%CI, 1.02-8.4; p = 0.046). After HAART availability, non-infectious lung diseases were not significantly more common in HIV-infected participants in either MACS or WIHS participants. HIV-infected participants in the HAART era with respiratory infections had an increased risk of death compared to those without infections (MACS adjusted-HR, 1.5; 95%CI, 1.3-1.7; p<0.001; WIHS adjusted-HR, 1.9; 95%CI, 1.5-2.4; p<0.001). Conclusion: HIV infection remained a significant risk for infectious respiratory diseases after the introduction of HAART, and infectious respiratory diseases were associated with an increased risk of mortality. © 2013 Gingo et al

Improved Survival of HIV-1-Infected Patients with Progressive Multifocal Leukoencephalopathy Receiving Early 5-Drug Combination Antiretroviral Therapy

Progressive multifocal leukoencephalopathy (PML), a rare devastating demyelinating disease caused by the polyomavirus JC (JCV), occurs in severely immunocompromised patients, most of whom have advanced-stage HIV infection. Despite combination antiretroviral therapy (cART), 50% of patients die within 6 months of PML onset. We conducted a multicenter, open-label pilot trial evaluating the survival benefit of a five-drug cART designed to accelerate HIV replication decay and JCV-specific immune recovery.All the patients received an optimized cART with three or more drugs for 12 months, plus the fusion inhibitor enfuvirtide during the first 6 months. The main endpoint was the one-year survival rate. A total of 28 patients were enrolled. At entry, median CD4+ T-cell count was 53 per microliter and 86% of patients had detectable plasma HIV RNA and CSF JCV DNA levels. Seven patients died, all before month 4. The one-year survival estimate was 0.75 (95% confidence interval, 0.61 to 0.93). At month 6, JCV DNA was undetectable in the CSF of 81% of survivors. At month 12, 81% of patients had undetectable plasma HIV RNA, and the median CD4+ T-cell increment was 105 per microliter. In univariate analysis, higher total and naive CD4+ T-cell counts and lower CSF JCV DNA level at baseline were associated with better survival. JCV-specific functional memory CD4+ T-cell responses, based on a proliferation assay, were detected in 4% of patients at baseline and 43% at M12 (P = 0.008).The early use of five-drug cART after PML diagnosis appears to improve survival. This is associated with recovery of anti-JCV T-cell responses and JCV clearance from CSF. A low CD4+ T-cell count (particularly naive subset) and high JCV DNA copies in CSF at PML diagnosis appear to be risk factors for death.ClinicalTrials.gov NCT00120367

Similar long-term survival of consecutive in-hospital and out-of-hospital cardiac arrest patients treated with targeted temperature management

Magaly Engsig,1 Helle S&oslash;holm,2 Fredrik Folke,3,4 Peter J Gadegaard,1 Julie Therese Wiis,5 Rune Molin,6 Thomas Mohr,1 Frederik N Engsig7 1Department of Anaesthesiology and Intensive Care, Copenhagen University Hospital, Hellerup, 2Department of Cardiology, Copenhagen University Hospital, Herlev, 3Department of Cardiology, Copenhagen University Hospital, Hellerup, 4Pre-Hospital Emergency Medical Services, Capital Region of Denmark, Ballerup, 5Department of Intensive Care, Copenhagen University Hospital, Copenhagen, 6Department of Anaesthesiology, Copenhagen University Hospital, Hiller&oslash;d, 7Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark Objective: The long-term survival of in-hospital cardiac arrest (IHCA) patients treated with targeted temperature management (TTM) is poorly described. The aim of this study was to compare the outcomes of consecutive IHCA with out-of-hospital cardiac arrest (OHCA) patients treated with TTM. Design, setting, and patients: Retrospectively collected data on all consecutive adult patients treated with TTM at a university tertiary heart center between 2005 and 2011 were analyzed. Measurements: Primary endpoints were survival to hospital discharge and long-term survival. Secondary endpoint was neurological outcome assessed using the Pittsburgh cerebral performance category (CPC). Results: A total of 282 patients were included in this study; 233 (83%) OHCA and 49 (17%) IHCA. The IHCA group presented more often with asystole, received bystander cardiopulmonary resuscitation (CPR) in all cases, and had shorter time to return of spontaneous circulation (ROSC). Survival to hospital discharge was 54% for OHCA and 53% for IHCA (adjusted odds ratio 0.98 [95% confidence interval {CI}; 0.43&ndash;2.24]). Age &le;60&nbsp;years, bystander CPR, time to ROSC &le;10 min, and shockable rhythm at presentation were associated with survival to hospital discharge. Good neurologic outcome among survivors was achieved by 86% of OHCA and 92% of IHCA (P=0.83). After a median follow-up time of &gt;5 years, 83% of OHCA and 77% of IHCA were alive (adjusted hazard ratio [HR] 1.51 [95% CI; 0.59&ndash;3.91]). Age &le;60 years was the only factor associated with long-term survival (adjusted HR 2.73 [95% CI; 1.36&ndash;5.52]). Conclusion: There was no difference in short- and long-term survival and no difference in neurologic outcome to hospital discharge between IHCA and OHCA patients treated with TTM despite higher frequency of asystole in IHCA. Keywords: retrospective observational study, in-hospital survival, neurological outcome, advanced life support, post-resuscitation car

Head and neck cancer in HIV patients and their parents: a Danish cohort study

Frederik N Engsig1, Jan Gerstoft1, Gitte Kronborg2, Carsten S Larsen3, Gitte Pedersen4, Court Pedersen5, Niels Obel11Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark; 2Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; 3Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark; 4Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark; 5Department of Infectious Diseases, Odense University Hospital, Odense, DenmarkBackground: The mechanism for the increased risk of head and neck cancer (HNC) observed in HIV patients is controversial. We hypothesized that family-related risk factors increase the risk of HNC why we estimated the risk of this type of cancer in both HIV patients and their parents.Methods: We estimated the cumulative incidence and incidence rate ratios (IRRs) of HNC in 1) a population of all Danish HIV patients identified from the Danish HIV Cohort Study (n = 5053) and a cohort of population controls matched on age and gender (n = 50,530) (study period; 1995&amp;ndash;2009) and 2) the parents of HIV patients and population controls (study period 1978&amp;ndash;2009). To assess the possible impact of human papilloma virus (HPV)&amp;ndash;associated cancers, the sites of squamous cell HNCs were categorized as HPV related, potentially HPV related, and potentially HPV unrelated.Results: Seventeen (0.3%) HIV patients vs 80 (0.2%) population controls were diagnosed with HNC cancer in the observation period. HIV patients had an increased risk of HNC (IRR 3.05 [95% CI 1.81&amp;ndash;5.15]). The IRR was considerably increased in HIV patients older than 50 years (adjusted IRR; 4.58 [95% CI 2.24&amp;ndash;9.35]), diagnosed after 1995 (adjusted IRR 6.31 [95% CI 2.82&amp;ndash;14.08]), previous or current smoker (adjusted IRR 4.51 [95% CI 2.47&amp;ndash;8.23]), with baseline CD4 count 350 cells/&amp;micro;L (adjusted IRR; 3.89 [95% CI 1.95&amp;ndash;7.78]), and men heterosexually infected with HIV (adjusted IRR 5.54 [95% CI 1.96&amp;ndash;15.66]). Fifteen (83%) of the HIV patients diagnosed with HNC were current or former smokers. The IRR of squamous cell HNC in HIV patients was high at HPV-relate sites, potentially HPV-related sites, and potentially HPV-unrelated sites. Both fathers and mothers of HIV patients had an increased risk of HNC (adjusted IRR for fathers 1.78 [95% CI 1.28&amp;ndash;2.48], adjusted IRR for mothers 2.07 [95% CI 1.05&amp;ndash;4.09]).Conclusion: HIV appears to be a marker of behavioral or family-related risk factors that affect the incidence of HNC in HIV patients.Keywords: HIV, head and neck cancer incidence, matched cohort, population controls, parent

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

Madeleine Touma,1 Line D Rasmussen,2 Raquel Martin-Iguacel,2 Frederik Neess Engsig,3 Nina Breinholt St&aelig;rke,4 Mette St&aelig;rkind,5 Niels Obel,1 Magnus Glindvad Ahlstr&ouml;m1 1Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, 2Department of Infectious Diseases, Odense University Hospital, Odense, 3Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, 4Department of Infectious Diseases, Aarhus University Hospital, Aarhus, 5Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark 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&ndash;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&ndash;1996, 1997&ndash;1999, and 2000&ndash;2014, respectively. Initiation of HAART was associated with decreased risk of acquiring CM [incidence rate ratio (IRR), 0.1 (95% CI, 0.05&ndash;0.22)]. African origin was associated with increased risk of CM [IRR, 2.05 (95% CI, 1.00&ndash;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 &lt;200 cells/&micro;l [median 26; interquartile range (IQR), 10&ndash;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. Keywords: cryptococcal meningitis, highly active antiretroviral therapy, HIV&nbsp

Existing Data Sources in Clinical Epidemiology: Database of Community Acquired Infections Requiring Hospital Referral in Eastern Denmark (DCAIED) 2018&ndash;2021

Jon Gitz Holler,1 Jens Ulrik Stæhr Jensen,2– 4 Frederik Neess Engsig,5 Morten H Bestle,3,6 Birgitte Lindegaard,1,3,7 Jens Henning Rasmussen,8 Henning Bundgaard,3,9 Finn Erland Nielsen,8 Kasper Karmark Iversen,3,10 Jesper Juul Larsen,11 Barbara Juliane Holzknecht,3,12 Jonas Boel,12,13 Pradeesh Sivapalan,2,3 Theis Skovsgaard Itenov3,14 1Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital - North Zealand, Hilleroed, Denmark; 2Department of Medicine, Section of Respiratory Medicine, Copenhagen University Hospital - Herlev and Gentofte Hospital, Copenhagen, Denmark; 3Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 4PERSIMUNE & CHIP: Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; 5Department of Emergency Medicine, Copenhagen University Hospital – Amager and Hvidovre, Copenhagen, Denmark; 6Department of Anesthesia and Intensive Care Medicine, Copenhagen University Hospital – North Zealand, Hilleroed, Denmark; 7Centre for Physical Activity, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; 8Department of Emergency Medicine, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, Denmark; 9Department of Cardiology, The Capital Region’s Unit of Inherited Cardiac Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; 10Department of Emergency Medicine, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark; 11Department of Emergency Medicine, Copenhagen University Hospital - North Zealand, Hilleroed, Denmark; 12Department of Clinical Microbiology, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark; 13Copenhagen University Hospital - Capital Region Pharmacy, Copenhagen, Denmark; 14Department of Anesthesiology and Intensive Care Medicine, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, DenmarkCorrespondence: Jon Gitz Holler, Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital - North Zealand, Copenhagen, Denmark, Tel +45-48292578, Fax +45-48293935, Email [email protected]: Infectious diseases are major health care challenges globally and a prevalent cause of admission to emergency departments. Epidemiologic characteristics and outcomes based on population level data are limited. The Database of Community Acquired Infections in Eastern Denmark (DCAIED) 2018– 2021 was established with the aim to explore and estimate the population characteristics, and outcomes of patients suffering from community acquired infections at the emergency departments in the Capital Region and the Zealand Region of Denmark using data from electronic medical records. Adult patients (≥ 18 years) presenting to the emergency department with suspected or confirmed infection are included in the cohort. Presence of sepsis and organ failure are assessed using modified criteria from the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). During the inclusion period from January 2018 to January 2022, 2,241,652 adult emergency department visits have been registered. Of these, 451,825 were unique encounters of which 60,316 fulfilled criteria of suspected infection and 28,472 fulfilled sepsis criteria and 8,027 were defined as septic shock. The database covers the entire Capital and Zealand Region of Denmark with an uptake area of 2.6 million inhabitants and includes demographic, laboratory and outcome indicators, with complete follow-up. The database is well-suited for epidemiological research for future national and international collaborations.Keywords: emergency department, infectious diseases, sepsis, shock, database, epidemiology, community acquire