Is Tocilizumab Plus Dexamethasone Associated with Superinfection in Critically Ill COVID-19 Patients?

BACKGROUND: Dexamethasone and tocilizumab are used to treat severely ill COVID-19 patients admitted to intensive care units (ICUs). We explored whether combination therapy increased the risk of superinfection compared to dexamethasone alone. METHODS: This observational, retrospective study included critically ill COVID-19 adult patients admitted to our ICU because of respiratory failure. Patients received dexamethasone with (Group 1) or without (Group 2) tocilizumab. Data were collected from electronic medical files. RESULTS: A total of 246 patients were included, of whom 150 received dexamethasone and tocilizumab, while 96 received dexamethasone alone. Acute respiratory distress syndrome was evident on admission in 226 patients, 56 of whom required mechanical ventilation (MV). Superinfections, mainly respiratory, were diagnosed in 59 patients, including 34/150 (23%) in Group 1 and 25/96 (26%) in Group 2 (p = 0.32). After multivariate analysis, the factors associated with a higher risk of superinfection included hematological malignancy (hazard ratio (HR): 2.47 (1.11-5.47), p = 0.03), MV (HR: 3.74 (1.92-7.26), p = 0.0001), and a higher SAPS-II score on admission (HR: 1.03 (1.01-1.06), p = 0.006). CONCLUSION: In critically ill COVID-19 patients, the addition of tocilizumab to dexamethasone was not associated with an increased risk of superinfection

Viruses

We proposed a new HIV-1 therapeutic vaccine based on conserved cytotoxic T lymphocyte (CTL) epitopes of archived HIV-1 DNA according to their affinity to the dominant HLA-A and -B alleles of the population investigated. Our proposal (Hla Fitted VAC, HFVAC) was composed of 15 peptides originating from the RT, gag and nef parts of proviral DNA. Our aim was to investigate baseline immune reactivity to the vaccine in HIV-1 chronically infected patients at success of antiretroviral therapy (ART) who would be eligible for a therapeutic vaccine. Forty-one patients were tested. Most of them had been infected with HIV-1 subtype B and all had been receiving successful ART for 2 to 20 years. The predominant HLA-A and -B alleles were those of a Caucasian population. ELISPOT was carried out using the HFVAC peptides. In 22 patients, the PD-1 marker was investigated on CD4+ and CD8+ T cells by flow cytometry in order to evaluate global T cell exhaustion. ELISPOT positivity was 65% overall and 69% in patients exhibiting at least one HLA allele fitting with HFVAC. The percentages of CD4+ and CD8+ T cells expressing PD-1 were high (median values 23.70 and 32.60, respectively), but did not seem to be associated with an impairment of the immune response investigated in vitro. In conclusion, reactivity to HFVAC was high in this ART-treated population with dominant HLA alleles, despite potential cellular exhaustion associated with the PD-1 marker

Longitudinal trends in causes of death among adults with HIV on antiretroviral therapy in Europe and North America from 1996 to 2020: a collaboration of cohort studies

Background Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America. Methods In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996-99, 2000-03, 2004-07, 2008-11, 2012-15, and 2016-20, adjusted for time-updated age, CD4 count, and whether the individual was ART -naive at the start of each period. Findings Among 189 301 people with HIV included in this study, 16 832 (8 center dot 9%) deaths were recorded during 1 519 200 person-years of follow-up. 13 180 (78 center dot 3%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25 center dot 0%), non-AIDS non -hepatitis malignancy (2311; 13 center dot 7%), and cardiovascular or heart-related (1403; 8 center dot 3%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996-99 to 16% during 2016-20. Rates of all-cause mortality per 1000 person-years decreased from 16 center dot 8 deaths (95% CI 15 center dot 4-18 center dot 4) during 1996-99 to 7 center dot 9 deaths (7 center dot 6-8 center dot 2) during 2016-20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0 center dot 85 (95% CI 0 center dot 84-0 center dot 86). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0 center dot 81; 0 center dot 79-0 center dot 83). There were also reductions in rates of cardiovascular-related (0 center dot 83, 0 center dot 79-0 center dot 87), liver-related (0 center dot 88, 0 center dot 84-0 center dot 93), non-AIDS infectionrelated (0 center dot 91, 0 center dot 86-0 center dot 96), non-AIDS-non-hepatocellular carcinoma malignancy-related (0 center dot 94, 0 center dot 90-0 center dot 97), and suicide or accident-related mortality (0 center dot 89, 0 center dot 82-0 center dot 95). Mortality rates among people who acquired HIV through injecting drug use increased in women (1 center dot 07, 1 center dot 00-1 center dot 14) and decreased slightly in men (0 center dot 96, 0 center dot 93-0 center dot 99). Interpretation Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population. Funding US National Institute on Alcohol Abuse and Alcoholism. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Contribution of alcohol use in HIV/hepatitis C virus co-infection to all-cause and cause-specific mortality: A collaboration of cohort studies

Among persons with HIV (PWH), higher alcohol use and having hepatitis C virus (HCV) are separately associated with increased morbidity and mortality. We investigated whether the association between alcohol use and mortality among PWH is modified by HCV. Data were combined from European and North American cohorts of adult PWH who started antiretroviral therapy (ART). Self-reported alcohol use data, collected in diverse ways between cohorts, were converted to grams/day. Eligible PWH started ART during 2001-2017 and were followed from ART initiation for mortality. Interactions between the associations of baseline alcohol use (0, 0.1-20.0, >20.0 g/day) and HCV status were assessed using multivariable Cox models. Of 58,769 PWH, 29,711 (51%), 23,974 (41%) and 5084 (9%) self-reported alcohol use of 0 g/day, 0.1-20.0 g/day, and > 20.0 g/day, respectively, and 4799 (8%) had HCV at baseline. There were 844 deaths in 37,729 person-years and 2755 deaths in 443,121 person-years among those with and without HCV, respectively. Among PWH without HCV, adjusted hazard ratios (aHRs) for mortality were 1.18 (95% CI: 1.08-1.29) for 0.0 g/day and 1.84 (1.62-2.09) for >20.0 g/day compared with 0.1-20.0 g/day. This J-shaped pattern was absent among those with HCV: aHRs were 1.00 (0.86-1.17) for 0.0 g/day and 1.64 (1.33-2.02) for >20.0 g/day compared with 0.1-20.0 g/day (interaction p < .001). Among PWH without HCV, mortality was higher in both non-drinkers and heavy drinkers compared with moderate alcohol drinkers. Among those with HCV, mortality was higher in heavy drinkers but not non-drinkers, potentially due to differing reasons for not drinking (e.g. illness) between those with and without HCV

Morbidity and Mortality of HIV-infected women in the combined Antiretroviral Therapy era

Les femmes représentent un tiers des personnes vivant avec le VIH en France. Les trois parties de cette thèse visent à explorer les principaux aspects cliniques de la maladie (causes de décès, morbidité grave) ou de la vie des femmes (ménopause) afin d’identifier des recommandations spécifiques pour la prise en charge des femmes dans un contexte d’accès aux soins similaire à celui des hommes.Les causes de décès des femmes infectées par le VIH ont été décrites grâce à l’enquête nationale ANRS EN19, Mortalité 2005. Les femmes décédaient plus fréquemment que les hommes de causes liées au sida (43% vs. 34% chez les hommes). Elles décédaient moins souvent de causes hépatiques (13 % vs. 16%), de cancers non sida-non hépatiques (14% vs. 17%) et de maladies cardiovasculaires (6% vs. 9%). La morbidité grave des patients infectés par le VIH a été étudiée au sein de la Cohorte ANRS CO3-Aquitaine, entre 2000 et 2008. Le taux d’incidence annuelle d’hospitalisation a diminué de moitié entre 2000 et 2008 (146 à 69 pour 1000 PA). Globalement, ce taux ne différait pas entre les femmes et les hommes. Les causes les plus fréquentes de morbidité grave conduisant à une hospitalisation étaient : les infections bactériennes, les événements sida, psychiatriques, hépatiques, hématologiques, infections virales, événements digestifs, infections parasitaires et les événements cardiovasculaires. Toutes ces causes ont eu une baisse de leur incidence annuelle entre 2000 et 2008 chez les hommes et les femmes, exceptés les événements hématologiques (de 2,5 à 15,1 pour 1000 PA), hépatiques (2,5 à11,5) et cardiovasculaires (6,3 à 14,2) qui ont augmenté chez les femmes. L’âge de survenue de la ménopause étudié grâce à une enquête menée au sein de la Cohorte ANRS CO3-Aquitaine était de 49 ans en médiane et 12% des femmes ont eu une ménopause précoce, survenant avant l’âge de 40 ans. L’origine africaine (RR : 8,2) et l’antécédent de toxicomanie IV (RR : 2,5) étaient liés à la survenue plus précoce de la ménopause. En conclusion, les femmes infectées par le VIH en France décèdent plus souvent de sida, mais présentent une morbidité grave caractérisée par une prédominance de complications non classant sida. Dans un contexte d’accès aux soins similaires à celui des hommes infectés par le VIH, les femmes ont un profil de maladies associées traduisant à la fois leurs co-morbidités (co-infections par les hépatites) ou l’inflammation chronique du VIH (maladies cardio-vasculaires) qui nécessitent d’être détectées précocement et prises spécifiquement en charge.Women represent one third of HIV-infected patients in France. The objective of this thesis was to study the clinical features (causes of death and severe morbidity) and the age and determinants of menopause of these patients in a context of equal access to care for all HIV-infected patients.Causes of death of HIV-infected women were identified in 2005, in a nation-wide survey (ANRS EN19, Mortalité 2005). Women died more often than men from AIDS-related causes (43% vs. 34%) and less frequently from hepatic (13% vs. 16%), non-AIDS non-hepatic cancers (14% vs. 17%) and cardiovascular diseases (6% vs. 9%). Severe morbidity was studied within the ANRS CO3-Aquitaine Cohort between 2000 and 2008. Annual incidence rates of hospitalization globally decreased for men and women from 146 per 1000 PY in 2000 to 69 in 2008. The most frequent causes of severe morbidity leading to hospitalization were: bacterial infections, AIDS events, psychiatric, hepatic, hematologic events, viral infections, digestive events, parasitical infections and cardiovascular events. All events had decreased between 2000 and 2008 in men and women excepted for hematologic (2.5 to 15.1 per 1000 PY), hepatic (2.5 to 11.5) and cardiovascular (6.3 à 14.2) events that increased overtime in women. Age at onset and associated factors of menopause were determined within the ANRS CO3-Aquitaine Cohort. Median age at menopause was 49 years and 12% reached menopause before 40 years (premature menopause). African origin (HR: 8.2) and history of injecting drug use (HR: 2.5) were associated with earlier menopause.In conclusion, HIV infected women in France, die more often from AIDS events but present with a predominantly non-AIDS severe morbidity. In a context of similar access to care than men, women’s health care should take into account their co-morbidities (hepatitis co-infections) and the cardiovascular complications of a long term HIV infection

Morbidity and Mortality of HIV-infected women in the combined Antiretroviral Therapy era

Les femmes représentent un tiers des personnes vivant avec le VIH en France. Les trois parties de cette thèse visent à explorer les principaux aspects cliniques de la maladie (causes de décès, morbidité grave) ou de la vie des femmes (ménopause) afin d’identifier des recommandations spécifiques pour la prise en charge des femmes dans un contexte d’accès aux soins similaire à celui des hommes.Les causes de décès des femmes infectées par le VIH ont été décrites grâce à l’enquête nationale ANRS EN19, Mortalité 2005. Les femmes décédaient plus fréquemment que les hommes de causes liées au sida (43% vs. 34% chez les hommes). Elles décédaient moins souvent de causes hépatiques (13 % vs. 16%), de cancers non sida-non hépatiques (14% vs. 17%) et de maladies cardiovasculaires (6% vs. 9%). La morbidité grave des patients infectés par le VIH a été étudiée au sein de la Cohorte ANRS CO3-Aquitaine, entre 2000 et 2008. Le taux d’incidence annuelle d’hospitalisation a diminué de moitié entre 2000 et 2008 (146 à 69 pour 1000 PA). Globalement, ce taux ne différait pas entre les femmes et les hommes. Les causes les plus fréquentes de morbidité grave conduisant à une hospitalisation étaient : les infections bactériennes, les événements sida, psychiatriques, hépatiques, hématologiques, infections virales, événements digestifs, infections parasitaires et les événements cardiovasculaires. Toutes ces causes ont eu une baisse de leur incidence annuelle entre 2000 et 2008 chez les hommes et les femmes, exceptés les événements hématologiques (de 2,5 à 15,1 pour 1000 PA), hépatiques (2,5 à11,5) et cardiovasculaires (6,3 à 14,2) qui ont augmenté chez les femmes. L’âge de survenue de la ménopause étudié grâce à une enquête menée au sein de la Cohorte ANRS CO3-Aquitaine était de 49 ans en médiane et 12% des femmes ont eu une ménopause précoce, survenant avant l’âge de 40 ans. L’origine africaine (RR : 8,2) et l’antécédent de toxicomanie IV (RR : 2,5) étaient liés à la survenue plus précoce de la ménopause. En conclusion, les femmes infectées par le VIH en France décèdent plus souvent de sida, mais présentent une morbidité grave caractérisée par une prédominance de complications non classant sida. Dans un contexte d’accès aux soins similaires à celui des hommes infectés par le VIH, les femmes ont un profil de maladies associées traduisant à la fois leurs co-morbidités (co-infections par les hépatites) ou l’inflammation chronique du VIH (maladies cardio-vasculaires) qui nécessitent d’être détectées précocement et prises spécifiquement en charge.Women represent one third of HIV-infected patients in France. The objective of this thesis was to study the clinical features (causes of death and severe morbidity) and the age and determinants of menopause of these patients in a context of equal access to care for all HIV-infected patients.Causes of death of HIV-infected women were identified in 2005, in a nation-wide survey (ANRS EN19, Mortalité 2005). Women died more often than men from AIDS-related causes (43% vs. 34%) and less frequently from hepatic (13% vs. 16%), non-AIDS non-hepatic cancers (14% vs. 17%) and cardiovascular diseases (6% vs. 9%). Severe morbidity was studied within the ANRS CO3-Aquitaine Cohort between 2000 and 2008. Annual incidence rates of hospitalization globally decreased for men and women from 146 per 1000 PY in 2000 to 69 in 2008. The most frequent causes of severe morbidity leading to hospitalization were: bacterial infections, AIDS events, psychiatric, hepatic, hematologic events, viral infections, digestive events, parasitical infections and cardiovascular events. All events had decreased between 2000 and 2008 in men and women excepted for hematologic (2.5 to 15.1 per 1000 PY), hepatic (2.5 to 11.5) and cardiovascular (6.3 à 14.2) events that increased overtime in women. Age at onset and associated factors of menopause were determined within the ANRS CO3-Aquitaine Cohort. Median age at menopause was 49 years and 12% reached menopause before 40 years (premature menopause). African origin (HR: 8.2) and history of injecting drug use (HR: 2.5) were associated with earlier menopause.In conclusion, HIV infected women in France, die more often from AIDS events but present with a predominantly non-AIDS severe morbidity. In a context of similar access to care than men, women’s health care should take into account their co-morbidities (hepatitis co-infections) and the cardiovascular complications of a long term HIV infection

Déterminants de l'échec virologique au traitement antirétroviral chez les patients infectés par le virus de l'immunodéficience humaine

A partir de 1996, les nouvelles thérapies ont bouleversé le cours de l'épidémie de l'infection par le VIH VIH. De ce fait, en France, le nombre de décès attribués au SIDA a considérablement reculé ces dernières années. L'infection à VIH est devenue une maladie chronique. L'échec virologique a pour conséquences une augmentation de la charge virale (CV), une baisse des défecses immunitaires et une augmentation du nombre de résistances aux molécules antirétrovirales (ARV). Ce travail est une étude descriptive dont l'objectif est de décrire et analyser les déterminants de l'échec virologique des patients infectés par le VIH recevant un traitement ARV. Nous avons collecté les données de mai 2008 à juin 2009. La cohorte de patients suivis à l'hôpital de jour de l'hôpital St André (CHU de Bordeaux) a été définie à partir des listes patients avec une charge virale détectable (supérieures à 40 copies/ml) fournie par le laboratoire de virologie, au cours de cette période. Les patients en échec représentent 14 % des patients suivis à l'HDJ. Un patient sur 2, est en échec majeur avec une CV supérieure à 500 copies/ml. 56 % sont en échec secondaire (rebond de la CV après indétectabilité), 44 % de la cohorte générale sont en échec primaire (CV détectable 6 mois après l'instauration de traitement ARV. La durée médiane de détectabilité est de 13 mois avec un intervalle interquartile (IIQ) de 4 à 39 mois. 1 patient sur 3 est en échec depuis moins de 6 mois, et 1 patient sur 2 est un "long échappeur", en échec depuis plus d'un an. En revanche, chez 33 % des patients en échec mineur (CV < 500 copies/ml) l'infection à VIH est globalement contrôlée, mais le virus réplique, même à faible taux, depuis plus d'un an, entraînant une risque majorée d'acquisition de mutations de résistance. Environ la moitié de la cohorte générale en échec a reçu une trithérapie d'emblée, 22 % ont reçu une monothérapie par l'AZT et 28 % ont reçu une bithérapie. Le nombre médian de lignes de traitement est de 5 lignes. La situation générale du patient, ses conditions de vie, son état psychologique, ont une incidence sur l'échec virologique. 7,9 % des patients de la cohorte en échec est susceptible d'avoir une sub-efficacité du traitement ARV à cause d'interactions entre les différents médicaments. Au moins un patient sur 2 de la cohorte est résistant au moins à une molécule de son traitement, cause de l'échappement thérapeutique. L'autre moitié de la cohorte est alors en échec à cause d'un problème d'observance pure. 30 % se disent observants : 42,2 % n'ont pas de mutation de résistance et posent le problème d'une observance non optimale. 21,5 % des patients de la cohorte présentent des résistances multiples aux ARV. L'observance est le déterminant principal de l'échec virologique qui conduit à la dégradation du système immunitaire. L'accompagnement et le soutien du patient, contribuent à une meilleure qualité de vie et sont essentiels dans l'amélioration de l'observance thérapeutique.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Causes of death in HIV-infected women: persistent role of AIDS. The 'Mortalité 2000 & 2005' Surveys (ANRS EN19).

International audienceBACKGROUND: Little is known about the causes of death in human immunodeficiency virus (HIV)-infected women in the era of combination antiretroviral therapy (ART). METHODS: In the French nationwide Mortalité 2000 and 2005 surveys, physicians reported causes of deaths in HIV-infected adults in 2000 and 2005, using a standardized questionnaire. We used multivariate logistic regression models to study the association between gender and AIDS-defining causes of death, adjusting for other characteristics. RESULTS: Of the 1013 HIV-infected adults who died in 2005, 247 (24%) were women. Half of women were infected through heterosexual contacts, compared with 25% men. In 2005, the proportion of AIDS-defining causes of death was higher in women than in men (43 vs 34%; P = 0.01), whereas it had been the same in 2000 (47% in women and men). In 2005, women died less frequently than men from respiratory malignancies (lung, ear/nose/throat) and cardiovascular disease (9% of all causes of death in women compared with 16% in men; P = 0.004), and suicides or accidents (4 vs 9%; P = 0.02). Socio-economic precariousness, younger age, less alcohol and tobacco consumption and lack of prior ART explained the higher proportion of deaths from AIDS in women compared with men. CONCLUSIONS: The higher proportion of AIDS-related deaths in women is probably explained by two factors: (i) some HIV-infected women, especially migrants in poor socio-economic conditions, may not have access to optimal care; and (ii) a lower prevalence of risk factors for respiratory, cardiovascular and violent deaths means that the risk of dying from non-AIDS causes may be lower in women