External validation of the Dat'AIDS score: A risk score for predicting 5-year overall mortality in people living with HIV aged 60 years or older.

OBJECTIVE: To perform an external validation of the Dat'AIDS score for predicting 5-year overall mortality among people with HIV (PWH) aged 60 years or older. METHODS: This was a multi-centre prospective cohort study at all sites participating in the Swiss HIV Cohort Study (SHCS). We calculated the Dat'AIDS score in PWH aged 60 years or older at their first visit between 1 January 2015 and 1 January 2020. People living with HIV-2 and those whose Dat'AIDS score could not be calculated were excluded. Patients were followed until 1 January 2020. The primary endpoint was all-cause mortality. Vital status was collected throughout the study period. We obtained population and score descriptive statistics and assessed the score's discrimination and calibration. RESULTS: We included 2205 participants (82% male) of median [interquartile range (IQR)] age 62.0 (60.3-67.0) years, mostly with viraemia <50 copies/mL (92.7%). Median follow-up time was 15.9 years and median (IQR) CD4 cell count at enrolment was 586 (420-782) cells/µL. In all, 152 deaths were recorded during a total follow-up period of 7147 patient-years. The median (IQR) observed Dat'AIDS score was 3 (0-8). Discriminative capacities were good as the C-statistic was 0.73 (95% CI: 0.69-0.77) and consistent across all subgroups. Comparison of observed and expected survival probabilities showed good calibration. CONCLUSIONS: External validation of the Dat'AIDS score in patients aged 60 years or older showed that it could be a useful tool not only for research purposes, but also to identify older patients at a higher mortality risk and to tailor the most appropriate interventions.

Immune response to the recombinant herpes zoster vaccine in people living with HIV over 50 years of age compared to non-HIV age-/gender-matched controls (SHINGR'HIV): a multicenter, international, non-randomized clinical trial study protocol.

BACKGROUND: The burden of herpes zoster (shingles) virus and associated complications, such as post-herpetic neuralgia, is higher in older adults and has a significant impact on quality of life. The incidence of herpes zoster and post-herpetic neuralgia is increased in people living with HIV (PLWH) compared to an age-matched general population, including PLWH on long-term antiretroviral therapy (ART) with no detectable viremia and normal CD4 counts. PLWH - even on effective ART may- exhibit sustained immune dysfunction, as well as defects in cells involved in the response to vaccines. In the context of herpes zoster, it is therefore important to assess the immune response to varicella zoster virus vaccination in older PLWH and to determine whether it significantly differs to that of HIV-uninfected healthy adults or younger PLWH. We aim at bridging these knowledge gaps by conducting a multicentric, international, non-randomised clinical study (SHINGR'HIV) with prospective data collection after vaccination with an adjuvant recombinant zoster vaccine (RZV) in two distinct populations: in PLWH on long-term ART (> 10 years) over 50 years of and age/gender matched controls. METHODS: We will recruit participants from two large established HIV cohorts in Switzerland and in France in addition to age-/gender-matched HIV-uninfected controls. Participants will receive two doses of RZV two months apart. In depth-evaluation of the humoral, cellular, and innate immune responses and safety profile of the RZV will be performed to address the combined effect of aging and potential immune deficiencies due to chronic HIV infection. The primary study outcome will compare the geometric mean titer (GMT) of gE-specific total IgG measured 1 month after the second dose of RZV between different age groups of PLWH and between PLWH and age-/gender-matched HIV-uninfected controls. DISCUSSION: The SHINGR'HIV trial will provide robust data on the immunogenicity and safety profile of RZV in older PLWH to support vaccination guidelines in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05575830. Registered on 12 October 2022. Eu Clinical Trial Register (EUCT number 2023-504482-23-00).

[Singularities of COVID-19 in immunosuppressed persons]. / Singularités du Covid-19 chez les personnes immunosupprimées.

Immunosuppressed persons are a heterogeneous population that represents approximately 3 % of the adult population. They are more vulnerable to infectious agents, such as SARS-CoV-2. This is reflected by a reduced response to vaccination, a higher rate of progression towards a severe form of the disease, and recurrent or persistent infections associated with intra-host viral evolution. This review summarizes the evidence regarding vaccine efficacy, clinical and virological singularities, and the management in immunosuppressed patients.

Les personnes immunosupprimées (PI) constituent une population hétérogène représentant environ 3 % de la population adulte et sont plus vulnérables aux infections, telles que le Covid-19, face auquel elles présentent une réponse vaccinale diminuée, un taux plus élevé d'évolution vers une forme sévère de la maladie, et des infections persistantes associées à une excrétion virale prolongée et à une possible évolution virale intrahôte. Cet article résume l'évidence concernant l'efficacité vaccinale, les particularités clinico-virologiques et la prise en charge spécifique, dans la population des PI.

Bone and joint infections caused by Clostridium perfringens: a case series.

The objective of this study was to evaluate antimicrobial therapy outcomes of bone and joint infections (BJI) caused by Clostridium perfringens. We investigated remission of symptoms and the absence of relapse or reinfection during follow-up. Among the 8 patients with C. perfringens BJI, the type of infection was early prosthesis infection (n = 2), osteosynthetic device infection (n = 4), and chronic osteomyeletis (n = 2). Clindamycin-rifampicin combination was given in 4 cases and metronidazole in 4 cases. The overall success rate was 87.5%. Among the 7 patients who completed antibiotic treatment, the success rate was 100%. The clindamycin-rifampicin combination appeared to be effective in patients with C. perfringens BJI.

Multimorbidity in Elderly Persons According to the Year of Diagnosis of Human Immunodeficiency Virus Infection: A Cross-sectional Dat'AIDS Cohort Study.

BACKGROUND: We assessed prevalence of multimorbidity (MM) according to year of human immunodeficiency virus (HIV) diagnosis in elderly people living with HIV (PLWH). METHODS: This was a cross-sectional study of MM in PLWH aged ≥70 years from the Dat'AIDS French multicenter cohort. MM was defined as at least 3 coexistent morbidities of high blood pressure, diabetes mellitus, osteoporosis, non-AIDS cancer, chronic renal failure, cardiovascular and cerebrovascular disease, obesity, undernutrition, or hypercholesterolemia. Logistic regression models evaluated the association between MM and calendar periods of HIV diagnosis (1983-1996, 1997-2006, and 2007-2018). The secondary analysis evaluated MM as a continuous outcome, and a sensitivity analysis excluded PLWH with nadir CD4 count <200 cells/µL. RESULTS: Between January 2017 and September 2018, 2476 PLWH were included. Median age was 73 years, 75% were men, median CD4 count was 578 cells/µL, and 94% had controlled viremia. MM prevalence was 71%. HBP and hypercholesterolemia were the most prevalent comorbidities. After adjustment for age, gender, smoking status, hepatitis C and hepatitis B virus coinfection, group of exposure, nadir CD4 count, CD4:CD8 ratio, and last CD4 level, calendar period of diagnosis was not associated with MM (P = .169). MM was associated with older age, CD4/CD8 ratio <0.8, and nadir CD4 count <200 cells/µL. Similar results were found with secondary and sensitivity analyses. CONCLUSIONS: MM prevalence was high and increased with age, low CD4/CD8 ratio, and nadir CD4 count <200 cells/µL but was not associated with calendar periods of HIV diagnosis. Known duration of HIV diagnosis does not seem to be a criterion for selecting elderly PLWH at risk of MM.

Prevalence of geophagy and knowledge about its health effects among native Sub-Saharan Africa, Caribbean and South America healthy adults living in France.

Geophagy is widespread among women from Sub-Saharan Africa, South America and the Caribbean and may persist in western countries. This practice may be associated with adverse effects such as anaemia, constipation or intestinal occlusion. We aimed to determine the prevalence of geophagy and the level of knowledge about its health effects among healthy adults originating from these countries and attending a travel medicine and international vaccination consultation in France. Among 101 travellers enrolled in the study, 83 (82.1%) were born in Sub-Saharan Africa and 13 (12.8%) in South America or the Caribbean. The mean duration of residence in France was 15.6 ± 10.4 years. Previous or current geophagy was present in 42 travellers [previous geophagy in 31 (30.7%) and current consumption in 11 (10.9%)]; 38 (90.5%) were women. The rate of awareness of harmful effects of geophagy as the risk of iron-deficient anaemia (18.8%) and soil-transmitted intestinal parasitic infections (11.9%) was low overall. Women with previous or current geophagy more often had history of iron therapy compared to those who never consumed, both during pregnancy (50.0 versus 14.3%; p = 0.0009) and outside pregnancy (47.4 versus 2.8%; p < 0.0001). Despite a long period of residence in France, geophagy was still a current practice among 10.9% of Sub-Saharan, South American and Caribbean travellers, who are poorly informed of its harmful effects. Therefore, specific information tailored to Sub-Saharan, South American and Caribbean about the risks of geophagy should be implemented in western countries.Level of evidence Level V, descriptive cross-sectional survey.

Bioclinical Test to Predict Nephropathia Epidemica Severity at Hospital Admission.

We conducted a multicenter, retrospective cohort study of hospitalized patients with serologically proven nephropathia epidemica (NE) living in Ardennes Department, France, during 2000-2014 to develop a bioclinical test predictive of severe disease. Among 205 patients, 45 (22.0%) had severe NE. We found the following factors predictive of severe NE: nephrotoxic drug exposure (p = 0.005, point value 10); visual disorders (p = 0.02, point value 8); microscopic or macroscopic hematuria (p = 0.04, point value 7); leukocyte count >10 × 109 cells/L (p = 0.01, point value 9); and thrombocytopenia <90 × 109/L (p = 0.003, point value 11). When point values for each factor were summed, we found a score of <10 identified low-risk patients (3.3% had severe disease), and a score >20 identified high-risk patients (45.3% had severe disease). If validated in future studies, this test could be used to stratify patients by severity in research studies and in clinical practice.

Factors Associated with Geophagy and Knowledge About Its Harmful Effects Among Native Sub-Saharan African, Caribbean and French Guiana HIV Patients Living in Northern France.

Geophagy, or the ingestion of earth or clay, is widespread among women of Sub-Saharan African, Caribbean or French Guiana origin. Little is known about this practice among HIV patients native of these countries and who are followed-up in France. The aims of this study were to determine (i) the prevalence and factors associated with geophagy among HIV patients native of these countries, (ii) patients' knowledge about the harmful effects of geophagy, and (iii) the association of geophagy with iron deficiency, or a history of anemia or constipation. Among the 119 included patients, current geophagy and previous geophagy were present in 11/119 (9%) and 47/119 (40%) patients, respectively. Female gender was the only factor associated with consumption (OR 5.37; 95% CI 2.07-15.92 p = 0.001). Awareness about the risk of iron-deficient anemia was low (24%). Preventive education should be integrated into the care of HIV adults from countries in which geophagy is a culture and widely accepted practice.

Rift Valley fever in kidney transplant recipient returning from Mali with viral RNA detected in semen up to four months from symptom onset, France, autumn 2015.

A 29-year-old kidney transplant recipient returning from Mali was diagnosed with Rift Valley fever (RVF) in France in autumn 2015. The patient was immunosuppressed due to his renal transplant. IgM and IgG specific to RVF virus (RVFV) were detected in cerebrospinal fluid and blood up to two months after symptom onset, whereas in urine, RVFV genomic RNA was detected by RT-PCR up to three months, and in semen up to four months post symptom onset.

Impact of Open Access status on journal metrics in infectious diseases and clinical microbiology - A cross-sectional study.

INTRODUCTION: While Open Access (OA) journals provide free access to articles, they entail high article processing charges (APC), limiting opportunities for young researchers and those from low-middle income countries to publish OA. METHODS: Cross-sectional study, evaluating APC and academic impact of full OA (FOA) journals in infectious diseases (ID) and clinical microbiology (CM) compared to hybrid journals. Data were collected from Journal Citation Reports and journals' websites. RESULTS: Among 255 journals, median APC was 2850 (interquartile range [IQR] 1325-3654$). Median APC for 120 FOA journals was significantly lower than for 119 hybrid journals (2000, IQR 648-2767$ versus 3550, IQR 2948-4120$, p < 0.001). FOA journals had lower citation numbers and impact metrics compared to hybrid journals. CONCLUSION: While FOA ID/CM journals have lower APCs, they also lower academic impact compared to hybrid journals. These findings highlight the need for reforms in the publication process in view of achieving equitable data dissemination.

Significantly reduced duration of antibiotic prescription for erysipelas subsequent to the 2019 French guidelines on skin and soft tissue infection: A before-after study.

BACKGROUND: New skin and soft tissue infections (SSTI) guidelines were published in 2019 in France, changing the recommended duration for antibiotic treatment. The objective of the present study was to assess the impact of the publication of the 2019 French guidelines on SSTIs on the duration of antibiotic prescription for erysipelas. METHODS: In a before-after study (a year before and a year after April 1st, 2019), we included all adult patients diagnosed with erysipelas in Reims University Hospital medical wards and the emergency department. We retrospectively retrieved antibiotic prescription duration in the patients' medical files. RESULTS: Among 50 patients in the "before" and 39 in the "after" group, the mean duration of antibiotic prescription was significantly shorter in the "after" group (9.4 ± 2.8 vs. 12.4 ± 3.8 days, p = 0.0001). CONCLUSIONS: A 25% decrease in the duration of antibiotic prescription for erysipelas was observed following the implementation of these guidelines, providing useful information for an antibiotic stewardship policy.

No Association Between HLA-B*57:01 and Prevalence and/or Outcome of Progressive Multifocal Leukoencephalopathy in a French Nationwide Human Immunodeficiency Virus Cohort.

Among 34,351 patients living with human immunodeficiency virus with available HLA-B*57:01 included in the Dat'AIDS cohort, 194 patients (0.56%) had a history of progressive multifocal leukoencephalopathy (PML) and 1,746 (5.08%) were carriers of HLA-B*57:01. The frequency of HLA-B*57:01 was similar among patients with history of PML compared with patients without a history of PML (6.19% [95% confidence interval, CI 2.8%-9.6%] vs. 5.08% [95% CI 4.8%-5.3%]; p = .48). Among patients with PML, clinical and biological characteristics at PML diagnosis and the PML outcome were not different according to HLA-B*57:01 status.

Epidemiology and characteristics of Paget's disease of bone in a French nationwide HIV cohort.

Paget's disease of bone (PDB) has rarely been reported in people with HIV (PWH). We describe the prevalence and characteristics of patients with PDB in the French multicenter Dat'AIDS cohort. Among 49 698 PWH actively followed in 2022, 9 had a diagnosis of PDB. The overall prevalence of PDB was 0.02% [95% confidence interval (CI) 0.01-0.03]. The prevalence of PDB in PWH is very low and does not appear to differ from the non-HIV population.

One Hundred Explicit Definitions of Potentially Inappropriate Prescriptions of Antibiotics in Hospitalized Older Patients: The Results of an Expert Consensus Study.

BACKGROUND: In geriatrics, explicit criteria for potentially inappropriate prescriptions (PIPs) are useful for optimizing drug use. OBJECTIVE: To produce an expert consensus on explicit definitions of antibiotic-PIPs for hospitalized older patients. METHODS: We conducted a Delphi survey involving French experts on antibiotic stewardship in hospital settings. During the survey's rounds, the experts gave their opinion on each explicit definition, and could suggest new definitions. Definitions with a 1-to-9 Likert score of between 7 and 9 from at least 75% of the participants were adopted. The results were discussed during consensus meetings after each round. RESULTS: Of the 155 invited experts, 128 (82.6%) participated in the whole survey: 59 (46%) infectious diseases specialists, 45 (35%) geriatricians, and 24 (19%) other specialists. In Round 1, 65 explicit definitions were adopted and 21 new definitions were suggested. In Round 2, 35 other explicit definitions were adopted. The results were validated during consensus meetings (with 44 participants after Round 1, and 54 after Round 2). CONCLUSIONS: The present study is the first to have provided a list of explicit definitions of potentially inappropriate antibiotic prescriptions for hospitalized older patients. It might help to disseminate key messages to prescribers and reduce inappropriate prescriptions of antibiotics.

Country of birth is associated with discrepancies in the prescription of two-drug regimens in successfully treated people with HIV in France.

OBJECTIVES: We aimed to examine the association of the country of birth and the other patients' characteristics with the prescription of two-drug regimens (2DRs) in virally suppressed people with HIV (PWH) in France. DESIGN: Observational study conducted from the national Dat'AIDS prospectively collected database. METHODS: We included all adults who were actively in care on 31 December 2020 in 26 French centers, with an HIV plasma viral load (pVL) <50 copies/ml for at least 6 months while on antiretroviral therapy (ART). Patients with chronic hepatitis B were excluded because they are not eligible to 2DRs. Univariate and multivariate logistic regressions were built to analyze relationships between patients' characteristics and receiving a 2DR. RESULTS: We analyzed data from 28 395 PWH: 41.7% men who have sex with men, 31.7% women and 26.5% heterosexual men; 35% born abroad. Median age was 53 years [interquartile range (IQR) 44-60]; ART duration 14 years (8-23); duration of virological suppression 87 months (42-142). 2DRs (mainly dolutegravir/rilpivirine, 53.8%, or dolutegravir/lamivudine, 41.7%) were prescribed in 16.3% of the patients and were less common in the 'born abroad' group (18.9% versus 11.5%). The multivariate model showed that individuals born in France were more likely to receive a 2DR [adjusted odds ratio (aOR): 1.62 [1.50-1.74]], independently of other characteristics. Older PLWH and those with higher CD4 + T-cell counts were also more likely to receive a 2DR. CONCLUSION: Despite unrestricted access to ART in France, independently from HIV disease parameters, PWH born abroad were less likely to receive 2DRs as a maintenance regimen than those born in France. Qualitative data are needed to better understand physicians' prescribing practices.

Country of birth is associated with antiretroviral therapy choice in treatment-naive persons with HIV in France.

OBJECTIVES: We aimed to describe factors associated with the choice of first antiretroviral therapy (ART) in persons with HIV (PWH) in France, included the country of birth, as well as the time to undetectable viral load and treatment discontinuation. DESIGN: Observational study conducted from the national Dat'AIDS prospectively collected database. METHODS: We included all adults who started their first ART between 01 January 2014 and 31 December 2020, with a pretherapeutic plasma viral load (pVL) at least 400 copies/ml. Univariable and multivariable logistic regressions were used to analyze PWH characteristics driving to an integrase strand transfer inhibitors (INSTI)-based first prescribed regimen. We also analyzed time to first line discontinuation, and to a first undetectable pVL, using Kaplan-Meier model. RESULTS: We analyzed data from 9094 PWH: 45% MSM, 27% women and 27% heterosexual men; 48% born abroad; 4.7 and 2.8% with concomitant hepatitis B and tuberculosis, respectively. INSTIs were prescribed as first-line therapy in 50% of PWH, which increased over time. Native French PWH were more likely to receive an INSTI-based regimen than PWH born abroad [adjusted prevalence ratio 1.47, 95% confidence interval (CI) 1.33-1.60], as were high pVL at diagnosis, hepatitis B or concomitant tuberculosis. Time before discontinuation of the first ART and reaching a first undetectable pVL was not different according to the place of birth. CONCLUSION: Despite unrestricted access to INSTIs in France, independently from HIV disease parameters, PWH born abroad received INSTIs less frequently as a first regimen than those born in France. Qualitative data are needed to better understand physicians' prescribing practices.

Early switching from intravenous to oral antibiotic therapy in bone and joint infections associated with methicillin-susceptible Staphylococcus aureus bacteremia.

OBJECTIVES: We aimed to evaluate the clinical outcomes of patients with bone and joint infection (BJI) associated with methicillin-susceptible Staphylococcus aureus bacteremia (MSSAB) treated with early oral switch to oral antibiotics (before day 14) versus later or no switch. PATIENTS AND METHODS: We included all cases reported between January 2016 and December 2021 in the University Hospital of Reims. RESULTS: Among 79 patients with BJI associated with MSSAB, 50.6% had an early switch to oral antibiotics, with median duration of intravenous antibiotics of 9 (IQR 6-11) days. The overall cure rate was 81% with follow-up of 6 months, and was 85.7% after excluding the 9 patients whose death was not related to BJI infection. Failure to control BJI did not differ between the two groups. CONCLUSION: An early (before day 14) switch to oral antibiotics may be a safe therapeutic option in BJI associated with MSSAB.

Association between Heparin Dose and 6-Week Mortality in Patients with COVID-19.

Background: Severe forms of SARS-CoV-2 infections are associated with high rates of thromboembolic complications. Professional societies and expert consensus reports have recommended anticoagulants for COVID-19 hospitalized patients. Our study aimed to compare the effect of therapeutic, intermediate and prophylactic doses of heparin on 6-week survival in patients hospitalized for COVID-19. Methods: The study sample is a French cohort of COVID-19 patients hospitalized between Feb 25th and Apr 30th 2020. Patients were assigned to one of 3 anticoagulation dose groups based on the maximum dose they received for at least three days (prophylactic, intermediate or therapeutic). The main outcome was survival up to 42 days after hospital admission. Multivariate Cox regression models were performed to adjust analyses for confounding factors. Results: A total of 323 patients were included. The mean age of the study sample was 71.6 ± 15 years, and 56.3% were men. Treatment with the intermediate versus prophylactic dose of anticoagulation (HR = 0.50, 95%CI = [0.26; 0.99], p = 0.047) and with therapeutic versus prophylactic dose (HR = 0.58 95%CI = [0.34; 0.98], p = 0.044) was associated with a significant reduction in 6-week mortality, after adjustment for potential confounding factors. Comparison of therapeutic versus intermediate doses showed no significant difference in survival. Conclusions: Our results reported a significant positive effect of intermediate and therapeutic doses of heparin on 6-week survival for hospitalized COVID-19 patients compared with a prophylactic dose.

Therapeutic Perspectives in the Systemic Treatment of Kaposi's Sarcoma.

In patients with Kaposi's sarcoma (KS), the therapeutic goal is to achieve a durable remission in the size and number of skin and visceral lesions. Although most patients show tumor regression in response to standard systemic chemotherapy regimens, alternative systemic treatments are needed for patients who develop refractory KS. Anti-angiogenic therapies represent attractive therapeutic targets in this context, due to the central role of angiogenesis in KS pathogenesis. Pomalidomide, which exhibits such anti-angiogenic activity through inhibition of VEGF, currently constitutes the most promising agent of this class and has been recently approved by the FDA. In addition, immune checkpoint blockade also represents an interesting alternative therapeutic approach through the restoration of immunity against HHV-8, the causative agent of KS, and improvement of tumor control. Although small series of cases treated successfully with these drugs have been reported, there is no marketing approval for anti-immune checkpoint antibodies for KS to date. In the present review, we will discuss potential therapeutic options for patients with recurrent or refractory KS, including systemic chemotherapies, immune checkpoint inhibitors, anti-herpesvirus agents, and anti-angiogenic drugs. Well-conducted clinical trials in this population are urgently needed to correctly address the efficacy of targeted agents and immunomodulators, while monitoring for adverse effects.