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.

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.

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.

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.

Idiopathic intracranial hypertension secondary to fluoroquinolone therapy: French pharmacovigilance data review.

We investigate spontaneous reports of IIH related to fluoroquinolones recorded in the French national pharmacovigilance database in order to detect a possible pharmacovigilance signal. The association between IIH risk and fluoroquinolone exposure was assessed using a case/non-case study. Between 1985 and July 2023, 17 reports of IIH after fluoroquinolone exposure were recorded. No specific fluoroquinolone was predominant. IIH led to death in one case and blindness in one case. The Reporting Odds Ratio was 2.58 (95% confidence interval 1.59-4.19). We highlight statistically significant disproportionality, which constitutes a pharmacovigilance signal. IIH risk after fluoroquinolone exposure is a class effect.

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.

Aetiology, clinical features, diagnostic studies, and outcomes of community-acquired pneumonia in kidney transplant recipients admitted to hospital: a multicentre retrospective French cohort study.

OBJECTIVES: To assess the aetiology, clinical features, diagnostic studies and outcomes of community-acquired pneumonia (CAP) in a French cohort of hospitalized kidney transplant recipients. METHODS: We performed a retrospective, multicentre study in kidney transplant recipients admitted to ten French centres for CAP from January 2016 to December 2018. CAP discharge diagnoses were clinically and radiologically validated. We assessed a descriptive analysis of all confirmed CAP including medical ward and intensive care unit admissions. RESULTS: One hundred sixty-five CAP episodes in 132 patients were included. Median time from transplantation to admission was 6.4 (interquartile range, 1.6-12.3) years, with corticosteroid exposure in 112/165 (67.9%) cases. Sputum culture was performed in 47/165 (28.5%) cases including 7/47 (14.9%) positive samples. Bronchoscopy was performed in 87/165 (52.7%) cases with pathogens identified in 39/87 (44.8%) cases. Microbiological studies led to identifying a respiratory pathogen in 64/165 (38.8%) CAP episodes including 11/64 (17.2%) polymicrobial cases. Among these 64 episodes, 75 microorganisms were identified; 46/75 (61.3%) were core respiratory pathogens and 29/75 (38.7%) were opportunistic or drug-resistant organisms including Pneumocystis jirovecii 9/75 (12%), Pseudomonas aeruginosa 5/75 (6.7%), multidrug-resistant Enterobacteriaceae 4/75 (5.3%), and Aspergillus 4/75 (5.3%). Patients required intensive care unit admission in 26/165 (15.8%) episodes, invasive ventilation in 20/165 (12.1%) cases, and 22/165 (13.3%) needed in-hospital dialysis. DISCUSSION: CAP episodes occurred in kidney transplant recipients with a long history of immunosuppressive drug exposure. Diagnostic studies identified a microorganism in more than one-third of CAP episodes, including drug-resistant and opportunistic pathogens.

Early plasma interferon-ß levels as a predictive marker of COVID-19 severe clinical events in adult patients.

We assessed relationships between early peripheral blood type I interferons (IFN) levels, clinical new early warning scores (NEWS), and clinical outcomes in hospitalized coronavirus disease-19 (COVID-19) adult patients. Early IFN-ß levels were lower among patients who further required intensive care unit (ICU) admission than those measured in patients who did not require an ICU admission during severe acute respiratory syndrome coronavirus type 2 infection. IFN-ß levels were inversely correlated with NEWS only in the subgroup of patients who further required ICU admission. To assess whether peripheral blood IFN-ß levels could be a potential relevant biomarker to predict further need for ICU admission, we performed receiver operating characteristic (ROC) curve analyses that showed for all study patients an area under ROC curve of 0.77 growing to 0.86 (p = 0.003) when the analysis was restricted to a subset of patients with NEWS ≥5 at the time of hospital admission. Overall, our findings indicated that early peripheral blood IFN-ß levels might be a relevant predictive marker of further need for an ICU admission in hospitalized COVID-19 adult patients, specifically when clinical score (NEWS) was graded as upper than 5 at the time of hospital admission.

Persistently elevated alkaline phosphatase could be related to Paget's disease of bone in a patient receiving tenofovir disoproxil fumarate.

The prevalence of Paget's disease of bone (PDB) reaches 1-2% of all adults aged ≥55 years old. However, reports describing PDB among HIV positive patients are extremely rare. We report here the case of a HIV positive person receiving tenofovir disoproxil fumarate (DF)-based antiretroviral therapy and who had persistently elevated alkaline phosphatase (AP) revealing PDB. It is well established that tenofovir-DF use is associated with reversible increases in serum AP levels. Clinicians should bear in mind that persistently elevated AP in a person receiving tenofovir DF-based cART could be related to PDB, in particular in person older than 50 years with no other notable biological abnormalities related to kidney tubular dysfunction.

Prevalence of post-acute coronavirus disease 2019 symptoms twelve months after hospitalization in participants retained in follow-up: analyses stratified by gender from a large prospective cohort.

OBJECTIVES: Persistent post-acute coronavirus disease 2019 (COVID-19) symptoms (PACSs) have been reported up to 6 months after hospital discharge. Herein we assessed the symptoms that persisted 12 months (M12) after admission for COVID-19 in the longitudinal prospective national French coronavirus disease cohort. METHODS: Hospitalized patients with a confirmed virological diagnosis of COVID-19 were enrolled. Follow-up was planned until M12 after admission. Associations between persistence of ≥3 PACSs at M12 and clinical characteristics at admission were assessed through logistic regression according to gender. RESULTS: We focused on participants enrolled between 24 January 2020 and 15 July 2020, to allow M12 follow-up. The M12 data were available for 737 participants. Median age was 61 years, 475 (64%) were men and 242/647 (37%) were admitted to intensive care units during the acute phase. At M12, 27% (194/710) of the participants had ≥3 persistent PACS, mostly fatigue, dyspnoea and joint pain. Among those who had a professional occupation before the acute phase, 91 out of 339 (27%) were still on sick leave at M12. Presence of ≥3 persistent PACS was associated with female gender, both anxiety and depression, impaired health-related quality of life and Medical Muscle Research Council Scale <57. Compared with men, women more often reported presence of ≥3 persistent PACSs (98/253, 39% vs. 96/457, 21%), depression and anxiety (18/152, 12% vs. 17/268, 6% and 33/156, 21% vs. 26/264, 10%, respectively), impaired physical health-related quality of life (76/141, 54% vs. 120/261, 46%). Women had less often returned to work than men (77/116, 66% vs. 171/223, 77%). CONCLUSIONS: One fourth of the individuals admitted to hospital for COVID-19 still had ≥3 persistent PACSs at M12 post-discharge. Women reported more often ≥3 persistent PACSs, suffered more from anxiety and depression and had less often returned to work than men.

Disappearance of anti-thyroglobulin antibodies from the cerebrospinal fluid in parallel with neurological improvement during treatment for Hashimoto's encephalopathy / Disparition des anticorps anti-thyroglobuline dans le liquide céphalo-rachidien après traitement de l'encéphalopathie de Hashimoto

Abnormal elevation of thyroid antibodies in the CSF is observed in 62-75% of Hashimoto's encephalopathy cases. However, the relationship between CSF thyroid antibody levels and response to therapy has been poorly evaluated. We report the case of a 68-year-old man with Hashimoto's encephalopathy, in whom there was a relation between the favorable clinical outcome and the disappearance of antithyroid antibodies from the CSF and a decrease in serum thyroid antibodies.

Une élévation anormale des anticorps thyroïdiens dans le LCR est observée dans 62 à 75 % des cas d'encéphalopathie de Hashimoto. Cependant, la relation entre les niveaux d'anticorps thyroïdiens dans le LCR et la réponse au traitement a été rarement évaluée. Nous rapportons le cas d'un homme de 68 ans atteint d'encéphalopathie de Hashimoto, chez qui l'évolution clinique favorable sous traitement était associée à la disparition des anticorps antithyroïdiens du LCR et une diminution des anticorps thyroïdiens sériques.

Incidence of cervical, breast and colorectal cancers between 2010 and 2015 in people living with HIV in France.

BACKGROUND: We aimed to evaluate the incidence rates between 2010 and 2015 for invasive cervical cancer (ICC), breast cancer (BC), and colorectal cancer (CRC) in people living with HIV (PLWH) in France, and to compare them with those in the French general population. These cancers are targeted by the national cancer-screening program. SETTING: This is a retrospective study based on the longitudinal data of the French Dat'AIDS cohort. METHODS: Standardized incidence ratios (SIR) for ICC and BC, and incidence rates for all three cancers were calculated overall and for specific sub-populations according to nadir CD4 cell count, HIV transmission category, HIV diagnosis period, and HCV coinfection. RESULTS: The 2010-2015 CRC incidence rate was 25.0 [95% confidence interval (CI): 18.6-33.4] per 100,000 person-years, in 44,642 PLWH (both men and women). Compared with the general population, the ICC incidence rate was significantly higher in HIV-infected women both overall (SIR = 1.93, 95% CI: 1.18-3.14) and in the following sub-populations: nadir CD4 ≤ 200 cells/mm3 (SIR = 2.62, 95% CI: 1.45-4.74), HIV transmission through intravenous drug use (SIR = 5.14, 95% CI: 1.93-13.70), HCV coinfection (SIR = 3.52, 95% CI: 1.47-8.47) and HIV diagnosis before 2000 (SIR = 2.06, 95% CI: 1.07-3.97). Conversely, the BC incidence rate was significantly lower in the study sample than in the general population (SIR = 0.56, 95% CI: 0.42-0.73). CONCLUSION: The present study showed no significant linear trend between 2010 and 2015 in the incidence rates of the three cancers explored in the PLWH study sample. Specific recommendations for ICC screening are still required for HIV-infected women and should focus on sub-populations at greatest risk.

Incidence, associated factors, and effect on renal function of amoxicillin crystalluria in patients receiving high doses of intravenous amoxicillin (The CRISTAMOX Study): A cohort study.

Background: Amoxicillin crystalluria (AC), potentially responsible for acute kidney injury (AKI), is reported more and more frequently in patients treated with high doses of intravenous amoxicillin (HDIVA). The main objective of this study was to evaluate AC incidence in these patients. The secondary objectives were to identify factors associated with AC and to evaluate its impact on the risk of AKI. Methods: This multicentre, observational, cohort study was conducted between Mar 18, 2014 and Aug 16, 2019 in Dijon, Nancy, and Reims University Hospitals as well as Châlon-sur-Saône, Charleville-Mézières, and Troyes general hospitals in France. Adult patients (≥18 years) treated with HDIVA and having been tested for AC at least once during treatment were included. Clinical, biological, and therapeutic characteristics of the patients were collected. A univariable mixed logistic regression model assessed the factors associated with AC. A multivariable Cox model with AC as a time-dependent variable assessed the prognostic factors for AKI. ClinicalTrials.gov number: NCT02853292. Findings: Of the 112 included patients, 27 (24.1%, 95% CI [16.2-32.0]) developed at least one episode of AC within a mean of 5.1 days. The factors associated with its occurrence were the concomitant use of angiotensin converting enzyme (ACE) inhibitors (OR=4.6, 95% CI [2.2-9.3], p<0.0001) and the decrease of urinary pH (OR=2.1 for one pH point decrease, 95% CI [1.2-3.7], p=0.009). 20 patients (17.9%) presented with AKI, within a mean time of 10.9 days. The main factor associated with the occurrence of AKI was the occurrence of AC (aHR=7.4, 95% CI [2.5-22.2], p=0.0003). Interpretation: AC occurred in a quarter of patients treated with HDIVA and was highly prognostic of AKI. Funding: None.

Raltegravir 1200 mg once daily as maintenance therapy in virologically suppressed HIV-1 infected adults: QDISS open-label trial.

BACKGROUND: Raltegravir (RAL) has favorable tolerability and safety profile, with few and manageable drug interactions. The use of RAL 1200 mg once daily (qd) for first-line therapy is well established. We assessed efficacy and safety of RAL 1200 mg qd, as part of triple combined antiretroviral therapy (cART), for maintenance strategy. METHODS: The QDISS trial (NCT03195452) was a 48-week multicenter, single-arm, open-label study designed to evaluate the ability of 2 NRTIs + RAL 1200 mg qd to maintain virological suppression in HIV-1 infected subjects on a stable cART with 2 NRTIs and a third agent for at least 6 months. The primary endpoint was the proportion of participants with HIV-1 RNA < 50 copies/mL at week 24, by the FDA snapshot algorithm. RESULTS: Of 100 participants 91% maintained viral suppression (95% CI: 83.6-95.8) at week 24 and 89% (81.2-94.4) at week 48. At week 24, there was one virological failure, without emergence of resistance-associated mutation and 10 participants had discontinued, 4 because of adverse events (AEs). Over 48 weeks, 7 AEs of grade 3-4 were reported, one possibly study-drug related (spontaneous abortion). BMI remained stable regardless of previous therapy or baseline BMI category. Over 48 weeks, total cholesterol (p = 0.023) and LDL-cholesterol (p = 0.009) decreased, lifestyle and ease subscale significantly improved (p = 0.04). The quality of life and Patients Reported Outcomes (PROs) also improved at W12 (p = 0.007). CONCLUSION: RAL 1200 mg qd as part of a maintenance triple therapy showed a high efficacy in virologically suppressed HIV-1 infected subjects, with good safety profile and improved lipid profile and patient reported outcomes. TRIAL REGISTRATION: Clinical trials.gov NCT03195452 and EudraCT 2016-003702-13.

No increased risk of Kaposi sarcoma relapse in patients with controlled HIV-1 infection after switching protease inhibitor-based antiretroviral therapy.

OBJECTIVES: Our aim was to assess if switching from a protease inhibitors (PI)-based regimen to a PI-free one is associated with an increased risk of Kaposi Sarcoma (KS) relapse among patients living with HIV (PLHIV) with history of KS and controlled HIV replication. METHODS: In a retrospective analysis of the prospectively collected Dat'AIDS database we selected patients who both had a past KS history and a HIV-1 viral load below 200 copies/mL while being PI-treated. We searched for KS relapses while persistent virological success was maintained for at least 6 months, whether patients kept taking the PI, or switched to PI-free regimen. RESULTS: Among the 216 patients with past KS event and a history of HIV-1 infection efficiently treated by a PI-based regimen, 148 patients (68.5%) later switched to a PI-sparing regimen. Their baseline characteristics were not different from non-switching patients. We described 7 cases of relapse (3.2% of the 216 patients). Five cases of relapse occurred in switching patients (3.4%). The remaining two relapses occurred in PI-treated patients (2.9%). At KS relapse, CD4 cell count was 459 cells/µL (range 225-560) for switching patients, compared with 362 and 136 cells/µL for the other two patients. CONCLUSIONS: In this large cohort of PLHIV with a history of KS and ART-controlled HIV replication, KS relapses were described in 3.2% of the patients, and were not more frequent when a PI-containing ART regimen has been switched to a PI-free regimen. Our results do not support a specific effect of PI on KS.

Eosinophilia during Hantavirus infection: a cohort study.

BACKGROUND: There are emerging eosinophil-related considerations concerning viral infections. The role of eosinophils has poorly been evaluated during Hantavirus infection. METHODS: The aim of this study was to determine the prevalence of eosinophilia (defined as an eosinophil count above 500 cells/mm3) during haemorrhagic fever with renal syndrome (HFRS) in a large cohort of patients, and to identify factors associated with eosinophilia. RESULTS: Among 387 patients hospitalized for HFRS, 98 (25.3%) had eosinophilia. By univariate analysis, eosinophilia was significantly associated with more severe thrombocytopenia, high C-reactive protein level, white blood cell count and neutrophil count and lower nephrotoxic drug intake. As there was a collinearity between white blood cell count and C-reactive protein level, only C-reactive protein level with platelet count and nephrotoxic drug intake were entered in the multivariable analysis. Elevated C-reactive protein concentrations remained independently associated with eosinophilia. CONCLUSION: Eosinophilia during HFRS affects one quarter of patients, and supports the role of eosinophils in antiviral immunity against hantavirus infection.

Progressive multifocal leukoencephalopathy in patients with immunovirological control and at least 6 months of combination antiretroviral therapy.

OBJECTIVES AND METHODS: : Progressive multifocal leukoencephalopathy (PML) has rarely been reported in people with HIV (PWH) with long-term HIV immune-virological control. We describe the clinical and biological characteristics of patients with confirmed PML among PWH with a CD4+ cell count more than 200 cells/µl and an undetectable HIV RNA viral load after at least 6 months of combined antiretroviral therapy (cART) at the time of PML diagnosis, in the large French multicenter Dat'AIDS cohort. RESULTS: : Among 571 diagnoses of PML reported in the Dat'AIDS cohort between 2000 and 2019, 10 cases (1.75%) occurred in PWH with a CD4+ cell count greater than 200 cells/µl and an undetectable HIV RNA viral load after at least 6 months of cART. Median CD4+ cell count at PML diagnosis was 395 cells/µl (IQR 310-477). The median duration between the last detectable HIV viral load and the PML diagnosis was 41.1 months (IQR 8.2-67.4). Only one patient treated with rituximab-based chemotherapy for a large B-cell lymphoma had an established risk factor for PML. Among the nine other patients with no apparent severe immunodeficiency, multiple factors of impaired immunity could have led to the development of PML: hepatitis C virus (HCV) co-infection (n = 6), cirrhosis (n = 4), HHV-8 co-infection (n = 3) with Kaposi's sarcoma (n = 2) in association with Castleman's disease (n = 1) and indolent IgA multiple myeloma (n = 1). CONCLUSION: : This study highlights that factors other than low CD4+ cell count and high HIV viral load may be associated with the occurrence of PML. Further studies are warranted to investigate in greater detail the immunologic characteristics of PWH with immune-virological control who develop PML.