Severe Bacterial Non-AIDS Infections in Persons With Human Immunodeficiency Virus: The Epidemiology and Evolution of Antibiotic Resistance Over an 18-Year Period (2000-2017) in the ANRS CO3 AquiVih-Nouvelle-Aquitaine Cohort.

BACKGROUND: Severe non-AIDS bacterial infections (SBIs) are among the leading causes of hospital admissions among persons with human immunodeficiency virus (PWH) in regions with high antiretroviral therapy coverage. METHODS: This large prospective cohort study of PWH examined the types of infections, bacterial documentation, and evolution of antibiotic resistance among PWH hospitalized with SBIs over an 18-year period. RESULTS: Between 2000 and 2017, 459 PWH had at least 1 SBI with bacterial documentation. Among the 847 SBIs, there were 280 cases of bacteremia, 269 cases of pneumonia, and 240 urinary tract infections. The 1025 isolated bacteria included Enterobacteriaceae (n = 394; mainly Escherichia coli), Staphylococcus aureus (n = 153), and Streptococcus pneumoniae (n = 82). The proportion of S. pneumoniae as the causative agent in pneumonia and bacteremia decreased sharply over time, from 34% to 8% and from 21% to 3%, respectively. The overall antibiotic resistance of S. aureus and S. pneumoniae decreased progressively but it increased for Enterobacteriaceae (from 24% to 48% for amoxicillin-clavulanate, from 4% to 18% for cefotaxime, and from 5% to 27% for ciprofloxacin). Cotrimoxazole prophylaxis was associated with higher nonsusceptibility of S. pneumoniae to amoxicillin and erythromycin, higher nonsusceptibility of Enterobacteriaceae to ß-lactams and fluoroquinolones, and a higher risk of extended-spectrum ß-lactamase-producing Enterobacteriaceae. CONCLUSIONS: The bacterial resistance pattern among PWH between 2014 and 2017 was broadly similar to that in the general population, with the exception of a higher resistance profile of Enterobacteriaceae to fluoroquinolones. The use of cotrimoxazole as prophylaxis was associated with an increased risk of antibiotic resistance.

Tobacco, alcohol, cannabis, and illicit drug use and their association with CD4/CD8 cell count ratio in people with controlled HIV: a cross-sectional study (ANRS CO3 AQUIVIH-NA-QuAliV).

BACKGROUND: To evaluate drug use (alcohol, tobacco, cannabis and other drugs) and its association with mean CD4/CD8 T cell count ratio, a marker of chronic inflammation, in virally suppressed people living with HIV-1 (PLWH) in Nouvelle Aquitaine, France. METHODS: A multi-centric, cross-sectional analysis was conducted in 2018-19 in the QuAliV study-ANRS CO3 AQUIVIH-NA cohort. Tobacco, alcohol, cannabis, and other drug use (poppers, cocaine, amphetamines, synthetic cathinones, GHB/GBL) were self-reported. CD4 and CD8 T cell counts and viral load measures, ± 2 years of self-report, and other characteristics were abstracted from medical records. Univariable and multivariable linear regression models, adjusted for age, sex, HIV risk group, time since HIV diagnosis, and other drug use were fit for each drug and most recent CD4/CD8 ratio. RESULTS: 660 PLWH, aged 54.7 ± 11.2, were included. 47.7% [315/660] had a CD4/CD8 ratio of < 1. Their mean CD4/CD8 ratio was 1.1 ± 0.6. 35% smoked; ~ 40% were considered to be hazardous drinkers or have alcohol use disorder; 19.9% used cannabis and 11.9% other drugs. Chemsex-associated drug users' CD4/CD8 ratio was on average 0.226 (95% confidence interval [95% CI] - 0.383, - 0.070) lower than that of non-users in univariable analysis (p = 0.005) and 0.165 lower [95% CI - 0.343, 0.012] in multivariable analysis (p = 0.068). CONCLUSIONS: Mean differences in CD4/CD8 ratio were not significantly different in tobacco, alcohol and cannabis users compared to non-users. However, Chemsex-associated drug users may represent a population at risk of chronic inflammation, the specific determinants of which merit further investigation. TRIAL REGISTRATION NUMBER: NCT03296202.

Long-term follow-up of HIV-1 multi-drug-resistant treatment-experienced participants treated with etravirine, raltegravir and boosted darunavir: towards drug-reduced regimen? ANRS CO3 Aquitaine Cohort 2007-2018.

OBJECTIVE: To assess the efficacy of raltegravir, etravirine and darunavir/ritonavir (TRIO regimen) in treatment-experienced patients with human immunodeficiency virus-1 (HIV-1) infection by describing the proportion of patients who experienced virological failure (VF) at Week 24. The secondary objectives were to assess the HIV-1 plasma viral load (pVL) after Week 24, the proportion of patients who were receiving dual therapy or monotherapy at the last visit, and the number of deaths. METHODS: Patients from the ANRS CO3 Aquitaine Cohort who were prescribed the TRIO regimen between February 2007 and September 2018 were classified into two groups based on their pVL at study inclusion: the virological failure group (VFG; pVL >50 copies/mL) and the virologically suppressed group (VSG; pVL <50 copies/mL). The impact of baseline pVL and genotypic susceptibility score (GSS) on VF was analysed. RESULTS: In total, 184 patients were enrolled in this study, with 123 (66.8%) in the VFG and 61 (33.2%) in the VSG. The median length of follow-up was 7.5 (interquartile range 4.1-9.6) years, and 29 (15.8%) patients died. Thirty-seven (25.5%) patients experienced VF at Week 24, including 32/145 (32.7%) in the VFG and 5/47 (10.6%) in the VSG (P<0.01). Resistance-associated mutations were detected in integrase, reverse transcriptase and protease for 7/37 (18.9%), 3/37 (8.1%) and 1/37 (2.7%) patients, respectively. High pVL and GSS at baseline were independently associated with VF. At the last visit, 76/184 (41.3%) patients were still receiving the TRIO regimen, while 55/184 (29.9%) were receiving dual therapy and 1/184 (0.5%) was receiving protease inhibitor monotherapy. Among the 56 patients receiving dual therapy or monotherapy, 51 (96.2%) had pVL <50 copies/mL. CONCLUSION: Despite a high level of mutation resistance at baseline, long-term virological follow-up was favourable and one-third of patients were eligible for drug-reducing strategies.

Retrospective Multicenter Study Comparing Infectious and Noninfectious Aortitis.

BACKGROUND: Determining the etiology of aortitis is often challenging, in particular to distinguish infectious aortitis (IA) and noninfectious aortitis (NIA). This study aims to describe and compare the clinical, biological, and radiological characteristics of IA and NIA and their outcomes. METHODS: A multicenter retrospective study was performed in 10 French centers, including patients with aortitis between 1 January 2014 and 31 December 2019. RESULTS: One hundred eighty-three patients were included. Of these, 66 had IA (36.1%); the causative organism was Enterobacterales and streptococci in 18.2% each, Staphylococcus aureus in 13.6%, and Coxiella burnetii in 10.6%. NIA was diagnosed in 117 patients (63.9%), mainly due to vasculitides (49.6%), followed by idiopathic aortitis (39.3%). IA was more frequently associated with aortic aneurysms compared with NIA (78.8% vs 17.6%, P < .001), especially located in the abdominal aorta (69.7% vs 23.1%, P < .001). Crude and adjusted survival were significantly lower in IA compared to NIA (P < .001 and P = .006, respectively). In the IA cohort, high American Society of Anesthesiologists score (hazard ratio [HR], 2.47 [95% confidence interval {CI}, 1.08-5.66]; P = .033) and free aneurysm rupture (HR, 9.54 [95% CI, 1.04-87.11]; P = .046) were significantly associated with mortality after adjusting for age, sex, and Charlson comorbidity score. Effective empiric antimicrobial therapy, initiated before any microbial documentation, was associated with a decreased mortality (HR, 0.23, 95% CI, .08-.71]; P = .01). CONCLUSIONS: IA was complicated by significantly higher mortality rates compared with NIA. An appropriate initial antibiotic therapy appeared as a protective factor in IA.

Efficacy and safety of anakinra in adults presenting deteriorating respiratory symptoms from COVID-19: A randomized controlled trial.

OBJECTIVE: We aimed to investigate whether anakinra, an interleukin-1receptor inhibitor, could improve outcome in moderate COVID-19 patients. METHODS: In this controlled, open-label trial, we enrolled adults with COVID-19 requiring oxygen. We randomly assigned patients to receive intravenous anakinra plus optimized standard of care (oSOC) vs. oSOC alone. The primary outcome was treatment success at day 14 defined as patient alive and not requiring mechanical ventilation or extracorporeal membrane oxygenation. RESULTS: Between 27th April and 6th October 2020, we enrolled 71 patients (240 patients planned to been enrolled): 37 were assigned to the anakinra group and 34 to oSOC group. The study ended prematurely by recommendation of the data and safety monitoring board due to safety concerns. On day 14, the proportion of treatment success was significantly lower in the anakinra group 70% (n = 26) vs. 91% (n = 31) in the oSOC group: risk difference-21 percentage points (95% CI, -39 to -2), odds ratio 0.23 (95% CI, 0.06 to 0.91), p = 0.027. After a 28-day follow-up, 9 patients in the anakinra group and 3 in the oSOC group had died. Overall survival at day 28 was 75% (95% CI, 62% to 91%) in the anakinra group versus 91% (95% CI, 82% to 100%) (p = 0.06) in the oSOC group. Serious adverse events occurred in 19 (51%) patients in the anakinra group and 18 (53%) in the oSOC group (p = 0·89). CONCLUSION: This trial did not show efficacy of anakinra in patients with COVID-19. Furthermore, contrary to our hypothesis, we found that anakinra was inferior to oSOC in patients with moderate COVID-19 pneumonia.

A comprehensive analysis of excess depressive disorder in women and men living with HIV in France compared to the general population.

We aimed to estimate the prevalence of depressive disorder in people living with HIV (PLWH) and evaluate its association with non-HIV-specific and HIV-specific factors in PLWH and in PLWH compared to the general population (GP). We used cross-sectional data from the QuAliV study, conducted within the ANRS-CO3 Aquitaine-AQUIVIH-NA cohort of PLWH in Nouvelle-Aquitaine (2018-2020), and a nationally-representative survey in the GP (EHIS-ESPS, 2014-2015), we included all participants aged ≥ 18 years old who had completed the Patient Health Questionnaire-8 (PHQ-8). Depressive disorder was defined as Patient Health Questionnaire-8 score greater or equal to 10. Its association with non-HIV-specific (demographic, socio-economic, behavioral, health status), HIV-specific factors (immuno-viral markers, antiretrovirals, level of perceived HIV-stigma), and HIV-status was assessed using Poisson regression models with robust variance in women and men separately. We included 914 PLWH (683 men/231 women). More than one in five PLWH had depressive disorder. It was strongly associated with being younger and experiencing severe pain in both sexes. Unemployment in women, being single, and lack of family ties in men were also associated with depressive disorder. More than 30% of our sample reported HIV-stigma, with a dose-response relationship between level of perceived HIV-stigma and depressive disorder. The crude prevalence of depressive disorder was 2.49 (95%CI 1.92-3.22) and 4.20 (95%CI 3.48-5.05) times higher in women and men living with HIV respectively compared to GP counterparts and 1.46 (95%CI 1.09-1.95) and 2.45 (95%CI 1.93-3.09) times higher after adjustment for non-HIV specific factors. The adjusted prevalence ratio of depressive disorder was not significantly different in HIV-stigma free women, but remained twice as high in HIV-stigma free men. The prevalence of depressive disorder compared to the GP tended to decrease with age in PLWH. Excess depressive disorder remains a major concern in PLWH. Our findings reaffirm the importance of regular screening. Tackling social inequalities and HIV-stigma should be prioritized to ensure that PLWH achieve good mental as well as physical health outcomes.

Polymicrobial Infections Among Patients with Vascular Q Fever, France, 2004-2020.

We report 5 cases of vascular Q fever complicated by polymicrobial superinfection in patients who had no risk factors for acute Q fever. Q fever was diagnosed by serologic and molecular assays for Coxiella burnetii. We confirmed additional infections using conventional graft cultures.

Prolonged cefazolin course for treatment of methicillin susceptible staphylococcus species infections and the impact on the emergence of multidrug-resistant bacteria during cloxacillin shortage.

OBJECTIVES: To describe the efficacy and safety of prolonged cefazolin course for Staphylococcus infection and the emergence of multidrug-resistant bacteria carriage after treatment. METHODS: Monocentric retrospective cohort study of patients hospitalized for blood stream infections (BSI) and osteoarticular infections (OAI) by methicillin susceptible staphylococcal species treated with cefazolin from January 2015 to July 2017. Rectal and nasal swabs were performed at cefazolin initiation and end of treatment to detect respectively methicillin resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) producing bacteria. RESULTS: Fifty-eight patients were included, 41 had a bacteremia including 22 endocarditis and 22 OAI. Mean duration of treatment was 21.5 days at a mean daily dose of 6.5g/d. Fifty-five (94.5%) received combination therapy. Fifty-two (89.7%) of patients achieved bacteriological cure. Four patients were ESBL carriers at inclusion. No additional ESBL or MRSA were detected by end of treatment. CONCLUSION: Cefazolin appears as an effective and safe treatment for BSI or osteoarticular infection and does not appear to select MRSA or ESBL.

Statin use and risk of severe bacterial infection in a population living with HIV: prospective cohort study of the ANRS CO3 Aquitaine Cohort 2000-2018.

OBJECTIVES: Bacterial infections remain one of the main causes of morbidity and death in people living with HIV (PLHIV) in the most recent years. Several studies have demonstrated a protective effect of statins in the primary prevention of bacterial infections in other immunocompromised populations, but this effect remains controversial. The objective of this study was to evaluate the effect of statin use on the occurrence of a first episode of severe bacterial infection (SBI) in PLHIV in the ANRS CO3 Aquitaine cohort between 2000 and 2018. METHODS: All individuals included in the prospective ANRS CO3 Aquitaine cohort who had at least two follow-up visits between 2000 and 2018 were included. The primary endpoint was the occurrence of a first episode of bacterial infection leading to hospitalization of ≥48 hours or death. Statin exposure was updated during follow-up. Marginal Cox structural models were developed to consider the potential indication bias and time-dependent confusion. Numerous sensitivity analyses were carried out. RESULTS: In this study 51 658 person-years were followed. The overall incidence of a first episode of SBI was 12.4/1000 person-years. No effect of statins on the occurrence of SBI was demonstrated when subjects were considered on statins throughout their follow-up after treatment initiation (HR = 0.97; 95%CI: 0.75-1.25). The results were similar for the effect of statins on the risk of pneumonia and for all sensitivity analyses. CONCLUSION: In this large cohort of PLHIV with 18 years of follow-up and a high risk of severe infections, we found no effect of statins on the risk of occurrence of SBI or pneumonia.

Assessing the psychometric properties of the French WHOQOL-HIV BREF within the ANRS CO3 Aquitaine Cohort's QuAliV ancillary study.

BACKGROUND: Antiretroviral therapy has prolonged the lives of those with human immunodeficiency virus (HIV), but the effects of chronic infection on their health-related quality of life (HRQoL) remain a concern. Numerous instruments have been developed to measure HRQoL, yet evidence of their cross-cultural equivalence and continued applicability is limited. We adapted the WHOQOL-HIV BREF to French and assessed its psychometric properties in a sample of community-dwelling adults living with HIV who were mostly virally suppressed. METHODS: We conducted a cross-sectional study within the ANRS CO3 Aquitaine cohort from July 2018 to May 2019. Five hundred eighty-six participants were consecutively enrolled at their HIV-consultations and completed either a web-based (n = 406) or paper self-administered assessment (n = 180). The means and standard deviations for items and domains were computed and the presence of floor and ceiling effects assessed. We evaluated internal consistency by calculating Cronbach's alpha coefficients per domain. We assessed construct validity by performing a Confirmatory Factor Analysis (CFA). Concurrent, convergent and discriminant validity were assessed with Pearson's correlations and known-group validity was assessed according to CD4 cell count, viral load, Centers for Disease Control and Prevention clinical categories for HIV, and hospitalization of more than 48 h within 2 years of the most recent consultation using one-way analysis of variance and independent t-tests. RESULTS: Five hundred eighty-six PLWH were included in this analysis. Their median age was 55; 73% were male; 85% were of French descent; 99% were on ART and 93% were virally suppressed. We found floor effects for one and ceiling effects for 11 items. Four of the six domains showed good internal consistency (α range: 0.63-0.79). CFA showed that the WHOQOL-HIV BREF's six-domain structure produced an acceptable fit (SRMR = 0.059; CFI = 0.834; RMSEA = 0.07; 90% CI: 0.06-0.08). It showed good concurrent, convergent and discriminant validity. There was some evidence of known-group validity. The personal beliefs domain had the highest score (15.04 ± 3.35) and the psychological health domain had the lowest (13.70 ± 2.78). CONCLUSIONS: The French WHOQOL-HIV BREF has acceptable measurement properties. Its broad conceptualisation of HRQoL, going beyond physical and mental health, may be of particular value in our older, treatment-experienced and virally suppressed population. TRIAL REGISTRATION: ClinicalTrials.gov NCT03296202 (Archived by WebCite at http://www.webcitation.org/6zgOBArps ).

Limbic encephalitis as a relapse of Whipple's disease with digestive involvement and spondylodiscitis.

INTRODUCTION: Many clinical manifestations can be related to Tropheryma whipplei infection. CASE REPORT: We report a Tropheryma whipplei limbic encephalitis developed as a relapse of classical Whipple's disease. DISCUSSION: This case is to the best of our knowledge the first proof of the effective brain-blood barrier crossing of both doxycycline and hydroxychloroquine as demonstrated by direct concentration monitoring on brain biopsy.

Efficacy of debridement, antibiotic therapy and implant retention within three months during postoperative instrumented spine infections.

BACKGROUND: Postoperative instrumented spine infection (PISI) is a severe complication of invasive spine procedures. METHODS: Retrospective study of patients treated for PISI between 1st January 2008 and 31st December 2012 in a French University Hospital. The objectives of this study were to describe the outcome of patients treated with debridement-irrigation, antibiotic therapy and implant retention (DAIR) within three months after the occurrence of PISI and to identify factors associated with relapse. RESULTS: Among 4290 patients who underwent spinal arthrodesis surgery during the 5-year study period, 129 had PISI treated by debridement-irrigation in the first three months (3.0%, 95% confidence interval [95%CI]: 2.5-3.5). Fifty-two (40%) were female and the median age was 57 years. Fourteen patients (10.8%) had diabetes and 73 (56.6%) had a BMI (Body Mass Index) ≥25 kg/m2. Staphylocccus aureus, enterobacteria or polymicrobial infections were identified in 44.0, 18.0 and 13.0% of cases, respectively. One hundred and six patients (82.2%) and one hundred and twenty-one patients (93.8%) were cured after one DAIR and after two DAIR, respectively. In multivariate logistic analysis, polymicrobial infection was associated with relapse (Odd Ratio [OR] = 3.81; 95%CI: 1.06-13.66; p = .03), while a BMI ≥25 kg/m2 was a protective factor (OR =0.25; 95%CI: 0.07-0.89; p = .03). CONCLUSION: DAIR may be effective for PISI when performed within the first 3 months after onset of infection. Relapses are significantly associated with polymicrobial infection and negatively associated with moderate overweight. These results need to be confirmed in future prospective studies.

Unusual transmission of Plasmodium falciparum, Bordeaux, France, 2009.

Plasmodium falciparum malaria is usually transmitted by mosquitoes. We report 2 cases in France transmitted by other modes: occupational blood exposure and blood transfusion. Even where malaria is not endemic, it should be considered as a cause of unexplained acute fever.