Occupational exposure to Coxiella burnetii during cardiac surgery: A case report and review of the literature.

We report a case of exposure to Coxiella burnetii in a surgical nurse who underwent an injury of her finger with a scalpel blade during a native aortic valve replacement with a bio-prosthetic cardiac valve conducted on a patient suffering from C. burnetii aortic endocarditis. Given the positivity of C. burnetii culture and PCR from the patient's aortic valve, she was prescribed prophylactic doxycycline 100 mg twice a day for 10 days. Q fever is an occupational zoonosis resulting usually of exposure to infected animals by inhalation of infected aerosols or consumption of contaminated raw milk. Apart from materno-foetal transmission, about 180 cases of human-to-human C. burnetii transmission have been published from 1949 to today, including transmission by blood transfusion, sexual relations, transmission in the healthcare setting to staff, patient attendants and other patients that were likely infected from inhalation of aerosol from respiratory or placental products, transmission to staff during autopsies of patients with Q fever and transmission in familial settings. As C. burnetii is a highly infectious bacterium, that may cause infection with a low inoculum, it should be added to the list of organisms which may be of concern following blood exposure among healthcare professionals.

Early combination therapy with hydroxychloroquine and azithromycin reduces mortality in 10,429 COVID-19 outpatients.

We evaluated the age-specific mortality of unselected adult outpatients infected with SARS-CoV-2 treated early in a dedicated COVID-19 day hospital and we assessed whether the use of hydroxychloroquine (HCQ) + azithromycin (AZ) was associated with improved survival in this cohort. A retrospective monocentric cohort study was conducted in the day hospital of our center from March to December 2020 in adults with PCR-proven infection who were treated as outpatients with a standardized protocol. The primary endpoint was 6-week mortality, and secondary endpoints were transfer to the intensive care unit and hospitalization rate. Among 10,429 patients (median age, 45 [IQR 32-57] years; 5597 [53.7%] women), 16 died (0.15%). The infection fatality rate was 0.06% among the 8315 patients treated with HCQ+AZ. No deaths occurred among the 8414 patients younger than 60 years. Older age and male sex were associated with a higher risk of death, ICU transfer, and hospitalization. Treatment with HCQ+AZ (0.17 [0.06-0.48]) was associated with a lower risk of death, independently of age, sex and epidemic period. Meta-analysis evidenced consistency with 4 previous outpatient studies (32,124 patients-Odds ratio 0.31 [0.20-0.47], I2 = 0%). Early ambulatory treatment of COVID-19 with HCQ+AZ as a standard of care is associated with very low mortality, and HCQ+AZ improve COVID-19 survival compared to other regimens.

Frailty phenotype is associated with antiretroviral exposure among older persons living with HIV.

PURPOSE OF REVIEW: This multicentre, cross-sectional study was carried out in the South of France to assess the association between frailty phenotype and antiretroviral therapy (ART) in older persons living with HIV (PLWHIV). Sociodemographic and HIV data, geriatric assessment, comorbidities, behavioral and age-related variables and the five frailty markers of Fried were recorded. Exposure to any pharmacological class of ART and all regimens were retrieved from medical records. RECENT FINDINGS: The 509 PLWHIV analysed (72.7% male) received a mean of 6.01 ART regimens and 12.5 years exposure to ART. The prevalence of at least one frailty marker [frail and prefrail phenotype (FPFP)] was 66.4%. Duration of exposure to protease inhibitors and reverse transcriptase inhibitors, number of ART regimens and comorbidities, dyslipidaemia, cancer, depression, falls, disability and pain were significantly associated with FPFP by univariate analysis. In logistic regression multivariable analysis, independent predictors for FPFP were a large number of ART regimens, presence of cancer and pain. No significant association was found with HIV-related parameters neither with ART class and duration. SUMMARY: A significant association was found between FPFP and a large number of different ART regimens among older PLWHIV. The burden of cancer and pain in these patients shows the importance of comprehensive care.

Incidence of diabetes in HIV-infected patients treated with first-line integrase strand transfer inhibitors: a French multicentre retrospective study.

BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are increasingly used in patients living with HIV due to their safety, effectiveness and high genetic barrier. However, an association with weight gain has recently been suggested and several cases of diabetes mellitus have been reported with raltegravir and dolutegravir. The long-time metabolic impact of these recent molecules remains unclear. OBJECTIVES: To assess if an INSTI as a third agent is statistically associated with new-onset diabetes mellitus compared with an NNRTI or a PI. PATIENTS AND METHODS: Patients undergoing first-line combined ART (cART) without diabetes at baseline were retrospectively included from the Dat'AIDS French cohort study (ClinicalTrials.gov NCT02898987). Incident diabetes mellitus was defined as a notification of new diabetes in the medical history, a glycated haemoglobin (HbA1c) level superior to 7.5% or the start of a diabetes therapy following the initiation of ART. RESULTS: From 2009 to 2017, 19 462 patients were included, among which 265 cases of diabetes mellitus occurred. Multivariate and survival analyses did not highlight an increase in new-onset diabetes in patients undergoing cART with an INSTI as a third agent compared with an NNRTI or a PI. BMI >30 kg/m2, age >37 years old (in survival analysis), black race or Hispanic ethnicity, arterial hypertension and AIDS were associated with a higher proportion of incident diabetes. CONCLUSIONS: INSTIs were not statistically associated with new-onset diabetes. However, clinicians should remain aware of this possible metabolic comorbidity, particularly in patients with a high BMI and older patients.

Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France.

BACKGROUND: In France, the combination hydroxychloroquine (HCQ) and azithromycin (AZ) is used in the treatment of COVID-19. METHODS: We retrospectively report on 1061 SARS-CoV-2 positive tested patients treated for at least three days with the following regimen: HCQ (200 mg three times daily for ten days) + AZ (500 mg on day 1 followed by 250 mg daily for the next four days). Outcomes were death, clinical worsening (transfer to ICU, and >10 day hospitalization) and viral shedding persistence (>10 days). RESULTS: A total of 1061 patients were included in this analysis (46.4% male, mean age 43.6 years - range 14-95 years). Good clinical outcome and virological cure were obtained in 973 patients within 10 days (91.7%). Prolonged viral carriage was observed in 47 patients (4.4%) and was associated to a higher viral load at diagnosis (p < .001) but viral culture was negative at day 10. All but one, were PCR-cleared at day 15. A poor clinical outcome (PClinO) was observed for 46 patients (4.3%) and 8 died (0.75%) (74-95 years old). All deaths resulted from respiratory failure and not from cardiac toxicity. Five patients are still hospitalized (98.7% of patients cured so far). PClinO was associated with older age (OR 1.11), severity of illness at admission (OR 10.05) and low HCQ serum concentration. PClinO was independently associated with the use of selective beta-blocking agents and angiotensin II receptor blockers (p < .05). A total of 2.3% of patients reported mild adverse events (gastrointestinal or skin symptoms, headache, insomnia and transient blurred vision). CONCLUSION: Administration of the HCQ+AZ combination before COVID-19 complications occur is safe and associated with a very low fatality rate in patients.

Factors associated with psoriasis in a French Nationwide HIV cohort: the independent role of HLA-B*57:01.

OBJECTIVE: Psoriasis is a T-cell-mediated inflammatory disease with genetic factors involved in its etiopathogenesis. In non-HIV populations, HLA-B57:01 has been associated with a higher risk of psoriasis. The aim of this study was to investigate demographic and immunovirological characteristics associated with psoriasis, and to assess whether HLA-B57:01 is associated with psoriasis among people living with HIV (PLHIV) followed in a large French multicenter Dat'AIDS cohort. METHODS: All PLHIV followed up from January 2000 to December 2018 with an available result for HLA-B57:01 were included. Logistic regression models were used to identify associations between psoriasis (outcome variable) and explanatory variables. RESULTS: Among 31 076 PLHIV, the overall prevalence of psoriasis and HLA-B57:01 were 2.25 and 4.73%, respectively and varied according to ethnicity. By multivariate analysis, male gender [OR 1.81 (95% CI 1.46-2.24), P < 10], positive HLA-B57:01 [OR 2.66 (95% CI 2.12-3.33), P < 10], nadir CD4 cell count less than 200 cells/µl [OR 1.41 (95% CI 1.19-1.67), P < 10] and positive HCV serology [OR 1.45 (95% CI 1.20-1.76), P < 10] were significantly associated with a higher risk of psoriasis. Being born in West and Central Africa [OR 0.15 (95% CI 0.10-0.25), P < 10], the Caribbean islands [OR 0.14 (95% CI 0.05-0.45), P = 0.0008] or Latin America [OR 0.31 (95% CI 0.14-0.69), P = 0.004] was associated with a lower risk of psoriasis compared with patients born in mainland France. CONCLUSION: PLHIV carrying HLA-B57:01 have around a three-fold increased risk of psoriasis. This association might provide a possible explanation for the observed differences in psoriasis prevalence between ethnic groups.

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.

[Frailty phenotype in older people living with HIV: concepts, prevention and issues]. / Le phénotype de fragilité chez les personnes vieillissantes avec le VIH : concepts, prévention et enjeux de prise en charge.

The life-span of people aging with HIV (PHIV) tends to reach people without infection, reflecting the effectiveness and tolerance of antiretroviral treatment and improvement of multidisciplinary management. Comorbidities or HIV-inflammaging seems to be the main determinants of frailty phenotype in PHIV. Prevalence of frailty in PHIV is frequent (5% from 28%) and appears earlier than in general population (50 versus 65 years). Almost half of people with HIV present prefrail phenotype before 50 years. The usefulness of integrate routinely measures of frailty phenotype is not yet known but several data are encouraging in terms of feasibility and prediction. Early determination of frailty in PHIV could lead to target interventions to improve global health and decrease adverse outcomes such as incapacities and early death.

Factors associated with social deprivation among older persons living with HIV.

Aging persons living with HIV may develop multiple health problems, including comorbidities, and altered physical and mental health, earlier than non-infected people. They may also experience social deprivation. We assessed the prevalence of social deprivation and its relationship with health indicators in older persons living with HIV. An 18-month, multicenter, cross-sectional study was carried out between 2013 and 2014 focusing on patients ≥50-years of age followed-up in 12 dedicated HIV medical hospital units located in the South of France and involved the VISAGE study group. Social deprivation was measured with the EPICES (Evaluation of Deprivation and Inequalities in Health Examination Centers) score (ES) and defined as ES ≥30.17. The following data were recorded: health indicators (gender, age, body mass index), comorbidities, frailty markers, socioeconomic, behavioral and age-related variables. Among 509 patients recruited, 494 completed the ES social deprivation evaluation. Mean age was 58.5 ± 7.0 years and 72.9% were male. The prevalence of social deprivation was 49.0%. Multivariable logistic regression analysis showed that higher social deprivation was significantly linked to alcohol consumption (OR = 4.07 [95%CI: 1.23-13.48]), risk of depression (OR = 3.59 [95%CI: 2.26-5.70]), chronic obstructive pulmonary disease (OR = 3.10 [95%CI: 1.36-7.09]), hepatitis C (OR = 1.96 [95%CI: 1.10-3.52]), and chronic pain (OR = 1.11 [95%CI: 1.01-1.21]). Social deprivation was not related to HIV status. Our study showed that not only did older patients with HIV suffer from social deprivation, but they also received little support from social workers. Physicians should be aware of this situation and should systematically evaluate social deprivation in order to provide comprehensive targeted care involving global, social, and psychological support to reduce the burden of social deprivation.

Emergence of uncommon HIV-1 non-B subtypes and circulating recombinant forms and trends in transmission of antiretroviral drug resistance in patients with primary infection during the 2013-2015 period in Marseille, Southeastern France.

Primary HIV-1 infections (PHI) with non-B subtypes are increasing in developed countries while transmission of HIV-1 harboring antiretroviral resistance-associated mutations (RAMs) remains a concern. This study assessed non-B HIV-1 subtypes and RAMs prevalence among patients with PHI in university hospitals of Marseille, Southeastern France, in 2005-2015 (11 years). HIV-1 sequences were obtained by in-house protocols from 115 patients with PHI, including 38 for the 2013-2015 period. On the basis of the phylogenetic analysis of the reverse transcriptase region, non-B subtypes were identified in 31% of these patients. They included 3 different subtypes (3A, 1C, 4F), 23 circulating recombinant forms (CRFs) (CRF02_AG, best BLAST hits being CRF 36_cpx and CRF30 in 7 and 1 cases, respectively), and 5 unclassified sequences (U). Non-B subtypes proportion increased significantly, particularly in 2011-2013 vs in 2005-2010 (P = .03). CRF02_AG viruses largely predominated in 2005-2013 whereas atypical strains more difficult to classify and undetermined recombinants emerged recently (2014-2015). The prevalence of protease, nucleos(t)ide reverse transcriptase, and first-generation nonnucleoside reverse transcriptase inhibitors-associated RAMs were 1.7% (World Health Organization [WHO] list, 2009/2.6% International AIDS Society [IAS] list, 2017), 5.2%/4.3%, and 5.2%/5.2%, respectively. Etravirine/rilpivirine-associated RAM (IAS) prevalence was 4.3%. Men who have sex with men (MSM) were more frequently infected with drug-resistant viruses than other patients (26% vs 7%; P = .011). The recent increase of these rare HIV-1 strains and the spread of drug-resistant HIV-1 among MSM in Southeastern France might be considered when implementing prevention strategies and starting therapies.

Frail and pre-frail phenotype is associated with pain in older HIV-infected patients.

As HIV-infected patients grow older, some accumulate multiple health problems earlier than the noninfected ones in particular frailty phenotypes. Patients with frailty phenotype are at higher risk of adverse outcomes (worsening mobility, disability, hospitalization, and death within three years).Our study aimed to evaluate prevalence of frailty in elderly HIV-infected patients and to assess whether frailty is associated with HIV and geriatric factors, comorbidities, and precariousness in a French cohort of older HIV infected.This 18-month cross-sectional multicenter study carried in 2013 to 2014 had involved 502 HIV-infected patients aged 50 years and older, cared in 18 HIV-dedicated hospital medical units, located in South of France.Prevalence of frailty was 6.3% and of pre-frailty 57.2%. Low physical activity and weakness were the main frailty markers, respectively 49.4% and 19.9%. In univariate models, precariousness, duration of HIV antiretroviral treatment >15 years, 2 comorbidities or more, risk of depression, activities of daily living disability, and presence of pain were significantly associated with frail and pre-frail phenotype. Multivariate logistic regression analyses showed that only pain was significantly different between frail and pre frail phenotype versus non frail phenotype (odds ratio = 1.2; P = .002).Our study is the first showing a significant association between pain and frailty phenotype in older patients infected by HIV. As frailty phenotype could be potentially reversible, a better understanding of the underlying determinant is warranted. Further studies are needed to confirm these first findings.

Metabarcoding analysis of eukaryotic microbiota in the gut of HIV-infected patients.

Research on the relationship between changes in the gut microbiota and human disease, including AIDS, is a growing field. However, studies on the eukaryotic component of the intestinal microbiota have just begun and have not yet been conducted in HIV-infected patients. Moreover, eukaryotic community profiling is influenced by the use of different methodologies at each step of culture-independent techniques. Herein, initially, four DNA extraction protocols were compared to test the efficiency of each method in recovering eukaryotic DNA from fecal samples. Our results revealed that recovering eukaryotic components from fecal samples differs significantly among DNA extraction methods. Subsequently, the composition of the intestinal eukaryotic microbiota was evaluated in HIV-infected patients and healthy volunteers through clone sequencing, high-throughput sequencing of nuclear ribosomal internal transcribed spacers 1 (ITS1) and 2 (ITS2) amplicons and real-time PCRs. Our results revealed that not only richness (Chao-1 index) and alpha diversity (Shannon diversity) differ between HIV-infected patients and healthy volunteers, depending on the molecular strategy used, but also the global eukaryotic community composition, with little overlapping taxa found between techniques. Moreover, our results based on cloning libraries and ITS1/ITS2 metabarcoding sequencing showed significant differences in fungal composition between HIV-infected patients and healthy volunteers, but without distinct clusters separating the two groups. Malassezia restricta was significantly more prevalent in fecal samples of HIV-infected patients, according to cloning libraries, whereas operational taxonomic units (OTUs) belonging to Candida albicans and Candida tropicalis were significantly more abundant in fecal samples of HIV-infected patients compared to healthy subjects in both ITS subregions. Finally, real-time PCR showed the presence of Microsporidia, Giardia lamblia, Blastocystis and Hymenolepis diminuta in different proportions in fecal samples from HIV patients as compared to healthy individuals. Our work revealed that the use of different sequencing approaches can impact the perceived eukaryotic diversity results of the human gut. We also provide a more comprehensive view of the eukaryotic community in the gut of HIV-infected patients through the complementarity of the different molecular techniques used. Combining these various methodologies may provide a gold standard for a more complete characterization of the eukaryotic microbiome in future studies.

Impact of baseline plasma HIV-1 RNA and time to virological suppression on virological rebound according to first-line antiretroviral regimen.

OBJECTIVES: We investigated the risk of virological rebound in HIV-1-infected patients achieving virological suppression on first-line combined ART (cART) according to baseline HIV-1 RNA, time to virological suppression and type of regimen. PATIENTS AND METHODS: Subjects were 10 836 adults who initiated first-line cART (two nucleoside or nucleotide reverse transcriptase inhibitors + efavirenz, a ritonavir-boosted protease inhibitor or an integrase inhibitor) from 1 January 2007 to 31 December 2014. Cox proportional hazards models with multiple adjustment and propensity score matching were used to investigate the effect of baseline HIV-1 RNA and time to virological suppression on the occurrence of virological rebound. RESULTS: During 411 436 patient-months of follow-up, risk of virological rebound was higher in patients with baseline HIV-1 RNA ≥100 000 copies/mL versus <100 000 copies/mL, in those achieving virological suppression in > 6 months versus <6 months, and lower with efavirenz or integrase inhibitors than with ritonavir-boosted protease inhibitors. Baseline HIV-1 RNA >100 000 copies/mL was associated with virological rebound for ritonavir-boosted protease inhibitors but not for efavirenz or integrase inhibitors. Time to virological suppression >6 months was strongly associated with virological rebound for all regimens. CONCLUSIONS: In HIV-1-infected patients starting cART, risk of virological rebound was lower with efavirenz or integrase inhibitors than with ritonavir-boosted protease inhibitors. These data, from a very large observational cohort, in addition to the more rapid initial virological suppression obtained with integrase inhibitors, reinforce the positioning of this class as the preferred one for first-line therapy.

Mycoplasma genitalium, an agent of reemerging sexually transmitted infections.

M. genitalium is a reemerging microorganism, responsible for sexually transmissible infections (STIs), with prevalence which varies depending on the country and population group studied. We report here M. genitalium prevalence among the specimens received for STI diagnosis in our routine microbiological laboratory in the university hospital in Marseille, France. We tested 4 624 samples from 3 793 patients using qPCR for M. genitalium, C. trachomatis, N. gonorrheae, T. pallidum. Of these samples, 528 (13.6%) patients were tested positive for at least one pathogen and 126 (3.3%) were positive for M. genitalium. M. genitalium is the second most prevalent micro-organism detected in women after C. trachomatis (10.4%) and the third most prevalent in men after C. trachomatis (5.1%) and N. gonorrhoeae (4.4%). We observed no significant differences between the prevalence of M. genitalium in vaginal, urethral and urine specimens (p = 0.9). Prevalence of M. genitalium is significantly higher in patients aged between 10-30 years (4.1%) compared to those aged between 30 and 50 years (2.7%) (p = 0.02, RR = 1.54 [1.06-2.24]) and patients over 50 years of age (1.1%) (p = 0.003, RR= 3.98 [1.47-10.8]). M. genitalium is a common agent of STI, therefore we suggest that this micro-organism should be systematically tested during chronic, recurrent, or antibiotic resistant genital infections and in populations at high-risk of STIs.

Evaluation of self-collected rectal swabs for the detection of bacteria responsible for sexually transmitted infections in a cohort of HIV-1-infected patients.

Purpose. The standard approach to screening sexually transmitted infections (STIs) has often been restricted to urogenital specimens. Most current guidelines, however, also recommend testing extra-genital sites, including rectal locations, because asymptomatic rectal carriage of pathogens has often been reported. The aim of our study was to evaluate self-collected rectal swabs to screen bacterial STIs in HIV-infected patients in Marseille, France.Methodology. Between January 2014 and December 2015, 118 HIV-infected patients (93 males and 25 females) agreed to self-sample anal swabs for detection of bacterial STI. Detection of Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, Mycoplasma genitalium and Haemophilus ducreyi was performed using in-house qPCR assay.Results/Key findings. Bacterial STIs were found in 8 % (9/118) of the patients. C. trachomatis was the most commonly detected bacterium (4.2 %) followed by N. gonorrhoeae (2.5 %), M. genitalium (1.7 %) and T. pallidum (0.8 %). All the positive patients were males. The rectal carriage of pathogenic bacteria was fortuitously discovered for seven men (78 %) who did not present rectal signs of STIs and was suspected for two men who presented proctitis (22 %).Conclusion. In conclusion, testing extra-genital sites is crucial for the diagnosis of STIs in men and women presenting or not concomitant urogenital infections in order to detect asymptomatic carriage with the aim of controlling and preventing transmission to their sexual partners.