Introduction:Capnocytophaga canimorsus is a commensal bacterium found in the saliva of dogs and cats. In most cases C. canimorsus causes local infection resulting from bite-wounds, scratches or licks but severe forms can occur. The following case describes a severe and rapidly fatal sepsis and disseminated intravascular coagulation with no evidence of bite in a patient without obvious cause of immunosuppression, diagnosed by polymerase chain reaction and 16S rRNA gene sequencing.Case report:Herein we present a rare case of a 39-year-old man who was taken care of by the emergency medical service for faintness, fever and chills associated with generalized mottling. Despite critical care management and broad-spectrum antibiotherapy, the patient presented an irrepressible shock with disseminated intravascular coagulation and multiple organ failure. He died during the night. The initial etiological assessment was negative but rod-shaped inclusions could be observed in his blood. A pan-bacterial polymerase chain reaction targeting part of the gene encoding 16S ribosomal ribonucleic acid (rRNA) was carried out directly on blood cultures; the sequencing identified Capnocytophaga canimorsus.Conclusions:This observation illustrates the potential severity of C. canimorsus infection even in a patient without neither obvious causes of immunosuppression nor evidence of bite. The presence of intracellular bacillary forms on the blood smear is an important information which should lead to performing a polymerase chain reaction and 16S rRNA gene sequencing.

To increase the knowledge about S. capitis in the neonatal setting, we conducted a nationwide 3-month survey in 38 neonatal intensive care units (NICUs) covering 56.6% of French NICU beds. We demonstrated 14.2% of S. capitis BSI (S.capBSI) among nosocomial BSIs. S.capBSI incidence rate was 0.59 per 1000 patient-days. A total of 55.0% of the S.capBSIs were late onset catheter-related BSIs. The S. capitis strains infected preterm babies (median gestational age 26 weeks, median birth weight 855 g). They were resistant to methicillin and aminoglycosides and belonged to the NRCS-A clone. Evolution was favorable in all but one case, following vancomycin treatment.

OBJECTIVE:The objective was to evaluate the association between age-related comorbidities (ARCs) and 5-year HIV-related excess mortality in people living with HIV aged ≥60 years.DESIGN:Cohort study using relative survival analysis (Estève's model).SETTING:The French multicentre prospective Dat'AIDS cohort that involves 12 French hospitals.PARTICIPANTS:Inclusion of 1415 HIV-1 infected patients actively followed aged ≥60 years on January 2008, with a 5-year follow-up period in the late combination antiretroviral therapy era.RESULTS:Among 1415 patients included, 154 died. By multivariable analysis, factors predictive of 5-year HIV-related excess mortality were non-AIDS-related cancer (adjusted excess HR (aEHR)=2.94; 95% CI 1.32 to 6.57), cardiovascular disease (aEHR=6.00; 95% CI 2.45 to 14.65), chronic renal disease (aEHR=4.86; 95% CI 2.24 to 10.53), cirrhosis (aEHR=3.58; 95% CI 1.25 to 10.28), hepatitis C co-infection (aEHR=3.63; 95% CI 1.44 to 9.12), body mass index<18.5 kg/m² (aEHR=4.10; 95% CI 1.61 to 10.48) and having a CD4 cell count ≤200/mm3 (aEHR=5.79; 95% CI 2.28 to 14.69).CONCLUSIONS:ARCs, particularly cardiovascular disease and chronic renal disease, are predictive of HIV-related excess mortality, with an increase in hazard similar to that of CD4 cell count.TRIAL REGISTRATION NUMBER:NCT02898987.

OBJECTIVESTo analyse the frequency and causes of treatment discontinuation in patients who were treated with an integrase strand transfer inhibitor (INSTI), with a focus on neuropsychiatric adverse events (NPAEs).METHODSPatients in 18 HIV reference centres in France were prospectively included in the Dat'AIDS cohort. Data were collected from all patients starting an INSTI-containing regimen between 1 January 2006 and 31 December 2016. All causes of INSTI-containing regimen discontinuations were analysed, and patients' characteristics related to discontinuation due to NPAEs were sought.RESULTSINSTIs were prescribed to 21315 patients: 6274 received dolutegravir, 3421 received elvitegravir boosted by cobicistat, and 11620 received raltegravir. Discontinuation was observed in 12.5%, 20.2% and 50.9% of the dolutegravir-, elvitegravir- and raltegravir-treated patients, respectively (P < 0.001). Discontinuation for NPAEs occurred in 2.7%, 1.3% and 1.7% of the dolutegravir-, elvitegravir-, and raltegravir-treated patients, respectively (P < 0.001). In the multivariate analysis, discontinuation for NPAEs was related to dolutegravir versus elvitegravir (HR = 2.27; 95% CI 1.63-3.17; P < 0.0001) and versus raltegravir (HR = 2.46; 95% CI 2.00-3.40; P < 0.0001), but neither gender (HR for women = 1.19; 95% CI 0.97-1.46; P = 0.09) nor age (P = 0.12) was related. The association with abacavir was not retained in the final model.CONCLUSIONSAlthough discontinuation for side effects was less frequent with dolutegravir than with boosted elvitegravir, discontinuation for NPAEs, although rare (2.7%), was more frequent with dolutegravir. No patient characteristic was found to be associated with these side effects in this very large population.

BACKGROUND:The influence of geographic origin on the risk of severe illness and death on cART has not been explored in European countries.METHOD:We studied antiretroviral-naïve heterosexual HIV-1-infected individuals enrolled in the FHDH-ANRS CO4 cohort in France who started cART between 2006 and 2011. Individuals originating from France (French natives), sub-Saharan Africa (SSA) and non-French West-Indies (NFW) were studied until 2012. Crude and adjusted rate ratios (aRR) of severe morbid events/deaths (AIDS-related and non-AIDS-related) were calculated using Poisson regression models stratified by sex, comparing each group of migrants to French natives.RESULTS:Among 2334 eligible men, 1379 (59.1%) originated from France, 838 (35.9%) from SSA and 117 (5.0%) from NFW. SSA male migrants had a higher aRR for non-AIDS infections, particularly bacterial infections (aRR 1.56 (95% CI 1.07-2.29), p = 0.0477), than French natives. Among 2596 eligible women, 1347 (51.9%) originated from France, 1131 (43.6%) from SSA, and 118 (4.5%) from NFW. SSA and NFW female migrants had a higher aRR for non-AIDS infections, particularly non-bacterial infections (respectively, 2.04 (1.18-3.53) and 7.87 (2.54-24.4), p = 0.0010), than French natives. We observed no other significant differences related to geographic origin as concerns the aRRs for AIDS-related infections or malignancies, or for other non-AIDS events/deaths such as cardiovascular disease, neurological/psychiatric disorders, non-AIDS malignancies and iatrogenic disorders, in either gender.CONCLUSION:Heterosexual migrants from SSA or NFW living in France have a higher risk of non-AIDS-defining infections than their French native counterparts. Special efforts are needed to prevent infectious diseases among HIV-infected migrants.

Background: More data are needed on the influence of geographic origin, sex, and the HIV transmission group on biological and clinical outcomes after first-line combined antiretroviral therapy (cART) initiation.Methods: We studied antiretroviral-naive HIV-1-infected adults enrolled in the French Hospital Database on HIV cohort in France and who started cART between 2006 and 2011. The censoring date of the study was 31 December 2012. According to geographic origin [ French natives (FRA) or sub-Saharan Africa/non-French West Indies (SSA/NFW)], sex, and HIV transmission group, we assessed 2-year Kaplan-Meier probabilities and adjusted hazard ratios (aHRs) for plasma viral load undetectability and CD4(+) cell recovery, and 5-year cumulative incidences and aHRs for negative clinical outcomes (AIDS-defining event, serious non-AIDS events, or death).Results: Of 9746 eligible individuals, 7297 (74.9%) were FRA and 2449 (25.1%) were sub-Saharan Africa/non-French West Indies migrants. More migrants (38.1%) than nonmigrants (27.5%) started cART with a CD4(+) cell count less than 200/ml (P < 0.0001). By comparison with FRA MSM, nonhomosexual men, whatever their geographic origin, had lower aHRs for viral undetectability; all patient groups, particularly migrants, had lower aHRs for CD4(+) cell recovery than FRA MSM; aHRs for negative clinical outcome (360 new AIDS-defining events, 1376 serious non-AIDS events, 38 deaths) were also higher in nonhomosexual men, regardless of geographic origin. Preexisting AIDS status, a lower CD4(+) cell count and older age at cART initiation had the biggest impact on changes between the crude and aHRs of clinical outcomes.Conclusion: Compared with FRA MSM, all migrants had a lower likelihood of CD4(+) cell recovery, and nonhomosexual men had a higher likelihood of negative virological and clinical outcomes. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

We report on 4 patients (1 immunocompetent, 3 immunosuppressed) in whom visceral leishmaniasis had become unresponsive to (or had relapsed after) treatment with appropriate doses of liposomal amphotericin B. Under close follow-up, full courses of pentavalent antimony were administered without life-threatening adverse events and resulted in rapid and sustained clinical and parasitological cure.

Objective To compare the time from entry into care for HIV infection until combination antiretroviral therapy (cART) initiation between migrants and non migrants in France, excluding late access to care. Methods Antiretroviral-naïve HIV-1-infected individuals newly enrolled in the FHDH cohort between 2002–2010, with CD4 cell counts >200/μL and no previous or current AIDS events were included. In three baseline CD4 cell count strata (200–349, 350-499, ≥500/μL), we examined the crude time until cART initiation within three years after enrolment according to geographic origin, and multivariable hazard ratios according to geographic origin, gender and HIV-transmission group, with adjustment for baseline age, enrolment period, region of care, plasma viral load, and HBV/HBC coinfection. Results Among 13338 individuals, 9605 (72.1%) were French natives (FRA), 2873 (21.4%) were migrants from sub-Saharan Africa/non-French West Indies (SSA/NFW), and 860 (6.5%) were migrants from other countries. Kaplan-Meier probabilities of cART initiation were significantly lower in SSA/NFW than in FRA individuals throughout the study period, regardless of the baseline CD4 stratum. After adjustment, the likelihood of cART initiation was respectively 15% (95%CI, 1–28) and 20% (95%CI, 2–38) lower in SSA/NFW men than in FRA men who had sex with men (MSM) in the 350-499 and ≥500 CD4 strata, while no difference was observed between other migrant groups and FRA MSM. Conclusion SSA/NFW migrant men living in France with CD4 >350/μL at entry into care are more likely to begin cART later than FRA MSM, despite free access to treatment. Administrative delays in obtaining healthcare coverage do not appear to be responsible.

We examined whether impaired kidney function is an independent risk factor for myocardial infarction in HIV-infected individuals without pre-existing coronary artery disease. The odds ratio for impaired kidney function fell from 1.22 (95% confidence interval 0.90–1.66) to 0.99 (95% confidence interval 0.69–1.41) after adjustment for cardiovascular risk factors and HIV-related parameters, with hypertension, high-density lipoprotein cholesterol, smoking and the CD4+ T-cell nadir as most influential confounders. In this setting, no association was found between impaired kidney function and the risk of myocardial infarction.

Objective: HIV-infected patients still experience higher Cardiovascular (CV) mortality rates, even if an adequate viral suppression is achieved. In addition, vitamin D insufficiency, a common condition in HIV-infected patients, is increasingly associated with CV risk. We therefore aim to investigate relationships between immunological parameters, antiretroviral therapy, plasma vitamin D and arterial parameters, including aortic stiffness and wave reflections, in HIV-infected patients who achieved viral suppression but possibly remain at increased CV risk. Methods: We conducted a cross-sectional study including 178 middle-aged HIV-infected patients. HIV infection was controlled in a large number of participants, representative of a real-world setting. In addition to carotid Intima Media Thickness (IMT), central hemodynamic parameters involved aortic Pulse Wave Velocity (PWV), carotid Augmentation index (AIx) and Pulse Pressure Amplification (PPA) measured noninvasively using applanation tonometry. Results: Aortic PWV was slightly but unsignificantly higher than the theoretical values obtained in general population according to age and blood pressure, and was independent of HIV-related parameters. In univariate and multivariate analyses, carotid AIx was positively correlated with current CD4 T-cell count and PPA was positively correlated with vitamin D, independently of other confounders. No HIV-related parameters or vitamin D entered the multivariate analysis of carotid IMT / plaque. Conclusion: In our chronically treated population, HIV infection was not associated with increased aortic stiffness but with a positive correlation between current CD4 T-cell count and degree of AIx, suggesting that patients with higher CD4 T-cell count may have higher wave reflections. The positive correlation between vitamin D and PPA suggests that vitamin D deficiency may be independently associated with altered central hemodynamics in well controlled HIV-infected patients. These findings should be confirmed in prospective studies.

The French Hospital Database on HIV (FHDH) is a hospital-based multicentre open cohort with inclusions ongoing since 1989. The research objectives focus mainly on mid- and long-term clinical outcomes and therapeutic strategies, as well as severe AIDS and non-AIDS morbidities, and public health issues relative to HIV infection. FHDH also serves to describe HIV-infected patients receiving hospital care in France. FHDH includes data on more than 120,000 HIV-infected patients from 70 French general or university hospitals distributed throughout France. Patients are eligible for inclusion if they are infected by HIV-1 or HIV-2 and give their written informed consent. Standardized variables are collected at each outpatient visit or hospital admission during which a new clinical manifestation is diagnosed, a new treatment is prescribed or a change in biological markers is noted, and/or at least every 6 months. Since its inception, variables collected in FHDH include demographic characteristics, HIV-related biological markers, the date and type of AIDS and non AIDS-defining events, antiretroviral treatments and the date and causes of death, as reported in the medical records. Since 2005, data have also been collected on: co-infection with hepatitis B or C virus; alcohol and tobacco use; and non HIV-related biomarkers. Anyone can submit a research project by completing a standardized form available on the FHDH website (http://www.ccde.fr/_fold/fl-1385734776-429.pdf) or from the corresponding author, describing the context and objectives of the study. All projects are reviewed by the scientific committee.

Toxoplasmosis can be a severe opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS), and also among solid organ transplant and allogeneic hematopoietic stem cell transplant (HSCT) patients. Patients with low-grade or chronic hematologic malignancies are treated with increasing immunosuppressive regimens and, therefore, represent an emerging population at risk for opportunistic diseases. We report here two cases of disseminated toxoplasmosis occurring in non-allografted hematologic patients with chronic lymphoproliferations. A review of 44 cases from the literature reveals that toxoplasmosis occurs increasingly in indolent B cell lymphoproliferative disorders. Aggressive lymphoproliferations, adenosine analogs, autologous HSCT, and the absence of chemoprophylaxis are the main risk factors for opportunistic toxoplasmosis. The central nervous system is the main organ involved. Fever is only present in half of all cases. Latent Toxoplasma cysts reactivation (LTCR) is the most common, but primary infection occurs in about 20% of cases. Global mortality is over 50%.

BACKGROUND:Individuals infected by human immunodeficiency virus (HIV) have a higher risk of cardiovascular disease than the general population. The specific effects of virological and immunological parameters on the risk of myocardial infarction (MI) in HIV-infected individuals are debated.METHODS:We conducted a nested case-control study within the French Hospital Database on HIV. Case patients (n = 289) were patients who, between January 2000 and December 2006, had a prospectively recorded and validated first MI. Up to 5 HIV-infected controls (n = 884) matched for age, sex, and clinical center were selected, at random with replacement, among patients with no history of MI. Conditional logistic regression models were used to identify predictors of the risk of MI.RESULTS:Plasma HIV-1 RNA levels >50 copies/mL, a low CD4 T-cell nadir, and a high CD8 T-cell count were independently associated with an increased risk of MI, with respective odds ratios of 1.51 (95% confidence interval, 1.09-2.10), 0.90 (.83-.97) per log(2) unit, and 1.48 (1.01-2.18) for the highest tertile of CD8 T-cell counts (>1150 cells/mm(3)) compared with the lowest (≤760 cells/mm(3)).CONCLUSIONS:Independently of cardiovascular risk factors and antiretroviral therapy, HIV replication, a low CD4 T-cell nadir and a high current CD8 T-cell count are associated with an increased risk of MI in HIV-infected individuals. This suggests new paths for interventions to diminish the risk of MI in HIV-infected patients.

We report the first case of Mycobacterium avium reactivation, after prolonged latency, in a HIV-infected patient receiving highly active antiretroviral therapy with undetectable viral replication and normal CD4 cell count. The patient presented with a painful swollen shoulder seven years after initial M. avium bacteriaemia. Articular puncture grew M. avium. The isolates of the first and second infection were identical using repetitive-sequence-based Polymerase Chain Reaction analyses.

OBJECTIVES To compare virological effectiveness in patients who continued on a virologically successful first-line boosted protease inhibitor (PI)-containing combination antiretroviral therapy (cART) regimen or who switched to a PI-free cART including efavirenz, nevirapine or abacavir. METHODS From the French Hospital Database on HIV, we selected 439 patients with undetectable viral load (VL) on a first-line boosted PI-containing cART regimen who switched to a PI-free combination including efavirenz, nevirapine or abacavir. Each of these patients was matched with three patients who continued to take their first-line cART regimen, on the basis of gender, age, CD4 cell count, VL, date of cART initiation and the duration of VL undetectability. Time to virological failure (VF) was analysed with Kaplan-Meier curves and Cox models. RESULTS The 12 month probabilities of VF were 3.7% and 5.7% in non-switch and switch patients, respectively, and 3.9%, 7.2% and 9.0% in patients switching to efavirenz-, nevirapine- and abacavir-containing cART, respectively. After adjustment, only patients switching to abacavir-containing cART had a higher risk of VF than non-switch patients (adjusted hazard ratio, 1.99; 95% confidence interval, 1.05-3.79). CONCLUSIONS Switching from a virologically successful first-line boosted PI-containing cART regimen to a non-nucleoside reverse transcriptase inhibitor-containing cART regimen containing either efavirenz or nevirapine is virologically safe, while switching to abacavir-containing cART should be avoided.

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK