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Background. Little is known on headaches long-term persistence after bacterial meningitis and on their impact on patients’ quality of life. Methods. In an ancillary study of the French national prospective cohort of community-acquired bacterial meningitis in adults (COMBAT) conducted between February 2013 and July 2015, we collected self-reported headaches before, at onset, and 12 months (M12) after meningitis. Determinants of persistent headache (PH) at M12, their association with M12 quality of life (SF 12), depression (Center for Epidemiologic Studies Depression Scale) and neuro-functional disability were analysed. Results. Among the 277 alive patients at M12 87/274 (31.8%), 213/271 (78.6%) and 86/277 (31.0%) reported headaches before, at the onset, and at M12, respectively. In multivariate analysis, female sex (OR: 2.75 [1.54–4.90]; p

International audience; Objectives: The value of Epstein–Barr virus (EBV) biomarkers on the prognosis of HIV-related non-Hodgkin's lymphoma (NHL) has been poorly explored in the combined antiretroviral therapy (cART) era. Design: We evaluated EBV DNA load and EBV antibodies in HIV-NHL patients enrolled in the French ANRS-CO16 Lymphovir Cohort between 2008 and 2015. Methods: Whole blood and plasma EBV DNA load and serological profiles were analyzed in 76 HIV-infected patients at diagnosis of NHL and 6 months after the initiation of chemotherapy. Results: Prechemotherapy whole blood (WB) and plasma EBV DNA loads were positive for 80 and 45% of HIV-NHL patients, respectively. Pretreatment WB EBV DNA positivity was associated with a positive plasma HIV-1 RNA load (relative risk (RR), 4.42 [1.33; 14.72]) and plasma EBV DNA positivity with EBV in situ detection (RR 10.62 [2.38; 47.49]). Following chemotherapy, the proportions of patients with positive WB or plasma EBV DNA declined from 81 to 23% (P < 0.0001) and from 43 to 8% (P < 0.0001), respectively. Estimated 2-year progression-free survival did not differ according to prechemotherapy WB positivity (82% versus 67%, P = 0.15) or plasma EBV DNA positivity (76% versus 81%, P = 0.52). Conclusions: The plasma EBV DNA load correlates with in situ EBV detection. The WB EBV DNA load correlates with HIV load. WB and plasma EBV DNA loads at NHL diagnosis do not constitute prognostic markers for HIV-NHL patients in the modern cART era.

Myalgia or muscle weakness is frequently observed during HIV infection (1), and 15% of HIV patients may have an increased serum creatine kinase (CK) level.1 Case reports or case series have suggested that HIV-associated myopathies represent a large spectrum of disease.2 To date, data on muscle involvement during HIV infection remain sparse and we aimed to describe the clinical characteristics and evolution of biopsy-proven HIV-associated myopathies. All HIV-positive patients who had a muscle biopsy performed at the Pitie-Salpetriere University Hospital between 2001 and 2012 were identified. Medical records were retrospectively reviewed to assess muscle disease features and HIV infection characteristics. Patients were classified histologically as polymyositis (PM), non-specific myositis (NSM), immune-mediated necrotizing myopathy (IMNM), or inclusion body myositis (IBM) according to the European Neuromuscular Center (ENMC) criteria.3 4 Isolated mitochondrial abnormality (IMA) was defined as presence of cytochrome c oxidase negative fibres and/or succinate dehydrogenase positive staining without inflammatory cell infiltrate or rimmed vacuoles. PM or NSM evolution towards IBM was evaluated at follow-up. Uncontrolled viral load was defined as >40 copies/mL. Categorical variables are reported herein as numbers and/or percentages and were compared using a χ2 or Fisher’s exact test. Quantitative variables are reported as median (IQR1–IQR3) and compared using non-parametric one-way one-way analysis of variance (ANOVA). For all statistical analyses, p

Objective Chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are associated with increased risks of lymphomas in the non-HIV setting. Their impacts on HIV-associated lymphomas deserved further studies in the modern combined antiretroviral therapy (cART) era. Design We evaluated the associations between HCV, HBV and HIV-related lymphomas in the Lymphovir-ANRS-CO16 cohort. Methods Prevalence of HCV seropositivity and chronic HBV infections were compared with those observed in the French Hospital Database on HIV (FHDH-ANRS-CO4). Results Between 2008 and 2015, 179 patients with HIV-related lymphomas from 32 French hospitals were enrolled, 69 had Hodgkin's lymphoma (39%), and 110 non-Hodgkin's lymphoma (NHL) (61%). The prevalence of HCV infection was higher in patients with NHL than in the FHDH-ANRS-CO4 [26 versus 14%, odd ratio (OR): 2.15; 95% confidence interval (1.35-3.32)] whereas there was no association between Hodgkin's lymphoma and chronic HCV infection. Chronic HBV infection was not associated with NHL in our cohort with a prevalence of 5 versus 7% in FHDH-ANRS-CO4 but tended to be associated with Hodgkin's lymphoma [prevalence of 14%, OR: 2.16 (0.98-4.27)]. Chronic HCV infection tended to pejoratively impact 2-year overall survival in patients with NHL: 72% [57%, 91%] versus 82% [74%, 91%], hazard ratio: 2.14 [0.95-4.84]. In contrast, chronic HBV infection did not correlate with outcome. Conclusion In the modern cART era, chronic HCV infection is associated with an increased risk of NHL in PLWHIV and tends to pejoratively impact overall survival. HBV infection is not associated with the risk of NHL but with a borderline increase of Hodgkin's lymphoma risk.

Epstein-Barr virus (EBV) has been implicated in lymphomagenesis of HIV-related classical Hodgkin lymphoma (HIV-cHL). The utility of EBV molecular and serological biomarkers has scarcely been examined in HIV-cHL in the recent combined antiretroviral therapy (cART) era.We evaluated EBV DNA load and a panel of EBV antibodies in HIV-cHL patients prospectively enrolled in the French ANRS-CO16 Lymphovir cohort between 2008 and 2015.Pretreatment whole blood, plasma EBV DNA load and serological profiles were analysed in 63 HIV-infected patients diagnosed with cHL. For the 42 patients with available material, comparisons were performed between values at diagnosis and 6 months after the initiation of chemotherapy.Pretreatment whole blood and plasma EBV DNA loads were positive in 84 and 59% of HIV-cHL patients, respectively. Two-year progression-free survival estimates did not differ between the patients with pretreatment whole blood (n = 53) or plasma (n = 37) EBV DNA(+) and the patients with pretreatment whole blood (n = 10) or plasma (n = 26) EBV DNA(-) (92 vs. 80% or 89 vs. 92%, P = 0.36 and 0.47, respectively). At diagnosis, 47% of patients harboured an EBV reactivation serological profile. Following chemotherapy, whole blood and plasma EBV DNA levels significantly declined from medians of 1570 [interquartile range, 230-3760) and 73 (0-320) copies/ml to 690 (0-1830) and 0 (0-0) copies/ml, respectively (P = 0.02 and P 0.0001, respectively]. Anti-EBV IgG antibody level significantly dropped at 6-month follow-up (P = 0.004).Whole blood and plasma EBV DNA loads do not constitute prognostic markers in HIV-cHL patients in the modern cART era.

BACKGROUND Human immunodeficiency virus (HIV) infection is associated with a high risk of classical Hodgkin's lymphoma (cHL) in the combined antiretroviral therapy (cART) era. METHODS We analyzed the characteristics and outcome of HIV-associated cHL diagnosed in the modern cART era. The French ANRS-CO16 Lymphovir cohort enrolled 159 HIV-positive patients with lymphoma, including 68 (43%) with cHL. HIV-HL patients were compared with a series of non-HV-infected patients consecutively diagnosed with HL. RESULTS Most patients (76%) had Ann-Arbor stages III-IV and 96% of patients were treated with ABVD. At diagnosis, median CD4 T-cell count was 387/µL and 94% of patients were treated with cART. All patients received cART after diagnosis. Five patients died from early progression (n = 2), sepsis (1) or after relapse (2). Two additional patients relapsed during follow-up. Two-year overall and progression free survivals (PFS) were 94% [95% CI, 89%, 100%] and 89% [82%, 97%], respectively. The only factor associated with progression or death was age with a relative risk of 8.1 [1.0; 67.0] above 45 years. The PFS of Lymphovir patients appeared similar to PFS of HIV-negative patients, 86% [82%, 90%], but patients with HIV infection displayed higher risk features than HIV-negative patients. CONCLUSIONS Although high-risk features still predominate in HIV-HL, the prognosis of these patients, treated with cART and mainly ABVD, has markedly improved in the modern cART era and is now similar to non-HIV-infected patients.

International audience; Objective: Non-Hodgkin's lymphoma (NHL) remains among the most frequent malignancies in persons living with HIV (PLWHIV). Survival among patients with HIV-associated diffuse large B-cell lymphoma (DLBCL), the most frequent NHL subtype, has improved markedly in recent years. We aimed to analyze characteristics and outcomes of DLBCL in HIV-infected patients in the era of modern combined antiretroviral therapy (cART).Design: PLWHIV with lymphoma were prospectively enrolled in the French ANRS-CO16 Lymphovir cohort between 2008 and 2015. We compared the patients treated with R-CHOP) (rituximab, cyclophosphamide, daunorubicin, vin-cristine, prednisolone) with HIV-negative DLBCL patients enrolled simultaneously in the R-CHOP arms of Lymphoma Study Association trials.Results: Among 110 PLWHIV with NHL, 52 (47%) had systemic DLBCL. These 52 cases had frequent extranodal disease (81%), poor performance status (35%) and advanced age-adjusted international prognostic index (aaIPI) (58%), and were mainly treated with R-CHOP (n = 44, 85%). Their median CD4(+) T-cell count was 233 cells/mu l, and 79% of patients were on cART. The 2-year overall and progression-free survival rates were both 75% (95% confidence interval: 64%, 88%). Factors associated with progression or death in univariate analysis were poor performance status [hazard ratio: 3.3 (1.2, 8.9)], more than one extranodal site [hazard ratio: 3.4 (1.1, 10.5)] and an advanced aaIPI [hazard ratio: 3.7 (1.0, 13.1)]. Progression-free survival after R-CHOP therapy did not differ from that of the HIV-negative counterparts (P = 0.11).Conclusion: In the recent cART era, despite frequent high-risk features, the 2-year overall survival of HIV-DLBCL patients reaches 75%. Outcomes after R-CHOP therapy are similar to those of HIV-negative patients with similar aaIPI. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

Introduction En France, la prevalence de l’hepatite B chronique (HBC) est estimee a 0,65 % en population generale, soit 1 280 000 porteurs chroniques de l’AgHBs, dont 150 000 ignorent leur statut serologique. Le depistage, obligatoire en cas de grossesse ou de don de sang est egalement recommande de facon plus large pour les personnes de plus de 16 ans non vaccinees susceptibles d’etre exposees au virus de l’hepatite B. Les Centres gratuits d’information, de depistage et de diagnostic (CeGIDD) integrent le depistage et la prevention de l’HBC ainsi que l’orientation vers le soin des personnes positives. L’objectif de cette etude est de decrire la cascade de soins suite a un depistage positif de l’AgHBs dans un CeGIDD, afin d’identifier les etapes sur lesquelles agir pour ameliorer l’efficience de la prise en charge. Materiels et methodes Il s’agit d’une etude transversale menee entre 2016 et 2018 chez tous les patients consultant dans un CeGIDD et ayant beneficie d’un depistage de l’AgHBs. Les etapes de la cascade de soins ont ete decrites a partir du depistage jusqu’a la mise sous traitement des sujets ayant une indication a etre traites. Resultats Parmi les 5741 personnes depistees, la prevalence de l’AgHBs positif etait de 1,1 % (n = 63, IC95 % : 0,86–1,40), avec un sex-ratio de4, 25 et un âge moyen de 31 ans ± 11 ans. La majorite des sujets etait originaire d’Afrique Subsaharienne (n = 59, 93,7 %) et 30 d’entre eux (47,6 %) n’avaient aucune couverture sociale. Une co-infection VIH etait associee dans 3 cas (3,8 %) et aucune co-infection VHC n’etait notee. Parmi ces sujets avec AgHBs positif, 81 % (n = 51)ont recupere leurs resultats,61,9 % (n = 39/63) ont realise leur bilan initial et 60,3 % (n = 38/63)ont beneficie d’un suivi ulterieur. Au total, 39,6 % patients (soit 25/63 des sujets depistes positifs) ont ete consideres comme perdus de vue a une des etapes de la cascade de soins. Selon les recommandations Europeennes de traitement de l’HBC, 10 patients parmi les 39 sujets evalues devaient beneficier d’un traitement (hepatite B chronique AgHBe positif = 1, hepatite B chronique AgHBe negatif = 5, immunotolerant de plus de 30 ans = 1 et co-infection VIH = 3). Le traitement a effectivement debute pour 8 des 10 sujets eligibles(Tenofovir n = 5, Entecavir n = 2 et Interferon n = 1). Conclusion Notre etude a retrouve une prevalence de l’HBC deux fois plus elevee que dans la population generale en France, et environ 40 % des sujets depistes positifs n’ont pas integre la cascade de soin (en particulier a ses stades precoces). Ces donnees suggerent qu’il est important d’augmenter l’adhesion au soin apres un depistage en CeGIDD afin d’optimiser les differentes etapes de la prise en charge de l’HBC en France.

International audience; Background: The preferred regimen for HIV post-exposure prophylaxis (PEP) is based mainly on safety and tolerability because it is given to immunocompetent people without HIV infection for a limited time (28 days). The frequency of adverse events (AEs) may be > 60%. Although AEs are generally not severe, they can lead to lack of adherence and failure to complete the regimen. We evaluated the co-formulation elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (Stribild ®) prescribed as one pill taken once daily for HIV PEP in terms of tolerability and adherence.MethodsThis was a prospective cohort study conducted in one hospital in Paris (April to December 2015. Each participant receiving the PEP treatment (FTC-150 mg/TDF-245 mg/elvitegravir-200 mg/cobicistat 150 mg once daily) at the pharmacy of the hospital were recruited consecutively. A clinical visit was planned at 8 weeks after sexual exposure. Reminders were sent to participants who missed the appointment. A standardized questionnaire was administered to evaluate completeness and tolerability at week 8.ResultsOverall, 284 participants (86% men; 80% MSM; median age 30 years) were prescribed Stribild®; 50 stopped after reassessment of risk. Among 234 participants who effectively received PEP, 215 (92%) completed 28 days of PEP with only three who switched from Stribild® to another PEP because of side effects. More than 60% of participants reported at least one AE, which were mild to moderate. Fatigue, central neurological and abdominal side effects were the most frequently reported.ConclusionsStribild® seems to be a good option for HIV PEP due to the easiness of use, the side effects profile and the high completion rate.

International audience; Physicians play a primary role in vaccination of the population. Strong initial training of medical students is therefore essential to enable them to fulfill this role. This cross-sectional nationwide online survey conducted between September 2015 and January 2016 obtained 2,118 completed surveys from 6,690 eligible respondents (response rate, 32%) at 27 of 32 medical schools in France regarding their education about vaccination. The data were analyzed in April-June 2016. The survey covered their knowledge, attitudes, practices, and perceptions, and assessed their level of perceived preparedness for their future practice as interns. Around a third of the students (n=708, 34%) felt insufficiently prepared for questions about vaccination, especially for communicating with patients on side effects (n=1,381, 66%) and strategies to respond to vaccine hesitancy (n=1,217, 58%). The mean knowledge score was 26/45 (SD=7.9). Lecture courses, which are the main education method used in French medical schools (1,891/5,660 responses, 33%), were considered effective by only 11% of students (693/6,155 responses), whereas practical training was significantly associated with better perceived preparedness (p

We conducted a study on 140 patients who sought advice at hospital after a non-occupational exposure. The full 28-day course of prophylactic antiretroviral therapy was completed by 109 patients. No HIV contamination was observed. Factors associated with suboptimal adherence were African ethnicity [odds ratio (OR) 13.3, 2.02-87.54] and oral sexual intercourse (OR 8.35, 1.66-41.99). Compliance with prophylactic antiretroviral therapy can be increased by addressing social and psychological barriers to adherence.

Cytomegalovirus (CMV) infection in immunosuppressed patients is associated with mortality if treatment is not prescribed. Strategies for the prevention of CMV disease is very important to establish. The choice of a strategy depends on epidemiologic factors (CMV-positivity of the patient or of the donor if transplantation), on the type of immunosuppression (allogeneic bone marrow transplantation, solid organ transplantation, HIV infected patients, long-term corticosteroid therapy). Several strategies for prevention can be proposed : prophylaxis for all patients, prophylaxis only for patients at high-risk, preemptive therapy when antigenemia or PCR (leucocytes or plasma) are positive, secondary prophylaxis. A treatment is proposed, except for CMV-negative patient, and CMV-negative donor if transplantation. It can be intravenous and/or oral ganciclovir, intravenous acyclovir or oral valaciclovir. Valganciclovir is an oral prodrug of ganciclovir that can be used in HIV patients with CMV disease. The strategy employed must have the better efficacy but quality of life and cost-effectivness have to be considered. Clinical evaluation is useful to determine the more adapted strategy.

OBJECTIVE The impact of early-untreated HIV infection on chronic hepatitis C was determined in a case-control study, aimed at limiting factors associated with the progression of immunodeficiency. METHODS HIV-infected patients attending for a medical examination during 1995-1996 were systematically screened for: previous intravenous drug use without other HIV or Hepatitis C virus (HCV) risk factor, CD4 cell count > 200/microl, no AIDS, no antiretroviral treatment, positive anti-HCV antibody, negative hepatitis B surface antigen, abnormal aminotransferase activity. Thirty-eight consecutive eligible HIV-infected patients (cases) were included. Thirty-eight HCV-infected patients without HIV infection whose unique risk factor was intravenous drug use (controls) were paired to cases according to age, sex, and duration of HCV infection. RESULTS Cases and controls had similar ages, sex ratios, duration of HCV infection, and alcohol intake. They were infected predominantly by genotypes 1 and 3. Viraemia was higher in cases than in controls. METAVIR histological scores of activity and fibrosis in cases versus controls were 2.2 +/- 0.8 versus 1.6 +/- 0.7 (P = 0.0008) and 1.8 +/- 1 versus 1.5 +/- 0.8 (P = 0.06), respectively. The percentage of cirrhosis was higher in cases, without reaching statistical difference. The progression rate of fibrosis was higher in cases. Age at contamination and METAVIR activity score were significantly associated with the progression of fibrosis in cases. CONCLUSION Early-untreated HIV infection is associated with higher HCV viraemia and more severe liver injury in intravenous drug users with chronic hepatitis C.

We designed a cohort in order to assess the long-term effects of triple-drug antiretroviral combinations in 608 patients infected with human immunodeficiency virus type 1 (HIV-1). We recruited patients who had been previously treated with nucleoside analogues as well as treatment-naive patients who were starting triple-drug antiretroviral combinations consisting of nucleoside analogues, either alone or in combination with a protease inhibitor. After a median follow-up time of 22 months, the incidence rates of acquired immune deficiency syndrome-defining events and death were, respectively, 6.9 (95% confidence interval [CI], 5.3-8.8) and 2.9 (95% CI, 1.9-4.2) per 100 person-years. Advanced clinical stage of disease (P=.004), a low CD4(+) cell count (P=.002), and a low quality-of-life score (P=.001) at baseline were independent predictors of clinical progression. The initial triple-drug combination was modified a total of 647 times in 321 patients. The only independent predictor of treatment modification was previous exposure to a nucleoside analogue in patients who did not receive a new nucleoside analogue at inclusion (P=.001). Plasma HIV RNA values below 500 copies/mL were obtained in 88% of the treatment-naive patients and in 57% of the previously treated patients (P or = 1 new nucleoside analogue at enrollment, previously treated patients who did not receive a new nucleoside analogue at enrollment were twice as likely to have plasma HIV RNA values >500 copies/mL at the last visit (adjusted odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.8), and the antiretroviral-naive patients were significantly less likely to have plasma HIV RNA values >500 copies/mL at the last visit (adjusted OR, 0.2; 95% CI, 0.1-0.4).

Objectives : (1) To determine the incidence and outcome of Pseudornonas aeruginosa infection in HIV-infected patients. (2) To study the antimicrobial susceptibility of P aeruginosa isolates in this particular population. (3) To identify risk factors for these infections. Patients and Methods : a retrospective case-control study performed in a 28-bed infectious-diseases unit in a 940-bed university hospital. All cases were defined as HIV-infected patients with severe infections due to P aeruginosa , including bacteriemia, lower or upper respiratory tract infections, infections related to a central venous catheter, and cutaneous/muscular infection. Each case was matched with an HIV-seropositive control not infected by P. aeruginosa and hospitalized on the same dates as the cases. Results : one thousand and thirty-five HIV-infected patients were hospitalized during the study period. A first severe P. aeruginosa infection was documented in 41 patients, giving an overall annual incidence note of 2.51 episodes per 100 admissions. Forty of the 41 case notes were available for analysis. They consisted of 17 cases of bacteraemia, four upper respiratory tract infections, 10 lower respiratory tract infections, three catheter-related infections, and six cutaneous/muscular infections. Of these 40 cases, 60% were nosocomial and the remainder were community-acquired. The overall mortality rate was 22% (47% in bacteraemic forms). Twenty five percent of patients relapsed after an average of 37 days. The case-control comparison showed that AIDS was more frequent among the cases (92% vs. 74%, P = 0.04 ), who also had a lower PN count ( P = 0.005 ), and a lower CD4 cell count (15.7 ± 18.8/mm 3 vs. 115 ± 211/mm 3 ; P = 0.0007 ). The number of days spent in hospital in the previous 3 months (29.3 ± 20.7 vs. 19.7 ± 14, P = 0.04) was significantly higher among the cases. In a multivariate analysis, examining treatments received in the previous month, only co-trimoxazole [OR = 5.5 (1.1-26.9)], penicillins [OR = 5.2 (1.1-25.3)], steroids [OR = 5.5, (1.2-25.5)] and a CD4 cell count below 50/mm 3 [OR = 13.2 (1.4-129.4)] were identified as risk factors. Conclusion : P. aeruginosa infection is a not frequent bacterial disease in highly immunodeficient HIV-infected patients. It is frequently fatal and must be borne in mind in the advanced stages of HIV disease, especially when patients have received co-trimoxazole (trianthoprim-sulphametboxazole), penicillins or steroids.

We describe 12 cases of AIDS-related primary pulmonary lymphoma occurring between 1986 and 1996 in a large French cohort of HIV-infected patients. Diagnostic criteria were: (1) histologically proven lymphomatous pulmonary involvement; (2) absence of mediastinal and/or hilar adenopathy on chest radiography; (3) absence of extrathoracic lymphoma extension. All patients were severely immunodeficient at the time of diagnosis. All but one patient presented with B and/or nonspecific respiratory symptoms. Chest radiography showed one or more marginated nodule(s) or large mass. CT scan showed a cavitary lesion in five patients. No lymph node enlargement or specific pleural effusion was detected. Transthoracic needle biopsies were performed in 10 patients and avoided open-lung biopsy for the diagnosis of lymphoma in five patients. All but one of the primary pulmonary lymphoma were high-grade B-cell non-Hodgkin's lymphomas. Using antilatent membrane protein-1 antibodies and an Epstein-Barr-Virus-encoded RNA transcript-specific probe, latent EBV infection of tumor cells was demonstrated in every case. All but one of the patients received chemotherapy. The median survival time was 4 mo, and no patient was still alive at the cut-off date for this analysis. Progessive pulmonary lymphoma was the main cause of death, but infections were also frequent.

Amphotericin B, alone or combined with flucytosine, is the reference curative treatment for neuromeningeal cryptococcosis associated with the acquired immune deficiency syndrome (AIDS). Treatment of non-meningeal forms is less well standardized. Out of 75 human immunodeficiency virus (HIV)-infected patients with cryptococcosis, 16 had no meningeal involvement. One died before receiving any treatment, another received amphotericine B and recovered, and the remaining 14 received curative therapy with fluconazole (200–400 mg/day); 11 of the latter entered complete remission, while three deteriorated during the first week of treatment but recovered on amphotericin B combined, in two cases, with fluconazole. Only one relapse occurred during maintenance treatment with low-dose fluconazole (100 mg/day). No adverse effects of fluconazole treatment were observed. One of the patients on amphotericin B developed acute renal impairment requiring drug withdrawal. These results suggest that first-line fluconazole therapy is effective and well tolerated in patients with AIDS-associated non meningeal cryptococcosis.

The outcome of bacterial bloodstream infections during pregnancy has greatly improved over the last few decades. However, there are no recent data on the characteristics of bacteremia in pregnant women. The aim of this study was to describe clinical and microbiological features of bacteremia and to assess maternal and fetal outcome. This retrospective study was conducted in the obstetrics departments of five teaching hospitals in Paris, France, from 2005 to 2009. The incidence of bacteremia was 0.3%. The most common sources of bacteremia were chorioamnionitis (47%) and the most common pathogen isolated was Escherichia coli. Empirical antimicrobial therapy was inappropriate in 29% of bacteremia cases, mostly (65%) when secondary to infection with an aminopenicillin-resistant microorganism. Bacteremia during pregnancy was associated with a 10% fetal mortality. Bacteremia during pregnancy is a rare occurrence, but it is associated with an unexpectedly poor fetal outcome and a high mortality rate.

International audience; 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.

purpose: Acquired immunodeficiency syndrome (AIDS)-associated invasive aspergillosis (IA) is a rare condition, which is mainly reported as isolated cases either antemortem or at autopsy. The role of AIDS itself is controversial, because many of the reported patients exhibited the classic risk factors such as neutropenia and steroid therapy. The aims of this study were to report 33 patients with IA during AIDS and their outcome, focusing on the risk factors and the value of diagnostic procedures. patients and methods: Thirty-three patients from 17 different medical centers in France were retrospectively included in the study. For pulmonary IA, we defined two types of patients: those with "confirmed IA," describing all the patients with histologically proven disease, and those with "probable IA," who had the development of a new pulmonary infiltrate on chest radiograph and a positive bronchoalveolar lavage (BAL) fluid culture for Aspergillus species without identification of other pathogens. For extra-pulmonary IA, the diagnostic criteria included both positive histology and culture. results: Of the 33 cases included in this series, 91% were recorded during the last 3 years (1989 to 1991), suggesting that aspergillosis is an emerging complication in AIDS. Approximately 50% of the patients did not exhibit any classic risk factor, i.e., neutropenia and steroid treatment; almost all patients had a CD4 cell count less than 50/mm 3 . The mycologic culture from BAL was the method of choice for the diagnosis of invasive pulmonary disease because it was known to correlate well with histology findings obtained either antemortem or postmortem. Of 28 patients with a positive BAL culture for Aspergillus , 15 underwent a biopsy or autopsy and 14 were positive at histology. Serum antigen detection was positive in only 4 of 16 tested patients. Clinical and radiologic signs did not differ from those observed in neutropenic patients without human immunodeficiency virus, except for the higher incidence of neurologic complications in AIDS. Interestingly, we observed three cases of invasive necrotizing tracheobronchial aspergillosis with acute dyspnea and wheezing. The use of amphotericin B (0.5 mg/kg/d) and/or itraconazole (200 to 600 mg/d) was most often unsuccessful. Only four patients experienced clinical and radiologic improvement. The mean interval between the diagnosis of IA and death was 8 weeks (range: 3 days to 13 months). conclusions: This study suggests that aspergillosis is an important life-threatening condition in the advanced stage of AIDS. It requires an early diagnosis with BAL fluid culture and careful therapeutic evaluation.

We conducted a descriptive study in 9 cases of acute hepatitis A diagnosed in patients with human immunodeficiency virus (HIV). Despite the small number of cases studied, the results indicate that moderate HIV infection does not impair the natural history of acute hepatitis A.

OBJECTIVE To evaluate the efficacy and tolerance of vapreotide, a new somatostatin analogue, in the treatment of refractory AIDS-related diarrhoea. DESIGN An open, non-comparative pilot trial. SETTING The trial was conducted in 10 medical centres in France. PATIENTS, PARTICIPANTS Thirty-four AIDS patients with chronic diarrhoea unresponsive to conventional antidiarrhoeal therapy were enrolled. Cryptosporidiosis was diagnosed in 21 out of 30 evaluable patients. Mean number of stools prior to therapy was 10.1 +/- 4.9 per day (range, 3-20 stools per day). INTERVENTION After initial baseline studies, patients received subcutaneous vapreotide at escalating doses of 400 (23 patients) or 500 micrograms (seven patients), between two and six times daily. MAIN OUTCOME MEASURES Efficacy was assessed after 14 days of therapy, when it was found to be effective. Responders were offered the opportunity to continue receiving therapy. RESULTS Four patients demonstrated a complete response and 12 a partial response with greater than 50% reduction in daily stool emission. Fourteen patients did not respond to doses up to 2400 micrograms/day. Patients with conditions other than cryptosporidiosis had a significantly higher probability of response (P = 0.013), as did those with milder diarrhoea (less than 10 stools per day). Median duration of response was 1.5 months (range, 0.5-5 months); relapse occurred in five out of eight responders despite maintenance therapy. Toxicity was minimal. CONCLUSIONS We conclude that AIDS patients with diarrhoea not caused by Cryptosporidium may benefit from vapreotide therapy.

Summary Neurological complications are particularly common during HIV infection. Among various opportunistic diseases, cytomegalovirus (CMV) is one of the most frequent causes of central and peripheral neurological manifestations. Previously, there have been several reports of cranial nerve infection by CMV, but to our knowledge, no cases of auditory nerve involvement have been described. We report two cases in which CMV infection was revealed by involvement of the VIII th cranial nerves. Cytomegalovirus (CMV) infection is frequent in severely immunodeficient patients infected by human immunodeficiency virus (HIV). The main targets of CMV are the retina, gastrointestinal tract and central nervous system. We describe two cases in which neurologic CMV infection was revealed by hearing loss.

Our aim was to identify factors predisposing HIV-infected patients on long-term antiretroviral therapy (ART) to major hypertriglyceridemia (HTG). We conducted a retrospective, casecontrol study involving 76 HIV-infected patients with HTG, defined by 12-hour fasting plasma triglyceride (TG) > 4.5 mmol/l on at least one occasion, and 150 HIV-infected matched control patients with TG consistently below 1.8 mmol/l. Patients coinfected by the hepatitis C virus appeared to be protected from HTG. In addition to known predisposing factors for HTG in HIV-infected patients (ART and immune/viral status), patients with a history of excess body weight were twice as likely to have HTG (odds ratio [OR] 2.8, 95% confidence interval [CI]: 1.1–6.9); HTG was also more frequent in patients who had a first-degree relative with cardiovascular disease (CVD) or a major risk factor for CVD (OR = 3.6, CI: 1.3–9.9). By identifying subgroups of highly predisposed patients, appropriate lifestyle and dietary measures could be recommended on ART initiation.

Background: Human Immunodeficiency Virus (HIV) infection is associated with an increased risk of classical Hodgkin (cHL) and non-Hodgkin lymphomas (NHL). In the combined antiretroviral therapy (cART) era, while the incidence of NHL has declined, HL incidence has remained stable. In comparison to their HIV-negative counterpart, HIV-associated HLs present frequent high-risk characteristics: 1- mixed cellularity histological subtype, 2- advanced stage, presence of B symptoms and higher International Prognostic Score (IPS). Methods: The national prospective cohort of HIV-related lymphomas (ANRS CO16 Lymphovir cohort sponsored by Inserm-ANRS) enrolled adult patients in 40 centers since July 2008. Pathological materials were centralized and reviewed. Diagnoses were based on World Health Organization criteria. Patients have been followed every 6 months during 5 years. HIV HL patients were compared to a series of HIV-negative adult patients consecutively diagnosed with HL during the same period in Paris Saint-Louis hospital. Results: Among 159 HIV-infected patients, 68 (43%) were diagnosed with cHL. Mixed cellularity (MC) subtype was predominant (n=42), followed by nodular sclerosing (11). Fifteen cases could not be subclassified mainly because of small needle biopsies. Median age was 44 years (ranging from 20 to 65), male/female ratio was 5.8. Most patients (75%) had advanced clinical stage (III/IV). HIV infection had been diagnosed for a median of 13 years (maximum of 26 years) before the diagnosis of cHL. Median CD4 T-cell count was 380/μl (range 37-1742) and plasma HIV RNA was < 50 in 78% of the patients. All except one patient had been treated with cART prior to cHL diagnosis. They were all treated with cART after diagnosis. Front-line chemotherapy with standard anthracyclin based regimen (ABVD) was given to 64 out of 68 patients, BEACOPP in 4 patients. ABVD was followed by radiotherapy in limited stages. Five patients died from early disease progression (n=2), sepsis during chemotherapy (1) and after relapse (2). Two-year overall survival and Progression Free Survivals (PFS) were 94% [95%CI 88, 100] and 89% [82, 97], respectively. The only factor associated with PFS was age with a relative risk of 8.09 [0.97; 67.18] above 45 years (Table). IPS and CD4 count were not significantly associated with PFS. In comparison with HIV-negative patients, patients with HIV infection displayed higher risk features for all prognostic factors of HL (older age, male predominance, MC subtype, more advanced stages, lower lymphocytic counts). Treatment of HIV-negative patients was similar to HIV-positive patients: ABVD (79%), BEACOPP (21%), with addition of radiotherapy in limited stages. Overall, the outcomes of the HIV-infected patients did not differ significantly from those of HIV-negative patients (Figure). Conclusion : Although high risk features still predominate in HIV-HL, the prognostic of these patients has markedly improved in the recent cART era. We report 2-years OS and PFS of 94% and 89%, respectively, in patients mainly treated with cART and ABVD. The outcome of HL in HIV infected patients now resembles to those of non HIV infected patients. Table: Univariate analysis of Progression Free Survival in HIV associated Hodgkin Lymphoma (Cox model) (N=68) N Progression or Death, N RR 95 % CI p-value Gender 0.95 F 9 1 1 M 59 6 0.94 [0.11 ; 7.77] Age 0.05 =40 18 1 1 0.2 45 4 1 ≤0.2 21 3 1.64 [0.37 ; 7.32] RR: Relative Risk CI: Confidency interval *: 3 missing values **: 8 missing values ***: 2 missing values Median follow-up: HIV(-) cHL: 37 months (IQR=37) Lymphovir: 33 months (IQR=34) 2- year PFS: HIV(-) cHL: 0.86 CI95%=[ 0.82, 0.90 ] Lymphovir: 0.89 CI95%=[ 0.82, 0.97 ] Figure: Progression free survival (PFS) of HIV associated Hodgkin’s Lymphoma (N= 68) compared with HIV negative patients (N=336) Figure:. Progression free survival (PFS) of HIV associated Hodgkin’s Lymphoma (N= 68) compared with HIV negative patients (N=336) IQR: Interquartile range CI: Confidency interval Disclosures Brice: Seattle Genetics, Inc.: Research Funding; Takeda Pharmaceuticals International Co.: Honoraria, Research Funding; Roche: Honoraria.

International audience

A retrospective analysis of all the cases of Clostridium difficile-associated diarrhea (CDAD) in hospitalized patients infected with HIV was performed over a 52-month period to assess the incidence, epidemiology, and risk factors of CDAD. A case of CDAD was defined as a patient with diarrhea and a positive stool cytotoxin B assay. Sixty-seven cases of CDAD were recorded in HIV-infected patients between January 1991 and April 1995. The annual incidence of CDAD ranged from 1.7 to 6.4 per 100 HIV-infected patients discharged from hospital. The 67 CDAD cases included 48 (72%) first episodes and 19 (28%) relapses. Serogroup C accounted for 69% of strains from initial episodes of CDAD. To identify risk factors for CDAD, 34 HIV-infected patients with a first episode were compared with 66 HIV-infected controls matched for the length of hospital stay. Three independent factors remained significantly associated with CDAD among HIV-infected patients: CD4(+) cell counts

To determine causes, incidence and factors associated with infections in neutropenic [polymorphonuclear neutrophil (PMN), 1000 x 10(6)/l] HIV-infected patients.Prospective study.Infectious disease service of a 1000-bed university teaching hospital in Paris, France.HIV-infected patients with a PMN count of1000 x 10(6)/l confirmed on two occasions were included in the study. Baseline characteristics, cause of neutropenia and occurrence of infectious episodes were analysed.The cause of neutropenia was lymphoma in four cases (6.5%), antineoplastic chemotherapy in seven (11.3%), zidovudine in 32 (51%), trimethoprim-sulphamethoxazole (TMP-SMX) in 28 (45%) and ganciclovir in 11 (18%). Fifteen patients (24%) developed infectious complications. Neutropenia induced by chemotherapy or lymphoma was more frequently complicate by infectious episodes (P = 0.02). Neutropenia in the previous 3 months (P = 0.05), presence of a central venous catheter (P = 0.05) and a trough PMN count (P = 0.02) were the three risk factors of infection retained in a logistic model.Neutropenia induced by zidovudine, gangiclovir or TMP-SMX, are less complicated by infectious episodes than neutropenia induced by antineoplastic chemotherapy. Overall, infectious episodes in neutropenic HIV-infected patients appear lower than in patients with haemobiologic malignancies.

The presence of human herpesvirus 8 (HHV-8) DNA sequences was sought by polymerase chain reaction (PCR) in peripheral blood mononuclear cells of 4 groups : 6 human immunodeficiency virus (HIV)-infected persons with well-defined dates of seroconversion, during the period between the diagnosis of HIV infection and the appearance of Kaposi's sarcoma (KS) ; 45 HIV-positive persons with no symptoms of HIV infection ; 11 AIDS patients with KS ; and 14 AIDS patients without KS. HHV-8 DNA PCR was positive in 3 of the 6 patients during HIV infection preceding the appearance of KS and in all but 1 of 11 AIDS patients with KS. HHV-8 DNA PCR was negative in all but 1 of the 45 HIV-positive persons with no symptoms of infection and in all but 1 AIDS patient without KS. These results indicate that HHV-8 DNA may be detected several years before the occurrence of KS in HIV-infected subjects.

International audience; We conducted a retrospective study of all hospitalized human immunodeficiency virus (HIV)-infected patients from whom a strain of Streptococcus pneumoniae was isolated (n = 45) between January 1992 and September 1994, in order to determine the clinical manifestations and outcome of and risk factors for infection by S. pneumoniae with decreased susceptibility to penicillin G. Such strains were isolated from 14 patients (31%), of whom 8 had pneumonia, 2 had bronchial superinfection, 2 had sinusitis, and 2 were colonized. All infected patients made a clinical recovery regardless of the MIC of the isolate. Indexes of HIV disease stage (CD4+ cell count and p24 antigenemia), antiretroviral treatment, and hospital admission in the previous 3 months did not influence the susceptibility of the isolates. For HIV-infected patients, treatment with antibacterial agents--particularly trimethoprim-sulfamethoxazole--in the previous 3 months is associated with an increased risk for isolation of S. pneumoniae with decreased susceptibility to penicillin G (relative risk, 5.0; 95% confidence interval, 1.9-13.3).

International audience; Since the beginning of the AIDS epidemic, Cryptosporidium has emerged as a pathogen responsible for diarrhea in humans. Cryptosporidiosis confined to the respiratory tract has been documented only rarely in humans. An HIV-infected patient is described here, who developed pulmonary and intestinal cryptosporidiosis. Lung involvement was proven by biopsy, which also revealed bronchiolitis but no other pathogens. The patient died of respiratory failure 2 months after the onset of respiratory symptoms.

International audience; We reviewed the records of 85 patients infected with both human immunodeficiency virus and Cryptococcus neoformans. Twenty-seven patients (32%) had pulmonary cryptococcosis. C. neoformans was cultured from bronchoalveolar lavage (BAL) or pleural fluid in 25 cases; the remaining two patients had cryptococcal antigen (CA) detected in BAL fluid and C. neoformans cultured from other sites. All but one of the 27 patients had detectable CA in serum. The CD4+ lymphocyte count was low in all cases (median, 24/mm3). Clinical manifestations of pulmonary cryptococcosis included fever (94%), cough (71%), dyspnea (7%), expectoration (4%), chest pain (2%), and hemoptysis (1%). Diffuse interstitial opacities (70.5%), focal interstitial abnormalities, alveolar opacities, adenopathies, cavitary lesions, and pleural effusions were evident. Outcome was poor (mean survival time, 23 weeks) despite treatment. Patients with localized pulmonary cryptococcosis appeared to have a higher CD4+ lymphocyte count, an earlier diagnosis, lower serum CA titers, fewer previous or concomitant infections, and a better prognosis than patients with disseminated cryptococcosis.

Abstract 2147 Background: Human Immunodeficiency Virus (HIV) infection is associated with an increased risk of Hodgkin lymphoma (HL) and B-cell non-Hodgkin lymphoma (NHL). Increased risk of NHL is strongly correlated to the severity of the underlying immunodeficiency. Introduction of combined antiretroviral therapy (cART) has reduced the incidence of NHL -but not of HL's- among HIV-infected individuals. Outcomes are reported to be poorer among HIV-infected patients with HL or NHL than among non-HIV-infected patients. We carry out a cohort with the aim to study the characteristics and outcome of HIV-related lymphomas. Methods: The multicentric prospective Cohort of HIV related lymphomas (ANRS-CO16 Lymphovir cohort) enrolled 116 adult patients in 32 centers between October 2007 and April 2012. Investigations were performed after approval of the ethic committee. Patients were included at diagnosis of lymphoma (n=108) or at first relapse (1 HL, 7 NHL). Data collection concerned HIV infection history, clinical, biological and histological presentation, treatment and evolution of lymphoma. Pathological materials were centralized and 91 cases were reviewed. Diagnoses were based on World Health Organization criteria. Each patient was followed every 6 months during 5 years. Results: Among the 116 patients, 39.7% (46) were diagnosed with HL and 60.3% (70) with NHL. Median age was 43.5 years (ranging from 20 to 61) among patients with HL and 47 years (23 to 67) among those with NHL. Gender (male/female) ratio was 8.2 (41/5) among patients with HL, 1.7 (44/26) among those with NHL. The histological distribution of NHL were diffuse large B-cell lymphoma (DLBCL) 54.3% (38), Burkitt lymphomas (BL) 18.6% (13), plasmablastic lymphoma 10% (7), marginal zone/lymphoplasmocytic lymphoma 7.1% (5), others 10%: PTLD- like lymphoma (2), primary effusion lymphoma (1), follicular lymphoma (1), anaplastic lymphoma (1), unclassified (2). There was a predominance of clinical stages III/IV versus I/II among HL (76.7%, 33/43) and NHL patients (73.5%, 50/68). Among patients with DLBCL, LDH level was elevated in 68.4% (26/38) and performance status altered (2–4 versus 0–1) in 38.5% (15/39). HIV infection had been diagnosed for a median of 151 months (0 to 312) among HL patients and 117 (0 to 327) among those with NHL. The interval between diagnoses of HIV infection and lymphoma was shorter than 3 months for 2 patients with HL and 13 with NHL. All other patients except 6 NHL patients had been treated with ART at diagnosis of lymphoma. Median durations of ARV were 128 months (2 to 238) among HL patients and 119 months (1 to 236) among those with NHL. Patients with HL had a median CD4 T-cell count at diagnosis of lymphoma of 353/mm3 (range 37–1120), those with NHL, 261/mm3 (range 7–1322)]. The median interval between lymphoma occurrence and last follow-up was 21 months (range 0–41). During follow-up, all patients were treated with ARV. Among first-line HL patients, 39 out of 40 were treated with ABVD. Out of 40 patients with DLBCL or BL, 30 received chemotherapies combined with rituximab. At 24 months, overall survival is 95% among patients with HL and 78% among those with NHL (Figure 1). Two HL patients died during follow-up: one HL patient included in relapse from progression, another from a second cancer. Sixteen NHL patients died during follow-up: there were 10 early deaths ( Conclusions: The present study points out the high proportion of HL among HIV infection with lymphoma in the cART era and their favourable outcome compared to previous reports. This study also strengthens the heterogeneity of HIV-related lymphomas and the frequency of early deaths among patients with NHL. Disclosures: No relevant conflicts of interest to declare.

Clostridium difficile is now well-established as the main cause of antibiotic-associated diarrhoea or colitis. Nosocomial acquisition of C. difficile has been described among various immunocompromised patient populations. From January to December 1992, 19 cases of antibiotic-associated diarrhoea occurred among AIDS patients in the same ward of a hospital. They all harboured C. difficile in their stools. All the strains were retrospectively typed by the random amplified polymorphic DNA (RAPD) method using two different 10-mer oligonucleotides. Twenty-five C. difficile strains (isolated from 15 patients) yielded the same RAPD pattern, suggesting they were identical. The timing and location of infections indicated that transmission of this highly resistant spore-forming bacterium can occur not only by direct patient-patient contact but also at a distance in time and space. This is the first report of an outbreak of C. difficile-associated diarrhoea in AIDS patients. Epidemiological markers are needed to recognize and control common-source outbreaks; RAPD assay is a simple, rapid and effective way of distinguishing isolates of C. difficile.

No predictive parameters of in utero or perinatal vertical transmission of HIV to newborns are known at present. Vertical transmission may be related to several biological parameters of maternal HIV infection: (1) immunological parameters (neutralizing antibodies); (2) the concentration of viral particles and/or infected cells; and (3) the selection of HIV subspecies of particular cellular tropism. The present study was designed to examine the relationship between cellular viral burden and transmission, and between maternal viral burden and CD4+ cell count and clinical status at delivery.We investigated mother-to-infant HIV-1 transmission at delivery in a cohort of 51 pairs of mothers and newborns. Twelve infants were HIV-infected, as determined by successive polymerase chain reaction and culture determinations within the first 6 months of life, and nine of these were diagnosed as HIV-infected during the first week of life. We determined peripheral blood mononuclear cell proviral DNA burden using a quantitative polymerase chain reaction assay. Polymerase chain reaction was performed in the HIV-1 gag gene, using [32P]-end-labelled primers. External standard DNA samples were from the 85-14 F2 cell line, which contains a unique defective proviral DNA genome.There was a linear relationship between the logarithms of c.p.m. and the number of HIV-1 DNA copies.We have previously reported that the number of HIV provirus copies in maternal blood cells is related to transmission of the virus. Quantification of the HIV provirus by polymerase chain reaction may be used as a predictive parameter of vertical transmission if accompanied by an exhaustive clinical and biological follow-up during pregnancy.

International audience; A reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect a human cytomegalovirus (HCMV) late mRNA in peripheral blood leukocytes (PBL) of 102 human immunodeficiency virus-infected individuals. The clinical value of this new technique for the diagnosis of acute HCMV disease was evaluated in comparison with viral culture and direct amplification of viral DNA (PCR). The sensitivity of the RT-PCR was slightly lower than that of the two other methods, but its specificity was 94%, compared to 55 and 32% for culture and PCR, respectively. Transcription of this late mRNA is linked to viral replication, and its detection in PBL confirms that these cells can support a complete viral cycle. The relationship between complete replicative cycles and HCMV disease makes RT-PCR a useful clinical tool.