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Introduction Despite the advent of HIV cure‐related clinical trials (HCRCT) for people living with HIV (PLWH), the risks and uncertainty involved raise ethical issues. Although research has provided insights into the levers and barriers to PLWH and physicians' participation in these trials, no information exists about stakeholders' preferences for HCRCT attributes, about the different ways PLWH and physicians value future HCRCT, or about how personal characteristics affect these preferences. The results from the present study will inform researchers' decisions about the most suitable HCRCT strategies to implement, and help them ensure ethical recruitment and well‐designed informed consent. Methods Between October 2016 and March 2017, a discrete choice experiment was conducted among 195 virally controlled PLWH and 160 physicians from 24 French HIV centres. Profiles within each group, based on individual characteristics, were obtained using hierarchical clustering. Trade‐offs between five HCRCT attributes (trial duration, consultation frequency, moderate (digestive disorders, flu‐type syndrome, fatigue) and severe (allergy, infections, risk of cancer) side effects (SE), outcomes) and utilities associated with four HCRCT candidates (latency reactivation, immunotherapy, gene therapy and a combination of latency reactivation and immunotherapy), were estimated using a mixed logit model. Results Apart from severe SE – the most decisive attribute in both groups – PLWH and physicians made different trade‐offs between HCRCT attributes, the latter being more concerned about outcomes, the former about the burden of participation (consultation frequency and moderate SE). These different trades‐offs resulted in differences in preferences regarding the four candidate HCRCT. PLWH significantly preferred immunotherapy, whereas physicians preferred immunotherapy and combined therapy. Despite the heterogeneity of characteristics within the PLWH and physician profiles, results show some homogeneity in trade‐offs and utilities regarding HCRCT. Conclusions Severe SE, not outcomes, was the most decisive attribute determining future HCRCT participation. Particular attention should be paid to providing clear information, in particular on severe SE, to potential participants. Immunotherapy would appear to be the best HCRCT candidate for both PLWH and physicians. However, if the risk of cancer could be avoided, gene therapy would become the preferred strategy for the latter and the second choice for the former.

The aim of this study was to examine the production of superantigenic toxins in vivo and in vitro in two patients with streptococcal toxic shock syndrome (TSS). In the first patient, a woman with puerperal fever and Streptococcus pyogenes peritonitis, flow cytometry of blood cells and in vitro studies of the isolate showed massive expansion of Vbeta 2-positive T cells corresponding to SpeC production. In the second case, involving a patient with streptococcal TSS and purpura fulminans following non-steroidal anti-inflammatory drug (NSAID) therapy, no Vbeta expansion of T cells was observed in vivo, but the SpeC Vbeta signature was also detected in vitro. In this latter patient, NSAID administration and/or severe disseminated infection might partly explain the absence of Vbeta T cell expansion in vivo. Combined in vivo and in vitro detection of a superantigenic toxin Vbeta signature may be useful to determine which superantigenic toxin is involved in individual cases of streptococcal TSS.

Linezolid is the first member of the new synthetic class of antibacterial agents that prevent the formation of the 70S ribosomal subunit. It represents an attractive choice in the therapeutic arsenal because it is effective against methicillin-resistant strains of Staphylococcus spp. Adverse hematological events have been reported. They are rapidly reversible after discontinuation of treatment and usually occur during treatment courses of more than 2 weeks. The advised duration of linezolid use is 28 days and the consequences of prolonged use are unknown. In addition, this drug has some dopaminergic properties that can induce the serotonin syndrome if a monoamine oxidase inhibitor is used simultaneously. Since linezolid became available for use in 2002, four cases of probable central and peripheral linezolid-induced neurotoxicity have been recorded in our unit. Two de novo peripheral neuropathies and one worsening of a preexisting toxic neuropathy have been observed. In each case, linezolid therapy was used during a prolonged duration of 8, 23, and 24 weeks, respectively. First neurological signs appeared in one case during the 2nd week of treatment and beyond the 1st month in the other cases. To date, all cases of peripheral neuropathy resulted in persistent neurological damage after discontinuation of linezolid. Assessments did not reveal any other explanation for these neurological impairments. Another case concerned a patient who developed transient encephalopathy attributed to linezolid during a coadministration with hydroxyzine. Linezolid may induce persistent peripheral neuropathy after prolonged use and may cause a transient central neurotoxicity in combination with an anticholinergic agent, such as an antihistamine. Close neurological monitoring should be recommended in prolonged linezolid therapy and coadministration of a serotonin reuptake inhibitor or antihistamine should be avoided to limit neurological adverse events.

BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age ( P =0.028), unrelated donor ( P =0.0178), stem cell source ( P =0.0001), HLA mismatching ( P =0.0022) and BU in conditioning regimen ( P =0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) ( P =0.0005) and peripheral blood stem cells ( P =0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity ( P =0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization ( P <0.0001), more RBC ( P =0.0003) and platelet transfusions ( P <0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at €2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.

Abstract Background In late 2013, France was one of the first countries to recommend initiation of combination antiretroviral therapy (cART) irrespective of CD4 cell count. Methods To assess the impact of achieving the second and third Joint United Nations Programme on HIV/AIDS 90-90-90 targets (ie, 90% of diagnosed people on sustained cART, and, of those, 90% virologically controlled) on human immunodeficiency virus (HIV) incidence, we conducted a longitudinal study to describe the epidemiology of primary HIV infection (PHI) and/or recent HIV infection (patients with CD4 cell count ≥500/mm3 at HIV diagnosis; (PRHI) between 2007 and 2017 in a large French multicenter cohort. To identify changes in trends in PHI and PRHI, we used single breakpoint linear segmented regression analysis. Results During the study period, 61 822 patients were followed in the Dat’AIDS cohort; 2027 (10.0%) had PHI and 7314 (36.1%) had PRHI. The second and third targets were reached in 2014 and 2013, respectively. The median delay between HIV diagnosis and cART initiation decreased from 9.07 (interquartile range [IQR], 1.39–33.47) months in 2007 to 0.77 (IQR, 0.37–1.60) months in 2017. A decrease in PHI (−35.1%) and PRHI (−25.4%) was observed starting in 2013. The breakpoints for PHI and PRHI were 2012.6 (95% confidence interval [CI], 2010.8–2014.4) and 2013.1 (95% CI, 2011.3–2014.8), respectively. Conclusions Our findings show that the achievements of 2 public health targets in France and the early initiation of cART were accompanied by a reduction of about one-third in PHI and PRHI between 2013 and 2017. Clinical Trials Registration NCT02898987. In France, reaching the second and third Joint United Nations Programme on HIV/AIDS 90-90-90 targets and the dramatic decrease in the time to combination antiretroviral therapy initiation were accompanied by a reduction of around one-third in primary and recent human immunodeficiency virus infections between 2013 and 2017.

We report a case of T. inkin endocarditis in a 46-year-old woman who presented with fever, cutaneous signs, and embolic manifestations nearly 4 years after a mitral valve replacement. Only nine cases of trichosporon endocarditis have been described to our knowledge, and this case report is believed to be the tenth--but it is the first one concerning T. inkin. A 46-year-old woman was admitted to our infectious diseases unit in September 1994 because of the recent onset of arthralgia, myalgia, fever, chills and sweats, and cutaneous manifestations (petechiae) on the lower limbs. She had undergone prosthetic mitral valve replacement for rheumatic valvular disease in 1991. The clinical onset of symptoms began 2 weeks before admission, with recurrence of pharyngitis; this was treated with methylprednisolone and cefpodoxime proxetil. A successful mitral valve replacement and left femoral embolectomy were performed on day 8. T. inkin was identified in both the valvular vegetation and the embolic material by cultures (in which septate hyphae with arthrospores and yeasts were noted) and by immunologic tests, which were positive for T. inkin--specific antibodies but negative for antibodies to T. mucoides and T. asahii. As soon as a mycologic diagnosis was established, three different blood samples were tested (over 1 month); antibodies to T. inkin were detected by agglutination and precipitation tests (double-diffusion and counter-electrophoresis precipitation techniques were used with strains isolated from valvular and embolic material and with the T. inkin reference strain number 15, from Institut Pasteur, Paris).

Cryptococcus neoformans is a human opportunistic fungal pathogen causing severe disseminated meningoencephalitis, mostly in patients with cellular immune defects. This species is divided into three serotypes: A, D, and the AD hybrid. Our objectives were to compare population structures of serotype A and D clinical isolates and to assess whether infections with AD hybrids differ from infections with the other serotypes. For this purpose, we analyzed 483 isolates and the corresponding clinical data from 234 patients enrolled during the CryptoA/D study or the nationwide survey on cryptococcosis in France. Isolates were characterized in terms of ploidy, serotype, mating type, and genotype, utilizing flow cytometry, serotype- and mating type-specific PCR amplifications, and multilocus sequence typing (MLST) methods. Our results suggest that C. neoformans serotypes A and D have different routes of multiplication (primarily clonal expansion versus recombination events for serotype A and serotype D, respectively) and important genomic differences. Cryptococcosis includes a high proportion of proven or probable infections (21.5%) due to a mixture of genotypes, serotypes, and/or ploidies. Multivariate analysis showed that parameters independently associated with failure to achieve cerebrospinal fluid (CSF) sterilization by week 2 were a high serum antigen titer, the lack of flucytosine during induction therapy, and the occurrence of mixed infection, while infections caused by AD hybrids were more likely to be associated with CSF sterilization. Our study provides additional evidence for the possible speciation of C. neoformans var. neoformans and grubii and highlights the importance of careful characterization of causative isolates. IMPORTANCE Cryptococcus neoformans is an environmental fungus causing severe disease, estimated to be responsible for 600,000 deaths per year worldwide. This species is divided into serotypes A and D and an AD hybrid, and these could be considered two different species and an interspecies hybrid. The objectives of our study were to compare population structures of serotype A and serotype D and to assess whether infections with AD hybrids differ from infections with serotype A or D isolates in terms of clinical presentation and outcome. For this purpose, we used clinical data and strains from patients diagnosed with cryptococcosis in France. Our results suggest that, according to the serotype, isolates have different routes of multiplication and high genomic differences, confirming the possible speciation of serotypes A and D. Furthermore, we observed a better prognosis for infections caused by AD hybrid than those caused by serotype A or D, at least for those diagnosed in France. Cryptococcus neoformans is an environmental fungus causing severe disease, estimated to be responsible for 600,000 deaths per year worldwide. This species is divided into serotypes A and D and an AD hybrid, and these could be considered two different species and an interspecies hybrid. The objectives of our study were to compare population structures of serotype A and serotype D and to assess whether infections with AD hybrids differ from infections with serotype A or D isolates in terms of clinical presentation and outcome. For this purpose, we used clinical data and strains from patients diagnosed with cryptococcosis in France. Our results suggest that, according to the serotype, isolates have different routes of multiplication and high genomic differences, confirming the possible speciation of serotypes A and D. Furthermore, we observed a better prognosis for infections caused by AD hybrid than those caused by serotype A or D, at least for those diagnosed in France.

Objectives: To determine if the interval between the last negative and the first positive HIV test is associated with demographic characteristics of HIV seroconverters. Methods: A prospective cohort of patients with HIV seroconversion enrolled in the Lyons HIV hospital database was analysed. Comparisons of demographic characteristics were performed after stratification on the duration of the interval between the last HIV negative screening test and the first HIV positive screening test, which ranged from 1 day to 24 months. Linear regression methods were used to identify the covariates associated with a negative HIV antibody test followed by a positive test. Results: Age (p=0.54), sex (p=0.78), heterosexual route of infection (p=0.78), other route (p=0.40) compared with homosexual route, and estimated year of HIV infection (p value ranged from 0.84 to 0.95) were not associated with a shorter seroconversion interval after multivariate analyses. The presence of an acute HIV illness was the only predictor of a short seroconversion interval (p=0.006) with a reduction of 84 days of the interval when it was reported. Conclusions: No selection bias for demographic characteristics of HIV seroconverters seems associated with the length of the seroconversion interval, at least for intervals ≤24 months.

The association between liver stiffness measurements (LSM) and mortality has not been fully described. In particular the effect of LSM on all-cause mortality taking sustained virological response (SVR) into account needs further study. HIV/HCV participants in the French nation-wide, prospective, multicenter ANRS CO13 HEPAVIH cohort, with ≥1 LSM by FibroScan (FS) and a detectable HCV RNA when the first valid FS was performed were included. Cox proportional hazards models with delayed entry were performed to determine factors associated with all-cause mortality. LSM and SVR were considered as time dependent covariates. 1,062 patients were included from 2005 to 2015 (69.8% men, median age 45.7 years (IQR 42.4-49.1)). 21.7% had baseline LSM >12.5 kPa. Median follow-up was 4.9 years (IQR 3.2-6.1). 727 (68.5%) were ever treated for HCV: 189 of them (26.0%) achieved SVR. 76 deaths were observed (26 liver-related, 10 HIV-related, 29 non-liver-non-HIV-related, 11 of unknown cause). At the age of 50, the mortality rate was 4.5% for patients with LSM ≤12.5 kPa and 10.8% for patients with LSM >12.5 kPa. LSM >12.5 kPa (adjusted Hazard Ratio [aHR] = 3.35 [2.06; 5.45], p<0.0001), history of HCV treatment (aHR = 0.53 [0.32; 0.90], p = 0.01) and smoking (past (aHR = 5.69 [1.56; 20.78]) and current (3.22 [0.93; 11.09]) versus never, p = 0.01) were associated with all-cause mortality independently of SVR, age, sex, alcohol use and metabolic disorders. Any LSM >12.5 kPa was strongly associated with all-cause mortality independently of SVR and other important covariates. Our results suggest that close follow-up of these patients should remain a priority even after achieving SVR.