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Background: Doravirine is a novel HIV-1 NNRTI recently shown to be non-inferior to both darunavir/ritonavir and efavirenz in combination therapy with two NRTIs in treatment-naive patients. Doravirine has an in vitro resistance profile that is distinct from other NNRTIs and retains activity against viruses containing the most frequently transmitted NNRTI mutations. Objectives: The aim of this study was to examine the prevalence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients in Europe. Methods: From 2010 to 2016, 9764 treatment-naive patients were tested for NNRTI antiretroviral drug resistance by bulk sequencing in Greece, Italy and France. We studied the prevalence of doravirine resistance-associated mutations previously identified in vitro: V106A/M, V108I, Y188L, V190S, H221Y, F227C/L/V, M230I/L, L234I, P236L, Y318F and K103N/Y181C. Results: Among 9764 sequences, 53.0% and 47.0% of patients had B and non-B subtypes, respectively. Overall, the presence of at least one doravirine resistance-associated mutation (n " 137; 1.4%) or the K103N/Y181C mutations (n " 5; 0.05%) was very rare. The most prevalent mutations were V108I (n " 62; 0.6%), Y188L (n " 18; 0.2%), H221Y (n " 18; 0.2%) and Y318F (n " 23; 0.2%). The frequency of doravirine resistance-associated mutations was similar between B and non-B subtypes. In comparison, the prevalence of rilpivirine, etravirine, nevirapine and efavirenz resistance was higher whatever algorithm was used (ANRS: 8.5%, 8.1%, 8.3% and 3.9%, respectively; Stanford: 9.9%, 10.0%, 7.5% and 9.4%, respectively). Conclusions: The prevalence of doravirine resistance-associated mutations is very low in antiretroviral-naive patients. These results are very reassuring for doravirine use in naive patients. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

The gamma delta T cell receptor (TcR) lymphocytes constitute 3-10% of human peripheral blood lymphocytes. Only a very small fraction of these cells is recognized by the delta TCS1 monoclonal antibody, directed against the V delta 1 chain of the receptor. We describe the immunological, virological and clinical data of a small group of seropositive subjects having high levels of gamma delta TcR T cells in the peripheral blood. Our flow cytometric studies show that most of these cells belong to the delta TCS1+ (V delta 1+), CD8 +/- (dim staining) subset. Patients with high gamma delta TcR T cell numbers were not characterized by the presence of an acute (IgM positive) or reactivated (as defined by high IgG titres against early antigen or IgA titres against viral capsidic antigen) Epstein-Barr virus infection. Cytomegalovirus infection was excluded by serological assays, and other herpes viral infections were not found after clinical examination. HIV p24 antigenaemia was present in two out of 11 subjects. AIDS patients had very high percentages of gamma delta TcR T cells. Altogether these data show that the selective expansion of delta TCS1+ cells in HIV1 seropositive subjects is not related to some exogenous antigen stimulation, but may be related to peculiar pathologic processes involving the immune system.

Lymphocytes bearing gamma delta T cell receptors (TCR) constitute a minor subpopulation of human peripheral blood lymphocytes. Their role and function during microbial infections are largely unknown. In 10 patients with Epstein-Barr virus-induced infectious mononucleosis, the gamma delta TCR-expressing T cell population expanded during the acute phase. These cells were largely delta TCS1-, CD4-, and CD8- but expressed activation antigens such as human leukocyte antigen-DR and CD38. The convalescent phase of infectious mononucleosis was characterized by a relative persistence of gamma delta T cells. Together these data suggest a possible role of gamma delta T cells in the control of primary Epstein-Barr virus infection in humans.

The difference between the ISS and NISS scores was determined for 1,533 inpatients consecutively admitted in 1998 in the Emergency Department of a University Hospital in São Paulo, Brazil. The average ISS was 12.49 +/- 12.72, and the average NISS was 16.99 +/- 17.60. The two predictive scores were identical in 47.75% of the patients and discrepant in 52.25%. In all cases of discrepant scores, the NISS was greater than ISS. NISS identified significantly more (42.47%) major trauma patients (scoreor = 16) than ISS (34.18%) (p0.001). For nonsurvivors the percentage of discrepant score was higher (75.68%) than for the survivors group (48.28%).

Dynamic modulation can be affected by inaccuracies when the required acceleration is larger than the highest allowed by the mechanical characteristics of the whole apparatus. In this study, inertia effects have been investigated with regard to the single absorber 1D modulation, analysing primarily how the acceleration performed by the modulating system affects the realization of 'single absorber' fluence profiles and the type of correction which could be devised. The observed percentage deviations from desired modulation at the lowest fluence coordinate of single minimum fluence profiles, when no correction is applied, were almost negligible for 'easy' modulations of the incident fluence (i.e. slow gradients); deviations became increasingly relevant as the moving absorber executed steeper gradients (a 17.6% higher dose being delivered in the minimum position when a 0.2 modulation is required). By applying the proposed corrections, the single absorber performances were improved to a satisfactory level, with a maximum deviation from desired modulation in the minima within 1.6%.

The severity of traumas in hospitalized patients was characterized by means of the Injury Severity Score (ISS) was studied prospectively. One hundred trauma patients hospitalized in a trauma referral health facility located in S. Paulo, Brazil, were analyzed. Of the total number of patients, 68 had blunt trauma and 32 penetrating trauma. As to ISS, it was discovered that 53.0% of the blunt trauma patients had mild trauma (ISS 1-15), 29.4% moderate trauma (ISS 16-24), and 17.6% showed severe trauma (ISS 25); 34.4% of the penetrating trauma patients had mild trauma, 18.7% moderate trauma and 46.9% severe trauma. The mean and standard deviations relating to the ISS of blut and penetrating trauma patients were, respectively, 14.9 +/- 8.1 and 20.8 +/- 11.0; the respective mortality rates were of 11.8% and 12.5%.

The expression of phenotypic markers on CD4 and CD8 lymphocytes during the acute and convalescent phases of Epstein Barr virus (EBV) induced infectious mononucleosis was examined by two colour flow cytometry. Activated CD8 cells constitute the major population increased during acute infectious mononucleosis; in this phase we observed a preferential expansion of the CD8 CD29+ compared to the CD8 CD45RA+ cells. Serum soluble CD8 levels were also raised during the acute phase and a correlation with CD8 CD38+ and CD8 CD29+ cell numbers was found. The convalescent phase of infectious mononucleosis was characterized by a progressive return of CD8 subset and of soluble CD8 to baseline normal values. These results demonstrate that acute EBV infection induces the expansion of a CD8 subset with peculiar surface antigenic profile.

The gamma delta T cell receptor (TcR) lymphocytes constitute 3-10% of human peripheral blood lymphocytes. Only a very small fraction of these cells is recognized by the delta TCS1 monoclonal antibody, directed against the V delta 1 chain of the receptor. We describe the immunological, virological and clinical data of a small group of seropositive subjects having high levels of gamma delta TcR T cells in the peripheral blood. Our flow cytometric studies show that most of these cells belong to the delta TCS1+ (V delta 1+), CD8 +/- (dim staining) subset. Patients with high gamma delta TcR T cell numbers were not characterized by the presence of an acute (IgM positive) or reactivated (as defined by high IgG titres against early antigen or IgA titres against viral capsidic antigen) Epstein-Barr virus infection. Cytomegalovirus infection was excluded by serological assays, and other herpes viral infections were not found after clinical examination. HIV p24 antigenaemia was present in two out of 11 subjects. AIDS patients had very high percentages of gamma delta TcR T cells. Altogether these data show that the selective expansion of delta TCS1+ cells in HIV1 seropositive subjects is not related to some exogenous antigen stimulation, but may be related to peculiar pathologic processes involving the immune system.

Lymphocytes bearing gamma delta T cell receptors (TCR) constitute a minor subpopulation of human peripheral blood lymphocytes. Their role and function during microbial infections are largely unknown. In 10 patients with Epstein-Barr virus-induced infectious mononucleosis, the gamma delta TCR-expressing T cell population expanded during the acute phase. These cells were largely delta TCS1-, CD4-, and CD8- but expressed activation antigens such as human leukocyte antigen-DR and CD38. The convalescent phase of infectious mononucleosis was characterized by a relative persistence of gamma delta T cells. Together these data suggest a possible role of gamma delta T cells in the control of primary Epstein-Barr virus infection in humans.

We have identified, in a patient with atopic dermatitis, a consistent population of peripheral blood lymphocytes expressing a CD3+ gamma/delta TCR complex, while being unreactive with CD2. Further immunofluorescence studies showed that these cells almost completely co-express CD29 and CD45RA and have high membrane levels of CD11a compared to the alpha/beta TCR T cells. Neither a genetic influence nor an acute or reactivated herpesvirus infection were found to be related to the expanded gamma/delta T-cell subpopulation. Our data confirm the previous observations regarding the presence in the peripheral blood of an expanded gamma/delta TCR, CD2- subset and show that these cells have a peculiar phenotypic profile. The reasons for this expansion are, however, still unknown.

The CD4 antigen has long been used as a surface marker for the indentification of a subset of T cells. CD4 acts also as the receptor for the Human Immunodeficiency Virus 1 HIV-1 and as a signal transducing molecule. Recently CD4 positive cells have been shown to release a soluble form of CD4 (sCD4). This molecule can interact with free gp 120 viral antigen and with serum immunoglobulins. Because of the importance of CD4 in the natural history of HIV-1 infection, we decided to monitor it's serum levels in HIV-1 seropositive subjects. sCD4 increases, on a per cell basis, in the late stages of infection, when CD4 cell counts dramatically fall and antigenemia is frequently found. Asymptomatic patients had a mean of 6 Units/ml of sCD4 every 100 CD4 T cells, while in AIDS patients we found a mean of 51 Units/ml every 100 CD4 T cells. These data suggest that sCD4 may be of value in monitoring the involvement of CD4 T cells during a pathological event.