Polymeric mannosides prevent DC-SIGN-mediated cell-infection by cytomegalovirus.

Human cytomegalovirus (HCMV) is a beta-herpesvirus with a high prevalence in the population. HCMV is asymptomatic for immunocompetent adults but is a leading cause of morbidity for new born and immunocompromised patients. It was recently shown that the envelope glycoprotein B (gB) of HCMV interacts with the Dendritic Cell-Specific ICAM-3 Grabbing Non integrin (DC-SIGN) to infect the host. In this work we developed a set of DC-SIGN blockers based on mono-, di-, tetra and polyvalent mannosides. The multivalent mannosides were designed to interact with the carbohydrate recognition domains of DC-SIGN in a chelate or bind and recapture process, and represent the first chemical antiadhesives of HCMV reported so far. Polymeric dextrans coated with triazolylheptylmannoside (THM) ligands were highly potent, blocking the gB and DC-SIGN interaction at nanomolar concentrations. The compounds were further assessed for their ability to prevent the DC-SIGN mediated HCMV infection of dendritic cells. A dextran polymer coated with an average of 902 THM ligands showed an outstanding effect in blocking the HCMV trans-infection with IC50 values down to the picomolar range (nanomolar when expressed in THM concentration). Each THM moiety on the polymer surpassed the antiadhesive effect of the methylmannoside reference by more than four orders of magnitude. The compound proved non-cytotoxic at the high concentration of 2 mM and therefore represents an interesting antiadhesive candidate against HCMV and potentially against other virus hijacking dendritic cells to infect the host.

Switching to emtricitabine, tenofovir and rilpivirine as single tablet regimen in virologically suppressed HIV-1-infected patients: a cohort study.

OBJECTIVES: Emtricitabine/tenofovir/rilpivirine as a single-tablet regimen (STR) is widely used without licence in treatment-experienced patients. The purpose of this retrospective observational study was to assess viral suppression of ART-experienced patients switching to STR. METHODS: We assessed 131 pretreated patients switching to STR with HIV RNA <400 HIV-1 RNA copies/mL. The primary outcome measure was the proportion of patients at week 24 with HIV RNA <40 copies/mL. RESULTS: By week 24, eight patients had stopped STR: four because of adverse events and four for other reasons. Three virological failures were observed; among these, at least one patient developed cross-resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs), in particular with the E138K pattern. In intent-to-treat analysis, 92% of participants (120 of 131) achieved HIV RNA <40 copies/mL. Only grade 1 to 2 adverse events were observed, mainly consisting of increased liver enzymes (n=33). Systemic exposure to rilpivirine was above the usually observed steady-state levels for the 18 measurements assessed. CONCLUSIONS: Efficacy and tolerability are similar to those in treatment-naïve patients.

Comparative study of body image among dancers and anorexic girls.

In order to examine the nature of body image distortions, we studied their perceptual and idealised components using a video distortion technique to create photographs of dancers, anorexics and controls that made their bodies look larger. Each subject was then asked to adjust the photograph until it reflected her estimated and desired body size. The results show that: 1) all three groups perceived themselves to be heavier than they actually are, but the dancers had a more realistic perception of their body weight; 2) the dancers would have liked to be thinner, whereas the controls and anorexics were satisfied with their body weight; 3) the scores of the anorexic subjects were characterised by a lack of correlation between their perceptual and idealised distortions, whereas those of the dancers--and even more so those of the controls--were characterised by consistency between the two types of distortion.

[Hepatitis A seroprevalence in HIV-infected patients]. / Séroprévalence de l'hépatite A chez des patients infectés par le VIH.

OBJECTIVE: The authors had for aim to prospectively study the hepatitis A seroprevalence of an HIV-infected population, followed-up in an outpatient clinic (CISIH Strasbourg). DESIGN: Blood tests were performed on all patients from September 2003 to March 2004 to screen for hepatitis A (total antibodies with Elisa). RESULTS: The overall seroprevalence was 219/514 (56.6%), similar in male and female patients. It increased with age, especially in European patients (P = 0.003). The seroprevalence was lower in European subjects: 46.3% (while it reached 100% in sub-Saharan Africans), the prevalence was similar whatever the HIV risk group (46% in homosexual as well as in heterosexual patients, 44% in intravenous drug users). Hepatitis B or C co-infection did not increase the seroprevalence of hepatitis A. The hepatitis A seroprevalence was similar in various CD4 T cell count categories. CONCLUSIONS: Our results stress the utility of hepatitis A serology in HIV-infected patients (more than 50% of European patients are non immune), and the importance of assessing hepatitis A vaccination.

Efavirenz as a substitute for protease inhibitors in HIV-1-infected patients with undetectable plasma viral load on HAART: a median follow-up of 64 weeks.

We investigated, in a prospective cohort follow-up study, whether substituting efavirenz (EFV) for protease inhibitors (PIs) could be safe in HIV-infected patients with optimal viral suppression achieved on PI-containing regimens. In patients with undetectable plasma viral load (pVL) <50 copies/ml who were naive to therapy with nonnucleoside reverse transcriptase inhibitors (NNRTIs), PIs were replaced by EFV whereas associated nucleoside analogs (NAs) were retained. 62 patients were enrolled. Median follow-up on EFV was 64 weeks (2-88 weeks). Side effects due to EFV occurred in 48 patients. Two patients experienced a high level viral rebound due to diminished compliance; 55 (88.7%) maintained a pVL <50 copies/ml; 3 showed one episode of viremia (52-89 copies/ml); 2 stopped EFV before any VL control. Mean CD4 cell count did not change significantly. One AIDS patient experienced a single cutaneous recurrence of Kaposi's sarcoma after 40 weeks on EFV. Replacing PI with EFV in patients with optimal pVL suppression appears to be safe both virologically and immunologically.