Meropenem vs standard of care for treatment of neonatal late onset sepsis (NeoMero1): A randomised controlled trial.

Background: The early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, recruited in single centres or countries, evaluated antibiotics not in clinical use anymore and had variable inclusion/exclusion criteria and outcome measures. Moreover, antibiotic-resistant bacteria have become a major problem in many countries worldwide.

Immunogenicity and safety of yellow fever vaccine in HIV-1-infected patients.

Objectives: The objective of this study is to investigate immunogenicity and safety of the yellow fever vaccine (YFV) in HIV-infected (HIV+) patients with high CD4 T-cell counts.

Design: In this prospective, comparative study of YFV-naive adults: 40 HIV+ under antiretroviral therapy (ART) with CD4 T-cell count above 350 cells/μl and plasma HIV-RNA less than 50 copies/ml for at least 6 months and 31 HIV-negative (HIV-) received one injection of the YF-17D strain vaccine.

Methods: Serologic response was assessed by using a plaque reduction neutralizing test and YFV-specific T cells by using an INFγ-Elispot assay.

Incidence and risk factors for liver enzymes elevations in highly treatment-experienced patients switching from enfuvirtide to raltegravir: a sub-study of the ANRS-138 EASIER trial.

Background: In the ANRS EASIER trial where treatment-experienced patients switched from enfuvirtide (ENF) to raltegravir (RAL), a high incidence of transaminase elevation was reported in the RAL arm.

Methods: We compared the incidence of emergent liver enzyme elevations (LEE) of grade 2 or more among patients randomized to the maintenance ENF arm or the switch RAL arm up to W24. We also assessed the overall incidence of LEE over the 48-week duration of the trial and baseline risk factors for grade 2 or more alanine aminotransferase (ALT) elevation using univariate and multivariate analyses.

High Cure Rate With 24 Weeks of Daclatasvir-Based Quadruple Therapy in Treatment-Experienced, Null-Responder Patients With HIV/Hepatitis C Virus Genotype 1/4 Coinfection: The ANRS HC30 QUADRIH Study.

Background: Few direct anti-hepatitis C virus (HCV) agents have been studied in difficult-to-treat null responder and cirrhotic human immunodeficiency virus (HIV)-coinfected patients. Daclatasvir and asunaprevir combined with pegylated interferon/ribavirin (peg-IFN/RBV) have shown promising results in HCV-monoinfected patients.

Methods: An open-label, single-arm, phase 2 study was conducted in HIV/HCV genotype 1/4-coinfected patients who were null responders to prior peg-IFN/RBV standard therapy and on a raltegravir-based regimen with HIV RNA <400 copies/mL.

Telaprevir enhances ribavirin-induced anaemia through renal function impairment.

Background: Alterations in renal function have been described with telaprevir (TVR). We examined the relationship between ribavirin (RBV) trough concentration (C), estimated glomerular filtration rate (eGFR) and severe anaemia, before and after TVR introduction in HIV-HCV-coinfected patients included in ANRS HC26 TelapreVIH study.

Methods: 69 HIV-HCV genotype-1 coinfected patients received 4 weeks of pegylated interferon (PEG-IFN)-α2a/RBV, followed by 12 weeks of TVR/PEG-IFN/RBV, then 32 to 56 weeks of PEG-IFN/RBV.

Early changes in coagulation but not inflammatory biomarkers under intermittent ART: the randomized ANRS 106 WINDOW trial.

Introduction: In the SMART trial, baseline plasma hsCRP, IL6 and D-dimer levels were strongly correlated to all-cause mortality. A case-control study has shown an increase of IL-6 and D-dimer levels after one month of antiretroviral therapy (ART) interruption, which was correlated to viral load. Restarting ART was associated to a decrease in D-dimer but not IL-6 or hsCRP levels.

Archived HIV-1 DNA resistance mutations to rilpivirine and etravirine in successfully treated HIV-1-infected individuals pre-exposed to efavirenz or nevirapine.

Objectives: Efavirenz and nevirapine failure is associated with a rapid selection of resistance-associated mutations (RAMs), which may impact on etravirine or rilpivirine susceptibility. However, RAMs for rilpivirine and etravirine cannot be reported on previous resistance genotypes because these specific RAMs were not analyzed at that time. Therefore, our objective was to determine, in virologically suppressed HIV-1-infected individuals, the presence of RAMs to rilpivirine, etravirine and the combination of tenofovir/emtricitabine/rilpivirine in HIV-1 DNA from individuals previously exposed to efavirenz and/or nevirapine.

Telaprevir for HIV/hepatitis C virus-coinfected patients failing treatment with pegylated interferon/ribavirin (ANRS HC26 TelapreVIH): an open-label, single-arm, phase 2 trial.

Background: Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained virological response (SVR) rates in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. There are limited data regarding the use of telaprevir plus peg-IFN/RBV in this population.

Methods: HIV type 1-infected patients who previously failed ≥12 weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single-arm, phase 2 trial.

Pharmacokinetic study of raltegravir in HIV-infected patients with end-stage liver disease: the LIVERAL-ANRS 148 study.

Background: The end-stage LIVER disease and RALtegravir-Agence Nationale de Recherche sur le Sida et les hépatites (LIVERAL-ANRS) 148 study aimed to evaluate the safety, efficacy, and pharmacokinetic parameters of raltegravir (RAL) in human immunodeficiency virus (HIV)-infected patients with end-stage liver disease (ESLD) (substudy 1) and to assess the lack of pharmacokinetic interaction between RAL and the immunosuppressive regimen introduced after liver transplant (substudy 2).

Methods: All patients received 400 mg RAL twice daily plus 2 nucleoside reverse transcriptase inhibitors. Liver function and immunovirological parameters were monitored throughout the study.

Anti-HBV DNA vaccination does not prevent relapse after discontinuation of analogues in the treatment of chronic hepatitis B: a randomised trial--ANRS HB02 VAC-ADN.

Objective: The antiviral efficacy of nucleos(t)ide analogues whose main limitation is relapse after discontinuation requires long-term therapy. To overcome the risk of relapse and virological breakthrough during long-term therapy, we performed a phase I/II, open, prospective, multicentre trial using a HBV envelope-expressing DNA vaccine.

Design: 70 patients treated effectively with nucleos(t)ide analogues for a median of 3 years (HBV DNA <12 IU/mL for at least 12 months) were randomised into two groups: one received five intramuscular injections of vaccine (weeks 0, 8, 16, 40 and 44) and one did not receive the vaccine.

Lymphoma and Epstein-Barr virus DNA in blood during interleukin-2 therapy in antiretroviral-naïve HIV-1-infected patients: a substudy of the ANRS 119 trial.

Objectives: Interleukin-2 (IL-2) therapy increased CD4 cell counts and delayed antiretroviral therapy (ART) initiation in HIV-infected patients in the Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) 119 trial. However, four cases of lymphoma were reported. Epstein-Barr virus (EBV) replication is associated with an increased risk of lymphoma in immunocompromised patients.

Effect of two injections of non-adjuvanted influenza A H1N1pdm2009 vaccine in renal transplant recipients: INSERM C09-32 TRANSFLUVAC trial.

Background: Enhancing vaccine immunogenicity in kidney transplant recipients, particularly against influenza, is required since the immunosuppression used to prevent graft rejection limits vaccine immunogenicity. We therefore investigated the immunogenicity and safety of a double dose non-adjuvanted vaccination regimen against influenza H1N1pdm2009 in kidney transplant adult recipients.

Methods: A prospective single-arm study was conducted including 121 renal transplant recipients under triple immunosuppressive regimen.

Long-term immunogenicity of two doses of 2009 A/H1N1v vaccine with and without AS03(A) adjuvant in HIV-1-infected adults.

Objective: In immunocompromised patients, alternative schedules more immunogenic than the standard influenza vaccine regimen are necessary to enhance and prolong vaccine efficacy. We previously reported that the AS03A-adjuvanted 2009 A/H1N1v vaccine yielded a higher short-term immune response than the nonadjuvanted one in HIV-1-infected adults. This study reports the long-term persistence of the immune response.

Comparison of resistance mutation patterns in historical plasma HIV RNA genotypes with those in current proviral HIV DNA genotypes among extensively treated patients with suppressed replication.

Objectives: Heavily treatment-experienced patients with good virological control could be at risk of virological failure on switching to a new regimen if pre-existing drug resistance is not taken into account. We examined whether genotyping based on cellular HIV-1 DNA during controlled viraemia identifies resistance mutations detected in plasma HIV-1 RNA during treatment with previous antiretroviral regimens.

Patients And Methods: All 169 patients enrolled in the Agence Nationale de Recherche sur le SIDA (ANRS) 138-intEgrase inhibitor MK_0518 to Avoid Subcutaneous Injections of EnfuviRtide (EASIER) trial had already received three antiretroviral drug classes [nucleoside reverse transcriptase inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI)] and had plasma HIV-1 RNA<400 copies/ml at baseline.

Presence of lamivudine or emtricitabine is associated with reduced emergence of nonnucleoside reverse transcriptase inhibitor mutations in an efavirenz-based intermittent antiretroviral treatment regimen.

Efavirenz concentrations were measured in 21 patients during an interruption cycle of the ANRS 106 Window trial. The median efavirenz concentrations in the patients 12 h, 3 days, and 7 days after discontinuation of the drug were 1,962 ng/ml, 416 ng/ml, and 112 ng/ml, respectively. The half-life ranged from 27 to 136 h.

Maternal immune response and neonatal seroprotection from a single dose of a monovalent nonadjuvanted 2009 influenza A(H1N1) vaccine: a single-group trial.

Background: Pregnant women and infants who get influenza are at increased risk for severe illness.

Objective: To evaluate the immunogenicity and transplacental antibody transfer of 2009 pandemic influenza A(H1N1) vaccine administered during pregnancy.

Design: Prospective, multicenter, single-group clinical trial.

Acceptability of an "on-demand" pre-exposure HIV prophylaxis trial among men who have sex with men living in France.

Although predictors of willingness to take daily, self-administered pre-exposure HIV prophylaxis (PrEP) for men who have sex with men (MSM) have been studied in the context of several PrEP trials internationally, little is known about MSM interested in participating in a trial on the use of PrEP on an "on -demand" basis, i.e., taking a first dose of combined tenofovir/emtricitabine a few hours before possible HIV sexual exposure and a second dose a few hours afterwards.

Meropenem vs standard of care for treatment of late onset sepsis in children of less than 90 days of age: study protocol for a randomised controlled trial.

Background: Late onset neonatal sepsis (LOS) with the mortality of 17 to 27% is still a serious disease. Meropenem is an antibiotic with wide antibacterial coverage. The advantage of it over standard of care could be its wider antibacterial coverage and thus the use of mono-instead of combination therapy.

Pharmacogenetics of toxicity, plasma trough concentration and treatment outcome with nevirapine-containing regimen in anti-retroviral-naïve HIV-infected adults: an exploratory study of the TRIANON ANRS 081 trial.

The aim of this exploratory study was to investigate in a homogeneous population of anti-retroviral naïve HIV-1-infected adults, the relationships between genetic polymorphisms involved in nevirapine metabolism [CYP2B6 516G>T, 785A>G and 1459C>T; CYP3A5 6986A>G (CYP3A5*3)], transport (ABCB1 2677G>T/A and 3435C>T), and antigen recognition (HLA-DRB1*0101), and the hepatic and/or cutaneous toxicity occurring within the first 8 or 72 weeks of treatment, plasma trough concentrations (C(trough) ) at week 8 and immuno-virological response to nevirapine at week 24. Associations between genetic polymorphisms and toxicity, C(trough) and response to nevirapine were performed in a population of 72 HIV-1 positive and nevirapine-treated patients followed during 72 weeks, as part of the previous study called: ANRS081 'Trianon' trial. Among the 18 patients who developed toxicity events during the 72 weeks of the study, 12 patients exhibited early toxicity before week 8.

Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure.

Unlabelled: The impact of minor drug-resistant variants of the type 1 immunodeficiency virus (HIV-1) on the failure of antiretroviral therapy remains unclear. We have evaluated the importance of detecting minor populations of viruses resistant to non-nucleoside reverse-transcriptase inhibitors (NNRTI) during intermittent antiretroviral therapy, a high-risk context for the emergence of drug-resistant HIV-1. We carried out a longitudinal study on plasma samples taken from 21 patients given efavirenz and enrolled in the intermittent arm of the ANRS 106 trial.

Efficacy and safety of raltegravir in treatment-experienced HIV-1-infected patients switching from enfuvirtide-based regimens: 48 week results of the randomized EASIER ANRS 138 trial.

Objectives: To assess the sustainable efficacy and safety of a switch from enfuvirtide to raltegravir in patients with multidrug-resistant HIV infection.

Methods: One hundred and seventy patients with multidrug-resistant HIV infection and suppressed plasma HIV RNA levels < 400 copies/mL under an enfuvirtide-based regimen were randomized to maintain their regimen or to switch to a raltegravir-based regimen (immediate group) in a 48 week prospective, randomized, open-label trial. At week 24, patients in the maintenance arm also switched to raltegravir (deferred group).

Safety and immunogenicity of a monovalent 2009 influenza A/H1N1v vaccine adjuvanted with AS03A or unadjuvanted in HIV-infected adults: a randomized, controlled trial.

Background: Human immunodeficiency virus (HIV)-infected patients have decreased immune response to vaccines. Few data are available about pandemic flu vaccination in this population.

Methods: We conducted a multicenter, patient-blinded, randomized trial in a cohort of HIV-infected adults.

Hyperlactataemia in HIV-infected subjects initiating antiretroviral therapy in a large randomized study (a substudy of the INITIO trial).

Objective: The aim of the study was to evaluate the predictive value of clinical and molecular risk factors, including peripheral blood mononuclear cell (PBMC) mitochondrial DNA (mtDNA) and mitochondrial RNA (mtRNA), for the development of lactic acidosis (LA) and symptomatic hyperlactataemia (SHL).

Methods: In a substudy of a large multicentre, randomized trial of three antiretroviral regimens, all containing didanosine (ddI) and stavudine (d4T), in antiretroviralnaïve, HIV-1-infected patients, patients with LA/SHL ('cases') were compared with those without LA/SHL in a univariate analysis, with significant parameters analysed in a multivariate model. In a molecular substudy, PBMC mtDNA and mtRNA from cases and matched controls at baseline and time of event were examined.