To describe HIV-1 DNA levels from baseline (W0) to week 52 (W52) among patients receiving either interleukin-2 (IL-2) + optimized background therapy (OBT) or OBT as salvage treatment.

This was evaluated in a substudy of the ETOILE Agence Nationale de Recherches sur le SIDA et les hépatites virales (ANRS) 123 trial (patients with CD4 ≤ 200/mm³, HIV RNA > 4 log₁₀ copies/mL and a genotypic score showing two or fewer active drugs). OBT included enfuvirtide whenever possible. HIV DNA was quantified with the ANRS assay.

Blood samples were available for 21 patients in the IL-2 + OBT arm and 23 in the OBT alone arm at baseline, and for 10 and 17 patients, respectively, at W52. Median baseline CD4 count was 47 cells/mm³ and 68 cells/mm³, respectively; median HIV RNA was 5.1 and 4.9 log₁₀ copies/mL. Baseline median HIV DNA load was 3.44 log₁₀ copies/10⁶ peripheral blood mononuclear cells (PBMCs) (interquartile range 3.31–4.08) and 3.51 (3.18–3.82) log₁₀ copies/10⁶ PBMCs, respectively. At W52, it was 3.18 log₁₀ copies/10⁶ PBMCs (2.75–3.52) and 3.48 log₁₀ copies/10⁶ PBMCs (3.10–3.67), respectively. Cells were available at both W0 and W52 for 7 patients in the IL-2 + OBT arm and 14 in the OBT arm. Change in HIV DNA load was not associated with IL-2 use, but decreased among the seven patients receiving enfuvirtide (–0.22 log₁₀ copies/mL) as compared with the other 14 patients (+0.20 log₁₀; P = 0.046). A steeper decrease in HIV DNA was observed among patients who had a larger increase in CD4 count (Pearson coefficient = 0.659, P = 0.001). Adjusted for enfuvirtide use, there was a trend for an association between upper baseline HIV DNA level and a less frequent CD4 gain ≥50 cells/mm³ at W52 (odds ratio = 0.17, P = 0.075).

HIV DNA levels were high in patients with advanced therapeutic failure. A larger viral reservoir may be associated with lower gains in CD4 count among patients receiving OBT. HIV DNA level could be a useful tool for the case management of patients in the late stages of disease.

To manage the interaction between fosamprenavir/ritonavir and posaconazole, we hypothesized that ritonavir can be replaced by posaconazole as an alternative booster of fosamprenavir with no significant influence on posaconazole pharmacokinetics.

This was an open-label, randomized, three period, cross-over, single-centre trial in 24 healthy volunteers. All subjects received the following three treatments for 10 days, separated by washout periods of 17 days: posaconazole 400 mg twice daily; fosamprenavir/ritonavir 700/100 mg twice daily; posaconazole 400 mg twice daily with fosamprenavir 700 mg twice daily.

Twenty subjects completed the trial. Geometric mean ratios (GMR; +90% confidence interval) of posaconazole AUC and C_max when taken with fosamprenavir versus posaconazole alone were 0.77 (0.68–0.87) and 0.79 (0.71–0.89), respectively. The GMRs of amprenavir AUC and C_max when taken as fosamprenavir and posaconazole versus fosamprenavir/ritonavir were 0.35 (0.32–0.39) and 0.64 (0.55–0.76), respectively. No serious adverse events were reported during the trial.

Unboosted fosamprenavir should not be used concomitantly with posaconazole.

Reports of Enterobacteriaceae resistant to all commonly used antimicrobial agents, including β-lactams, fluoroquinolones and aminoglycosides, are increasing in hospitals worldwide. The activity of ACHN-490, a next-generation aminoglycoside, was examined against clinical isolates of Escherichia coli and Klebsiella pneumoniae from hospitals in New York City, an area where multidrug-resistant organisms are endemic.

Unique patient isolates of E. coli and K. pneumoniae were gathered from 16 hospitals located in New York City in 2009 and underwent susceptibility testing to aminoglycosides and ACHN-490. Subsets of isolates were characterized by PCR for the presence of genes encoding aminoglycoside-modifying enzymes, ribosomal methylases and KPC-type carbapenemases.

Although most isolates of E. coli were susceptible to the aminoglycosides, the MIC₉₀ values of gentamicin, tobramycin and amikacin were 32, 8 and 4 mg/L, respectively. The MIC₉₀ of ACHN-490 was 1 mg/L. Multidrug resistance, including resistance to aminoglycosides and the presence of bla_KPC, was much more common in isolates of K. pneumoniae. However, the MIC₉₀ of ACHN-490 for K. pneumoniae was also 1 mg/L. The MICs of ACHN-490 did not correlate with the presence of commonly recovered aminoglycoside-modifying enzymes. Bactericidal activity was evident in most isolates at concentrations 4x the MIC.

The novel aminoglycoside ACHN-490 retains activity against most isolates of E. coli and K. pneumoniae, including multidrug-resistant strains. Additional studies examining the roles of efflux systems and outer membrane permeability alterations are recommended in isolates with reduced susceptibility to this agent.

We analysed the in vitro and in vivo effects of posaconazole and amphotericin B against three clinical isolates of zygomycetes: Lichtheimia corymbifera, F1; and Rhizopus oryzae, F5 and F6.

In vitro activities of both drugs were assessed by determining MICs, minimum fungicidal concentrations (MFCs) and fungal damage measured by the XTT assay against either the spores or the hyphal forms. Additionally, the survival curves of neutropenic mice systemically infected with the zygomycete isolates were used as the marker of antifungal response to amphotericin B (1 mg/kg/day) or posaconazole (2.5, 10 and 50 mg/kg/day).

In terms of MICs, posaconazole proved to be active against the three isolates (MICs ranging from 0.125 to 1.0 mg/L). The median posaconazole MFCs were 0.25, 0.5 and >16 mg/L for F1, F5 and F6, respectively. The XTT assay showed that posaconazole was active against spores of all three isolates, but only partially effective against the hyphae. The survival studies showed that amphotericin B at 1 mg/kg/day and posaconazole at 10 mg/kg/day prolonged the survival of the animals infected with L. corymbifera F1. In mice infected with R. oryzae F5, only posaconazole at 50 mg/kg/day significantly prolonged survival, whereas amphotericin B at 1 mg/kg/day was the only regimen active against R. oryzae F6.

Our findings showed that posaconazole could be useful in the treatment of zygomycosis. Also, we report that an isolate of R. oryzae with low MFC responded to posaconazole, while another isolate with high MFC did not.

To evaluate the changes in liver stiffness measurement (LSM) in patients infected by hepatitis C virus (HCV) under pegylated interferon (Peg-IFN) plus ribavirin therapy.

One hundred and forty-three HCV-infected patients, of whom 97 (68%) were also carrying HIV, who started treatment with Peg-IFN/ribavirin were included in this prospective cohort study. The outcome variable of the study was the change in LSM between baseline and the scheduled date for evaluating sustained virological response (SVR).

The median (Q1–Q3) LSM values at baseline and at the SVR assessment date were 8.1 (6.2–11.6) kPa and 6.8 (5.2–9.8) kPa (P < 0.001), respectively. The median (Q1–Q3) decrease between both timepoints was –1 (–2.75, 0.3) kPa. The baseline LSM decreased ≥20% in 37 (46%) patients with SVR and in 19 (30%) without SVR (P = 0.05). In the linear regression analysis, baseline LSM {beta [standard error (SE)] –0.712 (0.044), P = 0.004}, alcohol intake ≥50 g/day [beta (SE) 0.202 (0.030), P = 0.014] and achievement of SVR [beta (SE) –0.238 (0.026), P = 0.029] were independently associated with changes in LSM.

LSM decreases significantly among patients with chronic HCV infection who achieve SVR with Peg-IFN/ribavirin. These patients show a higher frequency of LSM reduction ≥20% at the date of SVR evaluation.

We determined the complete nucleotide sequence of pKOX105, a 54 641 bp plasmid from a Klebsiella oxytoca strain that was isolated from a resident of a long-term-care facility in Bolzano, Italy.

The plasmid was sequenced using a shotgun approach. Combinatorial PCRs, directed PCRs and walking reads were used to assemble the contigs and to fill in gaps. Gene sequences were compared with reference plasmids and aligned with GenBank data using BLAST and CLUSTAL W software.

pKOX105 belonged to incompatibility group IncN, harboured bla_VIM-1, bla_SHV-12, qnrS1, aacA4 and dfrA14 and conferred resistance to carbapenems, oxyimino-cephalosporins, quinolones, aminoglycosides and trimethoprim. It was highly related to the p9 and p12 plasmids from Klebsiella pneumoniae and K. oxytoca strains isolated at a New York City hospital in 2005 carrying bla_KPC-2 and bla_KPC-3, respectively.

IncN plasmids are broad host-range plasmids that have contributed significantly to the worldwide dissemination of many different resistance genes in Enterobacteriaceae from animal and human sources. This plasmid family is now playing a crucial role in the global spread of diverse carbapenemase genes in Klebsiella spp.