These two PTS branches cross-talk to each other, as the product of the fruB gene (a polyprotein EI-HPr-EIIA) can phosphorylate PtsN (EIIANtr) in vivo. This gives rise to a complex actuator device where diverse physiological inputs are ultimately translated into phosphorylation or not of PtsN (EIIANtr) which, in turn, checks the activity of key metabolic and regulatory proteins. Such a control HSP inhibitor of bacterial physiology highlights the prominence of biochemical homeostasis over genetic ruling –and not vice versa.

“
“Many chromosomes from Actinomycetales, an order within the Actinobacteria, have been sequenced over the last 10 years and the pace is increasing. This group of Gram-positive and high G+C% bacteria is economically and medically learn more important. However, this group of organisms also is just about the only order in the kingdom Bacteria to have a relatively high proportion of linear chromosomes. Chromosome topology varies within the order according to the genera. Streptomyces, Kitasatospora and Rhodococcus, at least as chromosome sequencing stands at present, have a very high proportion of linear chromosomes, whereas most other genera seem to have circular chromosomes. This review examines chromosome topology across the Actinomycetales and how this affects our concepts of chromosome evolution. The Actinomycetales are a major order

within the high percentage of G+C Gram-positive bacteria and fall within Thymidylate synthase the class Actinobacteria. The order Actinomycetales is made up of 13 suborders covering many species that are important pathogens, relevant to biotechnology and ecologically significant (Zhi et al., 2009). Because of their importance to humans and the environment, many genomes of class Actinobacteria (251), subclass Actinobacteridae (234) and order Actinomycetales (201) have been completely sequenced in the last 10 or so years (as of 8 December 2010 and including draft assemblies; http://www.ncbi.nlm.nih.gov). Thus the genome sequences available for members of the Actinomycetales consist of about a 10th of the available genomes

from Bacteria. The importance of these organisms to many fields seems to have focused genome research in the direction of the Actinomycetales. It is noteworthy that only 36 other chromosomes from the class Actinobacteria have been sequenced. Many, if not most, of the genera making up the Actinomycetales undergo differentiation to a greater or lesser extent (Flärdh & Buttner, 2009). The Actinobacteria are characterized by a unique molecular synapomorphy whereby there is a homologous insertion of about 100 nucleotides between helices 54 and 55 of the 23S rRNA gene (Chater & Chandra, 2006). Furthermore, the Actinomycetales are a coherent clade when analysed phylogenetically using 16S sequences (Fig. 1).

Briefly, SOEA and SOED primers were used to amplify the whole zurR region. This was then digested with restriction enzymes XbaI and EcoRI and ligated to a similarly digested pKSV7.

Following electroporation into E. coli DH5α, the construct was then extracted and transformed into competent EGDe ΔzurR. Plasmid integration, subsequent excision, and curing were carried out as described previously (Rea et al., 2004), with continuous passaging in BHI at 30 °C. The complementation Cisplatin ic50 was confirmed using primers SOE X and SOE Y. BHI motility agar plates or defined media motility agar plates were made up using 0.2% agar. Tetrazolium dye was added to the growth medium to enhance visualization of bacterial growth. Twenty millilitres of the desired media was added to each plate and allowed to solidify. Overnight cultures were pelleted by centrifugation and were washed

twice in PBS prior to use. Cultures were resuspended in PBS and were stabbed into the agar using a sterile inoculating needle. All plates were maintained at room temperature and were inspected daily for culture migration. One milliliter of overnight cultures of L. monocytogenes EGDe and ΔzurR was centrifuged (2938 g for 8 min) and washed twice with PBS. The resulting pellets were fixed in a primary fixative that consisted of 2% glutaraldehyde and 2.5% paraformaldehyde in 0.165 M phosphate buffer (pH 7.3). Following primary fixation, specimens were washed in buffer, postfixed in 2% osmium selleck inhibitor tetroxide

Midostaurin in the same buffer, dehydrated in graded acetones, and air dried from tetramethylsilane. Samples were mounted onto stubs using double sided carbon tape. All samples were sputter coated with a thin layer of gold using a Bio-RAD Polaron Sputter Coating Unit, before being examined using a scanning electron microscope, Jeol JSM-5510. Digital electron micrographs were obtained of areas of interest. For animal assays, 8–12-week female BALB/c mice were divided into groups of five for statistical analysis. For the infection assay, overnight listerial cultures were pelleted by centrifugation, washed twice with phosphate-buffered saline (PBS), resuspended in PBS, and subsequently diluted in PBS to approximately 1.5 × 106 CFU mL−1. In vivo survival was determined by inoculating 8–12-week-old female BALB/c mice intraperitoneally (i.p.) with approximately 3 × 105 CFU in 200 μL of PBS. The mice were euthanized 3 days postinfection. Bacterial numbers in the livers and spleens were determined by homogenization of the organs, serial dilution in PBS, and subsequent plating onto BHI agar. Plates were incubated for 24 h at 37 °C before colony counts were recorded. All murine experiments received prior approval by the University ethics committee. To determine the ability of strains to survival at lethal bile concentrations, stationary phase cultures of wild-type and mutant strains were subjected to lethal levels of bovine bile (oxgall).

As expected in this model, we did not observe loss of principal hippocampal neurons. Neuron damage was most pronounced in the hilus, where we also detected progressive loss of parvalbumin-positive GABAergic interneurons. Hilar neuron loss (or end-folium sclerosis), a common feature in patients with MTS, was accompanied by a progressively decreased glutamine synthetase (GS)-immunoreactivity Doxorubicin molecular weight from 2 (−15%) to 19 weeks (−33.5%) after SE. Immunoreactivity for excitatory amino-acid transporters, vesicular glutamate

transporter 1 and glial fibrillary acidic protein was unaffected. Our data show that SE elicited in 21-day-old rats induces a progressive reduction in hilar GS expression without affecting other key components of the glutamate–glutamine cycle. Reduced expression of glial enzyme GS was first detected 2 weeks after SE, and thus clearly before spontaneous recurrent seizures

occurred. These results support the hypothesis that reduced GS expression is an early event in the development of hippocampal sclerosis in MTS patients and emphasize the importance selleck chemicals llc of astrocytes in early epileptogenesis. “
“What are the precise molecular and cellular mechanisms that the human brain exploits to encode consciousness, identity and thought? This undoubtedly remains one of the greatest scientific challenges facing mankind. “
“Auditory stimulation with monaural or binaural auditory beats (i.e. sine waves with nearby frequencies presented either to both ears or to each ear separately) represents a non-invasive approach to influence electrical brain activity. It is

still unclear exactly which brain sites are affected by beat N-acetylglucosamine-1-phosphate transferase stimulation. In particular, an impact of beat stimulation on mediotemporal brain areas could possibly provide new options for memory enhancement or seizure control. Therefore, we examined how electroencephalography (EEG) power and phase synchronization are modulated by auditory stimulation with beat frequencies corresponding to dominant EEG rhythms based on intracranial recordings in presurgical epilepsy patients. Monaural and binaural beat stimuli with beat frequencies of 5, 10, 40 and 80 Hz and non-superposed control signals were administered with low amplitudes (60 dB SPL) and for short durations (5 s). EEG power was intracranially recorded from mediotemporal, temporo-basal and temporo-lateral and surface sites. Evoked and total EEG power and phase synchronization during beat vs. control stimulation were compared by the use of Bonferroni-corrected non-parametric label-permutation tests. We found that power and phase synchronization were significantly modulated by beat stimulation not only at temporo-basal, temporo-lateral and surface sites, but also at mediotemporal sites. Generally, more significant decreases than increases were observed. The most prominent power increases were seen after stimulation with monaural 40-Hz beats.

S4). Neither of these measures showed significant trends over the experiment. However, there were indications from light microscopy that some of the granules lost some structural integrity during the dosing as there was an appearance of fluffier material at days 49 and 58 (Fig. S5). Additionally, selleck chemical there was evidence of an increase in the effluent SS from approximately 100 mg L−1 before dosing to approximately 400 mg L−1 on days 42 and 56 (Fig. S6), suggesting that sludge settling was poorer due to granule biofilm disruption. The diversity

indices derived from 16S rRNA T-RFLP data indicated that there were changes in the community structure over the dosing period, with the Shannon diversity index decreasing over the last 14 days of dosing (Fig. 3). This appeared to be a result of the development of a less even community structure (Fig. S7) rather than the disappearance of particular operational taxonomic units (Fig. S8). While there was therefore some evidence

of a change in the diversity indices, i.e. those describing aggregate community characteristics, Everolimus datasheet there appeared to be little change in the relative abundance of two of the model organisms commonly found in EBPR systems. The relative abundance of a key organism responsible for EBPR, Candidatus‘Accumulibacter phosphatis’ (Hesselmann et al., 1999), was 27.1% on day 0 (92% congruency score) and 22.8% on day 42 (end of 100% OC dosing; 96% congruency score), as assessed ADAMTS5 by quantitative FISH. The relative abundance of a glycogen-accumulating organism and known EBPR antagonist, Candidatus‘Competibacter phosphatis’ (Crocetti et al., 2002), was below 1% on days 0 and 42. This is the first study in which the removal of OC, microbial diversity, nutrient removal performance and granule structure has been tested in a simulated activated sludge system exposed to OC and antibiotics in pandemic-scenario dosing. There was up to 41% removal of OC per 6-h SBR cycle, with the most successful

removal occurring in the first 35 days of dosing. It may be that in a real pandemic scenario, 35 days of significant removal at the beginning of an epidemic would reduce the amount of OC released into receiving waters. However, during the SBR operation, there was no evidence of significant OC removal after day 35. Hence, there does not appear to be sufficient selective pressure for the enrichment of OC degraders in the system investigated. There was no evidence of any adverse effects on reactor performance during the first 28 days of the simulated pandemic (i.e. up to 36 μg L−1 OC, 70 μg L−1 amoxicillin, 30 μg L−1 erythromycin and 10 μg L−1 levofloxacin). There was, however, evidence during and after the two-week high-OC dosing period (days 29–42; 360 μg L−1 OC) of a reduction in EBPR and nitrification, bacterial community diversity and disruption to granule structure.

Using SSH, we had isolated three fragments encoding the factors HrpF, HrpD4-HpaA, and HrpB8 in Xoo MAI1. Essential for bacteria–host interaction are hrp genes encoding proteins involved in the T3SS, as demonstrated for various plant pathogenic bacteria by different authors (Alfano & Collmer, 2004; He et al., 2004; Büttner & Bonas, 2006). HrpF is a putative translocon protein that is essential

for pathogenicity in plant-pathogenic bacteria (Büttner et al., 2002, 2007; Meyer et al., 2006; Büttner & He, 2009). The hrp regions also contain so-called hrp-associated (hpa) genes; the hpaA and hrpB genes are encoded STI571 manufacturer by the hrpD and hrpB operons, respectively. The gene hpaA is an important virulence factor that contributes to T3SS and Kinase Inhibitor Library effector protein translocation to host cells (Lorenz et al., 2008), whereas the translated sequence derived from hrpB8 is similar to the amino acid sequence of FliR, which has been determined to be a component in the T3SS flagellar export apparatus in Salmonella typhimurium (Fan et al., 1997). We also found DNA fragments that present similarity to genes encoding RTX (repeats in toxin) toxins (FI978128 and FI978182). In Bradyrhizobium elkanii, rtx genes are involved in rhizobitoxine biosynthesis, which inhibits ethylene biosynthesis in plants (Sugawara et al., 2007). Recently,

B. elkanii rtx gene homologs were found, forming gene clusters in Xoo genomes (Ochiai et al., 2005; Sugawara et al., 2007). In the animal pathogen Kingella kingae, disruption of these genes results in the loss of toxicity (Kehl-Fie & Geme, 2007). Of the 17 clones tested, 12 were present oxyclozanide in the Xoo strain MAI1 and absent from the corresponding

driver DNA (Xoo PXO86 and/or Xoc BLS256). Of the four fragments tested against several other X. oryzae strains from different geographical origins, one (FI978197) specifically hybridized to the Xoo strain MAI1 (data not shown). Three (FI978100, FI978105, and FI978167) yielded hybridization signals with all the African Xoo strains tested, but not with the Asian Xoo and Xoc strains (data not shown and Table 1). These fragments corresponded to genes of ‘unknown function’ and may represent specific Xoo MAI1 genes (i.e. FI978197) and/or specific genes of African strains. From the 134 SSH Xoo MAI1 nonredundant sequences, 20 were found in both libraries (Table 2). blast analysis showed that eight of these fragments correspond to hypothetical and/or unknown proteins. The remaining 12 fragments were distributed across seven functional categories (Table 2). Using blastn, the genome of Xoc strain BLS256 was searched for these 20 SSH Xoo MAI1 sequences, with 16 being found in the Xoc BLS256 genome. The ratio identities/sequence size, obtained after blast search, nevertheless indicated a low identity percentage, <50% for most cases (Table 2).

7% (95% CI 19.9–37.5%). Our study reflects learn more the need to monitor the evolution of resistance on a regular basis and trends of transmitted resistance. The initiation of highly active antiretroviral therapy (HAART) in developing countries where HIV-1 non-B subtypes circulate has been associated with good clinical outcomes when combined with appropriate clinical follow-up [1]. However, as HAART is scaled up, it is essential to monitor the emergence

of primary resistance, as this may impact on the success of an already limited choice of first-line therapies in resource-limited settings [2]. Furthermore, studies have shown that polymorphisms in non-B subtype genomes can lead to different pathways to drug resistance from those found in subtype B HIV-1 [3–5]. We have studied the rate of primary resistance in Mali, a resource-limited country in West Africa. With a population of 11 million inhabitants, Mali has an estimated HIV prevalence of 1.3%, representing 146 000 persons infected with HIV [6]. The first antiretroviral drugs became available in 1997, followed by roll-out of HAART through a national treatment programme in 2004 with stavudine, lamivudine and nevirapine recommended as first-line treatment [7]. A study in 2006 estimated that the overall prevalence of primary resistance in Mali was 11.5% [7]. In the context of the scale-up of HAART, we therefore decided to evaluate the evolution of primary

resistance in this country. A total of 101 antiretroviral-naïve HIV-infected individuals from Mali were prospectively enrolled in this study. Primary resistance was evaluated during the period from July 2007 to October LDK378 PAK5 2008. Individuals were recruited from three different sites in Bamako, Mali’s capital: 42 patients were recruited from the Centre d’Écoute de Soins, d’Animation et de Conseil (CESAC), which offers diagnostic services and care to HIV-infected individuals of rural and urban origin, 43 from the Gabriel Touré Hospital (HGT), and

16 from the Point G Hospital (HPG). HGT and HPG are the two largest hospitals in Mali. Although their patient populations are mainly urban, they are reference centres and see referrals from the entire country. Samples obtained from the patients were stored at −80 °C until they were sent on dry ice for genotyping at the retrovirology laboratory at the Centre Hospitalier de l’Université de Montréal (CHUM), Montréal, Canada. This study was approved by the ethics committees of Mali and CHUM research centre. Viral RNA was extracted using the viral QIAamp Spin Mini Kit (Qiagen, Mississauga, Ontario, Canada) and according to the protocol provided by Virco (Mechelem, Belgium). It was then amplified using Superscript III HIFI (Invitrogen, Carlsbad, CA, USA) with primers 5′out and 3′RT (Virco) covering the protease and reverse transcriptase (RT-PR) genes. For the nested PCR, we used the expand HF PCR (Roche Applied Science, Quebec, Canada) as the PCR enzyme and primers 5′IN and 3′IN (Virco).

5 and 1.4 pregnancies per 100 person-years, respectively Palbociclib manufacturer [43]. To project a possible range for the risk of teratogenic events, we used one-way and two-way sensitivity analyses to vary all uncertain parameters. The plausible range for

each parameter was based on 95% CIs when available, published data, or expert opinion. In the base case simulation model analysis, mean projected life expectancy for women receiving an efavirenz-based first-line ART regimen starting at CD4<350 cells/μL regardless of childbearing potential was 28.91 life years (Table 3). In comparison, mean life expectancy for women who delayed efavirenz use and were treated with an alternative initial ART regimen which did not contain efavirenz was 28.02 years. The life expectancy gain attributable to using an efavirenz-based initial antiretroviral regimen was 0.89 years. For

women receiving an efavirenz-based initial regimen, mean total exposure time to efavirenz was 4.07 years per woman. For women delaying efavirenz use and receiving alternate first-line therapy, mean exposure time to efavirenz was 3.37 years per woman. In the sensitivity analysis, we examined Fludarabine how the life expectancy gains attributed to initial and delayed use of efavirenz varied with changes in selected simulation model input parameters in one-way sensitivity analyses (Table 3). Results were most sensitive to changes in HIV RNA suppression and CD4 cell count gains attributable to ART, mortality attributable to AIDS, and the discount rate. The incremental life expectancy gain with efavirenz-based first-line ART ranged from 0.44 to 0.78 years of life as viral suppression rates of the first-line regimens were increased by 20% to a maximum of 95% and decreased by 20% (Table 3). When CD4 gains for first-line ART were increased

and decreased by 50%, incremental gains in life expectancy attributable to first-line efavirenz ranged from 0.89 to 0.67 years. For women delaying efavirenz use, estimated life expectancy increased from 28.02 to 28.74 years when the CD4 gains for the first and third regimens in the sequence were increased from 190 cells/μL at 48 weeks to 203cells/μL at 48 weeks for the first regimen and from 86 cells/μL at 16 weeks to Montelukast Sodium 273 cells/μL at 96 weeks for the second regimen, as reported in the literature. This increase in survival for women delaying efavirenz narrowed incremental survival gains attributable to first-line efavirenz use to 0.17 years (base case: 0.89 years). When an initial nevirapine-based regimen was substituted for the recommended efavirenz-based therapy and ART was initiated at CD4<250 cells/μL, the mean life expectancy for women receiving the nevirapine-based therapy was 25.49 years. For an efavirenz-based first-line ART regimen starting at CD4<250 cells/μL, estimated survival was 27.08 years. Time on initial treatment using a nevirapine-based regimen was 3.02 years compared with 4.00 years with first-line efavirenz.

, 2008), is the direct regulation of molecular target(s) modulating the flocculation behavior, then mutations that impair CheA1 or CheY1 functions should yield similar phenotypes. This study revealed several distinguishing features of the flocs formed by each of the mutant strains that are not consistent with a direct function of Che1 click here in the regulation of flocculation. First, although cells of both mutant strains were adherent and embedded in a complex matrix apparently comprised of fibrillar material, cell-to-cell contacts within the matrix of the AB102 (ΔcheY1) strain were separated by a

thick layer that was visible by AFM after 1 week. This layer formed a tight network around each individual cell within the floc. In contrast, in the flocs of AB101 (ΔcheA1), individual cells were distinctly defined and no obvious connecting features were observed between the cells. Because it is impossible to determine the composition of this material from imaging alone, we used flocculation inhibition and lectin-binding assays to analyze the different

structures observed between the two strains in more detail. The results of the lectin-binding assay PD98059 molecular weight suggest that AB101 (ΔcheA1) produces an exopolysaccharide that is more abundant in α-mannose and/or α-glucose, and N-acetyl galactosamine than the exopolysaccharide produced by AB102 (ΔcheY1). Previous studies have shown that the glucose content of exopolysaccharide is significantly lower during flocculation in the wild-type Sp7 strain and in other mutant derivative strains with increased aggregation capacity (Bahat-Samet et al., 2004). Consistent with these data, AB102 (ΔcheY1) strain displays a stronger flocculation phenotype and its extracellular matrix appears to have a reduced mannose and/or a glucose content relative to that of AB101 (ΔcheA1). An alternative explanation Rapamycin molecular weight for these data is that the structural organization of the AB102 (ΔcheY1) floc reduces the accessibility of the sugar residues to the lectin, thus limiting the amount of lectin

that binds to the cells and the surrounding matrix. Even though the floc structures of the two mutant strains showed different binding affinities for lectins, indicating possible differences in the polysaccharide composition of the exopolysaccharide produced during flocculation, these results do not necessarily demonstrate the contribution of specific polysaccharides to aggregation or flocculation. Previous studies showed that exopolysaccharide composition is modified over time from a glucose-rich exopolysaccharide to an arabinose-rich exopolysaccharide and that this temporal change correlates directly with the timing of flocculation (Bahat-Samet et al., 2004). In agreement with this observation, flocs formed by the ΔcheY1 mutant were more sensitive to the addition of arabinose in the flocculation inhibition assay, suggesting that the sugar residues comprising the matrix of these strains are different in structure and/or composition.

There is no ‘tell-tale’

sign elicitable by inspection, palpation, percussion or auscultation for this spectrum of illnesses. Laboratory investigations always draw a blank. Chronic pain disorders, therefore, cannot be diagnosed by this conventional approach.[5] Although chronic wide spread pain, fatigue, sleep disturbance and mental fogging are some of the hallmarks of these illnesses, familiarity with classification criteria is a prerequisite to identify a good number Small molecule library order of them. There are patients, however, with these illnesses that do not fulfill any criteria. Neurochemical misbalances, rather than anatomical lesions are more likely to cause these disorders; nor are they straightforward psychiatric illnesses, in spite of many reports of mind-body link in these conditions.[6, 7] While rheumatology clinics in the western and developed world are flooded with such patients and rheumatologists in those parts of the world are more familiar with these illnesses, developing world is less familiar with these maladies. Now that the epidemic seems to be reaching the less developed world, many unanswered questions need to be addressed on this subject. Is it globalization that is bringing it to the developing world, where people earlier could tolerate small aches and

pains better? Is it much less common amongst the underprivileged section of the society? Do lifestyle, dietary factors and other socioeconomic factors have some influence on pain threshold, if not on I BET 762 causation

of these new world diseases? Painful disorders with anatomical lesions like inflammatory arthropathies, connective tissue diseases and osteoarthritis may also cause vicious cycle of ‘pain begetting more pain’, which may be termed as secondary fibromyalgia.[8] On the contrary and paradoxically enough, there is a paradigm shift in the understanding of pain disorders; it is now believed widely that pain itself can cause localised inflammation in a significant proportion of cases and thereby induces this novel mechanism to perpetuate the vicious cycle of pain.[9] Whether this has a therapeutic implication is arguable, but breaking this cycle is important in arresting the pain process. Mimics of fibromyalgia comprise a wide spectrum. Clomifene On the one end, there are highly treatable low grade metabolic disorders like hypothyroidism and vitamin D deficiency causing chronic widespread pain. These relatively common disorders need to be excluded or diagnosed and treated, as the case may be, in a chronic pain scenario.[10] On the other end of this spectrum, there are more serious organic pathologies like enthesopathic pain of spondyloarthropathies and at times, out of proportion pain and tenderness of leukemic arthropathies, especially in children presenting as vague aches and pains. Attending physician need to be sensitized to avoid misdiagnosing these conditions as fibromyalgia.

Analyses were performed using intent-to-treat principles based on randomized treatment assignment. Analyses RG7204 mw included all available

data and missing values were ignored. Between-group statistical comparisons used the Wilcoxon rank-sum test for continuous variables and Fisher’s exact test for categorical variables. Within-group changes, from baseline to week 48, were investigated using the Wilcoxon signed rank-sum test. Additional analyses (as-treated) were performed which censored values after a change in any component of the treatment regimen. From March 2007 to April 2008, a total of 225 patients from the MONOI study were randomized. Of these, 156 patients (69%) – 81 patients from the darunavir/r triple-therapy group and 75 from the darunavir/r monotherapy group – were enrolled in the fat distribution substudy and underwent a DEXA scan at baseline. During follow-up, 141 and 129 patients had a DEXA evaluation at week 48 and week 96, respectively. Overall, 121 patients had a complete fat tissue evaluation, including measurements at baseline, week 48 and week 96. Eight patients were evaluated at baseline and week 96. The missing data for fat evaluation are summarized

in Figure 1. Of the initial 156 patients receiving darunavir/r at 600 mg bid, 92% switched to darunavir/r at 800/100 at week 48 in both treatment groups, as specified in the protocol. Over the 96 weeks of follow-up, 24 patients had a treatment modification, including, selleck products in the darunavir/r monotherapy group, a change from darunavir to atazanavir (one patient), raltegravir (one patient) or nevirapine (one patient), and

resumption of NRTIs, including tenofovir or abacavir (10 patients) and zidovudine (two patients); and in the darunavir/r triple-therapy arm, a switch from tenofovir to zidovudine (one patient), from zidovudine to abacavir (one patient) and from zidovudine to tenofovir (six patients), Carnitine palmitoyltransferase II and tenofovir discontinuation (one patient). Baseline patient characteristics were well matched between the two treatment groups (Table 1). Patients enrolled in the fat distribution substudy did not significantly vary from the total patient population. They were middle-aged (median 45 years), with a median duration of exposure to antiretroviral therapy (ART) of 9 years for NRTI regimens, 7.7 years for nonnucleoside reverse transcriptase inhibitors (NNRTIs), and 5.8 years for PIs. Sixty-nine patients (44%) had been exposed to all three classes of drugs. At enrolment, ART therapy for the 156 patients consisted of an NRTI regimen that included tenofovir in 41% of patients, abacavir in 20.5% and thymidine analogues in 32.6%. The NRTI backbone regimen was associated with a PI in 72.4% of patients and with an NNRTI in 27.5%. It should be noted that, during the first 48 weeks of the study, in the darunavir/r triple-therapy arm, 17 patients (21%) received a thymidine analogue, in most cases zidovudine.