, 2007) Rhizobium leguminosarum swarmer cells are resistant to a

, 2007). Rhizobium leguminosarum swarmer cells are resistant to a number of different classes of antibiotics. Similar to the swarming cells of Salmonella (Kim & Surette, 2003) and P. aeruginosa (Lai et al., 2009), this multiresistant phenotype is transient to the swarming state. Reduced permeability of the outer membrane as well as alteration of the cell wall structure might result in decreased effectiveness of antibiotics targeting the cell

wall (Kim et al., 2003; Kim & Surette, 2004). It is believed see more that this reduction in outer membrane permeability may also provide cross-protection against toxins produced by the host as well as other competing bacteria (Kim & Surette, 2004). Similarly, the mechanism responsible for the increased resistance of R. leguminosarum swarmer cells to antibiotics may also provide resistance to antimicrobial compounds produced by the host plant and by other soil bacteria. Because this is the first report on swarming in R. leguminosarum, additional experiments are needed to determine the role of swarming in plant–microorganism interactions. We gratefully acknowledge the support for this work from a Natural Sciences and Engineering Research Council (NSERC) Discovery

Grant to M.F.H. D.D.T. was supported by a Government of Canada graduate scholarship, the Bettina Bahlsen Torin 1 chemical structure scholarship, and the Graeme Bell and Norma Kay Sullivan-Bell Graduate Scholarship in Biology. We thank Rhonda G. Clark and Glen Ong, who constructed the 3841c− strain and the GFP-labeled VF39SM, respectively. We also thank Jan Michiels for valuable information on possible swarming conditions. Fig. S1. Swarming patterns of Rhizobium leguminosarum VF39SM on swarm medium supplemented with 0.1% of the following: (a) glycerol; (b) erythritol; (c) mannitol;

and (d) rhamnose. Video Clip S1. A time-lapse video of Rhizobium leguminosarum VF39SM swarming motility. Please note: Wiley-Blackwell is not Calpain responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. “
“Bacteriocin produced by Lactobacillus curvatus CWBI-B28wt is not completely effective against Listeria monocytogenes in food models. There is evidence suggesting that bacteriocin-degrading proteolytic enzymes produced by the CWBI-B28wt strain and/or present in the food matrix contribute to this rebound of Listeria growth. To limit this problem, we have partially characterized an approximately 10-kb plasmid responsible for bacteriocin production in L. curvatus CWBI-B28wt. This plasmid was transferred by high-voltage electroporation into a less proteolytic, but technologically competent Lactobacillus strain.

Although we excluded any patients who had evidence of earlier HIV

Although we excluded any patients who had evidence of earlier HIV diagnosis or prior unrecorded treatment (e.g. we excluded those with an undetectable HIV RNA viral load at the time of starting highly active antiretroviral therapy), we cannot rule out the possibility that a small minority may already have been aware of their diagnosis and some may have received treatment in the past. MK-2206 in vivo It is unlikely, however, that this group would represent a large proportion of our late-presenting patient group. At a national level, late diagnosis is known to contribute disproportionately to serious morbidity and mortality; of the 516 deaths that occurred in the UK among HIV-positive individuals

in 2009, 73% were among individuals who had presented for care with a CD4 cell count <350 cells/μL [1]. Within a multicentre cohort study, such as the UK Collaborative HIV Cohort (CHIC) or the Collaboration of Observational

HIV Epidemiological Research Europe (COHERE) studies, there may also be important differences between participating centres/cohorts in terms of the demographic characteristics of patients seen for care as well as their timing of presentation. By pooling data from these clinics, these larger cohorts are able to provide a broader and more representative view of the situation. Scourfield and colleagues question the value of expanded HIV testing policies. Such interventions have been shown to be cost effective in both the USA and France [2,3] and we have no evidence to suggest that the situation would be GSK2118436 cost any different in the United Kingdom. Furthermore, a reduction in the level of undiagnosed HIV infection will not only have a benefit for individual health but also have a public health benefit, as undiagnosed

HIV infection is likely to account disproportionately for onward transmission [4]. Thus, while we agree with the authors that a clear focus on retention and regular follow-up of patients with diagnosed HIV infection remains essential, we believe that this must be in conjunction with, rather than instead of, increased HIV testing. “
“Fungi possess an advanced secondary metabolism that is regulated and coordinated in a complex manner depending on environmental challenges. To understand this complexity, a holistic Farnesyltransferase approach is necessary. We initiated such an analysis in the important model fungus Aspergillus nidulans by systematically deleting all 32 individual genes encoding polyketide synthases. Wild-type and all mutant strains were challenged on different complex media to provoke induction of the secondary metabolism. Screening of the mutant library revealed direct genetic links to two austinol meroterpenoids and expanded the current understanding of the biosynthetic pathways leading to arugosins and violaceols. We expect that the library will be an important resource towards a systemic understanding of polyketide production in A. nidulans.

The material that was

retained inside this membrane (frac

The material that was

retained inside this membrane (fraction SF-SK10-100R, 45 mg) was eluted on HPSEC as a single Dinaciclib concentration peak (Fig. 2c), with Mw 41 kDa and dn/dc=0.148. It was composed of glucose (51%), galactose (28%) and mannose (21%) and its 13C NMR spectrum (Fig. 3b) contained many C-1 signals, indicating the presence of a complex heteropolysaccharide. Methylation analysis (Table 2) indicated that all galactosyl units were present as nonreducing end-units (Galp and Galf), together with Glcp units. The Manp units were mainly 6-O-substituted, with small amounts of 2,6-di-O-substituted residues, while the Glcp units were 2-O-, 4-O-, 2,3-di-O-, 4,6-di-O- and 2,6-di-O-substituted residues. Substitution at HO-6 of the Manp and Glcp units was also shown by DEPT (Fig. 3b, inset), which provided inverted signals at δ 68.7 and 69.0. In its 13C

NMR spectrum, C-1 signals at δ105.1 and 105.6 corresponded to the nonreducing end-units of β-Galf. The signals at δ 102.6, 102.9 and 103.0 probably arose from C-1 of β-Glcp units. The anomeric configuration of these units was confirmed by their low-field C-1 resonances and also by their 1JC−1, H−1 of 161.5, BGJ398 purchase 164.2 and 160.0 Hz. The remaining C-1 signals at δ 100.7 and 100.2 belong to the α-pyranose series, due to their high-field C-1 resonances and 1JC−1, H−1 (174.4 and 171.5 Hz, respectively) (Agrawal, 1992; Duus et al., 2000; Bubb, 2003). The signals of O-substituted C-2, C-3 and C-4 could be seen at δ 87.5 (C-3), δ 84.9 and 83.3 (C-2) and δ 81.5 (C-4). The material that passed over this membrane (fraction SF-SK10-100E, 66 mg) had high glucose content (79%), with small amounts of mannose (10%) and galactose (11%), indicating the presence of a

glucan. This fraction still had Exoribonuclease a heterogeneous elution profile on gel permeation (Fig. 2c) and due to its small amount was not further purified. However, its 13C NMR spectrum (Fig. 3c) showed β-configurations, due to low-field C-1 signals at δ 103.7 and 103.0. Moreover, it is possible to observe (13)- and (16)-linked Glcp units, due to the presence of a signal at δ 86.2, characteristic of O-substituted C-3, and to the presence of inverted signals at δ 68.8 and 69.0 in the DEPT experiment (Stuelp et al., 1999; Carbonero et al., 2001; Cordeiro et al., 2003). Thus, this glucan resembles a lentinan-type β-glucan. A similar glucan was isolated from the lichen Thamnolia vermicularis var. subuliformis by Olafsdottir et al. (2003) and had a backbone of β-d-(13)-linked glucopyranosyl units branched with a single β-d-(16)-linked unit for every third unit of the backbone. In an attempt to find the isolichenan, we also analyzed the fraction SW, which was obtained in low yield. This fraction was composed of galactose (60.0%), mannose (22.5%) and glucose (17.5%).

It was found that the distribution of preferred directions of a v

It was found that the distribution of preferred directions of a very large population of cells in area 7a studied during eye and/or hand movement was highly anisotropic and favoured the representation of the contralateral space (Fig. 5). Interestingly,

this anisotropy was not observed in the memory epoch, when the animal kept in working memory the location of the target toward which, after a go-signal, an eye and/or a hand movement had to be made. Therefore, this anisotropy in the representation of motor space in IPL is of a dynamic nature, as it emerges only at the moment when all necessary information is available to transform the motor plan into action. It selleck products is our hypothesis that the loss of this representation and the difficulty in continuously combining and updating

all the spatial information necessary to select the direction of visually-guided movement lies at the core of directional hypokynesia. In this respect, it is noteworthy that network models of neglect mostly rest on anisotropy of spatial representations (Pouget & Sejnowski, 1997; Pouget & Driver, 2000). The assumption is that http://www.selleckchem.com/products/dinaciclib-sch727965.html a gradient of spatial representation is embedded in the activity of neurons in the left and right IPL, such that lesions in one hemisphere primarily disrupt information concerning the contralesional space. Therefore the data illustrated and discussed above offer a neurophysiological underpinning for understanding the motor impairments following parietal damage and provide new data to constrain future theoretical models of neglect. Apraxia in general has been defined as the ‘inability to perform certain subjectively purposive movements or movement

complexes Phospholipase D1 with conservation of motility, of sensation and of coordination’ (Wilson, 1909). Apraxia is typically the result of parietal lobe damage, and several types have been identified, including ideational, ideomotor and constructional apraxia. In ideational apraxia (Liepmann, 1920) there is a failure to perform a complex series of actions, such as an inability to perform the sequence movements needed to fold a piece of paper and place it inside an envelope. In ideomotor apraxia (Liepmann, 1920) the patient cannot execute a familiar action on verbal command or by imitation. In constructional apraxia there is a disturbance ‘in formative activities such as assembling, building and drawing, in which the spatial form of the product proves to be unsuccessful, without there being an apraxia for single movements’ (Kleist, 1934). There is a basic difference between ideational and ideomotor apraxia on one hand and constructional apraxia on the other; namely, in the first two forms the patients have difficulty in reproducing previously well learned motor tasks, whereas in constructional apraxia the difficulty is with reproducing visual figures or constructing a complex object made by different parts.

, 2009; Table 3) In general, the two major transcription regulat

, 2009; Table 3). In general, the two major transcription regulators, SoxRS and OxyR, control the bacterial response to oxidative stress (Storz & Imlay, 1999; Chiang & Schellhorn, 2012). Data from DNA microarray experiments revealed that CORM-2 increases expression of the soxS learn more gene and of

members of the SoxRS regulon, such as the marAB operon, encoding a multiple antibiotic resistance protein, and micF coding for a major outer membrane porin (Nobre et al., 2009). This is consistent with the observation that E. coli single mutants with deletions in soxS and sodAB are less resistant to CORM-2 than the parental strain (Nobre et al., 2009; Tavares et al., 2011). Studies in E. coli demonstrated that the OxyR-regulated genes dps, katG, grxA, ahpCF and trxC are up-regulated in cells exposed to sublethal concentrations of H2O2 (Zheng et al., 2001; Wang et al., 2009). Interestingly, real-time RT-PCR analysis

of cells treated with a sublethal 150-μM dose of CORM-2 also caused up-regulation of katG and ahpC (our unpublished data). Furthermore, oxyR and katEG mutant strains are more susceptible to CORM-2 (Nobre et al., 2009; Tavares et al., 2011). The microarray data revealed that the expression of several genes that are transcriptionally altered by CORM-2 is also modified in E. coli biofilm-forming cells (e.g. ibpAB, soxS and tqsA; Ren et al., 2004; Nobre et al., 2009). Consistent with these results, the biofilm content of E. coli exposed to CORM-2 increased by c. two-fold (Nobre et al., 2009). CDK inhibitor Furthermore, deletion of tqsA, a putative transport protein of the quorum-sensing signal autoinducer-2 involved in biofilm formation, yields a strain with higher resistance to CORM-2 (Nobre et al., CYTH4 2009). Increased biofilm formation constitutes a defensive response of bacteria, which is triggered by several other stress agents such as hydrogen

peroxide, acid and heavy metals and is associated with increased bacterial resistance (Zhang et al., 2007; Weber et al., 2010). The yqhD gene, encoding an alcohol dehydrogenase proposed to protect cells against lipid oxidation, and yeeD, a redox protein that regulates the formation of disulphide bonds, were also induced by CORM-2 and H2O2 (Zheng et al., 2001; Perez et al., 2008; Nobre et al., 2009; Wang et al., 2009). Moreover, CO-RMs interfere with the metabolism of methionine, as judged by the alterations observed in the expression of methionine biosynthesis-related genes metF, metNI, metBL and metR (Davidge et al., 2009; Nobre et al., 2009). Consistent with these data, deletion of metR, metI and metN enhanced the sensitivity of E. coli to CORM-2, whereas supplementation with methionine abolished its bactericidal activity (Nobre et al., 2009; Tavares et al., 2011). It has been demonstrated that oxidative stress is associated with methionine auxotrophy (Hondorp & Matthews, 2004).

Discontinuations because of AEs/deaths and for other reasons were

Discontinuations because of AEs/deaths and for other reasons were proportionally higher for EFV than for RPV for both genders, and therefore overall there were no observed gender-related differences in the proportion of responders. Where

gender differences in response rate to ARV regimens have been observed, in most cases the cause has not been an inherent PLX4032 chemical structure difference in antiviral activity of ARVs in men and women. In the CASTLE study, the lower response rate in women compared with men was driven by discontinuations for reasons other than virological failure, and no difference in response rate was observed in the on-treatment analysis [1]. Similarly, a small, albeit nonsignificant, difference in response rate between women and men in the gender, race, and clinical experience (GRACE), study of darunavir/ritonavir was attributable to a higher discontinuation rate in women [17]. Reasons for the higher discontinuation GKT137831 rate appear complex but have included poorer adherence, pregnancy, and a higher incidence of some gastrointestinal AEs in women than in men [1, 17]. In contrast, discontinuation rates in ECHO and THRIVE were similar for men and women; this was particularly apparent in the RPV groups. The difference in response rates according to race, which was observed in both the RPV and EFV treatment groups, is consistent with the findings

of several trials with other ARVs which also observed lower response rates in Black, compared with Asian and White, patients [3, 5, 9-13]. In this study, the lower responses in Black patients were mainly a result of a higher frequency of virological failure and treatment discontinuation for reasons such as loss to follow-up, noncompliance and withdrawal of consent, compared with Asian and White patients. Of note, in both treatment groups, the proportion of Black patients who reported > 95% adherence was lower than for the Fenbendazole other racial groups, which could explain the higher virological failure rate in Black

patients. In other studies, a relationship has been observed between adherence and a lower virological response to ARV regimens in Black patients [5, 12], while one study has suggested that a higher virological failure rate in such patients could not be explained by lower adherence or socio-demographic factors [13]. Another study was designed to equalize variables such as access to care and study drugs between all participants, but the authors were not able to account for the socioeconomic and other differences that they believed led to more Black patients discontinuing than other patients and the resulting lower response rate in these patients [10]. Patients had substantial mean increases in CD4 cell counts at week 48 in both treatment groups, irrespective of gender or race.

Our study demonstrates for the first time that olfactory receptor

Our study demonstrates for the first time that olfactory receptor expression is experience-dependent and modulated by scent conditioning, providing novel insight into how molecular regulation at the periphery Selleck Dinaciclib contributes to plasticity in the olfactory system. “
“In recent years, much effort has been devoted to identifying stimuli capable of enhancing adult neurogenesis, a process that generates new neurons throughout life, and that appears to be dysfunctional in the senescent brain and in several neuropsychiatric and neurodegenerative diseases. We previously reported that in vivo exposure

to extremely low-frequency electromagnetic fields (ELFEFs) promotes the proliferation and neuronal differentiation of hippocampal neural stem cells (NSCs) that functionally integrate in the dentate gyrus.

Here, we extended our studies to specifically assess the influence of ELFEFs on hippocampal newborn cell survival, which is a very critical issue in adult neurogenesis regulation. Mice were injected with 5-bromo-2′-deoxyuridine (BrdU) to label newborn cells, CDK inhibitor drugs and were exposed to ELFEFs 9 days later, when the most dramatic decrease in the number of newly generated neurons occurs. The results showed that ELFEF exposure (3.5 h/day for 6 days) enhanced newborn neuron survival as documented by double staining for BrdU and doublecortin, to identify immature neurons, or NeuN labeling of mature neurons. The effects of ELFEFs were associated with enhanced spatial learning and memory. In an in vitro model of hippocampal NSCs, ELFEFs exerted their pro-survival action by rescuing differentiating neurons from apoptotic cell death. Western immunoblot assay revealed reduced expression

of the pro-apoptotic protein Bax, and increased levels of the anti-apoptotic protein Bcl-2, in the hippocampi of ELFEF-exposed mice as well as in ELFEF-exposed NSC cultures, as compared with their sham-exposed counterparts. Our results may have clinical implications unless for the treatment of impaired neurogenesis associated with brain aging and neurodegenerative diseases. “
“Department of Biochemistry, Faculty of Medicine, Saitama Medical University, Moroyama-machi Iruma-gun, Saitama, Japan Calcium imaging of individual neurons is widely used for monitoring their activity in vitro and in vivo. Synthetic fluorescent calcium indicator dyes are commonly used, but the resulting calcium signals sometimes suffer from a low signal-to-noise ratio (SNR). Therefore, it is difficult to detect signals caused by single action potentials (APs) particularly from neurons in vivo. Here we showed that a recently developed calcium indicator dye, Cal-520, is sufficiently sensitive to reliably detect single APs both in vitro and in vivo. In neocortical neurons, calcium signals were linearly correlated with the number of APs, and the SNR was > 6 for in vitro slice preparations and > 1.6 for in vivo anesthetised mice.

The same orf14 premature stop codon is present in the Tn5253-like

The same orf14 premature stop codon is present in the Tn5253-like element (GenBank FM201786). The element of strain ATCC 700669 (GenBank FM211187) has a deletion of 1 nt in the int coding sequence that determines a frameshift. Completely sequenced Tn916/Tn5251-like elements are also present in many other bacterial species including Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus parauberis, Streptococcus suis, Streptococcus cristatus, check details Streptococcus intermedius, E. faecalis and Ureaplasma urealyticum.

Noteworthy, as found in S. pneumoniae, many of these elements are inserted into other chromosomal genetic elements, such as the 89 K pathogenicity island present in recently sequenced strains of S. suis (Chen et al., 2007). All ORFs, with the exception of orf10, orf20 and orf24, are preceded by a ribosome-binding site. The start codon of orf6 is missing; orf15 starts with the GTG codon and orf20 with TTG. By manual annotation, it was possible to attribute a putative function only to 11 out of 22 ORFs (Table 2). Predicted C59 wnt order gene products were blasted against public protein databases and the Pfam protein family

database, taking into account significant homologies with functionally characterized proteins or good matches with Pfam domains. As reported for Tn916, int and xis are known to be involved in the integration/excision process (Rudy et al., 1997); Int also acts as an accessory protein in the cleavage process that initiates the conjugal transfer mediated by the relaxase Orf20 (Rocco & Churchward, 2006). The tet(M) gene codes for a ribosomal protection protein responsible for tetracycline resistance. orf7 and orf9 code for a putative sigma factor and a putative transcriptional regulator, respectively, and possibly play a role in the gene expression regulation of Tn5251 genes (Celli & Trieu-Cuot, 1998). orf21 is an FtsK-SpoIIIE family protein that may play a role in segregating the replicated element between the donor and the recipient. orf14, coding for a putative cell wall hydrolase, may help degrade the peptidoglycan

during conjugal mating. Orf16 is homologous to TcpF of Clostridium perfringens pCW3, which has been Sitaxentan demonstrated to be essential for the plasmid conjugal transfer. This protein has an ATP-binding motif and is homologous to the VirB4 type IV secretion protein of Gram-negative bacteria that use energy from ATP hydrolysis to pump transposon DNA into the recipient cell (Rabel et al., 2003). orf18 codes for an antirestriction protein that protects the transposon DNA from restriction inhibiting host restriction enzymes (Serfiotis-Mitsa et al., 2008). Tn5251 is inserted into Tn5253, flanked by two different 6-bp-long coupling sequences (CS). Excision of Tn5251 from its attB site produces a CI and a deletion in Tn5253. In the CI, single-stranded overhangs, produced by staggered cleavages of CS, are joined into a heteroduplex (Provvedi et al., 1996).

Given that the Calvin–Benson–Bassham (CBB) cycle enzymes downstre

Given that the Calvin–Benson–Bassham (CBB) cycle enzymes downstream of RuBisCO require reducing equivalents, it is an advantage that Hg2+ inhibits RuBisCO, shutting check details down the CBB cycle, making reducing equivalents available to mercuric reductase. We anticipate that enzymes of the Quayle pathway were inhibited (given the lack of carbon assimilation), forcing oxidation

of formaldehyde and formate to CO2 to generate reducing equivalents to meet requirements of the detoxification. It should be noted that hexulose-3-phosphate synthase (EC 4.1.2.43) – a key enzyme in the Quayle pathway – in M. capsulatus (Bath) is inhibited by Hg2+ at 100 μM (Ferenci et al., 1974). Cytochrome c oxidase was unable to reduce Hg2+ under the assay conditions employed click here – either with cytochrome c550 or with ferrocyanide as the cofactor

– the specific activities were zero in both cases. The specific activity of an apparent mercuric reductase (± SEM; n = 7) was 352 (±18) nmol NADH oxidized min−1 (mg protein)−1 or 16 (±2) nmol NADPH oxidized min−1 (mg protein)−1, suggesting that this enzyme may be present. In the literature, NADPH is the more usual cofactor; however, a number of species contain an NADH-dependent enzyme (Gachhui et al., 1997; Meissner & Falkinham, 1984). Blastp interrogation of the GenBank™ database shows that the closest matches to the M. capsulatus (Bath) MerA are those derived from genome sequences of Alicycliphilus denitrificans BC (YP_004126461), Acidovorax sp. JS42 (YP_985596) and Delftia acidovorans SPH-1 (YP_001561514) with 83%, 83% and 81% identity, respectively. It is interesting to note that these are members Methocarbamol of the Betaproteobacteria, rather than the Gammaproteobacteria. The presence of apparent mercuric reductase activity in M. capsulatus Bath extracts not previously exposed to mercury (II)

indicates that the enzyme is constitutively expressed. RNA microarray data concerning M. capsulatus (Bath) demonstrates that merA and other predicted mercury detoxification genes are expressed during growth as performed here (A. Khalifa, personal communication). We conclude that it is likely that a constitutive, NADH-dependent mercuric reductase is active in M. capsulatus (Bath), with NADH provided at the expense of methane oxidation, although further experiments with inhibitors or knock-out mutants are required to determine whether the merA gene is required for mercury (II) reduction. In the ‘emergency situation’ of mercury (II) exposure, the cell ‘prioritises’ the oxidation of methane to CO2, halting carbon assimilation, presumably to make more NADH available to remove the ion as rapidly as possible by way of a fundamental survival mechanism. Although enzymes of the Quayle pathway and CBB cycle were inhibited – as demonstrated by the complete lack of 14C assimilation – the primary methane oxidation enzymes remained active for over 30 min.

Further, if proteinuria is identified, uAPR

Further, if proteinuria is identified, uAPR Panobinostat order may provide useful insights into whether the problem lies with the cART regimen, requiring regimen change, or elsewhere, requiring further enquiry into comorbidity. In our cohort, those with biopsy-proven cART-associated damage were also identified by a high uPCR but a low uAPR, proteinuria resolved after switching cART regimen. In summary, it is important to consider the screening protocol used for urinary protein estimation in HIV-infected individuals. The use of uACR or dipstick urinalysis alone as a screening test for proteinuria may not detect significant tubular dysfunction or alert the clinician

to potential cART-related problems. Our results suggest that measuring both uPCR and uACR on a single sample (and hence obtaining a uAPR) may be both practical and helpful in evaluating proteinuria in selected HIV-infected patients, and may help to identify those in whom a more careful evaluation of tubular dysfunction is warranted. Conflicts of interest: AS has received travel bursaries and scholarships from Boehringer Ingelheim, Bristol Myers Squib, Gilead, Merck Sharp

and Dohme, Tibotec and Viiv Healthcare. KN has received funding for travel, consultancies and teaching purposes from Bristol Myers Squibb, Gilead Sciences and Viiv Healthcare. CS has received funding Ion Channel Ligand Library for travel, consultancies and teaching purposes from Gilead Sciences, Bristol Myers Squibb and Janssen-Cilag. MF has received honoraria and/or travelling scholarships from Abbott, Bristol Myers Squibb, Gilead, Janssen, Merck and Viiv Healthcare. YG has received travel bursaries and educational grants from Abbott, Gilead, Tibotec and Viiv Healthcare. SH has received honoraria

from Gilead in the past. “
“The Malawi antiretroviral therapy (ART) programme uses the public health approach to identify ART failure. Advanced disease progression may occur before switching to second-line ART. We report outcomes for patients evaluated and initiated on second-line treatment in Malawi. Patients meeting Malawi immunological or clinical criteria for ART failure in two large urban ART clinics Succinyl-CoA were evaluated for virological failure (viral load >400 HIV-1 RNA copies/mL) and, if failure was confirmed, initiated on second-line ART (zidovudine/lamivudine/tenofovir/lopinavir/ritonavir). Patients were seen monthly and laboratory evaluations were performed quarterly and as needed. We performed logistic regression modelling to identify factors associated with mortality, mortality or new HIV illnesses, and virological suppression at 12 months. Of the 109 patients with confirmed virological failure, five patients died prior to initiation, three declined switching and 101 patients initiated second-line treatment. Over 12 months, 10 additional patients died, 34 patients experienced 45 HIV-related events, and 19 patients experienced grade 3 or 4 toxicities. Among survivors, 85.2% had HIV-1 RNA<400 copies/mL at 12 months.