It is worth mentioning that sPBP6, which is the next nearest homolog of DacD, is inactive on pentapeptide substrate (Chowdhury et al., 2010). The crystal structures of sPBP5 and sPBP6 (Nicholas et al., 2003; Chen et al., 2009) show a similar secondary structure with no gross architectural differences. In the absence of crystal structure, CD spectral analysis would be of utmost importance to elucidate the biophysical characteristics of sDacD. It was evident from the CD spectra that purified protein was in a native conformation with characteristics of the molecular

spectra AZD8055 datasheet of alpha and beta structures, indicating the protein was active and stable at room temperature. Unlike sPBP5 and sPBP6 (Chowdhury et al., 2010), more beta-sheets were detected in sDacD (Table 3, Supporting Information, Fig. S1). The occurrence of a larger amount of β-sheet structure in sDacD may cause some structural alteration, which might exert different biological activity than PBP5.

Because DacD shared a high level of aa identity with PBP5, homology modelling (or comparative protein structure modelling) could be applied to generate the three-dimensional conformation of sDacD. For model building, the program modeller 9v1 was used with the pdb coordinate, 3BEC chain A (crystal structure of E. coli PBP5 in complex with a peptide-mimetic cephalosporin; Sauvage et al., 2008) as template. The secondary structure prediction by BTK inhibitor ic50 predict protein and psipred suggested that sDacD was a αβ protein with a larger amount of β-sheet structure (Table 3 and Fig. S2), which was consistent with the results obtained from CD spectroscopic analyses. The model of lowest energy value had 94.9% residues in the most favoured region in the Ramachandran plot and 98.35% residues had an average mafosfamide 3D-1D score above 0.2, as obtained through verify3d profile (Fig. 2), which affirms a well derived model. The model has been

deposited to the PMDB server (ID PM0076504). Like sPBP5, the sDacD model is composed of two Domains placed perpendicular to each other. Domain II is β-sheet-rich, whereas Domain I is composed of both α-helices and β-sheets (Fig. 2a). There is a relative increase in beta-sheet in Domain I of sDacD as compared with sPBP5. Comparison of the calculated secondary structure of the sDacD model generated by stride with that of sPBP5 indicates that residues Gln 38-Arg 39 and His158-Ser159-Ser160 of sDacD create a beta-sheet structure, whereas the respective positions of sPBP5 create coils and turns. Moreover, the Glu 230 and Met 233 of sPBP5 Domain I form turns, whereas the corresponding residues (Gln 229 and Arg 232, respectively) in the sDacD model adopt a beta-conformation. Therefore, both similarities and the differences exist when we take a closer view at the active-site of sDacD and sPBP5.

pulmonaria, intermingled

with other bacteria (Fig. 1). Burkholderia is present in the culturable fraction but hardly detected by in situ hybridization (Cardinale et al., 2006, 2008). Isolates of Burkholderia were retrieved from the same lichen samples used in this work (data not shown). Although evidences of either symbiotic relationship or pathogenicity were not yet shown in the lichen hosts, strains of Burkholderia are selleck chemical already known for their stable associations and symbiosis with fungi, such as mycorhiza (Partida-Martinez et al., 2007). Considering the protective and self-sustaining nature of the lichen symbiosis, it can be hypothesized that some of the lichen-associated Burkholderia strains play functional roles, as already proved in other fungal-Burkholderia associations, such as enabling the vegetative reproduction (Partida-Martinez et al., 2007) or supporting the nutrient uptake (Ruiz-Lozano & Bonfante, 1999) and pathogen defence (Opelt et al., 2007). We also analysed the diversity of nifH genes, which is related to the functional

group of nitrogen fixers. They include the Nostoc symbionts and further potential N-fixing species. The ability to grow on N-free substrate was already shown for bacterial strains belonging to different classes, isolated from different species of lichens (Cardinale et al., 2006; Grube et al., 2009). Grube & Berg (2009) suggested that, in the case of N-limiting conditions, bacterial N-fixation could be of considerable importance for the vitality of lichens. To test our hypothesis, we considered the theoretical pattern of distribution proposed by Hughes Martiny et al. (2006) as a consequence Raf inhibitor of prevailing historical or environmental influences. Lobaria pulmonaria

has very strict requirements for growing, so that the environmental parameters cannot differ very much across sites where it grows. Its associated bacteria live in their habitat (the thallus) where the environmental parameters are even more stable, because of the homeostatic effect generated by the hosting organism. The assumption of our study was that the lichen Lobaria offers a similar habitat, even across very distant regions. The lichen should thus represent one single ‘microbial habitat’ and the only differences O-methylated flavonoid between structures of bacterial taxa associated with lichen samples from different regions would result from historical contingencies as a biogeographical effect. Lichen samples were collected from northern Styria (47°37′35″ N, 14°41′35″ E), southern Styria (46°44′35″ N, 15°04′30″ E), Montenegro (42°53′55″ N, 19°35′51″ E) and Madeira (32°44′09″ N, 16°53′17″ W). These locations lie within a range of relative distances (102.4–3367 km) that allows the occurrence of both historical contingencies and contemporary environmental factors (Hughes Martiny et al., 2006). Four to seven independent replicates (composite samples of four lichen thalli) per sampling site were collected.

Depending on the growth substrate, different O-demethylases are induced in Acetobacterium dehalogenans. A vanillate- and a veratrol-O-demethylase of this organism have been described earlier. The methyltransferase I (MT I), a component of this enzyme system, catalyzes the ether cleavage and the transfer of the methyl group to a super-reduced corrinoid bound to a protein. Compound Library clinical trial The MT I of the vanillate- and veratrol-O-demethylase (MT Ivan and MT Iver) were found to be zinc-containing enzymes. By site-directed mutagenesis, putative zinc ligands were identified, from which the following unique zinc-binding motifs were derived: E-X14-E-X20-H for MT Ivan and D-X27-C-X39-C for MT Iver. Phenyl

methyl ethers are natural components of lignin and are formed upon lignin degradation by fungi. The methyl groups of the phenyl methyl ethers can be utilized as growth selleck chemical substrates by different acetogenic bacteria such as Acetobacterium dehalogenans, Acetobacterium woodii, Holophaga foetida, Moorella thermoacetica and Sporomusa ovata (Bache & Pfennig, 1981; Daniel et al., 1991; Traunecker

et al., 1991; Kasmi et al., 1994; Stupperich et al., 1996; Kaufmann et al., 1997; Kreft & Schink, 1997). The cleavage of the ether bond and the transfer of the methyl group to tetrahydrofolate are catalyzed by the O-demethylase enzyme system (Kaufmann et al., 1997; Engelmann et al., 2001; Naidu & Ragsdale, 2001). For A. dehalogenans, two O-demethylases have been described. They consist of two

methyltransferases (MT I and MT II), a corrinoid protein (CP) and an activating enzyme (AE) per enzyme system (Kaufmann et al., 1997; Engelmann et al., 2001). MT I mediates the cleavage of the ether bond and the transfer of the methyl group to the super-reduced corrinoid cofactor of CP. CP is subsequently demethylated by the second methyltransferase MT II and the methyl group is transferred to tetrahydrofolate. The methyl group of methyltetrahyrofolate is further oxidized to CO2 or converted to the methyl group of acetate (Drake et al., 2006). For the methylation of CP, the cobalamin cofactor has to be in its super-reduced form. Because Bumetanide of the negative redox potential of the cob(II)alamin/cob(I)alamin couple in CP ([CoI]/[CoII]≤550 mV; Siebert et al., 2005), inadvertent oxidation of the cofactor may occur, which leads to the formation of the inactive cob(II)alamin. Therefore, an AE (RACE protein; Schilhabel et al., 2009) is required that reduces the cob(II)alamin cofactor of CP to the super-reduced form in an ATP-dependent reaction. During the course of the activation, AE increases the redox potential of the corrinoid (Schilhabel et al., 2009). Acetobacterium dehalogenans induces different O-demethylase systems depending on the growth substrate of the organism (Kaufmann et al., 1997; Kaufmann et al., 1998; Engelmann et al., 2001). Two O-demethylase systems have been characterized so far, designated vanillate- and veratrol-O-demethylase (Kaufmann et al.

Recombinant Scl (rScl) proteins used in ELISA were expressed in Escherichia coli and purified by affinity chromatography using the Strep-tag selleck inhibitor II system (IBA-GmbH, Goettingen, Germany) as described previously (Xu et al., 2002; Han et al., 2006b). Briefly, the DNA fragments of several scl1 and scl2 alleles, encoding the extracellular portions of the Scl1 and Scl2 proteins, were amplified by PCR with Deep Vent Taq Polymerase (New England Biolabs, Beverly, MA) and cloned into the pASK-IBA2 vector designed for periplasmic expression. rScl proteins (0.5 μM) were immobilized onto Strep-Tactin-coated microplate wells for 1.5 h at

room temperature. Following overnight blocking with Tris-buffered saline (TBS) supplemented with 1% bovine serum albumin (BSA) at 4 °C, 1 μg of

each ligand that included plasma fibronectin (pFn), cellular fibronectin (cFn), laminin (Lm), bovine collagen types I and IV, decorin, heparin, and fibrinogen (all proteins were purchased from Sigma) was added to triplicate wells and the mixture was incubated at room temperature for 1 h. rScl-bound ligands were detected with specific primary LY2157299 price antibodies and appropriate secondary antibodies conjugated to horseradish peroxidase (HRP). The HRP reaction was developed with 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) substrate and recorded at OD415 nm after 15 min of color development. In the ligand competition experiments, purified cFn and Lm were used in a molar ratio 1 : 1. First, the primary ligands, for example cFn or Lm, were added to triplicate wells immobilized with P176 and incubated for 1 h at room temperature.

Following washes with TBS, secondary ligands were added to the appropriate wells, for example Lm was added to wells containing the Scl1–cFn complex and vice versa; samples were incubated for 1 h at room temperature. Subsequently, the ELISA proceeded as described above. To generate green fluorescent protein (GFP)-expressing GAS cells, the wild-type Sulfite dehydrogenase strain, the scl1-inactivated mutant, and mutant complemented in trans for Scl1.41-protein expression (plasmid pSL230) (Caswell et al., 2007) were transformed with the plasmid pSB027 (Cramer et al., 2003). Glass cover slips were placed in the wells of 24-well tissue culture plates and coated with 2.5 μg of purified ECM proteins or BSA overnight at 4 °C, and subsequently blocked with 1% BSA in TBS for 1 h. Approximately 1 × 107 CFU of fluorescent GAS cells were added to each well for 1 h at room temperature and unbound cells were removed by washing with PBS. ECM-bound GAS cells were fixed with 3% paraformaldehyde in PBS for 30 min. The cover slips were removed from the wells, air-dried, placed on microscope slides, and viewed by fluorescent microscopy using a 450–490 nm excitation channel at × 400 and × 1000 magnification. For quantification, GAS cells were counted in 10 random fields under × 1000 magnification.

Further studies

reported that a new galactosaminogalactan and the galactomannan were the major polysaccharides of the in vivo A. fumigatus EPS (Loussert et al., 2010). For A. niger, after germination upon a support, the new hyphae also produce an EPS (Villena & Gutierrez-Correa, 2007b). Singhal et al. (2011) recently reported that primary epithelial cells could support the growth of biofilms under flow conditions that were also associated with significant EPS production compared with biofilms formed under static condition (Singhal et al., 2011). The production of EPS has also been reported elsewhere, where it is shown to be produced on polystyrene and on CF bronchial selleck chemicals llc epithelial cells (Seidler et al., 2008). This study also reported that biofilm cells attaching to epithelial cells exhibited decreased sensitivity to antifungal drugs. Whilst the precise role of the EPS

5 FU is not known, it is hypothesized that it plays a significant role in antifungal resistance by preventing diffusion. This is supported from data emerging from the C. albicans biofilm field, where it was demonstrated that EPS expression (specifically beta-glucans), encoded through fks1, sequesters antifungal agents and reduces susceptibility (Nett et al., 2010a). Figure 2 illustrates the presence of EPS within A. fumigatus biofilms. Antifungal resistance is a defining characteristic of fungal biofilms. In A. fumigatus, biofilms antifungal resistance has been reported (Beauvais et al., 2007; Mowat et al., 2007; Seidler et al., 2008; Fiori et al., 2011), which has been shown to be phase dependant (Mowat et al., 2008b). Here, three phases of biofilm growth (8, 12 and 24 h) were investigated to assess the effects of antifungal agents on different phases of biofilm. Clear differences in susceptibility were observed in each biofilm population, where younger biofilms (8 h) were significantly Farnesyltransferase more susceptible than intermediate (12 h) and

mature biofilms (24 h) (Mowat et al., 2008b). Our recent study, supports the concept that this phase resistance is correlated with efflux pump activity. This study reported that efflux activity increases with biofilm maturity, and that sensitivity to voriconazole could be improved through the use of a competitive inhibitor. Transcriptomic analysis showed that maximum activity associated with the early filamentous phase (12 h), and in defined clinical isolates, maximal expression of mdr4 correlated with the highest increase in resistance in 12 h biofilm populations. Conversely, expression of this gene was minimal at 24 h, suggesting phase dependant efflux activity (Rajendran et al., 2011). It was therefore speculated that efflux pump activity plays a contributory role to antifungal resistance. It is conceivable that A.

This adds weight to the prime position of science within the MPharm curriculum and the view that a scientific foundation is vital for the future pharmacist. This research highlights the importance of the profession engaging more fully with different theoretical perspectives of knowledge within a vocational scientific programme of study. 1. Gibbons M. The New Production of Knowledge: The Dynamics of Science and Research in Contemporary

Societies. Sage, 1994. J. Sidhua, H. Zamanb, S. Whitea aKeele University, Newcastle-under-Lyme, UK, bUniversity of Bradford, Bradford, CP-868596 purchase UK This focus group study explored UK fourth year pharmacy students’ perceptions on interacting with people with mental health problems, focusing on changes in their perceptions since they were first year students, and compared these with

current first year students’ perceptions. Students talked about attempting to ‘treat them normally’ but that they ‘couldn’t help’ treating people differently. Fourth year students seemed to have greater professional discomfort about this. This suggests that students’ attitudes may change as they progress through the course, even if only to heighten their sense of professional discomfort about knowingly treating people differently. Previous research suggests that pharmacy workplace contact and the APO866 mental health content of undergraduate pharmacy education may not improve students’ negative attitudes towards people with mental health problems.1 However, studies have not explored students’ perspectives in depth on interactions with people with mental health problems and how these may change as they progress through the undergraduate course. This study aimed to explore the perceptions of fourth (final) year students in a UK school of pharmacy on these issues. The perceptions of a sample of first year students C-X-C chemokine receptor type 7 (CXCR-7) on interacting with people

with mental health problems were also explored and compared with the perceptions that the fourth year students reported as having when they were first years. Qualitative focus groups were used because this technique is suited to exploring the range and complexity in participants’ perspectives and for them to clarify their views, as well as for identifying cultural values or group norms. Following institutional ethical approval, an invitation was emailed to all fourth year students and first year students. The first author conducted three focus groups with 17 fourth year students and three focus groups with 15 first year students who volunteered. Groups ranged from four to six students. The sample included participants with different characteristics to represent a broad range of views. The interview guide was developed from objectives of the study and a review of the literature. Broad topics included perceptions of mental illness, key influences on these, and the effect of the MPharm course on these perceptions.

, 2002; Kang et al., 2007). These products with high biological activity can severely attack cell membranes, proteins and nucleic acids, cause enzyme inactivation, protein denaturation, lipid peroxidation and DNA mutation, and result in ecotoxicity through oxidative damage to cellular components (Imlay et al., 1998; Vandana et al., 2002). Therefore, mechanisms that protect the cell against the toxic effects of ROS such

as H2O2 and are needed. Many cells have developed an antioxidative defense system consisting of ROS-scavenging enzymes, e.g. SOD, CAT, ascorbate peroxidase (APX), and antioxidants such as ascorbate (AsA) and glutathione (GSH) (Mittler et al., 2004). Various antioxidant enzymes, whose function is to eliminate PD0325901 manufacturer oxygen free radicals and protect the organism, indirectly could reflect the changes of oxygen free radical content in living cells. SOD can catalyze to O2 and H2O2 rapidly (Gerlach et al., 1998) and then H2O2 is eliminated by the H2O2-scavenging enzyme CAT (Hidalgo et al., 2004). Among cellular functions, GST plays an important role in the detoxification of ROS and the regulation of redox balance (Siritantikorn et al., 2007). Total antioxidant capacity (T-AOC), which

is defined as a measure of the amount of free radical scavenging (MacDonald-Wicks et al., 2006), is a useful parameter to assess the antioxidant status of an organism. Microorganisms

frequently undergo stress conditions caused by herbicide BTK inhibitor application (Lü et al., 2009). Bacteria possess a wide variety of stress responses, including oxidative stress response, and they have the ability to sense the stress signal through a process in which many enzymes are involved (Niazi et al., 2008). There is considerable interest in free radical-mediated damage in biological systems following atrazine exposure. However, these studies focused mainly on damage to animals and plants cells. Few studies have shown the response of antioxidant enzymes in bacteria to the oxidative stress induced by atrazine. Moreover, information on general stress responses Florfenicol and their regulation in bacteria is limited. The purpose of the present work is to evaluate the response of antioxidant enzymes in two representative bacteria to atrazine stress. SOD, CAT, GST activities and T-AOC in one Gram-negative representative strain Escherichia coli K12 and one Gram-positive representative strain Bacillus subtilis B19 treated with atrazine were examined in this study. We believe that this work will be valuable for further study on atrazine stress tolerance of bacteria and defense mechanism of antioxidant enzymes against atrazine or other triazine herbicides.

The content of this publication is solely the responsibility of the authors and does not necessarily represent he official views of any of the institutions mentioned above. C. V. Mean, V. Saphonn* and

K. Vohith, National Center for HIV/AIDS, Dermatology & STDs, Phnom Penh, Cambodia; F. J. Zhang*, H. X. Zhao and N. Han, Beijing Ditan Hospital, Beijing, China; P. C. K. Li*† and M. P. Lee, Queen Elizabeth Hospital, Hong Kong, China; N. Kumarasamy* and S. Saghayam, YRG Centre for AIDS Research and Education, Chennai, India; S. Pujari* and K. Joshi, Institute of Infectious Diseases, Pune, India; T. P. Merati* and F. Yuliana, Faculty of learn more Medicine, Udayana University & Sanglah Hospital, Bali, Indonesia; S. Oka* and M. Honda, International Medical Centre of Japan, Tokyo, Japan; J. Y. Choi* and S. H. Han, Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea; C. K. C. Lee* and R. David, Hospital Sungai Buloh, Kuala Lumpur, Malaysia; A. Kamarulzaman* and A.

Kajindran, University of Malaya, Kuala Lumpur, Malaysia; G. Tau*, Port Moresby General Hospital, Port Moresby, Papua New Guinea; R. Ditangco* and R. Capistrano, Research Institute for Tropical Medicine, Manila, Philippines; Y. M. A. Chen*, W. W. Wong and Y. W. Yang, Taipei Veterans General Hospital and AIDS Prevention and Research Centre, National Yang-Ming University, BIBW2992 in vitro Taipei, Taiwan; P. L. Lim*, O. T. Ng and E. Foo,

Tan Tock Seng Hospital, Singapore; P. Phanuphak* and M. Khongphattanayothing, HIV-NAT/Thai Red Cross AIDS Research Centre, Bangkok, Thailand; S. Sungkanuparph* and B. Piyavong, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; T. Sirisanthana*‡ and W. Kotarathititum, Research Institute for Health Sciences, Chiang Mai, Thailand; J. Chuah*, Gold Coast Sexual Health Clinic, Miami, Queensland, Australia; A. H. Sohn*, J. Smith* and B. Nakornsri, The Foundation for AIDS Research, New York, USA; D. A. Cooper, M. G. Law* and J. Zhou*, National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Sydney, Australia. *TAHOD Steering Committee member; †Steering Committee chair; ‡co-chair. “
“Gender-specific data on the outcome of combination antiretroviral therapy (cART) are a subject of controversy. We aimed to compare treatment responses between genders selleck in a setting of equal access to cART over a 14-year period. Analyses included treatment-naïve participants in the Swiss HIV Cohort Study starting cART between 1998 and 2011 and were restricted to patients infected by heterosexual contacts or injecting drug use, excluding men who have sex with men. A total of 3925 patients (1984 men and 1941 women) were included in the analysis. Women were younger and had higher CD4 cell counts and lower HIV RNA at baseline than men. Women were less likely to achieve virological suppression < 50 HIV-1 RNA copies/mL at 1 year (75.

Following 1 and 2 h of co-incubation, the ∆TTSS-2 strain displayed a 2.6- and 1.6-fold decrease in translocation, respectively, compared to wt, although these decreases were not statistically significant (Fig. 3). These data demonstrate that the TTSS do not inhibit V. parahaemolyticus translocation. Instead the bacteria are transported across the M cell-like co-culture model independently

of TTSS-1, while TTSS-2 has a modest enhancing effect on translocation at early stages of infection. To investigate whether V. parahaemolyticus translocates across the M cell-like co-culture model by disrupting the epithelial monolayer, the TER was measured in response to infection with wt, ∆TTSS-1 or ∆TTSS-2 bacteria. Measurement of the TER is one of the main ways to examine epithelial integrity Sirolimus AG-014699 concentration in vitro (Terres et al., 1998) as it represents the resistance to ion flow across the epithelial monolayer. Infection of the co-culture model with the wt bacteria resulted in a sharp decrease in TER 1 h postinfection with a further decrease observed 2 h postinfection (Fig. 4a). Similar decreases were detected for the ∆TTSS-1 and ∆TTSS-2 bacteria. Consequently, examination of the effects of V. parahaemolyticus on the TER of the M cell-like co-culture model indicates

that the disruption occurs independently of either TTSS-1 or TTSS-2. Infection of the Caco-2 monolayer with wt bacteria also resulted in a decrease in TER (Fig. 4b). Comparison of these data indicates that V. parahaemolyticus infection results in an increase in TER disruption in co-culture models when compared to Caco-2 monolayers. Although Phosphoglycerate kinase not statistically significant, the difference

in TER decrease between Caco-2 and co-cultures was detected consistently. To determine whether MAPK activation has a role in the effects elicited by the bacteria on the co-culture, disruption of the TER in response to wt infection in the presence of MAPK inhibitors was examined. There was minimal difference between untreated co-cultures and co-cultures treated with the MAPK inhibitors (Fig. 4c). These nominal differences demonstrate that MAPK activation is not necessary for the disruption of the co-culture model in response to V. parahaemolyticus infection. Comparison of Caco-2 monolayers with a co-culture M cell model in this study indicates that V. parahaemolyticus is translocated in increased numbers (threefold increase) across the co-culture model. In the intestine, Peyer’s patch M cells actively endocytose bacteria and other foreign material for delivery to underlying lymphocytes, and this intracellular translocation would be the principal explanation for the observed increases (Neutra et al., 1996; Siebers & Finlay, 1996; Wong et al., 2003; Jang et al., 2004; Brayden et al., 2005). Enhanced transport of other M cell tropic bacteria such as Salmonella across an in vitro co-culture model (Martinez-Argudo & Jepson, 2008) and invasion through murine Peyer’s patches (Jones et al.

There are preliminary data demonstrating a direct effect of HIV on the fibrogenic process through the binding of gp120 to CCR5 receptors on Ku-0059436 mw hepatic stellate cells, the principal fibrogenic cell type in the liver [32–33] which triggers an increased expression of collagen and inflammatory chemokines. Additional data suggest that microbial translocation [34] plays a role

in accelerating liver fibrosis through toll-like receptor (TLR) signalling [35] and HIV may have a direct role through suppression of a major transcription factor in fibrogenesis (PPARγ). No RCT evidence exists addressing the HBV DNA level at which anti-HBV treatment should be commenced in HBV/HIV-infected individuals. The choice of >2000 IU/mL is based on indirect data: i) the level of HBV DNA is proportional to the risk of cirrhosis and HCC in observational studies in monoinfection [8,36–39]; buy Epacadostat ii) the degree

of HBV viral suppression achieved during treatment is an important determinant in reducing progression to cirrhosis, liver failure, HCC and need for liver transplantation [8,40]; iii) prolonged low level viraemia may be associated with progressive liver damage in HBV-monoinfection [37] and; iv) levels of HBV DNA 2000–20 000 IU/mL may be associated with a histological indication for treatment. We recommend TDF/FTC as part of a fully suppressive ART combination should be given to all patients where HBV treatment is deemed necessary (1C). We suggest adefovir or 48 weeks of PEG-IFN are alternative options in patients unwilling or unable to receive TDF/FTC as part of a fully suppressive ART combination but requiring HBV therapy (2C). We suggest PEG-IFN is only used in HBsAg-positive patients Casein kinase 1 with a repeatedly raised ALT, low HBV DNA (<2 × 106 IU/mL), and minimal fibrosis, irrespective of HBeAg antigen status (2D). Lack of HBV DNA response (reduction to <2000 IU/mL at 12 weeks) should prompt discontinuation. Repeat testing should be performed 3-monthly to observe the presence of seroconversion (2C).

Where ART is not indicated for HIV, and the CD4 count is ≥500 cells/μL, the optimum strategy is uncertain: to use agents with exclusive HBV and no HIV activity (i.e., PEG-IFN and adefovir) so that HIV resistance is not induced, or earlier initiation of ART. Seven drugs are available with HBV activity: pegylated interferon (PEG-IFN), lamivudine (3TC), emtricitabine (FTC), adefovir (ADV), entecavir, telbivudine and tenofovir (TDF). Four have additional HIV activity (3TC, FTC, TDF and entecavir) and two are only active against HBV at licensed doses (PEG-IFN, ADV). There is conflicting evidence on whether telbivudine exerts activity against HIV. Entecavir and tenofovir are recommended first-line therapies for HBV monoinfection and have demonstrated high efficacy with low rates of resistance and a favourable safety profile. Both are safe in patients with decompensated liver disease.