Cold-induced transcripts have a long 5′ UTR containing cold-box elements described in E. coli, B. subtilis or archeabacteria (Jiang et al., 1996; Chamot et al., 1999; Hunger et al., 2006). These cis-elements modulate the stability of cold-induced mRNAs at low temperatures (Gualerzi et al., 2003). Analysis of BC0259 5′-UTR revealed the presence of such cold-box elements, with (1) one box possibly located downstream of the +1 of transcription (thus on BC0259 mRNA) and (2) two other conserved KU-60019 purchase sequences located upstream from the +1 of transcription. The significance of these sequences upstream of the BC0259 promoter remains to be determined. However, the role of cold boxes in

the transcriptional regulation of cold genes has already been suggested elsewhere (Fang et al., 1997; Mitta et al., 1997). The cold phenotype of the 9H2 mutant is not due to a complete defect of RNA helicase encoding gene expression, as reported previously in other species with knockout mutants (Charollais et al., 2004; Ando & Nakamura, 2006). This study clearly shows that the expression level of the BC0259 gene and consequently the amount of transcripts in the cell has a huge impact on low-temperature adaptation of B. cereus. BC0259 was expressed at a higher level (about twofold) in WT cells grown at OD600 nm=0.2 when compared with cells grown at OD600 nm=1.0.

This suggests the importance of this gene during this stage of the kinetics of growth, many and is in agreement with the growth defect observed with the 9H2 mutant during the Ixazomib concentration lag phase. Four other RNA helicase-encoding genes are present in the B. cereus ATCC 14579 genome and may play a role in cold adaptation. Yet, they did not totally

counteract the effect of mutation in the BC0259 gene at 10 °C. The 9H2 mutant survived better than WT at a nonpermissive growth temperature, suggesting that the lower amount of BC0259 in the mutant had a positive effect on survival. Survival was improved in the presence of chloramphenicol for both the WT and the mutant, showing that a limited amount of protein synthesis was required for survival. Moreover, it has been shown that addition of chloramphenicol increases the level of cspA transcripts (Jiang et al., 1993), which is also dramatically induced in an E. coli RNA-helicase csdA mutant (Yamanaka & Inouye, 2001). This may suggest interactions between Csp and RNA helicases in B. cereus as described in B. subtilis (Hunger et al., 2006). Our transpositional approach revealed several genes that were clearly involved in low-temperature adaptation, with some also implicated in pH or salt stresses, suggesting possible cross responses in the adaptive potential of B. cereus ATCC 14579. This study also emphasizes the important role played by a DEAD-box RNA helicase in the cold-adaptive response of B. cereus, and further research is now needed to define the molecular function of this protein.

Strategies aimed at earlier diagnosis of HIV represent one approach to reduce the burden of immunosuppression. Our findings suggest that there are further opportunities to reduce severe immunosuppression in patients already attending for HIV care. The authors would like to thank Jorgen Engmann, Information Analyst for the CD4 Surveillance Scheme, HPA, London, who collated and

extracted the CD4 data for the two treatment centres for the study period. “
“The aim of the study was to evaluate fat tissue distribution in HIV-infected patients with suppressed viraemia treated with darunavir/ritonavir (darunavir/r) monotherapy versus darunavir/r triple Selleck isocitrate dehydrogenase inhibitor therapy. This study was a substudy of the randomized, multicentre, open-label MONOI-ANRS 136 trial. Body see more fat distribution and metabolic parameters were measured at baseline, week 48 and week 96. In total, 156 patients of the 225 initially enrolled in the MONOI trial participated in this study, 75 in the darunavir/r monotherapy arm and 81 in the darunavir/r triple-therapy arm. The median limb fat increase from baseline was +0.34 kg [interquartile range (IQR) –0.040 to +1.140 kg; P < 0.001] at week 48 and +0.33 kg (IQR –0.14 to +1.26 kg; P = 0.001) at week 96 in the monotherapy arm, while there was no change (–0.02 kg; IQR –0.53 to +0.52 kg) at week 48 and then an increase of +0.23 kg (IQR –0.45 to +0.87 kg; P = 0.046) at week 96 in the triple-therapy arm. The two arms differed significantly

at week 48 (P = 0.001) but not at week 96. The median increase in trunk fat was +0.73 kg (IQR –0.24 to +1.60 kg; P < 0.001) and 0.60 kg (IQR –0.41 to +1.49 kg; P = 0.03) at week

48 and +1.16 kg (IQR –0.17 to +2.75 kg; P < 0.001) and +0.90 kg (IQR –0.51 to +2.34 kg; P = 0.001) at week 96 in the monotherapy Amino acid and triple-therapy arms, respectively, with no difference between arms. At week 96, the only biological change was a glucose level elevation in the monotherapy arm (median +4.0 mg/dL; IQR –4.0 to +7.0 mg/dL) compared with the triple-therapy arm (P = 0.012). Overall, body fat tissue increased in patients on darunavir/r monotherapy and triple therapy, with no difference between the arms over 96 weeks. The only difference found was a delayed increase in limb fat tissue in the triple-therapy arm compared with the monotherapy arm in the first year. In the context of life-long antiretroviral therapy, management of comorbidities and metabolic complications has become a major issue in the care of HIV-infected patients [1]. Lipodystrophy, with its two components, lipoatrophy and lipohypertrophy, is a complex syndrome that may induce psychological stress and lead to decreased adherence to therapy [2]. The first generation of nucleoside reverse transcriptase inhibitors (NRTIs) and particularly thymidine analogues (TA), such as stavudine and zidovudine, have been shown to induce peripheral fat loss [3-5], which can be partially reversed by a switch to either abacavir or tenofovir [4-8].

At a time when there were two main models for revalidation: the medical one, using appraisals, and the dental model, focussing on CPD, the GPhC commissioned research to evaluate the utility of appraisals and alternative sources of evidence in pharmacy. This involved qualitative interviews and surveys with stakeholders in community, hospital, pharmaceutical industry, and academia, each from the perspective of registrants and those who may play a role in revalidation, particularly employers and indeed the regulator.(8-12) With pharmacy professionals working in a variety of sectors, selleck kinase inhibitor with most in direct patient

contact, it became clear that the options and requirements for different professionals in different sectors and organisations varied. Appraisals were common in the managed sector, but some (e.g. owners, locums, portfolio workers) were not covered. Appraisals may not be fit-for-purpose, as focus was organisational (business targets in community and industry; teaching/research in academia). Other than in NHS sectors, appraisals PS-341 in vitro did not address competence or fitness-to-practise, and were often conducted by non-pharmacists. Concerns over independence of assessment and the role of employers were raised. It is also worth

noting that revalidation is not just for pharmacists but also pharmacy technicians, which leads onto the next ‘big question’. At a time of debate in the profession about supervision, and the start of a programme to rebalance medicines legislation and pharmacy regulation, Pharmacy Research UK commissioned a study entitled ‘supervision in community pharmacy’. Its aim was to explore the role of skill mix and effective role delegation to enable pharmacists’ increasing clinical, patient-centred roles. A method called nominal group technique was used to identify which pharmacy activities could or could not be safely performed by appropriately trained support staff during a pharmacist’s

Rebamipide 2-hour absence. Views were explored in qualitative discussions, followed by a large scale survey of pharmacists and pharmacy technicians in community and hospital.(13;14) Safe, borderline and unsafe activities were identified, with borderline activities crucial for the flow of tasks involving more than one activity (e.g. cascade of dispensing). Community pharmacists were most reluctant to relinquish control, with trust in, and familiarity with, the team being important. Challenges underpinning effective delegation centred on clear roles, responsibilities and accountability, and quality of staff training and competence, with pharmacy technicians the most likely group to take on extended roles. My lecture will lay out the importance of research informing teaching and learning, policy, practice and regulation, illustrated through the context of big questions, the detail of addressing these and some of the key findings.

The current study is the first from our registry to report the retention rates of the anti-TNFα biologics and the factors associated with withdrawal of the drugs. Our results are similar to those reported in European registries in which IFX had the lowest retention rate among the anti-TNFα biological agents.[19-21] More recently, data from the REAL RA registry in Japan also reported lower retention rates of IFX and TCZ as Protein Tyrosine Kinase inhibitor compared to ETN.[22] Although the exact reasons for the difference in the retention rates of the anti-TNFα

biologics remain unclear, one important cause is the development of anti-drug antibodies (immunogenicity) which lower the serum levels of the corresponding drugs. Immunogenicity of the anti-TNFα biological agent has been implicated

for the development of secondary treatment failure[23] and DAPT infusion reaction (drug–anti-drug immune complexes).[24] This is illustrated by the high withdrawal rate of IFX over time because it is a chimeric monoclonal antibody that is associated with the highest incidence of anti-drug antibodies.[25] In our registry, a substantial proportion of withdrawals of IFX were due to infusion reaction, which could also be related to the development of immunogenicity to the drug. The rate of TB and serious non-TB infections combined was 2.26 per 100 patient-years of follow-up in our registry. This figure is lower than those reported in the British (4.2 per 100 patient-year)[11] and French registries (5.0 per 100 patient-year)[15] but similar to that of the Dutch DREAM registry (2.59 per 100 patient-year).[26] The major sites of infection were similar with the European registries,[15, 26, 27] with lower respiratory tract and skin/soft tissue infection being most common. Herpes zoster reactivation and opportunistic infections like candidiasis reported to our registry was also similar to those presented in the European[28-30]

and Japanese registries.[31] Tuberculosis is endemic in Asia, including our locality. There are around 6000 new cases of TB in Hong Kong every year and this rate has been constant Docetaxel over the past decade.[32] We calculated that the odds ratio of having TB in users of the anti-TNFα biologics was 3.71 (95% CI 2.62–5.25) when compared to our local general population. Given the increasing number of patients who are receiving the anti-TNFα biologics, this figure is not alarming at this juncture. The low relative risk of TB can be attributed to universal screening and treatment of latent TB before commencement of the anti-TNFα biologics, as well as the preference of using ETN in patients at risk of TB reactivation. Combined methotrexate (MTX) and the anti-TNF biologics has been shown to enhance clinical efficacy in RCTs.[33] The concomitant use of MTX has also been reported to reduce the incidence of immunogenicity and hence may help in reducing the rate of termination due to secondary treatment failure.

There are no direct comparisons of the boosted PIs in second-line treatment after first-line failure on an NNRTI-based regimen and choice would be individualized to the patient. Sequencing from an EFV or NVP-based regimen to ETV is not recommended [35] although it remains an option when switched as part of a new combination when only K103N is present. Switching to RAL

or MVC with two active NRTIs is an option but is also not recommended in a patient with historical or Trametinib cost existing RT mutations/previous NRTI virological failure [36]. Less than 1% of patients harbour viruses with primary PI mutations and 10–20% NRTI mutations at 48 weeks, with 75% having WT virus [24, 27-29, 37, 38]. There are currently limited data regarding the efficacy of switching to another PI/r, NNRTI, MVC or RAL-based regimen and again the decision is individualized to the patient. However, switching to RAL, MVC or NNRTI in a patient with historical or existing RT mutations is not recommended because of an increased risk of virological failure and further emergence of resistance [36]. By contrast, because

of the high genetic barrier of PI/r, sequencing to a regimen that includes a new PI/r is unlikely to lead to further emergent resistance and is recommended. Where PI/r mutations exist, DRV/r is the preferred agent unless resistance is likely. Up to one-half of patients harbour viruses with primary integrase mutations PLEKHB2 and 25% NRTI mutations at 48 weeks: approximately half have WT virus [26, 33, 37, 39]. Again, there find more are no data supporting a switch to PI/r, NNRTI or MVC but sequencing to a new regimen that includes PI/r is unlikely to lead to further emergent resistance and is recommended. Switching to NNRTI or MVC with two active NRTIs is an option but is also

not recommended in a patient with historical or existing RT mutations/previous NRTI virological failure. Patients experiencing virological failure on RAL should switch to a new regimen as soon as possible to reduce the risk of accumulating resistance mutations that may affect susceptibility to newer INIs such as dolutegravir. We recommend patients with persistent viraemia and with limited options to construct a fully suppressive regimen are discussed/referred for expert advice (or through virtual clinic referral) (GPP). We recommend patients with triple-class resistance switch to a new ART regimen containing at least two and preferably three fully active agents with at least one active PI/r such as DRV/r or TPV/r and one agent with a novel mechanism (CCR5 receptor antagonist or integrase/fusion inhibitor) with ETV an option based on viral susceptibility (1C). Risk of development of triple-class virological failure is relatively low at about 9% at 9 years from start of ART [40].

Escherichia coli strains were grown in Luria–Bertani (LB) medium. Listeria monocytogenes was grown in brain heart infusion (BHI) broth. Erythromycin (Ery) and chloramphenicol (Cm) were made up as concentrated stocks, and then added to media at the required levels. Where solid media was required, agar was added at 1.5%. Zinc limiting media was achieved via the addition of 0.5 M EDTA at the required concentration

followed by agitated overnight incubation to allow complete chelation. Where metals were AZD8055 used, they were prepared as 1 M stocks according to the manufacturer’s instructions and were added to media at the required concentrations. Gel extractions were performed using the Qiagen gel extraction kit (Qiagen). Plasmid DNA isolation was achieved utilizing the Qiagen QIAprep spin miniprep kit (Qiagen). Ligations were carried out using T4 DNA Ligase from Roche selleck screening library Diagnostics GmbH (Mannheim, Germany) according to the manufacturer’s instructions. Restriction enzymes were purchased

from New England Biolabs and were used according to the manufacturer’s recommendations. The splicing by overlap extension (SOEing) PCR procedure described by Horton et al. (1990) was used to create an isogenic nonpolar deletion mutant of zurR. Primers SOE AB and SOE CD were used to amplify regions of similar size flanking the sequence to be deleted. The resulting products were mixed in a 1 : 1 ration and were amplified using SOE A and D primers. The resulting product was digested with the appropriate restriction enzymes (XbaI and EcoRI), cloned into the temperature sensitive shuttle vector pKSV7, and transformed into E. coli DH5α.

The plasmid was subsequently transformed into L. monocytogenes EGDe. Chromosomal integration of the plasmid at 42 °C was selected by serial passage of a single colony in prewarmed BHI/Cm broth and streaking onto prewarmed BHI/Cm agar. Plasmid excision and curing was brought about by continuous passaging in BHI at 30 °C followed by spread plating onto BHI agar at 30 °C. Replica plating onto BHI and BHI/Cm was used to select for loss of plasmid and appropriate deletion events. The mutation was L-gulonolactone oxidase confirmed using primers upstream of SOE A (SOE X) and downstream of SOE D (SOE Y) (listed in Table 1). The pORI19 insertional mutant was constructed as outlined previously (Law et al., 1995; Rea et al., 2004). Briefly, a central portion of the zurR gene was amplified by PCR and cloned into the multiple cloning site of pORI19 (RepA−) and maintained in E. coli EC101. The plasmid was transformed by electroporation into L. monocytogenes EGDe containing the temperature sensitive RepA+ plasmid pVE6007. Loss of pVE6007 and integration of pORI19 to create zurR::pORI19 was carried out as described previously (Rea et al., 2004). No obvious specific ribosome-binding site was determined within zurM and zurR, which suggests a coupled translation mechanism (Dalet et al., 1999).

2b), suggesting that the WhcA protein undergoes conformational

changes, probably by losing its Fe–S cluster that leads to disulfide bond formation between cysteine residues. Collectively, these data indicated that the protein interaction was modulated by cellular redox conditions. Based on these data, the ORF NCgl0899-encoded protein was SB203580 molecular weight named SpiA (stress protein interacting with WhcA). The C. glutamicum WhcA has been suggested to play a negative role in the oxidative stress response pathway (Choi et al., 2009). However, it is not known how the action of WhcA is regulated. The WhcA protein appeared to contain Fe–S clusters. The primary sequence of WhcA contained a likely Fe–S cluster-binding motif consisting of four conserved cysteine residues C-X29-C-X2-C-X5-C (where X is any amino acid) (Jakimowicz et al., 2005). In addition, aerobically isolated WhcA protein was reddish-brown in color (data not shown), a characteristic feature of Fe–S cluster proteins, although the refolded protein showed a

diminished color. Fe–S proteins are known to play important roles in sensing Selleck Epacadostat external signals as well as the intracellular redox state of microbial cells (Green & Paget, 2004). Interacting proteins may transfer signals to the WhcA protein or help the WhcA protein sense cellular redox status. The isolated protein SpiA was annotated to encode 2-nitropropane dioxygenase, which is involved in the detoxification of nitroalkanes by oxidizing compounds to their corresponding carbonyl compounds and nitrite (Kido & Soda, 1978; Gorlatova et al., 1998). The protein contains FMN or FAD and belongs to a group of NADPH-dependent oxidoreductase (Marchler-Bauer et al., 2011). In accordance with this, the purified SpiA protein was yellowish in color (data not shown). The fact that the interaction between WhcA and SpiA was affected by oxidant diamide and menadione indicated that the activity of WhcA was probably modulated by SpiA. The annotated function of SpiA as an oxidoreductase (or dioxygenase) is in agreement with this notion. The WhiB3 protein from M. tuberculosis was shown to function as intracellular redox

sensor responding to O2 through its Fe–S cluster (Singh et al., Idoxuridine 2007). The WhiB4 protein also contains a Fe–S cluster. Upon exposure to O2, the holo-WhiB4 protein loses its Fe–S cluster and becomes active, functioning as a protein disulfide reductase. The apo-form of the protein accepts electrons either from an unidentified reductase or directly from an unidentified reductant and becomes activated (Alam et al., 2007). The active form of the protein then transfers the signal to the oxidized target proteins as a disulfide reductase (Alam et al., 2007). However, it is still not known how WhiB3 and WhiB4 proteins respond to O2. In C. glutamicum, the SpiA protein, annotated as oxygenases or oxidoreductases, might be the molecule that is involved in making the WhcA protein respond to O2.

, 2007). To compare relative expression levels of sas016 in wild type and mutant strains, overnight cultures were diluted to OD 0.05 in prewarmed LB broth and cultures grown to OD 1.5, except for the LCP triple mutant

that was sampled at OD 0.5 because of its severe growth defect. Uninduced culture samples were collected, and the remainder of the culture was induced with oxacillin (10 μg mL−1) for 30 min before induced samples were collected. Total RNA was extracted as described by Cheung et al. (1994). RNA samples (9 μg) were separated in a 1.5% agarose-20 mM guanidine thiocyanate gel in 1× TBE buffer (Goda & Minton, 1995). The sas016 digoxigenin (DIG)-labelled probe was amplified using the PCR DIG Probe synthesis kit (Roche) as previously described (Dengler et al., 2011). The transcriptional start site of sas016 was determined by primer extension, as previously described (McCallum et al., 2007), using primer LDK378 concentration SAS016.PErev (Table 1) and 20 μg of RNA BTK inhibitor price harvested from a culture of S. aureus COL that had been grown to OD 0.5 and induced with 10 μg mL−1 of teicoplanin for 30 min. The promoter region of the vraSR operon was PCR amplified from S. aureus strain COL using primer pair vra.lucF and vra.lucR (Table 1). The PCR product was digested with Asp718 and NcoI and ligated directly upstream of the promoterless luciferase

(luc+) gene in the vector pSP-luc+ (Promega). Fragments containing the resulting promoter-luc+ translational fusions were then excised with Asp718 and EcoRI and cloned into the Escherichia coli – S. aureus shuttle vector pBUS1 (Table 1). The fusion plasmids pvrap-luc+ Galeterone and psas016p-luc+ (McCallum et al., 2011) were then electroporated into S. aureus RN4220, re-isolated and electroporated into S. aureus SA113, SA113ΔtarO, MSSA1112 and all LCP and VraR/LCP mutants. Predicted VraR-binding sites of luciferase fusion constructs were disrupted by amplifying each promoter as two fragments, using primers listed in Table 1. Complementary fragments were digested and ligated together, to create recombinant promoters in which 6–18-bp regions were replaced by restriction

sites. Promoters were then fused to the luciferase gene as described above, and the resulting plasmids were electroporated into RN4220. To measure luciferase activities, cultures were grown from overnight cultures inoculated to an OD 0.05 in prewarmed LB broth containing tetracycline. One-millilitre culture samples were harvested by centrifugation, and the pellets frozen at −20 °C. To determine relative light units (RLU), pellets were thawed briefly and resuspended in PBS (pH 7.4) to an OD of either 10 or 1, depending on induction levels. Aliquots of the cell suspensions were then mixed with equal aliquots of Luciferase Assay System substrate (Promega), and luminescence was measured for 15 s after a delay of 3 s on a Turner Designs TD-20/20 luminometer (Promega) as previously described (Dengler et al., 2011).

Moreover, it was also significantly associated with the development of other ODs and death. The positive predictive value of a single CMV viral load was low, but increased for values >1000 copies/mL. As suppressing CMV viraemia has become simpler, our results support the idea of exploring strategies of prevention of CMV end-organ disease in a subset of critically ill patients with low CD4 cell counts. Guidelines

concerning the decision to start pre-emptive treatment should explore the potential of serial CMV DNA detection and the establishment of a CMV DNA cut-off value in plasma. “
“HIV infection is spreading relatively quickly among men who have sex with men (MSM) in China. Accurate knowledge of HIV status is of high importance BAY 73-4506 for public health prevention. We conducted a systematic review of literature published in either English or Chinese to collate available HIV testing data among MSM in China. Linear regression and Spearman’s rank correlation were used to study factors associated with

HIV testing rates. Fifty-five eligible Selleckchem TSA HDAC articles were identified in this review. The proportion of MSM who had ever been tested for HIV has significantly increased, from 10.8% in 2002 to 51.2% in 2009. In comparison, reported rates of HIV testing in the past 12 months have also significantly increased, from 11.0% in 2003 to 43.7% in 2009. Venetoclax concentration Chinese MSM have relatively low HIV testing rates compared with MSM in other settings. It is important to continue to promote HIV testing among MSM in China. Men who have sex with men (MSM) have been a priority population at higher

risk of HIV infection in most industrialized countries, compared with other population risk groups, since AIDS epidemics emerged in the early 1980s [1, 2]. In comparison, HIV epidemics emerged much later among MSM in most developing countries in Southeast Asia but have spread rapidly [3-7]. In China, HIV prevalence among MSM has substantially increased from 1.4 to 5.3% during the past decade [6], whereas the proportion of annual HIV diagnoses attributable to male-to-male sex increased from 12.2% in 2007 to 32.5% in 2009 [8]. HIV testing is highly important for both public health surveillance and prevention. MSM who are aware of their positive HIV status are more likely to change their sexual behaviours to reduce onward transmission to others [9-14]. Early diagnosis of HIV infection also enables infected individuals to initiate early treatment [9]. In general, HIV screening and confirmation tests were unaffordable to the majority of the Chinese population until 2003 [15, 16].

The UK NCRN trial randomized patients with advanced-stage HL to ABVD versus Stanford V and demonstrated no significant differences in terms of PFS and OS [38]. An Italian randomized study compared ABVD x6–8 with BEACOPP (4 escalated + 4 baseline) in patients with advanced-stage HL or high-risk (according

to Hasenclever score) early-stage HL and showed that whereas BEACOPP resulted in a superior freedom from progression than ABVD (85% vs. 73%, respectively, at 7 years, p = 0.004), this was not translated click here into a superior OS (7-year OS: 89% vs. 84%) as patients who failed ABVD could be rescued with second-line chemotherapy followed by high-dose chemotherapy with autologous stem cell rescue (HDT-ASCR) [39]. Another randomized study, only presented in abstract form, confirms these results [40], as does a recent meta-analysis [41]. In most of the studies of advanced-stage HL, RT is given to residual masses or sites of bulky disease at diagnosis. Ongoing studies are assessing the role Vincristine manufacturer of FDG-PET to enable omission of the RT. One large published series describing HIV patients treated with ABVD in the HAART era included 62 patients with advanced-stage HL and reported a CR rate of 87% with a 5-year event-free survival (EFS) and

5-year OS of 71% and 76%, respectively [42]. A recent study compared the outcome of patients with HL treated with ABVD according to their serological status and demonstrated comparable

results in terms of CR/CRu, EFS, disease-free survival (DFS) and OS for patients with and without HIV infection (Table 10.2) [17]. The analysis revealed no significant difference in response rate, EFS, DFS or OS between 93 HIV seropositive patients and 131 seronegative patients with HL, supporting the treatment of HIV-positive patients with HL with the same schedules as in HIV-negative patients. In this study, one of 93 HIV-positive patients died of neutropenic sepsis with a further patient dying of an opportunistic infection 1 year after finishing chemotherapy. There have not 3-mercaptopyruvate sulfurtransferase been studies comparing ABVD with more intensive regimens in the setting of HIV infection, but several Phase II studies have reported on the efficacy and toxicity of intensive regimens in this population. Spina et al. published results on 59 patients treated with the Stanford V chemotherapy regimen with G-CSF support and concomitant HAART. One-third of the patients could not complete the 12-week treatment plan and 31% required a dose reduction, with considerable myelotoxicity and nonhaematological toxicity. CR was achieved in 81% of the patients and after a median follow-up of only 17 months, the 3-year DFS was 68% and 3-year OS 51% [43]. A multicentre pilot study reported the use of the intensive BEACOPP chemotherapy in HIV-positive patients with HL. Twelve patients were included in this study, which started in the pre-HAART era.