The soluble isoform inhibitor of the RAGE receptor Torin 1 (sRAGE) was also used to confirm the result. As was shown, cleaved caspase-1 was significantly inhibited after blocking RAGE with sRAGE treatment (Fig. 5D). To further confirm that both TLR4 and RAGE receptors are involved in hypoxia-induced caspase-1 activation, Hepa1-6 cells were simultaneously treated with anti-TLR4 neutralizing antibody and sRAGE. Cleaved caspase-1 was almost completely inhibited by blocking both TLR4 and RAGE (Fig. 5E). These results suggest that hypoxia-induced caspase-1 activation occurs through both TLR4- and RAGE-signaling

pathways. To date, four cytoplasmic receptors have been described that form an inflammasome complex: NOD-like receptor family, pyrin domain-containing protein (NLRP)1, NLRP3, IPAF, and absent in melanoma 2 (AIM2).14

To investigate which one is involved in hypoxia-induced caspase-1 activation, Hepa1-6 cells were transfected with NLRP1 siRNA, NLRP3 siRNA, IPAF siRNA, and AIM2 siRNA. All receptors were efficiently silenced by their respective siRNA (data not shown), but only NLRP3 siRNA was found to inhibit hypoxia-induced caspase-1 activation (Fig. 6A; Supporting Fig. 4C,D). These results suggest that hypoxia-induced caspase-1 activation in HCC cells is NLRP3 dependent. Next, we investigated signaling pathways downstream of caspase-1. The cytokines, IL-1β and -18, begin as cytosolic precursors that require cleavage by the cysteine protease, caspase-1, to generate biologically active molecules. Cleaved caspase-1, IL-1β, and IL-18 learn more were all increased after hypoxia (Fig. 6B-D). In contrast, all three were decreased after treatment with the caspase-1 inhibitor, Z-YVAD-FMK (carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone) (Fig. 6B-D). As downstream effectors of caspase-1, both cytokines released from cancer cells can induce the production and secretion of other cytokines and chemokines, recruit stromal cells, and induce angiogenesis,

leading to tumor progression.15, 16 We next sought to determine the Florfenicol effects of hypoxia on HCC cell migration and invasion. Under hypoxia, Hepa1-6 cell migration was increased 2.04- ± 0.14-fold (P < 0.01; n = 6) in 1% O2 (Fig. 7A. Similarly, invasion of Hepa1-6 cells through reconstituted three-dimensional Matrigel matrices was increased 1.72- ± 0.12-fold (P < 0.01; n = 6) in 1% O2. To elucidate whether HMGB1-induced caspase-1 activation was responsible for the increase in cell invasion observed in hypoxia, Hepa1-6 cells were treated with anti-HMGB1 neutralizing antibodies. Blockade of HMGB1 inhibited the increase in cell invasion observed during hypoxia (Fig. 7B,C). We also examined caspase-1 inhibition in hypoxia-induced invasion. Hepa1-6 cells treated with the caspase-1 inhibitor, Z-YVAD-FMK, also exhibited significantly decreased hypoxia-induced invasion (Fig. 7B,C).

1.1.205) or guanine monophosphate synthetase (GMPS; EC 6.3.5.2) to produce 6-TGNs (Fig. 1).30 As yet the only support selleck chemicals for this hypothesis is the discovery of a 9 bp insertion within the promoter of IMPDH1 in an IBD patient who exhibited preferential 6-MMPR metabolism.31 The insertion, predicted to abolish a cAMP-response

element (CRE), significantly reduced gene expression in vitro (P-value < 0.001).31 Polymorphisms within xanthine oxidase (XO; EC 1.1.1.204), aldehyde oxidase (AOX1; EC 1.2.3.1) and hypoxanthine phosphoribosyl transferase (HPRT; EC 2.4.2.8) (Fig. 1), may contribute to non-response to azathioprine and 6-mercaptopurine. Several recent reports in the literature support this argument. A case report of a patient with unusually high XO activity, who was non-responsive to azathioprine, but produced toxic concentrations of 6-TGNs and 6-MMPR on a combination of 6-mercaptopurine and the XO inhibitor allopurinol demonstrates that elevated XO activity can cause thiopurine non-response.32 Although not explored, it is possible that the unusually high XO activity observed in this patient had a genetic basis. Lending weight

to this possibility is the discovery of gain-of-function SNPs which caused a significant increase in XO activity in vitro.33 In addition to XO, there is also preliminary evidence to suggest that alterations in AO may cause thiopurine non-response. Smith et al.34 reported association of a non-synonymous SNP in the

AOX1 gene with lack of clinical response to azathioprine. IBD patients who were heterozygous or homozygous for the minor allele of AOX1 this website c.3404A>G (Asn1135Ser) were significantly more likely to be refractory to azathioprine therapy than patients without this SNP (17% vs 34%; P = 0.035, OR = 2.54, 95% CI: 1.06–6.13).34 Genetic polymorphisms in a molecular target of thiopurine therapy.  Research has demonstrated that one of the 6-TGNs, 6-thioguanine triphosphate (6-TGTP) (Fig. 1), contributes significantly to the overall immunosuppressive effect of thiopurine therapy by binding to the small guanosine triphosphatase (GTPase) RAC1 on CD28 costimulation in CD4+ T cells.35 Binding of 6-TGTP to RAC1 blocks Vav exchange activity leading to the disruption of the Vav1-Rac1 signaling cascade and a therapeutic reduction in inflammation.36 As RAC1 is an not important molecular target of thiopurine metabolites it is possible that genetic polymorphisms that alter the expression or function of this GTPase may influence patient response to azathioprine and 6-mercaptopurine. Bourgine et al.37 have provided the first evidence for the existence of functional polymorphisms within the promoter of the RAC1 gene. Using a combination of PCR-single strand conformation polymorphism analysis and DNA sequencing, Bourgine et al.37 identified a total of 16 RAC1 polymorphisms across 92 healthy controls and 128 IBD patients receiving azathioprine.

The following selleck screening library year, at the annual meeting of the American Society of Hematology, the same group reported successful treatment of four additional subjects at the highest dose. Yet the total number of people who have received this promising

experimental therapy remains very low. What are the reasons for this low access rate to a seemingly successful new therapy? From a scientific standpoint, even if men with severe haemophilia B were waiting for gene therapy in a line that stretched around the block, roughly 40% of individuals would still be excluded based on the presence of pre-existing neutralizing antibodies to AAV. Prior exposure to the wild-type virus from which the vector is engineered is ubiquitous in the population, and many individuals carry antibodies to the vector capsid. Population screening of individuals from four continents reveals that the worldwide prevalence of these antibodies is similar, and that, at least among most of the naturally occurring serotypes, the prevalence of antibodies is similar [2]. Careful studies in non-human primates, who, similar to the human population,

carry pre-existing antibodies formed in response to infection with the wild-type virus, suggest that even modest titres completely inhibit transduction when vector is delivered through the check details circulation [3]. The field has proposed a number of strategies that could be used to circumvent this obstacle [4] (Table 1). At least one of these is currently undergoing clinical investigation

[5], but proof-of-concept has not been established for any of these in subjects with severe haemophilia B. Progress in manufacture of clinical grade AAV vectors since the first human studies were conducted in the 1990s has been dramatic, and most would now agree that methodology for generation, Nintedanib (BIBF 1120) purification and characterization of recombinant AAV under current Good Manufacturing Practice (cGMP) conditions is well in hand. The products used in the clinical trials to date thus have met regulatory standards for safety, quality and consistency. However, most production methods currently in use lead to lot sizes in the range of 1–5 × 1015 vg. Since a therapeutic dose for a 70 kg man based on current studies is ~ 2 × 1012 vg kg−1, each lot is adequate to infuse 7–35 subjects, depending on yields. Thus, considerable attention is now focused on larger scale production processes.

This is also true for the recently licensed protease

inhibitors, which see more markedly improved SVR rates in patients with CHC, GT-1.9-14 As far as we know, this is the first study to assess a potential selection bias in patients with CHC treated within randomized, controlled studies. At least, the outcome of cohort studies in hepatitis C may be influenced by a selection bias.21 Not surprisingly, some baseline characteristics, adherence to treatment, and the IL18B phenotype had the biggest effect on treatment outcome. Patients receiving SOC had more advanced liver disease, a more frequent history of psychiatric disorders, and a substantial proportion was on drug-substitution therapy. Differences in baseline characteristics22-25 reflect inclusion and exclusion criteria and may create “perfect to treat” patients. Whether the slight differences documented in this study are clinically relevant remains unknown, but history of psychiatric disorders, need of drug-substitution therapy, and a higher grade of liver fibrosis may influence treatment outcome, as well. Because of major differences in access to

NVP-BEZ235 in vitro medical care, data from a European study center cannot be directly applied to the U.S. population of HCV patients. It may also be difficult to draw conclusions from the largely homogenous population of HCV patients seen in Vienna to the largely heterogeneous population of HCV patients seen in the United States. In particular, in this study, except for 7 patients (2.3%; 5 Asians and 2 black Africans), all patients were Caucasians, whereas in the United States, approximately 19% and 40% of treatment eligible or noneligible

patients, respectively, are black.26 Analysis of data from the National Health and Nutrition Examination Survey, conducted in 2005-2008, revealed that HCV-positive patients were less likely to be insured than HCV-negative individuals (61.2% versus 81.2%). Of all HCV-positive patients, 66.7% acetylcholine were eligible for anti-HCV treatment, but only 54.3% of HCV-positive treatment candidates had any type of insurance coverage, and only 36.3% of treatment-eligible patients had health insurance.27 In contrast, approximately 99% of all Austrians are insured (including jobless people), and treatment for chronic hepatitis B and C is fully covered. A similar insurance coverage rate was reported from Taiwan.28 Thus, there is no direct financial benefit for patients to participate in a study, and no patient contacted our center for the sole purpose of being enrolled in a clinical trial. All patients were referred from general practitioners for evaluation of CHC and were offered treatment, if there were no contraindications. Our center treats approximately one third of all HCV patients from Vienna as well as the surrounding suburbs. These represent the “typical mix” of patients with CHC (36% with history of drug abuse, 19% infected by blood or blood products, and 42% of unknown etiology).

Substantial

differences are observed in over 25% of cases, and are associated with reduced collateralization. “
“We describe the essential diffusion tensor imaging (DTI) findings of right cerebral hemisphere infarctions and study whether the DTI parameters and neurological status differ in patients with visible wallerian degeneration (WD) or small hemorrhagic transformation (HT) in the chronic stage. Twenty-five stroke patients underwent DTI. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in the infarction area, its corresponding contralateral area and both hemispheres Epacadostat cost in the centrum semiovale, cerebral peduncle, thalamus, internal capsule, and in corpus callosum genu, truncus, and splenium. The neurological scores were assessed in the acute and chronic phase. The subgroup analysis of WD and HT was conducted. MD was higher in the right hemisphere (all P-values < .05), except on the internal capsule. FA was decreased in the infarction site, right cerebral peduncle, and centrum semiovale compared to the left side (P < .05). The

chronic Rankin Scale was worse in the WD group. Their DTI parameters were different in 3 locations compared to patients with no WD. The HT group received www.selleckchem.com/products/pexidartinib-plx3397.html fewer points in the chronic Barthel Index, and they had lower FA in the thalami. DTI reveals the changes after infarction in the lesion site and elsewhere. The patients with visible WD or HT have more changes in the DTI parameters and worse outcome scores. “
“Essential tremor (ET) is suggested to be a neural degenerative disease. The authors investigated the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) value in basal ganglia, thalamus, red nucleus, and substantia nigra in ET patients using diffusion tensor image (DTI). DTI examination was carried out in patients with ET and controls. FA and ADC values were obtained from various brain structures, including caudate,

putamen+pallidum, thalamus, red nucleus, and substantia nigra. The ADC value of the red nuclei in patients with ET was higher compared with controls Methocarbamol (.90 vs .77; P= .000). However, no significant differences were demonstrated for FA, or ADC values of other structures. The increased ADC value in the red nucleus indicates that there is neuronal damage or loss present, suggesting that ET may be a neurodegenerative disease. “
“Mortality in acute ischemic middle cerebral artery (MCA) stroke ranges from 5% to 45%. We identify a vascular imaging sign, presence of “prominent anterior temporal artery” on computed tomography (CT) angiography (CTA) and investigate whether it predicts mortality in acute M1-MCA occlusions. One hundred and two patients with acute M1-MCA occlusions from 2003–to 2007 were included in the study. A prominent anterior temporal artery arising from proximal M1 MCA was identified by two readers blinded to clinical outcome.

Moreover, mRNA levels of XRCC4 in cancerous tissues with rs28383151-GA or -AA were significantly lower than those with rs28383151-GG (Fig. 1C; P < 0.01). Together, these results suggest that this polymorphism should modify XRCC4 expression. LDE225 To explore whether rs28383151 polymorphism effects DNA repair capacity, we analyzed the effects of a mutant type of rs28383151 polymorphism (XRCC4mt) on AFB1 DNA adducts

levels in AFB1-treated QSG-7701 cells with overexpression of XRCC4 (see Supporting Materials). We found that XRCC4mt had higher AFB1 DNA adducts levels (0.68 ± 0.05 nmol/μg DNA), compared to the WT of rs28383151 polymorphism (XRCC4wt, 0.44 ± 0.05 nmol/μg DNA, P < 0.01; Fig. 1D; Supporting Table 10). Because TP53M is the most important molecular signature of AFB1-induced HCC,16 we investigated whether this polymorphism modified this mutation in the 1,499 cancerous tissue subjects. Results showed that risk genotypes of XRCC4 increased the frequency of TP53M (Fig. 1E), and corresponding risk values were 1.60 and 3.92 for rs28383151-GA and rs28383151-AA, respectively (Table 3). Taken together, these findings suggest that the rs28383151 polymorphism

might correlate with DNA repair capacity for repair of DNA damage caused by AFB1 exposure. To assess the clinical relevance of rs28383151 polymorphism, we analyzed the survival follow-up information of all HCC patients. Among these subjects, 1,092 without decompensated cirrhosis received the same curative resection treatment, according to Chinese Manage Criteria of HCC,17 and were included for final survival analysis. Association click here analysis between risk genotypes (namely, genotypes with rs28383151 A alleles; rs28383151-GA/AA) or nonrisk genotype (rs28383151-GG) and the clinic-pathologic characteristics

of HCC were first performed separately (Supporting Table GBA3 11). We observed a significant distribution difference of genotypes among different AFB1 exposure levels, tumor size, and recurrence status, but not in AFB1 exposure years, gender, minority, HBsAg, cirrhosis, or TNM stage (Supporting Table 11). Survival analysis next showed that HCC cases carrying rs28383151-GA/AA, compared with those with rs28383151-GG, had shorter RFS (median RFS time [MRT] was 16 versus 33 months; Fig. 2A) and higher recurring risk (Table 4), particularly under high AFB1 exposure conditions (Fig. 2A). Additionally, this polymorphism was related to the OS of HCC cases (Fig. 2B), and some evidence of multiplicative interaction was found for rs28383151 polymorphism and AFB1 exposure (Pinteraction < 0.05; Table 4). On the basis of a recent report showing that the dysregulation of XRCC4 is related to tumor metastasis,18 we investigated whether the rs28383151 polymorphism influenced the risk of PVT, the most common metastasis type of HCC,19, 20 in 1,092 HCC cases during follow-up after curative treatment (Table5). Results exhibited that rs28383151 A alleles significantly increased PVT risk (OR = 2.26; P = 3.94 × 10−5).

3 To date, molecular targeted therapy has shown promise for the treatment of advanced HCC,4 but it is unclear how these genetic changes cause the clinical characteristics observed in individual HCC patients.

Histone deacetylases (HDACs) are often recruited by corepressors or multiprotein transcriptional complexes to gene promoters, whereby they regulate transcription by way of chromatin modification without directly https://www.selleckchem.com/products/Deforolimus.html binding to DNA.5 There are 18 encoded human HDACs, which are classified as: class I (HDAC1, 2, 3, and 8), class II (HDAC4, 5, 6, 7, 9, and 10), class III (SIRT1-7), and class IV (HDAC11) enzymes,6 and evidence indicates that both histone acetyltransferases (HATs) and HDACs are involved in cell proliferation, differentiation, and cell cycle regulation.7 In addition, it has been reported that the pathological activity and deregulation of HDACs can lead to several diseases, such as cancer, immunological disturbances, and muscular dystrophy.8 However, despite the involvement of HDACs in the development of cancer, the specific roles fulfilled by individual HDACs in the regulation of cancer development remain unclear. HDAC6 is a member of the class IIb family of HDACs and acts as a cytoplasmic deacetylase that associates with microtubules and deacetylates α-tubulin.9 Microtubule-associated HDAC6 is a critical component of the lysosomal I-BET-762 cost protein degradation

pathway, and it has been recently suggested that HDAC6 plays an important role in the eventual clearance of aggresomes, which implies a functional connection between autophagic signaling and control of the fusion of autophagosomes and lysosomes associated with the control of autophagy by way of the recruitment of cortactin-dependent, actin-remodeling machinery to ubiquitinated protein aggregates.10 On the other hand, HDAC6 has been shown to be involved in carcinogenic transformation and to modulate the epithelial-mesenchymal transition in several cancers by way of the regulations of several critical cellular functions,11,

12 and accumulating evidence indicates that the expression of HDAC6 is correlated with oncogenic transformation, anchorage-independent proliferation, Branched chain aminotransferase and tumor aggressiveness. Furthermore, it has been shown that the inactivation of HDAC6 by genetic ablation or by specific short small interfering RNA (siRNA) increases resistance to oncogenic transformation and decreases the growth of human breast and ovarian cancer cell lines in vitro and in vivo.13, 14 Therefore, the up-regulation of HDAC6 in diverse tumors and cell lines suggests that HDAC6 plays an important role in cancer. However, our previous transcriptome analysis on multistep hepatopathogenesis suggested the down-regulation of HDAC6 in overt HCC as compared with noncancerous tissues, and our initial analysis of HDAC6 in human HCC tissues indicated the loss of HDAC6 expression in HCCs.

Moreover, only one of these reports, to our knowledge, evaluated the frequency of steatohepatitis in HIV/HCV-coinfected patients.5 Nutlin-3a research buy A recent longitudinal analysis of HIV/HCV-coinfected patients, who had undergone at least two liver biopsies, examined the rates of steatosis progression.15 The prevalence of HS at baseline was lower than that found in previous studies.1-11, 14 At the follow-up biopsy, HS did not progress in the majority of patients. Among progressors, ART was associated with a lower risk of HS progression.

The reasons for these findings are unclear. The racial background of the study cohort, overwhelmingly composed of HCV genotype 1–infected African Americans, may partly explain these striking results. Thus, there is a need for additional studies assessing the rates of HS progression and the risk factors for progression, including the role of antiretroviral drugs, in HIV/HCV-coinfected CP-868596 datasheet subjects, as it has been claimed by some experts.16 Furthermore, there are no data on the changes in steatohepatitis over time in HIV/HCV coinfection. In this study, we aimed at evaluating the changes in HS between liver biopsies and the predictors of HS progression among HIV/HCV-coinfected patients

with sequential liver biopsies. We also assessed the rates of steatohepatitis and factors associated with the persistence and progression thereof in these patients. ART, antiretroviral therapy; BMI, body mass index; CDC, Centers for Disease Control and Prevention; CI, confidence interval; DM, diabetes mellitus; ETR, end-of-treatment response; FPG, fasting plasma glucose; HCV, hepatitis C virus; HIV, human immunodeficiency virus; HS, hepatic steatosis; IQR, interquartile range; IR, insulin resistance; NAFLD, nonalcoholic fatty liver disease; NAS, NAFLD activity score; OR, odds ratio; SVR, sustained virological response; TGs, triglycerides. This was a retrospective study carried out in paired liver biopsies performed in HIV/HCV-coinfected patients who attended nine Spanish hospitals from January 1989 to January 2008. An analysis

of liver fibrosis Dimethyl sulfoxide progression in these sequential biopsies has been previously reported on.17 HIV-infected patients were included in the present study if they met the following: (1) active HCV infection, as determined by detectable serum HCV RNA; (2) underwent two liver biopsies, separated by at least 1 year; (3) liver biopsies have been performed as part of the assessment of HCV infection to establish the prognosis and/or to indicate treatment; and (4) no evidence of vascular, tumoral, biliary, or autimmune liver disease. Individuals with cirrhosis detected at the first liver biopsy were included for the present analysis. Biopsy samples with length lower than 15 mm or fragmented specimens were deemed as inadequate, and the corresponding patient was excluded.

A retraction of the iliopsoas leads to a hip flexion contracture which distorts posture and gait. Tightness in the iliopsoas causes downward rotation of the pelvis, and this position in turn causes exaggeration of the normal lumbar curvature. Careful stretching exercises should selleck chemical therefore be performed to restore mobility in hip extension. When the pain has disappeared and hip flessum has diminished, a specific muscle strengthening programme is advocated, beginning with isometric contractions and followed by concentric exercises. Care should be taken with

aggressive passive stretches. The decision to conclude the rehabilitation can be based on the patient’s ability to stretch the injured muscle to prebleed levels and the pain-free use of the injured muscle. Limited joint motion and muscle atrophy are key features of haemophilic end-stage arthropathy. If the limitation of movement in the arthropathic joint is as a result of contractures and the end of the joint feels hard and bony, manual physiotherapy techniques may have limited benefit. In the presence of chronic synovitis, the end range limitation of range of selleck chemicals motion (ROM) must be respected. Approaching the closed packed position, where the synovium could become impinged, or when the bony surfaces are coming into contact, should be avoided [54]. As an example, bleeding episodes in the ankle principally Sitaxentan affect the

tibiotalar and/or subtalar joints and may lead to severe degenerative changes. One of the hidden symptoms is decreased ROM of the midtarsal

and tarsometatarsal joints. This deficit could predispose the patient to increased pain, stiffness and disrupted proprioceptive input to the sensorimotor system. Therefore, improving accessory and physiological motion by selective mobilizations/manipulations in the entirety of the ankle and mid- and fore-foot joints is a clinical consideration. Adaptive and corrective splints and orthoses may also be considered for joint instability and deformity. The use of foot insoles and specially adapted shoes has been shown to reduce pain and improve ankle propulsion in patients with end-stage ankle arthropathy [55]. Provided that appropriate clotting factor levels are maintained post surgery, the rehabilitation of people with haemophilia largely mirrors that of their counterparts without haemophilia, but with some specific considerations. Due to the presence of arthrofibrosis and bone deformities in the preoperative stage, stiffness and loss of ROM continue to be a complication after total knee replacement (TKR) in people with haemophilia. The degree of preoperative flexion contracture is the most important variable influencing the postoperative ROM after TKR [56]. To improve outcomes, early postoperative knee mobilization should be performed as soon as possible, both in flexion and in extension.

Some reported long-term side effects of HAART are dyslipidaemia, insulin resistance/diabetes mellitus type-II and an increased risk of myocardial infarction [2-7]. An increased bleeding tendency (mainly joint,

muscle and subcutaneous bleeding, but also spontaneous intracranial bleeding) has been reported in patients with inherited bleeding disorders using protease inhibitors [8-11]. Over 25 years of follow-up is now available for haemophilia patients who were infected with HIV in the 1980s. The aim of this study was to retrospectively asses the course and complications of HIV infection, the presence of comorbidity and the effects of HAART in these patients. Data on the first 14 years of follow-up of a large proportion of our cohort were published by Roosendaal et al.

in 1998 [12]. As part of a retrospective evaluation of comorbidity Pexidartinib in a large cohort of haemophilia patients [13], data on HIV infection, its treatment and all types of comorbidity were collected of all HIV-positive haemophilia patients who were treated at the Van Creveldkliniek, a large haemophilia treatment centre in the learn more Netherlands, at any point between 1980 and 2010. Patients visit our clinic at least once a year, and their medical records have been meticulously kept since 1972, enabling reliable retrospective data collection. Follow-up ended at either last clinical evaluation before 1 September 2010, transfer to another treatment centre, or death. For patients who were still alive and treated at our centre in 2010, recent height, weight, blood pressure, HIV-RNA levels, CD4 counts Vildagliptin and cholesterol and triglyceride levels were recorded as well. The date of HIV seroconversion was estimated by calculating

the mid-point in time between the last-negative and first-positive anti-HIV ELISA tests. For patients for whom the date of seroconversion could not be calculated, the mean date of seroconversion of the total group was imputed. AIDS was diagnosed according to the 1993 European definition [14]. HAART was defined as a combination of at least three antiretroviral drugs that typically includes a protease inhibitor (PI) or a non-nucleoside-analogue reverse-transcriptase inhibitor (NNRTI) plus two nucleoside-analogue reverse-transcriptase inhibitors (NRTIs). Hypertension was defined as blood pressure over 140/90 mmHg and/or the use of antihypertensive medication. The study was approved by the Medical Ethics Review Board of the University Medical Center Utrecht. Kaplan–Meier survival analyses were performed to assess AIDS-free survival and overall survival. AIDS-free follow-up ended at the moment of diagnosis of the first AIDS-defining disease. Data were censored at the moment of death, transfer to another haemophilia treatment centre or last clinical visit before 1 September 2010.