Infection of the culture at OD600 nm 0.5 only rarely resulted in cell lysis and the turbidity test showed no sensitivity to ΦBP. However, SCH727965 supplier the result of plaque assay indicated the sensitivity of P. polymyxa CCM 1465 to ΦBP. We observed the plaques on the plates where the culture of this strain with ΦBP had been plated. Phage particles examined by TEM (Fig. 1) were recovered from the cell-free supernatant of spontaneously lysed culture of P. polymyxa CCM 7400 and CsCl gradient purified. The phages had polyhedral heads with a diameter of 56±4 nm (mean±SD) (n=24) and tails with

a length of 144±8 nm (n=6) (n=number of measurements). The structural proteins of ΦBP were analyzed by SDS-PAGE (Fig. 2). At least 11 bands were revealed with molecular masses of putative proteins estimated at 13, 16, 22, 25, 26, 28, 35, 38, 51, 79 and 160 kDa. The most abundant protein bands were 28, 35, 38 and 51 kDa in size. We extracted nucleic acid from purified phage particles. The purified nucleic acid was sensitive to DNAse and resistant to RNAse treatment. To determine the genome size, ΦBP DNA was cut with restriction endonucleases HindIII,

EcoRV and XbaI. The length of the genome of about 43 kb was calculated as the sum of the Linsitinib chemical structure lengths of the restriction fragments (Fig. 3a). Restriction enzymes XhoI, PstI, BamHI and SalI did not cut ΦBP DNA. Analysis with four restriction enzymes (EcoRI, HindIII, XbaI, SpeI) showed an identical restriction pattern for DNA extracted from phage particles, which were recovered from both spontaneously lysed culture of P. polymyxa CCM 7400 and culture after external ΦBP infection (data not shown). Sequence homology analysis of eight DNA fragments from EcoRI-digested ΦBP DNA (Fig. 3b, Carnitine palmitoyltransferase II Table 1) revealed regions

with significant similarity to typical phage genes for two of them. Two regions within the 2.5-kbp fragment with predicted ORFs of 507 and 996 bp shared significant homology to phage holin and lysin genes, respectively. They represent a putative cassette of lytic genes, where the gene coding for predicted holin is closely followed by the lysin gene. We detected an overlap of both genes over a 23-bp region. The third gene of this cluster seems to be the second holin gene (555 bp). Two predicted ORFs with the length of 552 and 744 bp were identified within the 1.2-kbp fragment as putative small and large terminase subunit genes. These ORFs are incomplete due to the interruption caused by EcoRI digestion with the genes overlapping by 83 bp. Restriction and ORF maps of the 1.2- and 2.5-kbp fragments were constructed from the primary sequencing data (Fig. 4). The basic data of eight analyzed sequenced fragments, the sizes of the known sequences and results of the homology search are summarized in Table 1. Two pairs of specific oligonucleotide primers were derived from the proposed small terminase and holin gene sequences to detect the presence of ΦBP DNA sequences on P. polymyxa chromosome.

23% (P = 0.0002). Dizziness and abnormal dreams/nightmares occurred significantly less frequently with rilpivirine vs. efavirenz (P < 0.01). In both groups, patients with prior neuropsychiatric history tended to report more neuropsychiatric AEs but rates Endocrinology antagonist remained lower for rilpivirine than for efavirenz. Rilpivirine was associated with fewer neurological and psychiatric AEs of interest than efavirenz over 48 weeks in treatment-naïve, HIV-1-infected adults. “
“The aim of the study was to assess the separate contributions of

smoking, diabetes and hypertension to acute coronary syndrome (ACS) in HIV-infected adults relative to uninfected adults. Two parallel case–control studies were carried out. In the first study, HIV-positive adults diagnosed with ACS between 1997 and 2009 (HIV+/ACS) were matched for age, gender and known duration of HIV infection with HIV-positive adults without ACS (HIV+/noACS), each individual in the HIV+/ACS group being matched with three individuals in the HIV+/noACS group. In the second study, each individual in the HIV+/ACS group in the first study was matched for age, gender and calendar date of ACS diagnosis with three HIV-negative individuals diagnosed with ACS between 1997 and 2009 (HIV–/ACS). Each individual in the

HIV–/ACS group was then matched for age and gender with an HIV-negative adult without ACS (HIV–/noACS). After matching, the ratio of numbers of individuals in the HIV+/ACS, HIV+/noACS, HIV–/ACS and HIV–/noACS groups was therefore 1 : 3 : 3 : 3, respectively. We performed logistic regression Orotidine 5′-phosphate decarboxylase analyses PLX4032 molecular weight to identify risk factors for ACS in each case–control study and calculated population attributable risks (PARs) for smoking, diabetes and hypertension in HIV-positive and HIV-negative individuals. There were

57 subjects in the HIV+/ACS group, 173 in the HIV+/noACS group, 168 in the HIV–/ACS group, and 171 in the HIV–/noACS group. Independent risk factors for ACS were smoking [odds ratio (OR) 4.091; 95% confidence interval (CI) 2.086–8.438; P < 0.0001] and a family history of cardiovascular disease (OR 7.676; 95% CI 1.976–32.168; P = 0.0003) in HIV-positive subjects, and smoking (OR 4.310; 95% CI 2.425–7.853; P < 0.0001), diabetes (OR 5.778; 95% CI 2.393–15.422; P = 0.0002) and hypertension (OR 6.589; 95% CI 3.554–12.700; P < 0.0001) in HIV-negative subjects. PARs for smoking, diabetes and hypertension were 54.35 and 30.58, 6.57 and 17.24, and 9.07 and 38.81% in HIV-positive and HIV-negative individuals, respectively. The contribution of smoking to ACS in HIV-positive adults was generally greater than the contributions of diabetes and hypertension, and was almost twice as high as that in HIV-negative adults. Development of effective smoking cessation strategies should be prioritized to prevent cardiovascular disease in HIV-positive adults.

We attempted to determine ZD1839 price the cut-off age whereby breastfeeding was considered detrimental for dental decay by categorizing the breastfeeding duration into various time points. Of the various time points analysed, we chose to segregate

children at the 10-month mark and found that children who breastfed for more than 10 months were significantly more likely to have severe dental decay (dt and ds) in this study. Gao et al.’s (2010) study also identified prolonged breastfeeding as a predictor for caries occurrence[4]. However, in her study, increased caries risk was associated with prolonged breastfeeding for ‘1–2 years’ and ‘beyond 2 years’ in comparison with those for ‘<12 months’. Despite the difference in the duration of breastfeeding, both studies suggest that the duration, rather than the history of breastfeeding, may play a significant role in caries activity. Some of the proposed hypotheses for this phenomenon may be because older children who continue to breastfeed had an overall higher number of food intakes per day than those who were weaned off breastfeeding at an earlier age.

Erickson et al.[25] proposed that although breast milk alone would not cause ECC, it could potentially aggravate ECC severity when combined with other carbohydrates. click here The data on breastfeeding and its impact on early childhood caries are limited, and more studies are needed to investigate this relationship. Malay children had significantly higher prevalence of dental decay (yes/no) but no difference in severity of dental decay when compared about with children of the other ethnicities. This may be attributed to several cariogenic homecare practices in Malay children. Compared with parents of other ethnicities, Malay parents were more likely to report that their child fell asleep while breastfeeding or drinking from a bottle containing milk, juice, or something sweet (P = 0.012), were more likely to breastfeed their children for a longer duration (P = 0.002), and were also less likely to withhold

between-meal cariogenic snacks from their children when they fussed for them (P = 0.047). Similar observations were found in Gao et al.’s (2010) study, where the Malay ethnicity had a significant link to oral homecare practices and caries rate[4]. The differences in homecare practices, however, were not identified in that study. Adair et al.[26] established that parental attitudes and their perceived ability to control their children’s tooth-brushing and sugar-snacking habits could significantly impact the establishment of habits favourable to oral health. Gao et al.’s (2010) study demonstrated that specific knowledge, such as the awareness of the detrimental effect of bedtime feeding and the awareness of sugar as the main reason for caries, was more important than generic parental knowledge or attitude (e.g., the awareness of early childhood caries) in influencing oral homecare practices[4].

Conclusion. We recommend extending serologic confirmation of immigrants’ hepatitis A immunity. If time is lacking, vaccination should

be considered. Hepatitis A vaccination is recommended to people traveling to countries where the disease is endemic. Hepatitis A virus (HAV) is transmitted by fecal–oral way. In most developing countries, hepatitis A antibodies appear early in life and remain detectable in adulthood. However, several reports have documented changing trends of hepatitis A epidemiology in previously highly endemic countries.1–13 Improvements in socioeconomic status and vaccination lead to continued decrease in HAV incidence, especially in the younger age groups. Immigrants originating from BKM120 clinical trial endemic countries and living in Europe may not be immunized against hepatitis A. Nonimmune, unprotected travelers are at risk of acquiring IDH assay hepatitis A when returning to their country of origin. Prior to vaccination we propose hepatitis A serology to individuals who have lived at least 1 year in a country at risk. The purpose of this study

was to assess hepatitis A seroprevalence in a population of travelers who had previously lived in a highly endemic country. We conducted a retrospective study of vaccination records at the International Vaccination Center of the Parisian Institut Pasteur between September 1, 2008, and February 28, 2010. At the vaccination center we use a standard questionnaire designed for all travelers, in which date and country of birth, sex, the period spent at a country at risk, the reason of the journey, medical history, and vaccination status are recorded. Before a journey to endemic areas, hepatitis A serology is recommended to people who have lived in a country at risk. We contact patients whose test is negative and recommend Fludarabine cost vaccination. In our study, we included records of people who lived at least 1 year in a country at risk. We excluded cases where the name of the country of risk was missing as well as people who had received hepatitis A vaccine at any time prior

to serology. Serology was considered positive if total or immunoglobulin G (IgG) antibodies (by enzyme-linked immunosorbent assay) were present. Data were analyzed by chi-square test and Fisher exact test for categorical variables, and t-test for continuous variables. Logistic regression was used for multivariate analysis. During the 18-month study period we included the charts of 989 subjects, to whom we had prescribed hepatitis A serology according to the above criteria. A total of 788 subjects traveled for vacation or business and 201 did humanitarian work. Test results were available for 646 of them. Hepatitis A serology was positive in 532 and negative in 114 subjects. Overall seroprevalence was 82.4%. Mean age of the 646 subjects was 37.2 years and age range from 6 to 86 years. Sex ratio male/female was 0.99, 1.07 for hepatitis A positive group and 0.

oligospora ORS 18692 S7 and could enhance fungal activity against the nematode, but the mechanisms were unknown (Duponnois et al., 1998). The mechanisms by which Chryseobacterium sp. TFB-induced traps in A. oligospora are being investigated. The addition of nutrients decreased the formation of MT and CT. This type of trap formation is in agreement with studies where a low nutrient status might favour the initiation of trap formation (Nordbring-Hertz, 1973, 1977; Friman et al., 1985; Persmark & Nordbring-Hertz,

1997). However, very low nutrient APO866 concentration levels could decrease the induciveness for trap formation. It is possible that at very low nutrient levels, bacteria produce fewer metabolites that can enhance the attachment of its cell to fungal hyphae, and thus it induced fewer traps in fungi. Nematode-trapping fungi are facultative parasites of nematodes with varying saprophytic/parasitic ability (Cooke, 1964). They may be divided into the spontaneous trap formers (in our study A. dactyloides and M. ellipsosporum), which are considered as efficient parasites, and the nonspontaneous trap formers (in our study A. oligospora and A. musiformis), which are considered as good saprophytes. The study of Persmark & Nordbring-Hertz (1997) showed that fungi with the highest saprophytic ability had the lowest capacity

this website to form CT when cultured with soil bacteria. However, in our study, A. oligospora showed the highest capacity. The recent study (Warmink et al., 2009) supported the viewpoint that the fungal mycosphere could indeed exert a selective pressure on particular soil bacteria. In our study, Chryseobacterium sp. TFB was isolated from the soil in which A. oligospora was the preponderant

species (Zhang et al., 2005). Thus, it is possible that this bacterium may be selected by A. oligospora and can induce traps in A. oligospora Pyruvate dehydrogenase efficiently. We are currently examining this possibility. This work was performed with financial support from the Natural Science Foundation of China (Grant no. 20762014, 50761007 and u1036602) and the Natural Science Foundation of Yunnan province (Grant no. 2006E0008Q). We are grateful to Dr J-P Xu (McMaster University, Canada) for his critical reading of this manuscript. L.L. and M.M. contributed equally to this work. Fig. S1. Influence of Chryseobacterium sp. TFB cell-free filtrates (CF) on Arthrobotrys oligospora. Fig. S2. Effect of nutrient addition on trap formation in Arthrobotrys oligospora by Chryseobacterium sp. TFB cells (1.67×107 CFU mL-1) with bacterial cell-free culture filtrate (20%). Please note: Wiley-Blackwell is not 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.

Dr J Dhar has received conference support from ViiV. Mrs K Gandhi has no conflicts of interest to declare.

Dr Y Gilleece has received lecture and consultancy fees from ViiV. Dr K Harding has received lecture and consultancy fees from ViiV. Dr D Hawkins has no conflicts of interest to declare. Dr P Hay has received lecture and consultancy fees from Abbott, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead, Johnson and Johnson (Tibotec) and ViiV. He has received conference support from Bristol-Myers Squibb, Gilead and Janssen and his department has received research grant support from Abbott, Boehringer Ingelheim, Gilead, Janssen and ViiV. Ms J Kennedy has no conflicts of interest to declare. Dr N Low-Beer has no conflicts selleck products click here of interest to declare. Dr H Lyall has received lecture fees from Danone and ViiV. Dr F Lyons has no conflicts of interest to declare. Dr D Mercey has no conflicts of interest to declare. Dr P Tookey has received research grant support from AbbVie. Dr S Welch has no conflicts of interest to declare. Dr E Wilkins

has received lecture and consultancy fees from Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp and Dohme and ViiV. BHIVA revised and updated the Association’s guideline development manual in 2011 [364]. BHIVA has adopted the modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for the assessment, evaluation and grading of evidence and the development of recommendations [365, 366]. only 1A Strong recommendation. High-quality evidence. Benefits clearly outweigh risk and burdens, or vice versa. Consistent evidence from well-performed, randomized, controlled trials or overwhelming evidence of some other form. Further research is unlikely to change our confidence in the estimate of benefit and risk. Strong recommendations, can apply to most patients in most circumstances without reservation.

Clinicians should follow a strong recommendation unless there is a clear rationale for an alternative approach. 1B Strong recommendation. Moderate-quality evidence. Benefits clearly outweigh risk and burdens, or vice versa. Evidence from randomized, controlled trials with important limitations (inconsistent results, methods flaws, indirect or imprecise), or very strong evidence of some other research design. Further research may impact on our confidence in the estimate of benefit and risk. Strong recommendation and applies to most patients. Clinicians should follow a strong recommendation unless a clear and compelling rationale for an alternative approach is present. 1C Strong recommendation. Low-quality evidence. Benefits appear to outweigh risk and burdens, or vice versa. Evidence from observational studies, unsystematic clinical experience, or from randomized, controlled trials with serious flaws. Any estimate of effect is uncertain. Strong recommendation, and applies to most patients.

Dr J Dhar has received conference support from ViiV. Mrs K Gandhi has no conflicts of interest to declare.

Dr Y Gilleece has received lecture and consultancy fees from ViiV. Dr K Harding has received lecture and consultancy fees from ViiV. Dr D Hawkins has no conflicts of interest to declare. Dr P Hay has received lecture and consultancy fees from Abbott, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead, Johnson and Johnson (Tibotec) and ViiV. He has received conference support from Bristol-Myers Squibb, Gilead and Janssen and his department has received research grant support from Abbott, Boehringer Ingelheim, Gilead, Janssen and ViiV. Ms J Kennedy has no conflicts of interest to declare. Dr N Low-Beer has no conflicts Fluorouracil CP-868596 cell line of interest to declare. Dr H Lyall has received lecture fees from Danone and ViiV. Dr F Lyons has no conflicts of interest to declare. Dr D Mercey has no conflicts of interest to declare. Dr P Tookey has received research grant support from AbbVie. Dr S Welch has no conflicts of interest to declare. Dr E Wilkins

has received lecture and consultancy fees from Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp and Dohme and ViiV. BHIVA revised and updated the Association’s guideline development manual in 2011 [364]. BHIVA has adopted the modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for the assessment, evaluation and grading of evidence and the development of recommendations [365, 366]. Thiamet G 1A Strong recommendation. High-quality evidence. Benefits clearly outweigh risk and burdens, or vice versa. Consistent evidence from well-performed, randomized, controlled trials or overwhelming evidence of some other form. Further research is unlikely to change our confidence in the estimate of benefit and risk. Strong recommendations, can apply to most patients in most circumstances without reservation.

Clinicians should follow a strong recommendation unless there is a clear rationale for an alternative approach. 1B Strong recommendation. Moderate-quality evidence. Benefits clearly outweigh risk and burdens, or vice versa. Evidence from randomized, controlled trials with important limitations (inconsistent results, methods flaws, indirect or imprecise), or very strong evidence of some other research design. Further research may impact on our confidence in the estimate of benefit and risk. Strong recommendation and applies to most patients. Clinicians should follow a strong recommendation unless a clear and compelling rationale for an alternative approach is present. 1C Strong recommendation. Low-quality evidence. Benefits appear to outweigh risk and burdens, or vice versa. Evidence from observational studies, unsystematic clinical experience, or from randomized, controlled trials with serious flaws. Any estimate of effect is uncertain. Strong recommendation, and applies to most patients.

Forward [f] and reverse [r] primer pairs: CB58 [f] and CB57 [r] (icmW–CBU1651–icmX), CB59 [f] and CB60 [r] (icmV–dotA), CB718 [f] and CB716 [r] (dotA–CBU1647), CB603 [f] and CB602 [r] (dotB–CBU1646), PI3K inhibitor CB63 [f] and CB64 [r] (dotD–dotC–dotB), and CB62 [f] and CB61 [r] (icmT–icmS–dotD), were used to demonstrate transcriptional linkage. RT-PCR analysis of icmT, icmV, and icmW ORFs was performed using CB78 [f] and CB79 [r], CB70 [f] and CB71 [r], and CB40 [f] and CB41 [r], respectively. Oligonucleotide primers

(Table 1) for RT-qPCR analysis of icmX, icmW, icmV, dotA, dotB, and icmT were designed using primer3plus (Andreas Untergasser et al., 2007). The primer efficiency of all primer sets were within the efficiency window for the calculation method (Livak & Schmittgen, 2001; Schmittgen & Livak, 2008). Single-step RT-qPCR analysis using SuperScript III (Invitrogen) reverse transcriptase and the SYBR Green Master Mix Kit (Applied Biosystems) was performed on an ABI 7500 cycler. Each reaction contained 15 μL total volume and 20 ng total RNA. To calculate the relative temporal RNA

expression fold changes over the time course, to each individual gene was used, respectively. For each gene, the respective mean time-zero cycle threshold (CT) value was used as ABT-737 mouse the baseline reference point for all other (respective) mean time point CT values over the evaluation period. Therefore, for each individual gene, their relative fold expression at each time point is internally referenced to time zero RNA levels. Each time-zero point

has been referenced to themselves, resulting in a calculated fold value of 1. Statistical significance between the time points was evaluated by single-factor anova with a 95% confidence interval using ms excel 2007 (Microsoft). A P-value of <0.05 was considered significant. Recombinant C. burnetii IcmT  and protein-specific antibody were the same as described previously (Morgan et al., 2010). Briefly, to ensure specificity, the rabbit sera against recombinant C. burnetii IcmT were absorbed against Vero cell lysates as well as the Escherichia coli DH5α expression strain to remove cross-reactive antibodies. This antibody was designated RαIcmT. For immunoblot analysis, purified C. burnetii NMII was pelleted and resuspended in protein lysis/running buffer [Tris-HCl, pH 6.8, 62.5 mM, much sodium dodecyl sulfate (SDS) 2%, glycerol 25%, bromophenol blue 0.01%, and 2-mercaptoethanol 5% added before loading]. Protein representing 108C. burnetii genome equivalents and 104 Vero cells, respectively, was separated by 16% SDS-polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane (Whatman, Dassel, Germany) along with a protein ladder (Bio-Rad, Hercules, CA). Immunoblot analysis was carried out using a Pico Western Chemilluominescent Kit (Pierce, Rockford, IL) following the manufacturer’s directions using the RαIcmT primary antibody at a 1 : 1000 dilution in a hybridization buffer.

Overall, the mean scores on all of the subscales and the total score in the HIV-positive group were significantly higher than those in the control group (t=6.45–16.09; P<0.001). The total score for the HIV-positive group was >160, which suggests psychological distress. Ivacaftor ic50 In particular, the mean

scores on the obsessive–compulsive, depression, anxiety and anger/hostility subscales for the HIV-positive group were higher than the threshold score (2.0) (Table 2). Both male and female HIV-positive participants had significantly higher scores and mean subscale scores than their control counterparts (P<0.05). There was no significant difference in SCL-90 scores between the male and female control groups (P>0.05). In the HIV-positive group, female subjects had significantly higher mean depression and anxiety subscale scores than male subjects (P<0.05), and these were the highest among the mean scores of all subscales for both male and female subjects (Table 3). The percentage of HIV-positive participants with mean subscale scores >2.0 was higher for female than for male HIV-positive participants (P<0.05 for obsessive–compulsive disorder, interpersonal sensitivity, depression, anxiety, phobic anxiety and psychoticism; P>0.05 for hostility, paranoid

ideation and somatization) (Fig. 1). The average number of subscales with mean scores selleck inhibitor >2.0 was 4.1 for female HIV-positive individuals and 3.7 for male HIV-positive individuals. The four most frequent types of psychological distress were depression

(66.7% for male HIV-positive individuals and 84.6% for female HIV-positive individuals), anxiety (58.6% for male HIV-positive individuals and 63.5% for female HIV-positive individuals), obsessive–compulsiveness (53.1% for male HIV-positive individuals and 55.8% for female HIV-positive individuals) and anger/hostility (52.5% for male HIV-positive individuals and 51.9% for female HIV-positive individuals). The most common psychosocial experiences of HIV-positive participants regarding HIV infection were fear (36.9%) and helplessness (31.8%). Overall, 90.2% of participants were reluctant to tell others about their HIV infection for fear of their family members being discriminated against (42.5%) or being excluded (26.9%) or abandoned (23.3%). However, the HIV-positive status of the people studied mafosfamide in this paper was known in their communities. The main stresses in their daily lives were discrimination from their acquaintances (colleagues, friends and neighbours; 38.8%) and potential job loss and reduced quality of life (36.9%), while the financial burden of the disease was not a main stress of daily life for these HIV-positive individuals (only 10.3% reported financial burdens). After discovering their HIV-positive status, most members of their communities, including neighbours, colleagues, doctors and family members, showed negative attitudes towards the HIV-positive participant. More than 80% of people showed alienation, coldness, aversion or fear.

Periods off cART with a duration of >90 days were omitted from the primary analysis. A new cART regimen was defined as a regimen created from an existing Fluorouracil chemical structure regimen by the addition of one or more new antiretrovirals, or by the replacement of one or more antiretrovirals in the existing regimen with one or more new antiretrovirals. NeurocART status was assigned

to those regimens with a CPE rank of 8 or more, with the CPE rank calculated using the 2010 rankings process [17]. CD4 cell counts and viral loads were taken as the latest measurement from up to 90 days prior to regimen commencement. HIV viral load measurements of ≤400 copies/mL were defined as undetectable because more sensitive assays were not uniformly available for all observations. Coinfection with hepatitis

B virus (HBV) or hepatitis C virus (HCV) was defined as the detection of HBV surface antigen or HCV antibody, respectively. A secondary composite endpoint of AIDS or mortality within 90 days of cessation of treatment was also investigated. Follow-up was calculated from the start date of each new cART regimen (or the date of cohort enrolment if later), until cessation of that cART regimen. Loss to follow-up was defined as no clinic visit in the 12 months prior to 31 March 2009 (cohort censoring date). Patients lost to follow-up were censored at their last clinic visit. We used an intention-to-continue treatment approach and ignored any changes to, or interruptions or termination of, treatment after baseline. For each new cART regimen we created a new set of baseline covariates and assessed this website the risk of death on that cART regimen adjusted for those baseline covariates. Variables updated at change in cART regimen were neurocART status, O-methylated flavonoid CD4 count (<50, 50–99, 100–199, 200–349 and ≥350 cells/μL, or missing), HIV viral load (≤400 or >400 HIV-1 RNA copies/mL,

or missing), prior AIDS-defining illness (ADI), cART regimen count (first, second, third, fourth or more), months of prior neurocART exposure (never, or 1–9, 10–18 or >18 months), and months of prior cART (not neurocART) exposure (never, or 1–18 or >18 months). Additional variables examined were age (<30, 30–39, 40–49 or ≥50 years), sex, mode of HIV exposure [men who have sex with men (MSM), heterosexual, injecting drug use (IDU), other or missing], HCV coinfection, HBV coinfection, and neurocART type prior to entry (naïve, cART and not neurocART, or neurocART). We also analysed the incidence of HAD. As there is some evidence that progressive multifocal leucoencephalopathy (PML) may respond better to neurocART than non-neurocART [20], PML data were also analysed. We did not have data on patients’ CD4 cell count nadirs. An administrative censoring date of 31 March 2009 was used. Univariate Cox proportional hazards models were developed for all variables.