As noted, greater immunosuppression was also associated with a stepwise increased

likelihood of bacteraemia. Compared with those with CD4 Alectinib counts >500 cells/μL, those with CD4 counts of 201–350 cells/μL (AOR 1.77, 95% CI 1.46, 2.15), 51–200 cells/μL (AOR 3.23, 95% CI 2.65, 3.94) and ≤50 cells/μL (AOR 7.64, 95% CI 6.14, 9.51) had higher odds of bacteraemia. In addition, compared with those with HIV-1 RNA ≤400 copies/mL, those with higher HIV-1 RNA levels had higher odds of bacteraemia. The likelihood of bacteraemia was higher among IDUs compared with MSM (AOR 1.67, 95% CI 1.43, 1.95), patients aged ≥50 years compared with the youngest group (AOR 1.62, 95% CI 1.22, 2.16) and among Blacks compared with Whites (AOR 1.43, 95% CI 1.20, 1.69). Patients with public coverage and those who were uninsured had higher

odds than those covered by private insurance. In multivariate analysis, the odds of bacteraemia were not significantly associated with receipt of HAART. The unadjusted association of HAART with any episode of bacteraemia was, however, significant (AOR 1.18, 95% CI 1.06, 1.32). The difference arises from the association between HAART, CD4 cell count and HIV-1 RNA. Adjusting for CD4 cell count and HIV-1 RNA is sufficient to reduce the HAART effect (AOR 0.95, 95% CI 0.83, 1.07; data not shown). HAART can result in changes in CD4 and HIV-1 RNA; these variables thus can be considered to be on the causal pathway through which HAART affects bacteraemia, and adjusting for such ‘downstream’ Veliparib chemical structure variables will

reduce the direct effect of a causally prior variable. This study has several important findings. First, in the current Etofibrate HAART era the rate of bacteraemia in HIV-infected patients remains significantly higher than that of the general population [9,15,16]. In addition, the adjusted odds of bacteraemia appear to be increasing in recent years. Several modifiable factors appear to be protective against development of bacteraemia, including use of HAART, high CD4 cell count and not using injection drugs. The overall incidence of bacteraemia from 2000 to 2008 in this sample was 13.8 per 1000 PY. Tumbarello et al. reported a bacteraemia incidence rate of 62/1000 PY and Meynard et al. reported an incidence of 55/1000 HIV hospitalizations, both in 1998 [5,8]. While our estimates are lower, these studies were both restricted to hospitalized patients at one clinic site in Europe during the early HAART era, and may not be applicable to HIV-infected patients living in the USA in the current HAART era. Our incidence rate estimates are lower than the estimates in these prior studies, as we included all patients, regardless of hospitalization, in the denominator. Incidence fluctuated over this time period, decreasing from 2000 to 2002, and then rising from 2003 to 2007. It is not clear what produced this nonlinear pattern. Another study examining the incidence of S.

5-fold higher than the general population has been excluded. Amongst other currently used agents (abacavir, atazanavir and efavirenz) there

are now more than 200 prospective reports of first-trimester exposure with no signal of increased risk (and a greater than two-fold higher rate than in the general population has been excluded) [50]. For the newer agents (raltegravir, etravirine, maraviroc and rilpivirine) and a number of less commonly prescribed STA-9090 molecular weight older compounds (saquinavir, fosamprenavir, enfuvirtide and tipranavir) there have been insufficient reported outcomes of first-trimester exposure to exclude such risk. There are insufficient data to recommend routinely switching from efavirenz to another agent. The earlier recommendation that efavirenz be avoided in women who may conceive [51] was based on preclinical animal studies that had not been conducted on any other ART, the FDA reclassification of efavirenz to category D and the paucity of human http://www.selleckchem.com/products/pexidartinib-plx3397.html data. Three of 20 offspring of cynomolgus macaques exposed to efavirenz in the first trimester had significant abnormalities at birth: one had anencephaly and unilateral anophthalmia; the second had microphthalmia; and the third had a cleft palate [52]. Subsequently four anecdotal

cases of myelomeningocoele and two of Dandy Walker syndrome were reported following human first-trimester efavirenz exposure. No

prospective data were available, causation was not proven and a lack of data on the number of cases reported compared to the number of exposures meant that the relative risk of the putative association could not be calculated. Based on the emerging prospective data in which no evidence of human teratogenicity has been seen, the Writing Group consider that there are insufficient data to support the former position and furthermore recommend 4��8C that efavirenz can be both continued and commenced (see below) in pregnancy. The data considered were: Antiretroviral Pregnancy Registry [53] Sufficient numbers of first trimester exposures of efavirenz have been monitored to detect at least a two-fold increase in risk of overall birth defects and no such increases have been detected to date. A single case of myelomeningocoele and one case of anophthalmia have been prospectively reported in live births. There have been six retrospective reports of findings consistent with neural tube defects, including myelomeningocoele. It is important to note that not all HIV pregnancies are reported to the APR as reporting is voluntary. A web and literature search reveals two case reports of myelomeningocoele associated with first-trimester efavirenz exposure [54, 55].

37 Hybrid techniques. If required, it is often beneficial to perform both open surgical and endovascular CH5424802 mw techniques at the same sitting. An example of this is in the presence of combined femoral artery occlusive disease in the groin and an iliac stenosis proximally. In this case, access for iliac angioplasty via the femoral artery is not possible. The ‘hybrid’ option would be to perform a femoral endarterectomy (removal of intimal atheroma) combined with iliac angioplasty at the same sitting. Amputation. Major amputation should still be considered as a treatment option in CLI. In patients who truly have no suitable distal target vessels for

revascularisation, major amputation can provide a definitive treatment for pain or tissue loss or where mobility is already severely compromised. However, it is vital that this decision is not taken until a multidisciplinary team discussion has been undertaken, all options for revascularisation considered,10 and the patient’s views sought. This may help in reducing the current variability in amputation rates across England.1 It is important to involve the prosthetics and rehabilitation services in assessing a patient’s potential to

rehabilitate prior to surgery. Peripheral arterial disease is more common in patients with diabetes and is associated with worse outcomes and a higher risk of limb loss.5,10 Critical limb ischaemia is a manifestation of diabetic foot disease and requires early recognition with urgent onward referral and management. selleck chemical This demands good communication between the community and specialist teams with agreed integrated pathways of care if amputation rates are to be minimised. There are no conflicts of interest declared. References are available

in Practical Diabetes online at www.practicaldiabetes.com. RVX-208 Critical limb ischaemia (CLI) is a potentially limb and life-threatening complication, and is more common in those with diabetes In a patient with diabetes, CLI may present with no current or previous history of limb pain. Signs in the foot may be subtle, and CLI can reduce the normal evidence of foot infection Urgent referral and management by a foot multidisciplinary team are vital, if CLI is suspected, within an integrated pathway of care with an overall aim to reduce amputation rates Ensure cardiovascular risk factors are also investigated and managed appropriately Any associated foot infection must be vigorously treated in those with CLI All potential management options for revascularisation should be considered by the multidisciplinary team, and the patient’s views sought “
“Cycling is increasing in popularity for both recreational and practical purposes. Marked changes in blood glucose are seen during and following cycling, with risk of hypoglycaemia.

, 2011), which may represent additional adaptive traits that promote distribution of the plasmid, or its genes, among nosocomial bacteria. chrA gene homologues from plasmids of Pseudomonas Obeticholic Acid concentration sp. (Tauch

et al., 2003) and Comamonas sp. (Ma et al., 2007), as well as from the chromosomes of Ochrobactrum tritici 5bvl1 (Branco et al., 2008), Bacillus cereus SJ1 (He et al., 2010), and Pseudomonas sp. (Petrova et al., 2011), are also located on putative transposable elements. In conclusion, our results showed that chrA gene homologues are frequently found in plasmids of enterobacterial isolates of nosocomial origin and suggest that CrR genes may be transferred among hospital bacteria owing to their location within genetic mobile elements, probably coselected by antibiotic exposure. The present work was partially supported by grants from Coordinación de Investigación Científica (UMSNH; 2.6 and 2.35) and Consejo Nacional de Ciencia y Tecnología, México (Conacyt no. 79190). GGC-F and YMA-N were recipients of postgraduate and graduate fellowships from Conacyt, respectively. “
“In Streptococcus mutans, ComX, an alternative sigma factor, selleck kinase inhibitor drives the transcription

of the ‘late-competence genes’ required for genetic transformation. ComX activity is modulated by inputs from two signaling pathways, ComDE and ComRS, that respond to the competence-stimulating peptide (CSP) and the SigX-inducing peptide (XIP), respectively. In particular, the comRS, encoding the ComR regulatory protein and the ComS precursor to XIP, functions as the proximal regulatory system for ComX activation. Here, we investigated the individual and combinatorial effects of CSP and XIP on genetic transformation and cell killing of S. mutans. Our transformation results confirm oxyclozanide the recent reports by Mashburn-Warren et al. and Desai et al. that XIP functions optimally in a chemically defined medium, whereas its activity is inhibited

when cells are grown in complex medium. Using tandem mass spectrometry (MS/MS) fragmentation, a drastic reduction in XIP levels in ComX-deficient cultures were observed, suggesting a ComX-mediated positive feedback mechanism for XIP synthesis. Our evaluation of cell viability in the presence of 10 μM XIP resulted in killing nearly 82% of the population. The killing activity was shown to be dependent on the presence of comR/S and comX. These results suggest a novel role for XIP as a compelling effector of cell death. This is the first report that demonstrates a role for XIP in cell killing. The acquisition of novel, heritable DNA by genetically competent bacteria not only propagates antibiotic resistance and virulence determinants, but also shapes bacterial genomes contributing to rapid evolutionary changes (Kroll et al., 1988; Seifert et al., 1988; Feil et al., 1999; Cody et al., 2003; Didelot & Maiden, 2010).

Electron microscopy also showed that in the case of the wild-type S. Enteritidis uptake, the Salmonella-containing vacuoles (SCV) developed towards the spacious ones while in the case of all the rfa mutants, the vacuole closely fitted the S. Enteritidis cell inside and signs of bacterial cell disintegration could be observed inside the vacuole (Fig. 2). In this study, we have characterized the interactions between attenuated S. Enteritidis mutants and porcine WBC in vitro. Such knowledge might be useful for the prediction of the properties of attenuated check details S. enterica mutants used as vaccines against salmonellosis itself or as vectors for targeting particular cell types including cancer cells. Three different

types of association profiles have been found among the tested attenuated mutants. First, the phoP and aroA mutants did not differ from the wild-type S. Enteritidis in any of the assays. Second, the Enzalutamide research buy fliC and ΔSPI1-5 mutants, exhibited only minor differences when compared with the wild-type strain – likely due to the defect in chemotaxis in the fliC mutant (Khoramian-Falsafi et al., 1990; Jones et al., 1992) and the defect in cell invasion in the ΔSPI1-5 mutant (Kaniga et al., 1995). The last group comprising of rfaC,

rfaG and rfaL mutants was characterized by a highly increased association with the host immune cells. The differences from the interaction with the wild-type strain could also be seen in the development of SCV, which, unlike the spacious one seen after the wild-type strain infection (Alpuche-Aranda et al., 1994; Boyen et al., 2006), fitted closely to the surface of the rfaC mutant (Fig. 2). Our results show that type III secretion systems encoded by SPI-1, SPI-2 or flagellar operons have only a minor influence on the initial interactions of S. Enteritidis with porcine leukocytes. Instead, this interaction was dependent on the oligosaccharides buy Forskolin exposed at the surface of S. Enteritidis. Interestingly, even within the rfa mutants, there were certain differences. In the absence of serum, the rfaL mutant expressing

lipopolysaccharide without the O-antigen exhibited an increased affinity for T-lymphocytes while the rfaC and rfaG mutants expressing lipopolysaccharide without the outer and the inner oligosaccharide core, respectively, associated more than the rfaL mutant with B-lymphocytes. All of these results might be used in rational vaccine design. However, if critically evaluated, live Salmonella vaccines for animal use are administered orally and therefore will be exposed to blood leukocytes only very rarely. On the other hand, attenuated S. enterica strains that were tested for tumor therapy in mice and humans were administered intravenously (Toso et al., 2002; Zhao et al., 2005; Leschner et al., 2009; Vendrell et al., 2011), i.e. they were immediately subjected to interactions with the blood leukocytes and via the circulation also to other cell types.

It has been postulated that pathogenic organisms decrease expression of their virulence genes, to aide in establishment of persistent infection (Hennig et al., 1999). Previous qRT-PCR results, using samples recovered 6–12 h

following infection, showed that nmaA declined during the sampling period (S. Sathiamoorthy click here et al., unpublished). The levels reported here were even lower. Again, at 6 days postinfection, slowed growth rate may obviate the need to express genes involved in capsule biosynthesis. Another potential virulence factor of M. hemolytica A1, the serotype-specific antigen (Ssa1) was down-regulated 27-fold in vivo. Ssa1 has been implicated in colonization of the nasopharynx and may contain protease activity (Highlander, 2001). It is an outer membrane protein that is recognized by sera from healthy animals resistant to pneumonic pasteurellosis (Lo et al., 1991). This is the first study to show the expression of ssa in vivo. As Ssa1

may be required for colonization of the http://www.selleckchem.com/products/dabrafenib-gsk2118436.html nasopharynx, reduced expression in lung washings is not unexpected. Microarray analysis of the M. hemolytica A1 transcriptome, from bacteria isolated from infected calves at 6 days postinfection, has provided some clues about gene expression in the later stages of infection and disease. Expression of several known virulence factor genes was reduced at this point of infection, while their expression has been shown to be higher during earlier stages. At 6 days after challenge, the results suggest that the bacterial metabolism was changing and perhaps decreasing. Genes involved in energy metabolism, capsule biosynthesis, and amino acid synthesis, all showed lower expression in vivo relative to in vitro while a number of uncharacterized hypothetical protein genes had higher expression. Nevertheless, Calpain caution must be exercised when

comparing gene expression data from different studies, due not only to inter-animal variation but also to the different stages of infection studied. In this study, by making the threshold for differential expression more stringent, fewer, and possibly more biologically relevant hypothetical proteins were identified. This research was funded by the Natural Sciences and Research Council of Canada through the scholarships and research grants. Funding for calves and animal housing was provided by Ontario Ministry of Agriculture, Food and Rural Affairs. Funds for microarray design and the implementation were provided to S.K.H. from USDA grant 2004-01320. “
“In this study, a total of 25 endophytic fungi were successfully isolated from the inner bark of Taxus baccata grown in Iran by the aseptic technique. Genomic DNA was extracted from isolated endophytic fungi and subjected to polymerase chain reaction (PCR) analysis for the presence of the Taxus taxadiene synthase (ts) gene, which encodes the enzyme catalyzing the first committed step of taxol biosynthesis.

(2009). It has been suggested that higher levels of colonization and thereby enhanced stx2 exposure might

be responsible, at least partly, for the increased pathogenic potential seen in SF O157 compared to NSF O157 (Rosser et al., 2008). Although no evidence of in vitro increased stx2EDL933 expression in SF O157 compared to NSF O157 has been observed, so far only two SF O157 have been GSK2118436 examined (Rosser et al., 2008), and to our knowledge, the in vivo level has never been investigated. It cannot be excluded that the qO111:H− gene identified in all Norwegian SF O157 isolates, as opposed to q933 and q21 previously found in NSF O157 (LeJeune et al., 2004; Koitabashi et al., 2006; Matsumoto et al., 2008), may contribute to the increased virulence observed in SF O157, by virtue of increased stx2 level and/or enhanced resistance of the bacteria concerned (Ferens & Hovde, 2011). Additional investigations are needed to elucidate the activity of the QO111:H− protein in SF O157 strains. Lambdoid phages are introducing tRNA genes into the bacteria, which may be required for efficient expression of foreign genes encoded by the phages, as for instance the stx genes (Plunkett et al., 1999; Hayashi

et al., 2001; Schmidt, 2001). The tRNA genes ileZ-argN-argO located close to the stx genes, in both SF O157 and NSF O157 as well as in other EHEC, might thus serve as a supplement to the host tRNA pool and lead to a more efficient translation of foreign genes (Plunkett et al., 1999). In strains 1106-4002 (FR874039) and 1109-0113 MDV3100 (FR874040), the tRNA genes ileZ-argN-argO showed identical sequences to the ones in the O111:H− strain 11128 (AP010960). However, strain 1108-2781 (FR874041) exhibited an ileZ-argN-argO sequence identical to that found in NSF O157 EDL933 (AE005174), except for a single

nucleotide polymorphism in the argN gene observed neither in the O111:H− strain 11128, the O157:H7 strain EDL933 nor the SF O157 strains 1106-4002 and 1109-0113. These observations might suggest different origin of the bacteriophages and/or rearrangements within the phage DNA in SF O157 (Allison, 2007). Whether the observed base substitutions seen within the tRNA ileZ-argN-argO sequence next contribute to enhanced virulence in the SF O157, compared to NSF O157, needs to be further explored. Phenotypic characteristics as well as the presence of specific virulence genes are in part different between SF O157 and NSF O157 (Karch & Bielaszewska, 2001; Rosser et al., 2008). Genetic characterization of SF O157 showed that our results were in concordance with previous reports (they all carried rfbO157, fliCH7, SRL and dinB) (Karch & Bielaszewska, 2001; Taylor et al., 2002; Janka et al., 2005; Orth et al., 2007). Additionally, all SF O157 harboured the eae and stx2EDL933 genes. Eighty-eight per cent of the strains carried ehxA, and cdt was present in 82% of our SF O157 isolates, which is in agreement with earlier studies (Karch & Bielaszewska, 2001; Janka et al.

This most troublesome of

all the genitourinary Neratinib clinical trial complications of diabetes is often overlooked. Copyright © 2011 John Wiley & Sons. “
“Type 2 diabetes (T2DM) in the young is a growing concern in many countries worldwide. In previous studies, positive associations with obesity, female gender, and family history have been noted. Newham, East London, has one of the highest prevalence of T2DM in the UK as well as one of the youngest populations. Our aim was to establish the prevalence and characteristics of T2DM in young people in Newham, and compare findings with existing data. Forty-four young people (≤25 years) with T2DM and an equal number of young people with type 1 diabetes were examined. A retrospective analysis of existing patient records utilising diabetes and pathology databases was conducted. The age-specific prevalence of T2DM in children and young VE-821 cell line adults within Newham was noted to be the highest in the UK at 0.57/1000 (58 out of 100 300). There was a strong association with obesity and 77% of those with T2DM were found to have a body mass index ≥25kg/m2. Many had features of the metabolic syndrome. This analysis confirms the high prevalence of T2DM with obesity in young people, particularly among minority ethnic groups, and adds to concern among health care providers and commissioners about the need for preventative strategies to tackle

this problem. Copyright © 2012 John Wiley & Sons. “
“The

aim of this study was to identify the efficacy of a staged diabetes management (SDM) clinic serving a low socio-economic Hispanic population in achieving glycaemic goal. We analysed prospectively collected data from patients discharged from the clinic in 2008 with an admission HbA1c >8% (64mmol/mol) and >one clinic Exoribonuclease visit. Adjusted odds ratios (AOR) were determined for factors significantly associated with glycaemic goal achievement. Both those patients who achieved the clinic HbA1c goal of ≤8% (n=277) and those who did not (n=209) had a clinically significant decrease in HbA1c (-3.13±1.80, -1.08±1.78). After adjustment, the following were associated with failure to achieve goal: higher admission HbA1c (%) 11.0±1.8 vs 10.3±1.7, AOR (95% CI) 1.22 (1.08, 1.37), p=0.0016; higher admission insulin (IU/kg/day) 0.56±0.58 vs 0.26±0.41, AOR 2.08 (1.09, 4.00), p=0.026; greater increase in insulin (IU/kg/day) 0.23±0.46 vs 0.09±0.32, AOR 2.38 (1.15, 5.00), p=0.02; and a longer stay (days) 229±110 vs 172±84, AOR 1.007 (1.003, 1.012), p=0.0008. In this SDM clinic, most patients achieved significant reduction in HbA1c. The study identified factors associated with a lower likelihood of achieving goal thereby demonstrating the value of review of the response to an SDM protocol in indicating areas for further improvement. Copyright © 2010 John Wiley & Sons.

Attack rates among Dutch travelers to developing regions declined for hepatitis

A, shigellosis, and typhoid fever. Region-specific trends in attack rates of shigellosis resembled trends of hepatitis A and typhoid fever. Declining attack rates of the three fecal-orally transmitted diseases correlated this website with improvements in socioeconomic, sanitary, and water supply conditions of the local population at travel destination. Conclusions. These findings suggest that improved hygienic standards at travel destination strongly contributed to the overall decline in attack rates of fecal-orally transmitted diseases among visiting travelers. In industrialized countries, the incidence of fecal-orally transmitted infections, such as hepatitis A, typhoid fever, and shigellosis, has declined substantially.1–4 Currently, most cases in these countries arise from visits to non-industrialized countries.2 A few studies have addressed trends in hepatitis A or typhoid fever among international travelers, learn more finding that, over the past decades, their risk of acquiring

hepatitis A or typhoid fever has decreased.5–7 This decline is often attributed to pretravel vaccination and improvements in hygienic and sanitary conditions at travel destinations. However, their absolute or relative contributions are unknown, given the lack of studies on the influence of hygienic factors on the incidence of fecal-orally transmitted diseases. This study analyzes region-specific trends in attack rates of hepatitis A, typhoid fever, and shigellosis among Dutch travelers, combining Dutch travelers’ statistics with information from the national infectious diseases notification system. All three diseases are transmitted through fecally contaminated water or food. Hepatitis A virus (HAV) infection causes an acute viral liver disease and confers lifelong immunity.

It is a common childhood disease in developing countries, but the prevalence of hepatitis A antibodies is low in developed regions.1,8 In the Netherlands, an inactivated HAV vaccine is available ifenprodil for risk groups, such as travelers, and is almost 100% effective.9 Typhoid fever is a bacterial systemic infection caused by Salmonella enterica serotype Typhi.3,10 Immunity following infection is limited and can be overcome.9 Two parenteral capsular polysaccharide vaccines are available in the Netherlands, and studies report their efficacy at 35% to 70%.11 Shigellosis is a bacterial enteric disease, caused by one of the four serogroups of Shigella. Immunity following infection is type-specific and probably limited.4 No vaccine is available. To study if the attack rates of fecal-orally transmitted diseases in travelers are influenced by improvements in hygienic standards at travel destinations, we compared trends in vaccine-preventable hepatitis A and typhoid fever with trends in non-vaccine-preventable shigellosis.

Only six patients underwent a switch in NNRTI between t0 and t1: four patients switched from nevirapine to efavirenz and two patients did the opposite and were classified according to their NNRTI exposure at t0. At the first GRT in a pair, the median number of drugs in the

regimen was 4 (IQR 3–4) and the most frequently used NRTIs at t0 together with the NNRTI were lamivudine (56%), stavudine (49%) and didanosine (36%). At t0, two NRTIs plus either nevirapine or efavirenz were used in 189 (41%) of the pairs while the remaining pairs were on combinations including PIs (Table 1b). The frequency of use of other antiretrovirals besides nevirapine/efavirenz at t1 was similar to that observed at t0 (data

not shown), suggesting Forskolin that these patients had in most cases been kept on the same drugs over t0–t1 despite virological failure. The median number of NNRTI mutations detected at baseline-t0 was 2 (range 0–8) and the majority of patients (66%) had at least one NNRTI mutation (supporting information, Table S4). For only 36 of the GRT pairs (8%) were no NNRTI mutations detected at both GRTs. In 2% of http://www.selleckchem.com/products/pci-32765.html the patients included in the study, NNRTI mutations were detected at the GRT performed prior to the estimated date of virological failure. Table 2a shows the prevalence of patients with at least one IAS NNRTI mutation, the distribution of individual IAS NNRTI mutations detected in major virus populations at t0 and the estimated proportions at t1. Table 2a also shows the total number of NNRTI mutations (overall and stratified by specific NNRTI drug) at t0 and t1, and the estimate of the rate of accumulation of NNRTI resistance over the observation period. The highest rate of accumulation was observed for mutations

103N (27.6 new mutations per 100 years; 95% CI 20.7–35.3), 181C (12.2/100 years; 95% CI 8.0–17.7) 190A (9.4/100 years; 95% CI 5.8–14.3) and Selleck Erastin 108I (6.7/100 years; 95% CI 4.0–10.6). Other mutations such as 98G, 100I, 101E, 181I and 188L were also accumulated, although at the lower rate of 0.2–0.4/100 years. The number of pairs for which there was at least one NNRTI mutation that was detected at t1 but not at t0 was 39/49 PYFU, giving a rate of accumulation of at least 0.79 new NNRTI mutations/year (95% CI 0.66–0.90; Table 2a). Overall, 180 IAS NNRTI resistance mutations were accumulated over 295 PYFU (average rate of 0.61 per year; 95% CI 0.55–0.67), while the rate of accumulation of NNRTI drug-specific mutations was somewhat slower, at 0.46/year, and that of etravirine mutations was a little lower compared with nevirapine or efavirenz mutations.