Switch to fixed-dose doravirine (100 mg) with islatravir (0·75 mg) once daily in virologically suppressed adults with HIV-1 on bictegravir, emtricitabine, and tenofovir alafenamide: 48-week results of a phase 3, randomised, controlled, double-blind, non-inferiority trial.

BACKGROUND: Doravirine and islatravir is an investigational, once-daily regimen with high antiviral potency, favourable safety and tolerability, and a low propensity for resistance. We investigated a switch from bictegravir, emtricitabine, and tenofovir alafenamide to doravirine (100 mg) and islatravir (0·75 mg) in virologically suppressed adults with HIV-1. METHODS: We conducted a phase 3, multicentre, randomised, active-controlled, double-blind, double-dummy, non-inferiority trial at 89 research, community, and hospital-based clinics in 11 countries. Adults aged 18 years or older with fewer than 50 HIV-1 RNA copies per mL for at least 3 months on bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) and no history of previous virological failure on any past or current regimen were randomly assigned (1:1) by a computer-generated randomisation allocation schedule, with block randomisation based on a block size of four, to switch to doravirine (100 mg) and islatravir (0·75 mg) or continue bictegravir, emtricitabine, and tenofovir alafenamide orally once daily, with matching placebos taken by all participants. Participants, investigators, study staff, and sponsor personnel involved in study drug administration or clinical evaluation of participants were masked to treatment assignment until week 48. Participants were instructed at each visit to take one tablet from each of the two bottles received, one of study drug and one of placebo, once daily, and participants were assessed at baseline and weeks 4, 12, 24, 36, and 48. The primary endpoint was the proportion of participants with greater than or equal to 50 HIV-1 RNA copies per mL at week 48 in the full analysis set (ie, all participants who received at least one dose of study drug; US Food and Drug Administration snapshot; prespecified non-inferiority margin 4%). The study is ongoing, with all remaining participants in post-treatment follow-up, and is registered with ClinicalTrials.gov, NCT04223791. FINDINGS: We screened 726 individuals for eligibility between Feb 18 and Sept 3, 2020, of whom 643 (88·6%) participants were randomly assigned to a treatment group (183 [28·5%] women and 460 [71·5%] men). 322 participants were switched to doravirine (100 mg) and islatravir (0·75 mg) and 321 continued bictegravir, emtricitabine, and tenofovir alafenamide (two participants [one with a protocol deviation and one who withdrew] assigned to bictegravir, emtricitabine, and tenofovir alafenamide did not receive treatment). The last follow-up visit for the week 48 analysis occurred on Aug 26, 2021. At week 48, two (0·6%) of 322 participants in the doravirine and islatravir group compared with one (0·3%) of 319 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group had greater than or equal to 50 HIV-1 RNA copies per mL (difference 0·3%, 95% CI -1·2 to 2·0). The per-protocol analysis showed consistent results. 25 (7·8%) participants in the doravirine and islatravir group had headache compared with 23 [7·2%] participants in the bictegravir, emtricitabine, and tenofovir alafenamide group; 101 (31·4%) compared with 98 (30·7%) had infections; and eight (2·5%) participants in each group discontinued therapy due to adverse events. 32 (9·9%) participants had treatment-related adverse events in the islatravir and doravirine group comapred with 38 (11·9%) in the bictegravir, emtricitabine, and tenofovir alafenamide group. In the islatravir and doravirine group, CD4 cell counts (mean change -19·7 cells per µL) and total lymphocyte counts (mean change -0·20 × 109/L) were decreased at 48 weeks. INTERPRETATION: Switching to daily doravirine (100 mg) and islatravir (0·75 mg) was non-inferior to bictegravir, emtricitabine, and tenofovir alafenamide at week 48. However, decreases in CD4 cell and total lymphocyte counts do not support the further development of once-daily doravirine (100 mg) and islatravir (0·75 mg). FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.

Shape memory histocompatible and biodegradable sponges for subcutaneous defect filling and repair: greatly reducing surgical incision.

Reducing surgical incision for large area subcutaneous defect filling and repair is a great challenge in the biomedical field, especially for plastic surgery. In this study, a novel hydroxyethyl cellulose/soy protein isolate (HEC/SPI) composite sponge (EHSS) with a fluid responsive shape memory property was constructed, whose thickness could be controlled by hot-pressing conditions to reduce the required surgical incision greatly. Effects of the main factors such as pressure, temperature and hot-pressing cycles on the recovery degree of EHSS were investigated systematically. The structure and physical properties of the sponges were characterized by FTIR spectroscopy, XRD, SEM etc. The results showed that EHSS could be pressed into thin disks with much smaller thickness, and the thickness retention ratio and recovery ratio were affected by hot-pressing conditions such as pressure and temperature. Especially, EHSS could be hot-pressed into a dense thin disk (EHSS-PT-130) at 130 °C with the pressure of 30 MPa, which could quickly recover its original shape by soaking in hydrophilic fluids. EHSS-PT-130 also exhibited good hydrophilicity, cytocompatibility, histocompatibility and in vivo biodegradability. Compared with the original EHSS, in vivo shape memory EHSS-PT-130 required much smaller surgical incision to reach the same repair effect and no need of extra sterilization, showing potential application for subcutaneous defect filling and repair.

Doravirine dose selection and 96-week safety and efficacy versus efavirenz in antiretroviral therapy-naive adults with HIV-1 infection in a Phase IIb trial.

BACKGROUND: The safety and efficacy of doravirine were compared with that of efavirenz as initial treatment of adults living with HIV-1 infection (NCT01632345). METHODS: A Phase IIb double-blind trial with participants stratified by screening HIV-1 RNA (≤ or >100,000 copies/ml) and randomized 1:1:1:1:1 to receive once-daily doravirine (25, 50, 100 or 200 mg) or efavirenz 600 mg (Part I) for up to 96 weeks, with open-label tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg (TDF/FTC). After dose selection at week 24, doravirine 100 mg was provided to participants receiving the other doses of doravirine and additional participants were randomized 1:1 to receive once-daily doravirine 100 mg or efavirenz 600 mg for 96 weeks with TDF/FTC (Part II). Primary outcomes were the proportion of participants with HIV-1 RNA <40 copies/ml at week 24, and central nervous system (CNS) adverse events (AEs) by weeks 8 and 24 (Parts I+II combined). RESULTS: 210 and 132 participants were randomized in Parts I and II, respectively, and 216 (108 on doravirine 100 mg, 108 on efavirenz) were evaluable for Parts I+II combined. At week 24, the proportion of participants with HIV-1 RNA <40 copies/ml was 72.9% for doravirine 100 mg and 73.1% for efavirenz (difference -0.5 [95% CI -12.3, 11.2]). In addition, CNS AEs were reported by 26.9% and 47.2% of doravirine and efavirenz recipients, respectively (difference -20.4 [95% CI -32.6, -7.5]; P=0.002). CONCLUSIONS: Doravirine 100 mg with TDF/FTC demonstrated similar antiretroviral activity and superior CNS safety compared with efavirenz 600 mg with TDF/FTC.

Should mentoring be routinely introduced into general dental practice to reduce the risk of occupational stress?

Introduction Occupational stress within general dental practice can potentially have an adverse impact on a practitioner's wellbeing and the quality of healthcare provided by that individual. Mentoring has routinely been utilised in other professions for stress management, however, there is little in the dental literature discussing the benefits of mentorship on the reduction of occupational stress for dental practitioners.Aim The aim of this study was to explore the perceptions of experienced foundation dental trainers within the Health Education, Kent, Surrey and Sussex postgraduate deanery as to the usefulness of routine mentoring as a tool to reduce occupational stress.Methods Using a qualitative approach, six individual semi-structured interviews were undertaken. Recorded interviews were transcribed and transcriptions were analysed using thematic coding to identify overarching themes.Results Both similarities and differences with the existing literature on routine mentoring within professional settings were identified. Foundation dental trainers were positive towards the concept of routine mentoring, although there was also a degree of scepticism regarding the potential uptake among colleagues. There was a perception that mentoring might more practically be used as a reactionary tool. Multiple potential barriers to routine mentoring were identified, included funding, scheduling and a lack of training.Conclusions The analysis identified that currently, experienced foundation dental practitioners do not consider routine mentoring as a practical option in the prevention of occupational stress. The results would suggest that further education is required as to the benefits of routine mentoring as a strategy for occupational stress management. However, with additional resources buying time, a hybrid model of mentoring and coaching has significant potential in general dental practice.

The impact of short and long sleep duration on instrumental activities of daily living among stroke survivors.

OBJECTIVE: Stroke survivors generally have problems completing instrumental activities of daily living (IADL; eg, preparing meals, chores, taking a bath, and managing finances). However, it is unclear how stroke survivors might stave off IADL issues. Studies indicating that sleep has restorative neurological effects provide potential mechanisms to address issues with IADL. The aim of this study was to ascertain the association between sleep duration (short or long sleep duration) and IADL among stroke survivors and those without a stroke history. METHODS: Data of 486,619 participants were analyzed from the 2000 to 2015 National Health Interview Survey (NHIS), a nationally representative sample. Measures of self-reported stroke, sociodemographic variables, sleep duration, and IADL problems were collected. Binary logistic regression was utilized to analyze the relationship of short (≤6 hours) and long (≥9 hours) sleep duration with limitations to IADL. RESULTS: Of the sample, 3% reported a physician-diagnosed stroke event. The mean age was 45.73 years; 52.7% were female; 77.4% were White; 14.2% were Black; 41.3% were married, 62.7% were employed; 31.1% reported that annual family income was less than $35,000; 87% reported good-to-excellent health; and 29.7% reported short sleep (≤6 hours). Approximately 30% of stroke survivors reported IADL problems, and 34.4% who reported IADL problems were short sleepers. Among stroke survivors, long sleepers were 97% more likely than average sleepers to report IADL problems (OR =1.97, 95% CI =1.71-2.26, P<0.001) adjusting for age, sex, race, marital status, poverty, and health. CONCLUSION: Findings from our study indicate that, among stroke survivors, long sleepers were more likely to report IADL problems compared to average sleepers (7-8 hours). Future studies should investigate other potential mediators such as severity of stroke, medication, comorbidities, level of impairment, and whether improving sleep among stroke survivors may improve IADL.

Accelerated skin wound healing by soy protein isolate-modified hydroxypropyl chitosan composite films.

In this study, a series of hydroxypropyl chitosan (HPCS)/soy protein isolate (SPI) composite films (HCSFs) with different SPI contents were developed via crosslinking, solution casting, and evaporation process. Effects of the SPI content on the structure and physical properties of the HCSFs were characterized by Fourier transform infrared spectroscopy, X-ray diffraction patterns, scanning electron microscopy, swelling kinetics analysis, and mechanical testing. The HCSFs exhibited a lower swelling ratio with an increase in the SPI content. The tensile strength was in a tunable range from 7.88 ±â€¯3.08 to 40.44 ±â€¯2.31 MPa by adjusting the SPI content. Cytocompatibility and hemocompatibility of the HCSFs were evaluated by a series of in vitro assays, including MTT assay, live/dead assay, cell morphology observation, hemolysis ratio testing, and plasma recalcification time measurement. Results showed that the HCSFs support L929 cells attachment and proliferation without obvious hemolysis, indicating good cytocompatibility and hemocompatibility. The potential of resultant HCSFs as the wound dressings was investigated using a full-thickness skin wound model in rats. Results exhibited that the HCSFs with 50% SPI content had the fastest healing speed and the best skin regeneration efficiency and may be a potential candidate as the wound dressing.

Fixed-dose combination dolutegravir, abacavir, and lamivudine versus ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate and emtricitabine in previously untreated women with HIV-1 infection (ARIA): week 48 results from a randomised, open-label, non-inferiority, phase 3b study.

BACKGROUND: Dolutegravir is a once-daily integrase strand transfer inhibitor with no need for pharmacokinetic boosting that is approved for the treatment of HIV-1 infection. Because women are often under-represented in HIV clinical trials, we addressed the safety and efficacy of dolutegravir in women with HIV-1. METHODS: The ARIA study is a randomised, open-label, multicentre, active-controlled, parallel-group, non-inferiority phase 3b study done in 86 hospital and university infectious disease clinics, local health clinics, and private infectious disease clinics in 12 countries and one US territory, in North America, South America, Europe, Africa, and Asia. Eligible participants were women aged 18 years or older who had HIV-1 RNA viral loads of 500 copies per mL or greater, had received 10 days or less of previous antiretroviral therapy, and had tested negative for the HLA-B*5701 allele. Pregnant women were excluded. Eligible women were randomly assigned (1:1) to receive either a single-tablet regimen of dolutegravir plus abacavir and lamivudine once a day (dolutegravir group) or a three-tablet combination of ritonavir-boosted atazanavir plus coformulated tenofovir disoproxil fumarate and emtricitabine once a day (atazanavir group). Random treatment group assignment was stratified by plasma HIV-1 RNA viral loads and CD4 cell count at baseline. The primary endpoint was the proportion of participants with HIV-1 RNA viral loads of less than 50 copies per mL at week 48 in all participants who received at least one dose of study medication (intention-to-treat exposed population). We used a non-inferiority margin of -12%. Investigators monitored adverse events to assess safety. This study is registered with ClinicalTrials.gov, number NCT01910402. FINDINGS: Between Aug 22, 2013, and Sept 22, 2015, of 705 women assessed, 499 were randomly assigned to either the dolutegravir group (n=250) or the atazanavir group (n=249); two participants from each group were randomised to treatment but did not receive study medication. At week 48, 203 (82%) of 248 participants in the dolutegravir group compared with 176 (71%) of 247 in the atazanavir group had HIV-1 RNA viral loads of less than 50 copies per mL (mean difference 10·5%, 95% CI 3·1-17·8, p=0·005). One participant in the atazanavir group had nucleoside reverse transcriptase inhibitor-associated resistance that led to reduced emtricitabine susceptibility. Adverse events were similar between the dolutegravir and atazanavir groups; the most common were nausea (46 [19%] of 248 in the dolutegravir group vs 49 [20%] of 247 in the atazanavir group) and headache (28 [11%] vs 32 [13%]). Fewer participants in the dolutegravir group than the atazanavir group reported drug-related adverse events (83 [33%] vs 121 [49%]) or adverse events that led to discontinuation (ten [4%] vs 17 [7%]). One death was reported in each treatment group, but neither was considered related to the study medications. INTERPRETATION: The non-inferior efficacy and similar safety profile of the dolutegravir combined regimen compared with the atazanavir regimen support the use of dolutegravir for HIV-1 infection in treatment-naive women. FUNDING: ViiV Healthcare.

A systematic review of oral herpetic viral infections in cancer patients: commonly used outcome measures and interventions.

PURPOSE: To review the literature for outcome measures for oral viral infections in cancer patients. A secondary aim was to update the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) clinical practice guidelines for the management of oral viral infections in cancer patients. METHODS: Databases were searched for articles published in the English language, 1981-2013. Studies that met the eligibility criteria were reviewed systematically. The data about the outcome measures were classified according to the aim of the study: prevention, treatment, or non-interventional. The results of interventional studies were compared to the 2010 MASCC/ISOO publication. RESULTS: Multiple clinical and laboratory tests were used to measure oral viral infections, with great variability between studies. Most of the studies were about Herpes Simplex Virus (HSV). The outcome measure that was most commonly used was the presence of HSV infection diagnosed based on a combination of suggestive clinical presentation with a positive laboratory result. HSV culture was the most commonly reported laboratory outcome measure. Acyclovir and valacyclovir were consistently reported to be efficacious in the management of oral herpetic infections. No new data on the quality of life and economic aspects was found. CONCLUSIONS: Considering the variability in outcome measures reported to assess oral herpetic infections the researcher should select carefully the appropriate measures based on the objective of the study. Acyclovir and valacyclovir are effective in the management of oral herpetic infections in patients receiving treatment for cancer. Studies on newer anti-viral drugs may be useful to address the issue of anti-viral resistance.

Porous cellulose spheres: Preparation, modification and adsorption properties.

Porous cellulose spheres (PCS) were fabricated by precipitating the spheres from a cellulose ionic liquid solution, followed by freezing, solvent exchange, and drying. PCS had low crystallinity and a large surface area that facilitated modification with trisodium trimetaphosphate (STMP) to introduce phosphate ester groups into the porous structure of the heterogeneous system. The STMP-modified PCS (SPCS) were used to remove heavy metal ions from aqueous solution. With increasing STMP dosage, the adsorption capacity of SPCS obviously improved due to chelation between Pb2+ and phosphate ester groups. The kinetic adsorption and isotherm data matched the pseudo-second order model and the Langmuir model well. The maximum adsorption capacity reached 150.6 mg g-1 for SPCS. SPCS were competitive with other absorbents because the phosphate ester groups and porous structure contributed to Pb2+ adsorption. Moreover, SPCS can be regenerated with ethylenediamine tetraacetic acid disodium salt (EDTA) solution for repetitious adsorption of Pb2+.

Epichlorohydrin-Cross-linked Hydroxyethyl Cellulose/Soy Protein Isolate Composite Films as Biocompatible and Biodegradable Implants for Tissue Engineering.

A series of epichlorohydrin-cross-linked hydroxyethyl cellulose/soy protein isolate composite films (EHSF) was fabricated from hydroxyethyl cellulose (HEC) and soy protein isolate (SPI) using a process involving blending, cross-linking, solution casting, and evaporation. The films were characterized with FTIR, solid-state (13)C NMR, UV-vis spectroscopy, and mechanical testing. The results indicated that cross-linking interactions occurred in the inter- and intramolecules of HEC and SPI during the fabrication process. The EHSF films exhibited homogeneous structure and relative high light transmittance, indicating there was a certain degree of miscibility between HEC and SPI. The EHSF films exhibited a relative high mechanical strength in humid state and an adjustable water uptake ratio and moisture absorption ratio. Cytocompatibility, hemocompatibility and biodegradability were evaluated by a series of in vitro and in vivo experiments. These results showed that the EHSF films had good biocompatibility, hemocompatibility, and anticoagulant effect. Furthermore, EHSF films could be degraded in vitro and in vivo, and the degradation rate could be controlled by adjusting the SPI content. Hence, EHSF films might have a great potential for use in the biomedical field.

The Effects of Interpreter Use on Agreement Between Clinician- and Self-Ratings of Functioning in Hispanic Integrated Care Patients.

This study explored whether concordance between self- and clinician- assessment of functioning differs when an interpreter is used in therapy versus when there is language congruence between the clinician and the patient, and whether concordance is affected by patient distress. Participants were 418 Spanish-speaking patients seen at one of three primary care clinics. Patients were primarily Hispanic (94 %), uninsured (65 %), and female (84 %), and ranged in age from 18 to 73 years (M = 41.70, SD = 10.70). Pearson's correlation coefficients assessed the association between self- and clinician- reports of patient functioning with and without use of an interpreter. Fisher's z transformations assessed the significance of the difference between the correlation coefficients. Although interpreter use did not significantly disrupt communication of functioning when the patient was highly distressed, there was significant discordance in clinician and patient reports in patients experiencing milder levels of distress communicating by means of an interpreter.

Cabotegravir plus rilpivirine, once a day, after induction with cabotegravir plus nucleoside reverse transcriptase inhibitors in antiretroviral-naive adults with HIV-1 infection (LATTE): a randomised, phase 2b, dose-ranging trial.

BACKGROUND: In phase 1 trials, the HIV-1 integrase strand transfer inhibitor cabotegravir (GSK1265744) was well tolerated, both alone, and in combination with the non-nucleoside reverse transcriptase inhibitor rilpivirine. We assessed cabotegravir plus rilpivirine, as a two-drug oral antiretroviral regimen, for the maintenance of viral suppression in antiretroviral-naive HIV-1-infected individuals. METHODS: In the phase 2b Long-Acting antireTroviral Treatment Enabling (LATTE) trial, a multicentre study done in Canada and the USA, antiretroviral-naive HIV-1-infected adults (aged ≥18 years) were randomly allocated in a 1:1:1:1 ratio to oral cabotegravir 10 mg once a day, 30 mg once a day, 60 mg once a day, or oral efavirenz 600 mg once a day with dual nucleoside reverse transcriptase inhibitors (NRTIs) for 24 weeks of induction. Patients who were virologically suppressed by week 24 received a two-drug maintenance regimen consisting of their randomly allocated cabotegravir dose plus oral rilpivirine 25 mg or continued efavirenz plus NRTIs for an additional 72 weeks. Patients and investigators were masked to doses of cabotegravir received for 96 weeks, but not to the assignment of cabotegravir or efavirenz. The primary endpoint was the proportion of patients with fewer than 50 copies per mL of HIV-1 RNA (US Food and Drug Administration snapshot algorithm) at week 48. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, NCT01641809. FINDINGS: Of 243 patients randomly allocated and treated, 156 (86%) of 181 patients in the cabotegravir groups (52 [87%] of 60, 51 [85%] of 60, and 53 [87%] of 61 patients in the 10 mg, 30 mg, and 60 mg groups, respectively) and 46 (74%) of 62 in the efavirenz group had fewer than 50 copies per mL of HIV-1 RNA after induction therapy. After patients in the cabotegravir groups were changed over from dual NRTIs to rilpivirine at week 24, 149 (82%; 95% CI 77-88) patients in the cabotegravir groups (48 [80%; 70-90], 48 [80%; 70-90], and 53 [87%; 78-95] patients in the 10 mg, 30 mg, and 60 mg groups, respectively) versus 44 (71%; 60-82) in the efavirenz group were virologically suppressed at week 48, and 137 (76%; 69-82) receiving cabotegravir (41 [68%; 57-80], 45 [75%; 64-86], and 51 [84%; 74-93] patients in the 10 mg, 30 mg, and 60 mg groups, respectively) versus 39 (63%; 51-75) in the efavirenz group were virologically suppressed at week 96. Treatment-related adverse events were reported by 93 (51%) cabotegravir-treated patients (28 [47%], 32 [53%], and 33 [54%] patients in the 10 mg, 30 mg, and 60 mg groups, respectively) and 42 (68%) efavirenz-treated patients. Six (3%) patients in the cabotegravir groups (one [2%], one [2%], and four [7%] patients in the 10 mg, 30 mg, and 60 mg groups, respectively) withdrew because of treatment-emergent adverse events compared with nine (15%) in the efavirenz group. INTERPRETATION: Cabotegravir plus dual NRTI therapy had potent antiviral activity during the induction phase. As a two-drug maintenance therapy, cabotegravir plus rilpivirine provided antiviral activity similar to efavirenz plus dual NRTIs until the end of week 96. Combined efficacy and safety results lend support to our selection of oral cabotegravir 30 mg once a day for further assessment. LATTE precedes studies of the assessment of longacting injectable formulations of both drugs as a two-drug regimen for the treatment of HIV-1 infection. FUNDING: ViiV Healthcare and Janssen Research and Development.

Modification of porous starch for the adsorption of heavy metal ions from aqueous solution.

Porous starch xanthate (PSX) and porous starch citrate (PSC) were prepared in anticipation of the attached xanthate and carboxylate groups respectively forming chelation and electrostatic interactions with heavy metal ions in the subsequent adsorption process. The lead(II) ion was selected as the model metal and its adsorption by PSX and PSC was characterized. The adsorption capacity was highly dependent on the carbon disulfide/starch and citric acid/starch mole ratios used during preparation. The adsorption behaviors of lead(II) ion on PSXs and PSCs fit both the pseudo-second-order kinetic model and the Langmuir isotherm model. The maximum adsorption capacity from the Langmuir isotherm equation reached 109.1 and 57.6 mg/g for PSX and PSC when preparation conditions were optimized, and the adsorption times were just 20 and 60 min, respectively. PSX and PSC may be used as effective adsorbents for removal of heavy metals from contaminated liquid.

Dolutegravir versus placebo in subjects harbouring HIV-1 with integrase inhibitor resistance associated substitutions: 48-week results from VIKING-4, a randomized study.

BACKGROUND: The Phase III VIKING-3 study demonstrated that dolutegravir (DTG) 50 mg twice daily was efficacious in antiretroviral therapy (ART)-experienced subjects harbouring raltegravir- and/or elvitegravir-resistant HIV-1. VIKING-4 (ING116529) included a placebo-controlled 7-day monotherapy phase to demonstrate that short-term antiviral activity was attributable to DTG. METHODS: VIKING-4 is a Phase III randomized, double-blind study in therapy-experienced adults with integrase inhibitor (INI)-resistant virus randomized to DTG 50 mg twice daily or placebo while continuing their failing regimen (without raltegravir or elvitegravir) for 7 days (clinicaltrials.gov identifier NCT01568892). At day 8, all subjects switched to open-label DTG 50 mg twice daily and optimized background therapy including ≥1 fully active drug. The primary end point was change from baseline in plasma HIV-1 RNA at day 8. RESULTS: The study population (n=30) was highly ART-experienced with advanced HIV disease. Patients had extensive baseline resistance to all approved antiretroviral classes. Adjusted mean change in HIV-1 RNA at day 8 was -1.06 log10 copies/ml for the DTG arm and 0.10 log10 copies/ml for the placebo arm (treatment difference -1.16 log10 copies/ml [-1.52, -0.80]; P<0.001). Overall, 47% and 57% of subjects had plasma HIV-1 RNA <50 and <400 copies/ml at week 24, and 40% and 53% at week 48, respectively. No discontinuations due to drug-related adverse events occurred in the study. CONCLUSIONS: The observed day 8 antiviral activity in this highly treatment-experienced population with INI-resistant HIV-1 was attributable to DTG. Longer-term efficacy (after considering baseline ART resistance) and safety during the open-label phase were in-line with the results of the larger VIKING-3 study.

Forty-eight-week efficacy and safety and early CNS tolerability of doravirine (MK-1439), a novel NNRTI, with TDF/FTC in ART-naive HIV-positive patients.

INTRODUCTION: Doravirine (DOR) is an investigational NNRTI (aka MK-1439) that retains activity against common NNRTI-resistant mutants. We have previously reported the Part 1 results from a two-part, randomized, double-blind, Phase IIb study in ART-naïve HIV-1-positive patients (1). At doses of 25, 50, 100 and 200 mg qd, DOR plus open-label tenofovir/emtricitabine (TDF/FTC) demonstrated potent antiretroviral activity comparable to EFV 600 mg qhs plus TDF/FTC and was generally well tolerated at week 24. DOR 100 mg was selected for use in patients continuing in Part 1 and those newly enrolled in Part 2. METHODS: Patients receiving DOR 25, 50 or 200 mg in Part 1 were switched to 100 mg after dose selection. In Part 2, 132 additional patients were randomized 1:1 to DOR 100 mg qd or EFV 600 mg qhs (each with TDF/FTC). We present week 48 efficacy and safety results for all patients in Part 1, and early (week 8) CNS tolerability only for patients randomized to DOR 100 mg or to EFV in Parts 1 and 2 combined. The primary safety endpoint is the % of patients with pre-specified CNS events (all causality) by week 8 for DOR 100 mg qd vs EFV (Parts 1 + 2 combined). RESULTS: Part 1 week 48 efficacy and safety results are shown below. CONCLUSIONS: In ART-naïve, HIV-1-positive patients also receiving TDF/FTC, DOR 100 mg qd demonstrated potent antiretroviral activity and immunological effect at week 48 and was generally safe and well tolerated. Patients who received DOR 100 mg qd had significantly fewer treatment-emergent CNS AEs by week 8 than those who received EFV.

Nanocomposites based on plasticized starch and rectorite clay: structure and properties.

Sodium rectorite clay (REC) was attached to cationic guar gum (CGG) using a cationic-exchange reaction to obtain CGG modified-REC (CREC). It was found that CGG appeared on the surface of REC's layered structure and represented about 30.1% wt. in CREC. REC and CREC were, respectively, used as fillers in a plasticized starch (PS) matrix to prepare PS/REC and PS/CREC composites using the casting process. Rapid Visco Analyser and scanning electron microscopy revealed that an interaction existed between the REC (or CREC) filler and the matrix. Both REC and CREC had obvious reinforcing effects on the matrix. Compared to the neat matrix, REC or CREC improved the thermal stability of the composites. By increasing the filler content from 0 to 10 wt%, water vapor permeability (WVP) values of PS/REC composites obviously decreased, while WVP values of PS/CREC composites decreased slightly.

Characterization of magnetic soluble starch-functionalized carbon nanotubes and its application for the adsorption of the dyes.

Soluble starch-functionalized multiwall carbon nanotube composites (MWCNT-starch) were prepared to improve the hydrophilicity and biocompatibility of MWCNTs. Characterization of the MWCNT-starch by Fourier transform infrared (FTIR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, X-ray diffraction (XRD), transmission electron microscope (TEM) and thermogravimetric analysis (TG), showed that the starch component (about 14.3 wt%) was covalently grafted onto the surface of MWCNT. MWCNT-starch-iron oxide composites, intended for use as adsorbents for the removal of dyes from aqueous solutions, were prepared by synthesizing iron oxide nanoparticles at the surface of MWCNT-starch. Starch acts as a template for growth of iron oxide nanoparticles which are uniformly dispersed on the surface of the MWCNT-starch. MWCNT-starch-iron oxide exhibits superparamagnetic properties with a saturation magnetization (23.15 emu/g) and better adsorption for anionic methyl orange (MO) and cationic methylene blue (MB) dyes than MWCNT-iron oxide.

Preparation, characterization, and in vitro and in vivo evaluation of cellulose/soy protein isolate composite sponges.

A series of cellulose/soy protein isolate (SPI) sponges was prepared using a freeze-drying process. The effect of the SPI content on the structure of the sponges was characterized by Fourier transform infrared spectrometry (FT-IR), X-ray diffraction analysis (XRD) and scanning electron microscopy (SEM). It showed that the sponges were porous in structure, and that the size of the pores increased and the thickness of the pore walls decreased as the SPI content of the sponges increased. The biocompatibility and biodegradability of the sponges were evaluated in vitro and in vivo. The cell culture experiment and SEM observations showed that L929 fibroblast cells grew and spread well on the surface and cross-section of the composite sponges. The results from MTT (3-[4,5-dimethyl-2-thiazoly1]-2,5-diphenyl-2H-tetrazolium bromide) assay indicated that the cell viability of L929 cultured in extracts from SPI-containing sponges was higher than that from the pure cellulose sponge. The historical analysis and SEM observation revealed that the SPI-containing sponges implanted from 1 to 8 months in rats exhibited better in vivo biocompatibility and biodegradability than the pure cellulose sponge. This was due to the incorporation of SPI into cellulose and to the freeze-drying process which formed large pores and thin pore walls in the composite sponges, promoting the migration of cells and tissue into the sponges, leading to gradual fusing with the implants. The new cellulose/SPI sponges thus have potential applications as biomaterials with good biocompatibility and biodegradability.