The role of dolutegravir in the management of HIV infections Misty M Miller,1 Michelle D Liedtke,1 Staci M Lockhart,2 R Chris Rathbun1 1Department of Pharmacy: Clinical and Administrative Sciences, University of Oklahoma College of Pharmacy, Oklahoma City, OK, USA; 2AbbVie Inc., Oklahoma City, OK, USA Abstract: Dolutegravir is the most recent integrase strand transfer inhibitor approved for HIV-1 infection in both treatment-naïve and experienced patients. As a tricyclic carbamoyl pyridone analog, dolutegravir is rapidly absorbed and distributes through the cerebrospinal fluid. It is hepatically metabolized by uridine diphosphate glucuronosyl transferase 1A1; no inhibition or induction of cytochrome P450 enzymes is noted. As a substrate of CYP 3A4, dolutegravir is affected by rifampin, efavirenz, tipranavir/ritonavir, fosamprenavir/ritonavir, and dose increase is required. Dolutegravir inhibits the organic cation transporter 2, resulting in decreased creatinine clearance with no apparent decrease
Reports of dolutegravir pharmacokinetics (PK) in human pregnancy are limited to two studies and a series of case reports.2-7 In a safety and PK study of 21 pregnant women, dolutegravir plasma concentrations were lower during pregnancy than postpartum, but HIV-1 RNA in the third trimester was below 50 copies/mL in all 15 women for whom third-trimester data were available. Dolutegravir was well tolerated by these pregnant women.4 In a study of five European pregnant women, dolutegravir was well tolerated and plasma exposures during pregnancy were similar to that postpartum.7 In the case reports, dolutegravir was used safely and effectively in pregnancy and plasma exposures were adequate.2,3,5,6. Placental and Breast Milk Passage ...
The second generation integrase inhibitor dolutegravir has demonstrated good virological and immunological outcomes in antiretroviral-naive subjects, compared with efavirenz, (SPRING 1 study). As well, it is active against HIV strains resistant to first-generation inhibitors raltegravir and elvitegravir in heavily treatment-experienced patients (VIKING study).. Additionally, it was safe and well tolerated after two years of use. It is administered once daily with no need for boosting, no food requirements and has a long half-life. The easy posology and its pharmacokinetics, together with the antiviral potency, make this drug a good alternative as a simplification approach. However, no clinical data are available supporting the switch of protease inhibitors or no nucleoside reverse transcriptase inhibitors to dolutegravir in virologically suppressed HIV-treated subjects.. Protease inhibitors (PI) have been associated with an acceleration of bone mineral density loss in HIV-infected individuals ...
The second generation integrase inhibitor dolutegravir has demonstrated good virological and immunological outcomes in antiretroviral-naive subjects, compared with efavirenz, (SPRING 1 study). As well, it is active against HIV strains resistant to first-generation inhibitors raltegravir and elvitegravir in heavily treatment-experienced patients (VIKING study).. Additionally, it was safe and well tolerated after two years of use. It is administered once daily with no need for boosting, no food requirements and has a long half-life. The easy posology and its pharmacokinetics, together with the antiviral potency, make this drug a good alternative as a simplification approach. However, no clinical data are available supporting the switch of protease inhibitors or no nucleoside reverse transcriptase inhibitors to dolutegravir in virologically suppressed HIV-treated subjects.. Protease inhibitors (PI) have been associated with an acceleration of bone mineral density loss in HIV-infected individuals ...
Direct comparisons between lamivudine plus bPIs and lamivudine plus dolutegravir as maintenance strategies in virologically-suppressed HIV positive patients are lacking. Time to treatment discontinuation (TD) and virological failure (VF) were compared in a cohort of HIV+ patients on a virologically-effective ART starting lamivudine with either darunavir/r, atazanavir/r or dolutegravir. Changes in laboratory parameters were also evaluated. Four-hundred-ninety-four patients were analyzed (170 switching to darunavir/r, 141 to atazanavir/r, 183 to dolutegravir): median age was 49 years, with 8 years since ART start. Groups differed for age, HIV-risk factor, time since HIV-diagnosis and on ART, previous therapy and reasons for switching. Estimated proportions free from TD at week 48 and 96 were 79.8 and 48.3% of patients with darunavir/r, 87.0 and 70.9% with atazanavir/r, and 88.2 and 82.6% with dolutegravir, respectively (p | 0.001). Calendar years, HIV-risk factor, higher baseline cholesterol and an InSTI
TY - JOUR. T1 - SLC22A2 variants and dolutegravir levels correlate with psychiatric symptoms in persons with HIV. AU - Ciccarelli, Nicoletta. AU - Tamburrini, Enrica. AU - Di Giambenedetto, Simona. AU - Lombardi, Francesca. AU - Colafigli, Manuela. AU - Delle Donne, Valentina. AU - Visconti, Elena. AU - De Luca, Andrea. AU - Calcagno, A.. AU - Cusato, J.. AU - DAvolio, A.. AU - Colafigli, M.. AU - Di Perri, G.. AU - De Luca, A.. AU - Bonora, S.. PY - 2019. Y1 - 2019. N2 - Background: Neuropsychiatric symptoms (NPs) have been reported with dolutegravir use. We hypothesized that increasing dolutegravir trough concentrations (Ctrough) and/or polymorphism in the SLC22A2 gene, encoding the organic cation transporter-2 (OCT2), which is involved in monoamine clearance in the CNS and is inhibited by dolutegravir, might be associated with NPs. Methods: A cross-sectional cohort of HIV-positive patients treated with a dolutegravir-containing regimen underwent determination of allelic discrimination for ...
As described above, the integrase inhibitor dolutegravir (Tivicay, DTG) has proved to be a potent and durable antiretroviral agent. Initial reports of a ...
Within the framework of the XXII International #AIDS Conference (#AIDS2018) taking place these days, scientists presented the latest developments in the field of #HIV treatment and prevention. In particular, the experts described new data proving the efficacy and safety of the integrase inhibitor #dolutegravir (#DTG) in a two-component treatment regimen.
Table of Contents What Is Dolutegravir? Dolutegravir (formerly S/GSK1349572) is a drug used for antiviral therapy against HIV. It is manufactured by ViiV ...
Concentration of dolutegravir was also evaluated in the female reproductive tract (FRT) in 14 NSG mice receiving a single subcutaneous injection of ultra-LA dolutegravir. Vagina, cervix, uterus, and plasma from treated mice were collected 1, 4, and 12 weeks post administration and dolutegravir concentrations determined (Fig. 1c). One week after ultra-LA dolutegravir administration, the median concentration of dolutegravir in plasma, vagina, cervix, and uterus were 1350 ng/ml, 196 ng/mg, 158 ng/mg, and 272 ng/ml, respectively. One month post administration, the median dolutegravir concentrations were 958 ng/ml, 233 ng/mg, 262 ng/mg, and 303, ng/mg, respectively, and 12 weeks post administration the median concentrations were 1200 ng/ml, 356 ng/mg, 170 ng/mg, and 284 ng/mg, respectively (Fig. 1c, Table 1). Differences in DTG concentrations within each compartment (vagina, cervix, uterus, and plasma) comparing 1 week, 4 weeks, and 12 weeks (n = 6 per group) did not reach statistical significance ...
Our rates of AEs leading to dolutegravir discontinuation were, however, higher than those reported in clinical trials, particularly with regard to neuropsychiatric AEs. In four RCTs in treatment-naïve patients (SPRING-1, SPRING-2, SINGLE and FLAMINGO) and in one RCT in treatment-experienced patients (SAILING), all AEs ascribed to dolutegravir led to drug cessation in 1.2-2.5% of patients within the first year, comparable to rates of AEs leading to discontinuation of raltegravir and lower than those leading to discontinuation of efavirenz and darunavir/ritonavir [1, 3, 10, 11, 15]. However, although discontinuation rates were low, significant numbers of neuropsychiatric AEs, although usually mild, were observed in all the RCTs. For example, in SPRING-1, SPRING-2 and SINGLE, the rates for dizziness of any grade were 3, 6 and 9%, respectively. The corresponding rates for sleep disturbances were 2, 5 and 23% [4]. It has been speculated that the higher prevalence of insomnia observed in the SINGLE ...
Four HIV-positive patients who had undergone gastric bypass were treated with dolutegravir containing antiretroviral therapy. Three of the patients had undergone bypass operation before HIV-infection while one patient was HIV-positive before the surgical procedure. Seventeen dolutegravir plasma levels were measured at different time points. Drug levels were well above IC90 and mostly comparable to historic data. The authors conclude that sufficient drug levels are achieved with standard therapy of 50 mg QD but speculate that a transient decrease in plasma levels may occur in the early phase after surgery and that a temporary dosage increase to 50 mg BID could be considered.. Piso et al. AIDS 2017;31:1052-1054. Comment: Gastric bypass has become a common procedure and it is important to study the pharmacokinetics of antiretroviral drugs in these patients. It is reassuring that adequate drug ...
The antiretroviral Dolutegravir has been incorporated in Brazils National Antiretroviral Treatment Guidelines an option for first line treatment, as announced recently through the decree nº 35, issued by the Ministry of Health of Brazil, along with the scale-up of the antiretroviral Darunavir as a second line treatment.. In ABIAs view, adopting Dolutegravir on initial treatment and authorizing the use of Darunavir in second line regimens are crucial measures that will improve treatment adherence for recently diagnosed people. This will have a significant impact in the assurance of the right to health and wellbeing of people living with HIV.. ABIA, together with other civil society organizations, has been denouncing the impact of side effects on adherence to treatment and demanding that quality of life for people living with HIV be seen as a priority in treatment strategies.. At the moment the decree was announced, ABIA and the Working Group on Intellectual Property (GTPI) - a collective of ...
The study population was approximately 60% female, had median CD4 counts of between 322 cells/mm3 and 349 cells/mm3. Approximately 20% had a viral load above 100,000 copies/ml.. Intent-to-treat analysis showed no significant difference between the three combinations in the proportion with viral load below 50 copies/ml at week 48 (TDF/emtricitabine/dolutegravir 85%, TAF/emtricitabine/dolutegravir 84%, TDF/emtricitabine/efavirenz 79%).. Age and employment status were strongly associated with viral suppression, said Venter. Whereas very high rates of viral suppression were seen in older people in employment, the rate of viral suppression in young unemployed people was little more than 60%, reflecting the structural factors that affect viral suppression and engagement in care in South Africa.. Virological resuppression was common for those who experienced virological failure during the study. In most cases, virological failure consisted of viral rebound below 1000 copies/ml but virological ...
Cross-resistance profile of the novel integrase inhibitor Dolutegravir (S/GSK1349572) using clonal viral variants selected in patients failing raltegravir ...
Basal-like breast cancer is an aggressive disease for which targeted therapies are lacking. Recent studies showed that basal-like breast cancer is frequently associated with an increased activity of the phosphatidylinositol 3-kinase (PI3K) pathway, which is critical for cell growth, survival, and angiogenesis. To investigate the therapeutic potential of PI3K pathway inhibition in the treatment of basal-like breast cancer, we evaluated the antitumor effect of the mTOR inhibitor MK-8669 and AKT inhibitor MK-2206 in WU-BC4 and WU-BC5, two patient-derived xenograft models of basal-like breast cancer. Both models showed high levels of AKT phosphorylation and loss of PTEN expression. We observed a synergistic effect of MK-8669 and MK-2206 on tumor growth and cell proliferation in vivo. In addition, MK-8669 and MK-2206 inhibited angiogenesis as determined by CD31 immunohistochemistry. Biomarker studies indicated that treatment with MK-2206 inhibited AKT activation induced by MK-8669. To evaluate the ...
Purpose Anomalies of Akt rules, including overexpression in lung malignancy, impart level of resistance to conventional chemotherapy and rays, thereby implicating this kinase like a therapeutic treatment point. triggered a G1 stage arrest at 100 nM but resulted in apoptosis at higher dosages. BIA-6 also exhibited synergism with regular chemotherapeutic agents. Summary BIA-6 is definitely a book, allosteric Akt inhibitor with powerful anti-cancer activity in lung malignancy cell lines, that efficiently blocks the phosphoinositide-3 kinase/Akt pathway with a higher margin selectivity towards regular cells. mutations with erlotinib led to a lot more than 60% response prices and significant progression-free success [7,8]. The impressive outcomes with EGFR inhibitors in molecularly chosen populations of NSCLC accelerated the search for particular and safer targeted therapies because of this feared disease. Akt, also called proteins kinase B, is certainly a serine-threonine kinase, an essential ...
Background: NPC is endemic to Asia and over 40% of cases harbor PIK3CA amplification. MK2206 is an allosteric AKT inhibitor with activity in NPC in vitro.. Methods: Pts who had progressed after palliative chemotherapy (chemo) for metastatic or recurrent NPC, received oral MK-2206 at 200 mg on Days 1, 8, 15 & 22 of each 28-day cycle until disease progression. Plasma samples were collected at serial time points during cycle 1 for EBV DNA analysis, archived tumor samples were collected where feasible. The primary dual endpoints (2-stage design) consisted of RECIST-defined tumor response rate (RR) and 6-month (m) progression-free survival (PFS) rate. Secondary endpoints were overall survival (OS), PFS and adverse events (AEs).. Results: Of the 21 pts enrolled, the median age was 47 years (range: 32-67), 91% were male, 81% had prior radiotherapy and 81% had , 1 prior line of palliative chemo. At the time of analysis, 20 out of 21 pts have ended treatment. The best responses were: 1 partial response ...
This study is investigating the pharmakokinetics of dolutegravir and elitegravir/cobicistat in healthy volunteers following drug intake cessation.
Polly Clayden, HIV i-Base. Modest placental transfer of dolutegravir (DTG) shown in an ex vivo human placenta perfusion model was presented in a poster at the 16th International Workshop on Clinical Pharmacology of HIV & Hepatitis Therapy.. Clinical data showing placental transfer of DTG is not yet available. Dual perfusion of a single placental lobule (cotyledon) is an experimental model used to predict placental drug transfer.. Investigators from the Departments of Pharmacy, Pharmacology and Toxicology, and Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands, developed a placenta perfusion model to estimate foetal exposure to DTG pregnancy.. The method involves cannulating a foetal vein and artery of an intact cotyledon ex vivo. The foetal circulation (6 mL/min) and the maternal circulation (12 mL/min) were initiated by inserting four cannulas into the intervillous space.. The perfusion medium was Krebs-Henseleit buffer supplemented with 10.1 mM glucose, 30 ...
ViiV Healthcare today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending marketing authorisation for Tivicay® (dolutegravir).
Dolutegravir has been approved since January 2014 in combination with other antiretroviral drugs for the treatment of human immunodeficiency virus (HIV) infected adults and adolescents above 12 years of age. In an early benefit ...
Given the number of independent groups reporting data from studies using dolutegravir monotherapy at the EACS conference in October 2015, it was strange ...
Although dolutegravir was linked to a higher risk for neural tube defects among newborns, it prevented many more deaths and HIV transmissions among women than efavirenz, according to findings published in Annals of Internal Medicine. … [Caitlin M. Dugdale, MD, from Massachusetts General Hospital and Harvard Medical School, and colleagues] used a computer model to project the clinical outcomes of ART policies, including maternal and child deaths, sexual and perinatal transmission, and neural tube defects, for women with HIV of child-bearing age in South Africa. … In an accompanying editorial, Risa M. Hoffman, MD, MPH, from David Geffen School of Medicine at the University of California, Los Angeles, and Lynne M. Mofenson, MD, from the Elizabeth Glaser Pediatric AIDS Foundation, wrote that the study by Dugdale and colleagues underscores the complexity of choosing treatment for pregnant women… (4/1).. Additional coverage of the study and its implications for HIV treatment is available from ...
Dolutegravir was found in Johns Hopkins Guides. Official website of the Johns Hopkins Antibiotic (ABX), HIV, Diabetes, and Psychiatry Guides, powered by Unbound Medicine. Johns Hopkins Guide App for iOS, iPhone, iPad, and Android included.
JULUCA (Dolutegravir,Rilpivirine ) drug information & product resources from MPR including dosage information, educational materials, & patient assistance.
ClinicalTrials.gov summary of Drug Interaction Study Between Dolutegravir and an Oral Contraceptive Containing Norgestimate and Ethinylestradiol
Detailed drug Information for abacavir, dolutegravir, and lamivudine. Includes common brand names, drug descriptions, warnings, side effects and dosing information.
Preliminary analysis of an ongoing clinical birth surveillance study suggested increased risk of NTDs in newborns from mothers taking dolutegravir at the time of conception (Zash et al., 2018). Dolutegravir is an integrase inhibitor for the treatment of HIV, a drug class that also includes cabotegravir, bictegravir, raltegravir, and elvitegravir (Han et al., 2017). Folate deficiency increases the incidence rate of NTDs (Daly et al., 1995; Botto et al., 1999; Crider et al., 2014; Kancherla et al., 2018). Folate relies on transport via PCFT for intestinal absorption, FRα-mediated endocytosis along with transport by PCFT and RFC for tissue distribution, including to the fetus, and renal sparing via active tubular reabsorption after extensive glomerular filtration (Fig. 1, Solanky et al., 2010; Zhao et al., 2011).. The aim of the present work was to determine whether dolutegravir and other integrase inhibitor drugs may be clinically relevant inhibitors of the three major folate transport pathways, ...
BACKGROUND: Effective two-drug regimens could decrease long-term drug exposure and toxicity with HIV-1 antiretroviral therapy (ART). We therefore aimed to evaluate the efficacy and safety of a two-drug regimen compared with a three-drug regimen for the treatment of HIV-1 infection in ART-naive adults.. METHODS: We conducted two identically designed, multicentre, double-blind, randomised, non-inferiority, phase 3 trials: GEMINI-1 and GEMINI-2. Both studies were done at 192 centres in 21 countries. We included participants (≥18 years) with HIV-1 infection and a screening HIV-1 RNA of 500 000 copies per mL or less, and who were naive to ART. We randomly assigned participants (1:1) to receive a once-daily two-drug regimen of dolutegravir (50 mg) plus lamivudine (300 mg) or a once-daily three-drug regimen of dolutegravir (50 mg) plus tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Both drug regimens were administered orally. We masked participants and investigators to treatment ...
The guidelines also recommend that anyone on a failing first-line regimen that does not contain dolutegravir should switch to a second-line regimen of dolutegravir plus a new NRTI backbone.. The new recommendations stress the importance of switching to dolutegravir in settings where resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) is rising. Dr Silvia Bertagnolio told a symposium organised by WHO that resistance to NNRTIs is present in over 15% of people starting antiretroviral treatment in Uganda, 20% in South Africa and over 25% in Honduras. Use of efavirenz in these settings is likely to result in treatment failure and further transmission of drug-resistant virus.. Implementing the recommendations is an urgent priority for countries as they work towards achieving the UNAIDS 90-90-90 targets - 90% of people living with HIV knowing their status, 90% of those diagnosed being on antiretroviral therapy and 90% of those on treatment having viral suppression by 2020. ...
TY - JOUR. T1 - Penicillium purpurogenum produces a novel, acidic, GH3 beta-xylosidase. T2 - Heterologous expression and characterization of the enzyme. AU - Faúndez, Carolina. AU - Pérez, Rodrigo. AU - Ravanal, María Cristina. AU - Eyzaguirre, J.. PY - 2019/8/1. Y1 - 2019/8/1. N2 - Xylan, a component of plant cell walls, is composed of a backbone of β-1,4-linked xylopyranosyl units with a number of substituents. The complete degradation of xylan requires the action of several enzymes, among them β-xylosidase. The fungus Penicillium purpurogenum secretes a number of enzymes participating in the degradation of xylan. In this study, a β-xylosidase from this fungus was expressed in Pichia pastoris, and characterized. This enzyme (Xyl2) is a member of glycoside hydrolase family 3; it consists of a sequence of 792 residues including a signal peptide of 20 residues, with a theoretical molecular mass for the mature protein of 84.2 KDa and an isoelectric point of 5.07. The highest identity with a ...
This phase II clinical trial is studying how well Akt inhibitor MK2206 works in treating patients with advanced gastric or gastroesophageal junction can
The FDA approved a new once-daily integrase inhibitor, Tivicay (dolutegravir), to treat HIV. Clinical studies show that it had superior results over ...
RESULTS: Antiretroviral therapy is recommended for all adults with HIV infection. Evidence for benefits of treatment and quality of available data increase at lower CD4 cell counts. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (NRTIs; abacavir/lamivudine or tenofovir disoproxil fumarate/emtricitabine) and a third single or boosted drug, which should be an integrase strand transfer inhibitor (dolutegravir, elvitegravir, or raltegravir), a nonnucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine) or a boosted protease inhibitor (darunavir or atazanavir). Alternative regimens are available. Boosted protease inhibitor monotherapy is generally not recommended, but NRTI-sparing approaches may be considered. New guidance for optimal timing of monitoring of laboratory parameters is provided. Suspected treatment failure warrants rapid confirmation, performance of resistance testing while the patient is receiving the failing regimen, and evaluation of ...
Polly Clayden, HIV i-Base. Unsurprisingly, dolutegravir (DTG) was superior to lopinavir/ritonavir (LPV/r) in a comparison of DTG-based regimen vs WHO-recommended second-line. These data were presented as a late breaker at IAS 2017.. DAWNING is a non-inferiority, randomised, phase 3b, open label study conducted to evaluate the safety and efficacy of DTG + 2 NRTIs compared with LPV/r + 2 NRTIs in participants failing first-line ART of an NNRTI + 2 NRTIs.. Investigator-selected NRTIs had to include at least one that was fully active based on resistance testing at screening.. Eligible participants were on first-line NNRTI + 2 NRTI for at least six months and failing virologically with no primary resistance to PIs or INSTIs. The primary endpoint was proportion with viral load ,50 copies/mL at week 48 (FDA snapshot; 12% non-inferiority margin). DAWNING enrolled from December 2014 to August 2016 and is ongoing.. After two of three pre-planned analyses, the study Independent Data Monitoring Committee ...
Clinical trial for Human Immunodeficiency Virus | Infection | HIV infection , Switch Study to Evaluate Dolutegravir Plus Lamivudine in Virologically Suppressed Human Immunodeficiency Virus Type 1 Positive Adults (TANGO)
Clinical trial for HIV Infected Population With Latent Tuberculosis | Adverse Effects | Breast Cancer - HER2 Positive | Peripheral Arterial Occlusive Disease | Vaginal Atrophy | Healthy Volunteers | Injection Port | Chronic Shoulder Pain | Anal Dysplasia | Near-Sighted Corrective Surgery | Metastatic Triple-Negative Breast Cancer | Primary Immunodeficiency | Razor Bumps (Pseudofolliculitis Barbae) | Pediatric Health | Diet and Nutrition | Recurrent Respiratory Papillomatosis | Brain Function | Skin Wounds | Chronic Diarrhea | Drugs , Impact of Once-Weekly Rifapentine and Isoniazid on the Steady State Pharmacokinetics of Dolutegravir and Darunavir Boosted With Cobicistat in Healthy Volunteers
At the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, 48-week results from a somewhat small Phase 2 study in people new to treatment showed that the Gilead Sciences experimental integrase inhibitor bictegravir suppressed HIV levels as well as ViiVs integrase in...
MEXICO CITY - Responding to expanded data gathered in Botswana and Brazil, and to input from communities of women living with HIV, the World Health Organization announced updated guidelines for the use of dolutegravir, restoring the agencys recommendation that the antiretroviral medicine with fewer side effects, lower resistance, and quicker viral suppression than alternatives is a preferred drug for all people with HIV. WHO categorizes that recommendation as strong, an upgrade from the earlier conditional recommendation.. For 15 months preceding the update, however, following findings in Botswana of four babies born with defects to the brain, spine or spinal cord, among 426 women taking dolutegravir at conception - a rate of 0.9% - WHO guidelines cautioning against the use of dolutegravir among pregnant women led to policies withholding the preferred drug from women who might become pregnant. During that time the drug was difficult, and, more often, impossible for women perceived to be of ...
BACKGROUND: Efficacy, safety and pharmacokinetics of simeprevir (TMC435), a once-daily, noncovalent, oral hepatitis C virus (HCV) NS3/4A protease inhibitor, was evaluated in combination with peginterferon α-2a/ribavirin (PegIFNα-2a/RBV) for treatment-naïve, HCV genotype 1-infected patients in Japan. METHODS: In a multicenter, randomized clinical trial in Japan, ninety-two patients received either simeprevir (50 or 100 mg QD) for 12 or 24 weeks with PegIFNα-2a/RBV for 24 or 48 weeks (according to response-guided therapy [RGT] criteria), or PegIFNα-2a/RBV for 48 weeks (PR48 group). RESULTS: Compared with the PR48 group, plasma HCV RNA reductions in the simeprevir groups were rapid and more substantial (Week 4: -5.2, -5.2 and -2.9 log10IU/mL for simeprevir 50 mg combined, 100 mg combined, and PR48 groups, respectively). High rapid virologic response rates (83, 90, and 8 % for simeprevir 50 mg combined, 100 mg combined, and PR48 groups, respectively) led to high sustained virologic response ...
Effects of treatment strategies to suppress ischemia in patients with coronary artery disease: 12-week results of the Asymptomatic Cardiac Ischemia Pilot (ACIP) ...
The causes of the formerly described effect of the limitation of infection of surface citric acid fermentation byPenicillium purpurogenum by the action of an increased air supply have been ascertained. The influence of the increased air supply on the composition ofAspergillus niger mycelium and cell walls was followed, as well as their assailability by the lytic enzyme ofPenicillium purpurogenum. Further the effect of temperature, humidity, oxygen supply and presence of carbon dioxide on the growth of the parasitic mould was evaluated. The main cause of the mentioned effect seems to be the drainage of humidity by increased air supply.
The two-drug antiretroviral combination dolutegravir and lamivudine is virologically effective and safe in people starting HIV therapy for the first time, according to US research published in the online edition of Clinical Infectious Diseases.. The phase 2 pilot study recruited 120 antiretroviral-naïve adults. After 24 weeks of treatment, 90% of participants had viral suppression and none of the participants discontinued therapy because of side-effects. There were few virological failures, and these were linked to poor adherence. Modern antiretroviral therapy usually consists of three separate drugs and is highly effective. Safety and cost considerations mean there is interest in identifying effective two drug combinations. Dolutegravir and lamivudine performed well in a small study with high rates of virological suppression over 96 weeks.. Investigators in the US wanted to build on this research. They therefore designed a pilot, phase 2, open-label study (ACTG A5353) involving adults with a ...
DAWNING study modified to allow patients the opportunity to receive dolutegravir-based regimens ViiV Healthcare, the global specialist HIV company, majority owned by
...HAYWARD Calif. June 28 2011 /- Intarcia Therapeutics ...(Logo: We are very encouraged by the robust results observed in this stud...,Intarcia,Presents,Positive,Phase,2,48-week,Results,From,ITCA,650,Study,at,the,American,Diabetes,Association,71st,Scientific,Sessions,biological,advanced biology technology,biology laboratory technology,biology device technology,latest biology technology
MBT stands for Masai Barefoot Technology, and the shoes are designed to simulate walking in sand. Its a multi-layered, curved sole that accomplishes this by creating a natural but uneven walking surface. This technology is meant to make the core strengthening muscles more active, creating better posture and increasing shock absorbtion for all of the joints. It also makes wearing the shoes quite a unique experience, and a bit of a workout ...
Individuals who have virologic suppression of HIV with daily oral dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) can be switched safely with or without an oral lead-in phase to monthly injectable cabotegravir plus rilpirivine (CAB/RPV) with comparable efficacy and safety, new data suggest.. Among 232 patients who had virologic suppression (HIV-1 RNA less than 50 copies/mL) following 100 weeks of therapy with DTG/ABC/3TC, the safety and tolerability of the long-acting CAB/RPV formulation was similar whether patients were immediately switched to it or transitioned over 1 month with an oral lead-in phase, reported Ronald DAmico, MD, from ViiV Healthcare, and colleagues during the annual HIV Glasgow drug therapy meeting, which was held virtually this year because of the pandemic.. Virologic suppression rates 24 weeks after the switch were 99.1% for patients switched directly to the long-acting CAB/RPV and 93.4% for patients who had an oral lead-in; virologic data at this time point was not ...
Viiv Healthcare Ltd., of London, said the FDA approved a supplemental new drug application for dolutegravir 10 mg and 25 mg oral tablets, reducing the weight limit from at least 40 kg to at least 30 kg, in patient, ages 6 to under 12 years old, for the treatment of HIV-1.
This trial investigated the efficacy and safety of sofosbuvir + daclatasvir and sofosbuvir + simeprevir in patients with advanced liver disease.
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Jobless claims point convincingly at strength in the labor market. Initial claims fell a very sizable 22,000 in the Dec. 26 week to 432,000 (prior week revised slightly higher to 454,000). Market News International says the Labor Department is comfortable with the weeks results and is not warning about holiday-adjustment factors. The four-week average helps smooth out any week-to-week bumps and is clearly pointing to improvement at 460,250 for a decrease of more than 20,000 from a month ago. The four-week average is down 30 percent from its cycle peak in April at 658,750. Continuing claims, at 4.981 million, are down 57,000 in the latest week and down 27 percent from their cycle peak in June at 6.774 million ...
Jobless claims point convincingly at strength in the labor market. Initial claims fell a very sizable 22,000 in the Dec. 26 week to 432,000 (prior week revised slightly higher to 454,000). Market News International says the Labor Department is comfortable with the weeks results and is not warning about holiday-adjustment factors. The four-week average helps smooth out any week-to-week bumps and is clearly pointing to improvement at 460,250 for a decrease of more than 20,000 from a month ago. The four-week average is down 30 percent from its cycle peak in April at 658,750. Continuing claims, at 4.981 million, are down 57,000 in the latest week and down 27 percent from their cycle peak in June at 6.774 million ...
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