Simplified regimens with reduced pill burden and fewer side-effects are desirable for people living with HIV. We investigated the efficacy and safety of switching to a single-tablet regimen of ...darunavir, cobicistat, emtricitabine, and tenofovir alafenamide versus continuing a regimen of boosted protease inhibitor, emtricitabine, and tenofovir disoproxil fumarate.
EMERALD was a phase-3, randomised, active-controlled, open-label, international, multicentre trial, done at 106 sites across nine countries in North America and Europe. HIV-1-infected adults were eligible to participate if they were treatment-experienced and virologically suppressed (viral load <50 copies per mL for ≥2 months; one viral load of 50-200 copies per mL was allowed within 12 months before screening), and patients with a history of virological failure on non-darunavir regimens were allowed. Randomisation was by computer-generated interactive web-response system and stratified by boosted protease inhibitor use at baseline. Patients were randomly assigned (2:1) to switch to the open-label study regimen or continue the control regimen. The study regimen consisted of a fixed-dose tablet containing darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg, which was taken once per day for 48 weeks. The primary outcome was the proportion of participants with virological rebound (confirmed viral load ≥50 copies per mL or premature discontinuations, with last viral load ≥50 copies per mL) cumulative through week 48; we tested non-inferiority (4% margin) of the study regimen versus the control regimen in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT02269917.
The study began on April 1, 2015, and the cutoff date for the week 48 primary analysis was Feb 24, 2017. Of 1141 patients (763 in the study group and 378 in the control group), 664 (58%) had previously received five or more antiretrovirals, including screening antiretrovirals, and 169 (15%) had previous virological failure on a non-darunavir regimen. The study regimen was non-inferior to the control for virological rebound cumulative through week 48 (19 2·5% of 763 patients in the study group vs eight (2·1%) of 378 patients in the control group; difference 0·4%, 95% CI -1·5 to 2·2; p<0·0001). No resistance to any study drug was observed. Numbers of discontinuations related to adverse events (11 1% of 763 patients in the study group vs four 1% of 378 patients in the control group) and grade 3-4 adverse events (52 7% patients vs 31 8% patients) were similar between the two groups. There was a small non-clinically relevant but statistically significant (0·2 SD 1·1 vs 0·1 1·1, p=0.010) difference between the two groups in change from baseline in total cholesterol to HDL-cholesterol ratio. Only one serious adverse event (pancreatitis in the study group) was deemed as possibly related to the study regimen.
Our findings show the safety and efficacy of single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide as a potential switch option for the treatment of HIV-1 infection in adults with viral suppression.
Janssen.
Based on the notion that the local dark-matter field of axions or axionlike particles (ALPs) in our Galaxy induces oscillating couplings to the spins of nucleons and nuclei (via the electric dipole ...moment of the latter and/or the paramagnetic axion-wind effect), we establish the feasibility of a new method to search for ALPs in storage rings. Based on previous work that allows us to maintain the in-plane polarization of a stored deuteron beam for a few hundred seconds, we perform a first proof-of-principle experiment at the Cooler Synchrotron (COSY) to scan momenta near 970 MeV/c. This entails a scan of the spin-precession frequency. At resonance between the spin-precession frequency of deuterons and the ALP-induced electric dipole moment (EDM) oscillation frequency, there is an accumulation of the polarization component out of the ring plane. Since the axion frequency is unknown, the momentum of the beam and, consequently, the spin-precession frequency are ramped to search for a vertical polarization change that occurs when the resonance is crossed. At COSY, four beam bunches with different polarization directions are used to make sure that no resonance is missed because of the unknown relative phase between the polarization precession and the axion or ALP field. A frequency window of 1.5 kHz width around the spin-precession frequency of 121 kHz is scanned. We describe the experimental procedure and a test of the methodology with the help of a radio-frequency Wien filter located on the COSY ring. No ALP resonance is observed. As a consequence, an upper limit of the oscillating EDM component of the deuteron as well as its axion coupling constants are provided.
Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is being investigated in two Phase III trials, AMBER (NCT02431247; treatment-naive adults) and EMERALD ...(NCT02269917; treatment-experienced, virologically suppressed adults). Week 48 AMBER and EMERALD resistance analyses are presented. Postbaseline samples for genotyping/phenotyping were analyzed from protocol-defined virologic failures (PDVFs) with viral load (VL) ≥400 copies/mL at failure/later time points.
analyses were deep sequencing in AMBER, and HIV-1 proviral DNA from baseline samples (VL <50 copies/mL) in EMERALD. Through week 48 across both studies, no darunavir, primary PI, or tenofovir resistance-associated mutations (RAMs) were observed in HIV-1 viruses of 1,125 participants receiving D/C/F/TAF or 629 receiving boosted darunavir plus emtricitabine/tenofovir-disoproxil-fumarate. In AMBER, the nucleos(t)ide analog reverse transcriptase inhibitor (N(t)RTI) RAM M184I/V was identified in HIV-1 of one participant during D/C/F/TAF treatment. M184V was detected pretreatment as a minority variant (9%). In EMERALD, in participants with prior VF and genoarchive data (
= 140; 98 D/C/F/TAF and 42 control), 4% had viruses with darunavir RAMs, 38% with emtricitabine RAMs, mainly at position 184 (41% not fully susceptible to emtricitabine), 4% with tenofovir RAMs, and 21% ≥ 3 thymidine analog-associated mutations (24% not fully susceptible to tenofovir) detected at screening. All achieved VL <50 copies/mL at week 48 or prior discontinuation. D/C/F/TAF has a high genetic barrier to resistance; no darunavir, primary PI, or tenofovir RAMs were observed through 48 weeks in AMBER and EMERALD. Only one postbaseline M184I/V RAM was observed in HIV-1 of an AMBER participant. In EMERALD, baseline archived RAMs to darunavir, emtricitabine, and tenofovir in participants with prior VF did not preclude virologic response.
Introduction
Prompt diagnosis and treatment of blood stream infections in an immunocompromised host can result in a decrease in mortality with appropriate antibiotic coverage. Signs, symptoms, ...physical examination, cultures and sensitivity findings must be evaluated and interpreted together to accurately diagnose and manage the problem.
Case presentation
We present a case of
Sphingomonas paucimobilis
bacteremia in a patient with Human Immunodeficiency virus (HIV) and hepatitis C virus co-infection.
Conclusion
To our knowledge, this is the first reported case of this organism in a patient with HIV co-infected with chronic hepatitis C virus.
Sustained virologic response rates for hepatitis C virus are difficult to achieve in patients infected with human immunodeficiency virus, especially if they have other poor predictors of response. ...Rates of sustained virologic response for hepatitis C virus genotype 1 in patients with end stage kidney disease are lower than patients with normal renal function. We present the first case report of a co-infected African American man with end stage kidney disease, who was haemodialysis dependant, and an interferon non-responder with advanced liver fibrosis, who achieved sustained virologic response on a telaprevir-based regimen.
The long-term impact of pegylated-interferon plus ribavirin treatment outcome on CD4 T cell course in patients coinfected with human immunodeficiency virus and hepatitis C virus is largely unclear in ...the literature. The aim of this study was to investigate the impact of HCV-RNA clearance by standard anti-HCV therapy on long-term CD4 cells recovery in HIV/HCV patients on successful combined antiretroviral therapy. We retrospectively enrolled HIV/HCV-coinfected patients on HIV medications and treated for hepatitis C. CD4 + T cell counts were registered at baseline and after hepatitis C therapy. Multiple linear regression analysis was performed to identify independent predictors of CD4 + T cell change following the anti-HCV treatment outcome. Of the 116 patients enrolled, 54 (46.6%) reached a sustained virological response. During a follow-up of 24 months, the SVR group showed a mean annual increase in CD4 + T cell from baseline of 84 cells/ll at 1 year and of a further 38 cells/ll within the second year ( P = 0.01 , 0.001, resp.). An insignificant mean increase of 77 cells/ll occurred in the non-SVR group within month 24 ( P = 0.06 ). Variables associated with greater CD4 gains were higher nadir, lower preinterferon CD4 counts, and lower body mass index (BMI).
Summary
Intravenous drug use and sexual practices account for 60% of hepatitis C (HCV) and B (HBV) infection. Disclosing these activities can be embarrassing and reduce risk reporting, blood testing ...and diagnosis. In diagnosed patients, linkage to care remains a challenge. Audio‐computer‐assisted survey interview (Audio‐CASI) was used to guide HCV and HBV infection testing in urban clinics. Risk reporting, blood testing and serology results were compared to historical controls. A patient navigator (PN) followed up blood test results and provided patients with positive serology linkage to care (LTC). Of 1932 patients surveyed, 574 (30%) were at risk for chronic viral hepatitis. A total of 254 (44.3%) patients were tested, 34 (13.5%) had serology warranting treatment evaluation, and 64% required HBV vaccination. Of 16 patients with infection, seven HCV and three HBV patients started treatment following patient LTC. Of 146 HBV‐naïve patients, 70 completed vaccination. About 75% and 49% of HCV antibody and HBV surface antigen‐positive patients were born between 1945 and 1965. Subsequently, automated HCV testing of patients born between 1945 and 1965 was built into our hospital electronic medical records. Average monthly HCV antibody testing increased from 245 (January‐June) to 1187 (July‐October). Patient navigator directed LTC for HCV antibody‐positive patients was 61.6%. In conclusion, audio‐CASI can identify patients at risk for HCV or HBV infection and those in need of HBV vaccination in urban medical clinics. Although blood testing once a patient is identified at risk for infection needs to increase, a PN is useful to provide LTC of newly diagnosed patients.
An implementation of the polynomial chaos expansion is introduced as a fast solver of the equations of beam and spin motion of charged particles in electromagnetic fields. We show that, based on the ...stochastic Galerkin method, our computational framework substantially reduces the required number of tracking calculations compared to the widely used Monte Carlo method.
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