Safety of oral tenofovir disoproxil fumarate-based pre-exposure prophylaxis for HIV prevention.

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Mugwanya, Kenneth K; Baeten, Jared M

2016-01-01

Tenofovir disoproxil fumarate (TDF)-based pre-exposure prophylaxis is a novel HIV prevention strategy for individuals at increased sexual risk for HIV infection. For any biomedical prevention intervention, the bar for tolerating adverse effects in healthy persons is high compared to therapeutic interventions. We provide a concise summary of the clinical safety of TDF-based pre-exposure prophylaxis with focus on TDF-related effects on tolerability, kidney function, bone density, HIV resistance, sexual and reproductive health. The evidence base for this review is derived from a literature search of both randomized and observational studies evaluating efficacy and safety of TDF-based PrEP, TDF alone or in combination with emtricitabine, identified from PUBMED and EMBASE electronic databases, clinicaltrials.gov and major HIV conferences. TDF-based pre-exposure prophylaxis is a potent intervention against HIV acquisition when taken which is generally safe and well tolerated. The risk of the small, non-progressive, and reversible decline in glomerular filtration rate and bone mineral density as well as the potential selection for drug resistance associated with PrEP are outweighed, at the population level and broadly for individuals, by PrEP's substantial reduction in the risk of HIV infection.

Decline in bone mass with tenofovir disoproxil fumarate/emtricitabine is associated with hormonal changes in the absence of renal impairment when used by HIV uninfected adolescent boys and young men for HIV pre-exposure

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Background. We aimed to define the relative importance of renal and endocrine changes in tenofovir disoproxil fumarate (TDF)-related bone toxicity. Methods. In a study of daily TDF/emtricitabine (FTC) pre-exposure prophylaxis (PrEP) in HIV uninfected young men who have sex with men, we measured ch...

A 68-year old male presenting with rhabdomyolysis-associated acute kidney injury following concomitant use of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate and pravastatin/fenofibrate: a case report

OpenAIRE

Suttels, Veronique; Florence, Eric; Leys, John; Vekemans, Marc; Van den Ende, Jef; Vlieghe, Erika; Kenyon, Chris

2015-01-01

Introduction We present what we believe to be the first case in the literature of rhabdomyolysis-induced renal failure caused by a probable drug interaction between elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) and pravastatin/fenofibrate. Case presentation A 68-year old Caucasian man presented with progressive pain in both legs two weeks after commencing treatment with EVG/COBI/FTC/TDF. He was found to have biochemical evidence of rhabdomyolysis and a...

Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis.

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Solomon, Marc M; Lama, Javier R; Glidden, David V; Mulligan, Kathleen; McMahan, Vanessa; Liu, Albert Y; Guanira, Juan Vicente; Veloso, Valdilea G; Mayer, Kenneth H; Chariyalertsak, Suwat; Schechter, Mauro; Bekker, Linda-Gail; Kallás, Esper Georges; Burns, David N; Grant, Robert M

2014-03-27

Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis decreases sexual acquisition of HIV infection. We sought to evaluate the renal safety of TDF in HIV-uninfected persons. The Iniciativa Profilaxis Pre-Exposición (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily TDF coformulated with emtricitabine (FTC/TDF) or placebo. Serum creatinine and phosphorus during randomized treatment and after discontinuation were measured, and creatinine clearance (CrCl) was estimated by the Cockcroft-Gault equation. Indicators of proximal renal tubulopathy (fractional excretion of phosphorus and uric acid, urine protein, and glucose) were measured in a substudy. There was a small but statistically significant decrease in CrCl from baseline in the active arm, compared to placebo, which was first observed at week 4 (mean change: -2.4 vs. -1.1 ml/min; P=0.02), persisted through the last on-treatment visit (mean change: +0.3 vs. +1.8 ml/min; P=0.02), and resolved after stopping pre-exposure prophylaxis (mean change: -0.1 vs. 0.0 ml/min; P=0.83). The effect was confirmed when stratifying by drug detection. The effect of FTC/TDF on CrCl did not vary by race, age, or history of hypertension. There was no difference in serum phosphate trends between the treatment arms. In the substudy, two participants receiving placebo had indicators of tubulopathy. In HIV-seronegative MSM, randomization to FTC/TDF was associated with a very mild nonprogressive decrease in CrCl that was reversible and managed with routine serum creatinine monitoring.

Safety of Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy Regimens in Pregnancy for HIV-Infected Women and Their Infants: A Systematic Review and Meta-Analysis.

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Nachega, Jean B; Uthman, Olalekan A; Mofenson, Lynne M; Anderson, Jean R; Kanters, Steve; Renaud, Francoise; Ford, Nathan; Essajee, Shaffiq; Doherty, Meg C; Mills, Edward J

2017-09-01

There are limited data on adverse effects of tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) on pregnant women and their infants. We conducted a systematic review of studies published between January 1980 and January 2017 that compared adverse outcomes in HIV-infected women receiving TDF- vs. non-TDF-based ART during pregnancy. The risk ratio (RR) for associations was pooled using a fixed-effects model. Seventeen studies met the study inclusion criteria. We found that the rate of preterm (14 days) (RR = 0.65; 95% CI: 0.23 to 1.85), but increased neonatal mortality (age <14 days) risk (RR = 5.64, 95% CI: 1.70 to 18.79) with TDR-based ART exposure. No differences were found for anthropomorphic parameters at birth; one study reported minor differences in z-scores for length and head circumference at age 1 year. TDF-based ART in pregnancy seems generally safe for women and their infants. However, data remain limited and further studies are needed, particularly to assess neonatal mortality and infant growth/bone effects.

Switching patients with lamivudine resistant chronic hepatitis B virus from tenofovir to adefovir results in less potent HBV-DNA suppression

NARCIS (Netherlands)

Leemans, W F; Janssen, H L A; Niesters, H G M; de Man, R A

The nucleotide analogues, tenofovir disoproxil fumarate and adefovir dipivoxil, inhibit viral replication and are both effective against the hepatitis B virus (HBV). In our department, tenofovir was prescribed in addition to lamivudine for the treatment of lamivudine resistant chronic hepatitis B.

Quantitative Analysis of Tenofovir by Titrimetric, Extractive Ion-pair ...

African Journals Online (AJOL)

Methods: Tenofovir disoproxil forms a complex of 1:1 molar ratio with fumaric acid that was employed in its aqueous titration with sodium hydroxide. Non-aqueous titration was also employed for its determination. Extractive ion-pair spectrophotometric technique using methyl orange was similarly employed to evaluate ...

Urinary β2 microglobulin can predict tenofovir disoproxil fumarate-related renal dysfunction in HIV-1-infected patients who initiate tenofovir disoproxil fumarate-containing antiretroviral therapy.

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Nishijima, Takeshi; Kurosawa, Takuma; Tanaka, Noriko; Kawasaki, Yohei; Kikuchi, Yoshimi; Oka, Shinichi; Gatanaga, Hiroyuki

2016-06-19

In nephrotoxicity induced by tenofovir disoproxil fumarate (TDF), tubular dysfunction precedes the decline in GFR, suggesting that tubular markers are more sensitive than estimated glomerular filtration rate (eGFR). The hypothesis that urinary β2 microglobulin (β2 M), a tubular function marker, can predict TDF-renal dysfunction in HIV-1-infected patients was tested. A single-center observational study. The inclusion criteria were: HIV-1-infected patients who started TDF-containing antiretroviral therapy from 2004 to 2013, urinary β2 M after and closest to the day of TDF initiation within 180 days (termed 'β2 M after TDF') was measured. The associations between 'β2 M after TDF' and four renal end points (>10 ml/min per 1.73 m decrement in eGFR relative to baseline, >20 decrement, >25% decrement, and eGFR model. The association between 'β2 M after TDF' and longitudinal changes in eGFR after initiation of TDF was estimated with a mixed-model. A total 655 study patients were analyzed (96% men, median age 38, median CD4 238 cells/μl, 63% treatment naïve). The median baseline eGFR was 117 ml/min per 1.73 m (IQR 110-125), and the median duration of TDF use was 3.32 years (IQR 2.02-5.31). 'β2 M after TDF' was significantly associated with more than 20 decrement in eGFR (P = 0.024) and more than 25% decrement (P = 0.014), and was marginally associated with eGFR less than 60 (P = 0.076). It was also significantly associated with the longitudinal eGFR after initiation of TDF (P < 0.0001). 'β2 M after TDF' of 1700 μg/l was identified as the optimal cutoff value for the prediction of longitudinal eGFR. Urinary β2 M measured within 180 days after initiation of TDF predicts renal dysfunction related to long-term TDF use.

The Role of Drug Transporters in the Kidney: Lessons from Tenofovir

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Darren Michael Moss

2014-11-01

Full Text Available Tenofovir disoproxil fumarate, the prodrug of nucleotide reverse transcriptase inhibitor tenofovir, shows high efficacy and relatively low toxicity in HIV patients. However, long-term kidney toxicity is now acknowledged as a modest but significant risk for tenofovir-containing regimens, and continuous use of tenofovir in HIV therapy is currently under question by practitioners and researchers. Co-morbidities (hepatitis C, diabetes, low body weight, older age, concomitant administration of potentially nephrotoxic drugs, low CD4 count, and duration of therapy are all risk factors associated with tenofovir-associated tubular dysfunction. Tenofovir is predominantly eliminated via the proximal tubules of the kidney, therefore drug transporters expressed in renal proximal tubule cells are believed to influence tenofovir plasma concentration and toxicity in the kidney. We review here the current evidence that the actions, pharmacogenetics and drug interactions of drug transporters are relevant factors for tenofovir-associated tubular dysfunction. The use of creatinine and novel biomarkers for kidney damage, and the role that drug transporters play in biomarker disposition, is discussed. The lessons learnt from investigating the role of transporters in tenofovir kidney elimination and toxicity can be utilised for future drug development and clinical management programs.

Acquisition of wild-type HIV-1 infection in a patient on pre-exposure prophylaxis with high intracellular concentrations of tenofovir diphosphate: a case report.

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Hoornenborg, Elske; Prins, Maria; Achterbergh, Roel C A; Woittiez, Lycke R; Cornelissen, Marion; Jurriaans, Suzanne; Kootstra, Neeltje A; Anderson, Peter L; Reiss, Peter; de Vries, Henry J C; Prins, Jan M; de Bree, Godelieve J

2017-01-01

Pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate is highly effective against acquisition of HIV infection, and only two cases of infection with a multidrug-resistant virus have been reported under adequate long-term adherence, as evidenced by tenofovir diphosphate

QbD based approach for optimization of Tenofovir disoproxil fumarate loaded liquid crystal precursor with improved permeability

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Sharvil Patil

2017-11-01

Full Text Available BCS class III drugs suffer from a drawback of low permeability even though they have high aqueous solubility. The objective of current work was to screen the suitability of glyceryl monooleate (GMO/Pluronic F127 cubic phase liquid crystals precursors for permeation enhancement and in turn the bioavailability of tenofovir disoproxil fumarate (TDF, a BCS class III drug. Spray-drying method was used for preparation of TDF loaded liquid crystal precursors (LCP consisting of GMO/Pluronic F127 and lactose monohydrate with an ability to in situ transform into stable cubic phases upon hydration. The quality by design (QbD approach (Factorial design was used for batch optimization. Spherical TDF loaded LCP as revealed by scanning electron microscopy photographs when hydrated and analyzed by small angle X-ray scattering confirmed formation of cubic phase. Differential scanning calorimetry and X-ray diffraction studies confirmed the molecular dispersion of TDF in polymer matrix and also suggested the conversion of TDF from crystalline to amorphous form. In vitro TDF release from prepared LCP showed controlled drug release over a period of 10 h. Further ex vivo studies revealed permeation enhancing activity of prepared LCP, which was highest when tested in presence of digestive enzyme extract. Thus, formulation of stable liquid crystal powder precursor can serve as an alternative for designing oral delivery system for drugs with low permeability.

Safety of oral tenofovir disoproxil fumarate-based HIV pre-exposure prophylaxis use in lactating HIV-uninfected women.

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Mugwanya, Kenneth K; John-Stewart, Grace; Baeten, Jared

2017-07-01

In settings where HIV is prevalent in heterosexual populations, pregnancy and postpartum breastfeeding periods can be associated with substantial HIV acquisition risk. Pre-exposure prophylaxis (PrEP) with daily oral tenofovir disoproxil fumarate (TDF)/emtricitabine is an attractive HIV prevention option for women who are lactating but data are limited on its safety during the lactation period. Areas covered: We provide a concise synthesis and summary of current evidence on the safety of TDF-based PrEP during breastfeeding. We conducted a review, searching Pubmed database and major PrEP conferences for primary studies with TDF-based PrEP exposure during postpartum breastfeeding. Expert opinion: TDF-based oral PrEP is an effective female-controlled HIV prevention option. There is evidence supporting the safety of TDF use for infant outcomes during breastfeeding in antiretroviral treatment regimens for HIV and hepatitis B virus, and more limited, but consistently safe, data from use of TDF as PrEP. The potential for risk is arguably outweighed for at-risk individuals by HIV prevention benefits, including indirect protection to the infant as a result of preventing HIV in the breastfeeding mother. As PrEP delivery is scaled up in heterosexual populations in high HIV prevalence settings and for at-risk persons in other settings, implementation science studies can provide a framework to increase the accrual of safety, acceptability, and use data related to PrEP during lactation.

Long-term Therapy With Tenofovir Is Effective for Patients Co-Infected With Human Immunodeficiency Virus and Hepatitis B Virus

NARCIS (Netherlands)

de Vries-Sluijs, Theodora E. M. S.; Reijnders, Jurriën G. P.; Hansen, Bettina E.; Zaaijer, Hans L.; Prins, Jan M.; Pas, Suzan D.; Schutten, Martin; Hoepelman, Andy I. M.; Richter, Clemens; Mulder, Jan W.; de Man, Rob A.; Janssen, Harry L. A.; van der Ende, Marchina E.

2010-01-01

BACKGROUND & AIMS: We investigated the long-term efficacy and renal safety of tenofovir disoproxil fumarate (TDF), administered to patients co-infected with human immunodeficiency virus and hepatitis B virus (HBV) as part of an antiretroviral therapy. METHODS: We performed a multicenter, prospective

Hypophosphatemic osteomalacia induced by tenofovir in HIV-infected patients.

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Mateo, Lourdes; Holgado, Susana; Mariñoso, Maria Luisa; Pérez-Andrés, Ricard; Bonjoch, Anna; Romeu, Joan; Olivé, Alejandro

2016-05-01

Tenofovir disoproxil fumarate (TDF) is an adenine analogue reverse transcription inhibitor widely used in first-line treatment of human immunodeficiency virus (HIV) infection and also in hepatitis B virus infection. Its use has been linked to sporadic Fanconi syndrome, renal failure and bone disease. We present the clinical characteristics of tenofovir-induced osteomalacia, discuss bone biopsy findings, describe predisposing factors and compare our results with other reported cases. We describe five cases of hypophosphatemic osteomalacia induced by TDF and recorded at the rheumatology service of a university hospital between 2010 and 2014. We also report the characteristics of bone biopsies of this pathology, which have not been previously described. We include a review of published cases of proximal renal tubulopathy (PRT) and osteomalacia induced by TDF (PubMed 1995-2014; keywords: osteomalacia, tenofovir, Fanconi syndrome, hypophosphatemic osteomalacia, proximal renal tubulopathy, bone biopsy). Five HIV patients who developed hypophosphatemic osteomalacia under TDF treatment (>5 years) presented increasing bone pain and a progressive inability to walk without assistance as a result of multiple insufficiency fractures. Bone biopsy performed in three patients after tetracycline labelling showed increased osteoid thickness, confirming osteomalacia. A literature review retrieved 17 publications on this condition, including 53 cases: 26 patients developed isolated PRT, 25 presented PRT and with multiple insufficiency fractures and two presented isolated bone disease, including osteomalacia and osteoporosis. Rheumatologists should be alert to this complication in patients receiving tenofovir. The main complaint reported by these patients is diffuse pain, predominantly in the lower limbs, indicating multiple stress fractures. Serum phosphate and appropriate screening for abnormal proximal tubule function should be monitored. Bone scintigraphy should be carried out in

Virologic breakthrough in a patient with chronic hepatitis B by combination treatment with tenofovir disoproxil fumarate and entecavir

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Suzuki F

2014-06-01

Full Text Available Fumitaka Suzuki,1,2 Hitomi Sezaki,1 Norio Akuta,1 Yoshiyuki Suzuki,1 Yusuke Kawamura,1 Tetsuya Hosaka,1 Masahiro Kobayashi,1 Satoshi Saitoh,1 Yasuji Arase,1 Kenji Ikeda,1 Mariko Kobayashi,3 Sachiyo Watahiki,3 Rie Mineta,3 Yukiko Suzuki,3 Hiromitsu Kumada1 1Department of Hepatology, Toranomon Hospital, Tokyo, Japan; 2Okinaka Memorial Institute for Medical Research, Tokyo, Japan; 3Research Institute for Hepatology, Toranomon Branch Hospital, Kawasaki, Japan Abstract: Tenofovir disoproxil fumarate (TDF is widely used to treat hepatitis B virus (HBV patients in the USA and Europe. No confirmed report of resistance selection during treatment with TDF in treatment-naïve and nucleoside/nucleotide analog-treated chronic hepatitis B patients has yet been reported. Here, we report for the first time a patient with chronic hepatitis B and cirrhosis who emerged with virologic breakthrough during combination therapy with TDF and entecavir (ETV, against ETV-resistant virus. A 51-year-old Japanese woman with hepatitis B e-antigen (HBeAg, whose genotype was C, received ETV monotherapy continuously followed by TDF and ETV combination therapy, because her HBV DNA levels had been >3.5 log copies/mL. At the start of combination therapy, amino acid substitutions of the reverse transcriptase (rt gene, rtL180M, rtT184I/M, and rtM204V, were detected. After this, serum HBV DNA decreased to less than 2.1 log copies/mL and remained at this level until 31 months of combination therapy, when it again began to increase. Amino acid substitutions of rtL180M, rtS202G, and rtM204V emerged and were associated with an increase in serum HBV DNA at virologic breakthrough. Long-term therapy with TDF against the ETV-resistant virus has the potential to induce virologic breakthrough and resistance, and careful follow-up should be carried out. Keywords: hepatitis B virus, resistant

Design and evaluation of mucoadhesive vaginal tablets of tenofovir disoproxil fumarate for pre-exposure prophylaxis of HIV.

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Khan, Arshad Bashir; Thakur, Ram Sharnagat

2018-03-01

To design and evaluate novel, feasible, safe, mucoadhesive intravaginal tablets of tenofovir disoproxil fumarate (TDF). It may provide pre-exposure prophylaxis for women against HIV. TDF intravaginal tablets were formulated employing poylvinylpyrrolidone (PVP) as the matrix forming polymer and various mucoadhesive polymers such as carbopol 934, 940, chitosan, and sodium carboxymethylcellulose (SCMC). Wet granulation was used. The evaluation involved testing drug-excipient compatibility, precompression parameters such as percentage yield, bulk density and tapped density of the granules, Carr's index, Hausner ratio, angle of repose, post compression parameters such as color, shape, physical dimensions, weight variation, hardness, friability, swelling index, assay, in vitro dissolution study and ex vivo mucoadhesion studies. Based on in vitro evaluation, C1 was selected as the best formulation and evaluated further for release kinetics, curve fitting analysis, absorption studies using liquid chromatography-mass spectrometry (LC-MS) technique and histopathological assessment in female Sprague-Dawley rats. C1 followed Higuchi model kinetics. Accelerated stability study was as per ICH guidelines by keeping C1 at 40 ± 2 °C and 75 ± 5% RH for six months. C1 was selected as the best formulation due to better swelling index (65.93% at 24 h), prolonged release of 100.62% cumulative drug release (CDR) at 24 h, superior mucoadhesion force (35.93 × 10 2 dynes/cm 2 ) and retention time (16 h). The study revealed that C1 remained stable for six months. C1 showed nil systemic absorption which is desirable and according to histopathological study, C1, exhibited minimal damage on the rat vaginal epithelium indicating safety.

Tenofovir alafenamide in the treatment of chronic hepatitis B: design, development, and place in therapy

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Ogawa E

2017-11-01

Full Text Available Eiichi Ogawa,1 Norihiro Furusyo,1 Mindie H Nguyen2 1Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan; 2Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA Abstract: Tenofovir alafenamide (TAF, a novel prodrug of tenofovir (TFV, has been approved for the treatment of chronic hepatitis B virus (HBV infection. TAF has been shown to be a potent inhibitor of HBV replication at a low dose, with high intracellular concentration and more than 90% lower systemic TFV concentration than tenofovir disoproxil fumarate (TDF. In two randomized, double-blind, multinational, Phase 3, non-inferiority trials for hepatitis B e antigen (HBeAg-positive and -negative patients (primary analysis: 48 weeks, TAF 25 mg orally once-daily was not inferior to TDF 300 mg in achieving an HBV DNA level <29 IU/mL at week 48. No amino-acid substitutions associated with viral breakthrough were detected by deep sequencing, and no resistance to TAF was found through week 96. In addition, no difference in the frequency of HBeAg or hepatitis B surface antigen loss was observed. However, TAF was associated with a significantly higher ALT normalization rate than was TDF, based on the American Association for the Study of Liver Diseases criteria (male: ALT ≤30 U/L and female: ALT ≤19 U/L. An analysis of renal safety showed that patients treated with TAF had a significantly lower decrease in the estimated glomerular filtration rate level than did patients treated with TDF. Similarly, the declines of hip and spine bone mineral density were significantly less in the TAF group. These trends of efficacy and renal/bone safety continued through week 96. Longer term follow-up and real-world data will be required to determine if the differences in viral/biochemical response and renal/bone safety seen with TAF in comparison with TDF are clinically relevant. Keywords: hepatitis B virus

Real-World Assessment of Renal and Bone Safety among Patients with HIV Infection Exposed to Tenofovir Disoproxil Fumarate-Containing Single-Tablet Regimens.

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Nkhoma, Ella T; Rosenblatt, Lisa; Myers, Joel; Villasis-Keever, Angelina; Coumbis, John

2016-01-01

Tenofovir disoproxil fumarate (TDF)-containing antiretroviral regimens have been associated with an increased incidence of renal and bone adverse outcomes. Here, we estimated the real-world incidence of renal and bone adverse outcomes among patients with HIV infection receiving different TDF-containing single-tablet regimens (STRs). This cohort study used US health insurance data spanning the years 2008-2014. We identified HIV-infected patients aged ≥18 years (all HIV patients) and those with ≥6 months of continuous enrollment prior to initiating efavirenz/emtricitabine/TDF (EFV/FTC/TDF), rilpivirine/FTC/TDF (RPV/FTC/TDF) or elvitegravir/cobicistat/FTC/TDF (EVG/COBI/FTC/TDF). Renal adverse outcomes were identified using renal International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. Bone adverse outcomes were identified using ICD-9-CM diagnosis codes for fracture. Incidence rates (IRs) and associated 95% confidence intervals (CIs) were estimated assuming a Poisson distribution, and outcomes between STRs were compared using IR ratios (IRRs) and IR differences (IRDs). We identified 9876 and 10,383 eligible patients for the renal and fracture analyses, respectively. Observed IRs for renal adverse outcomes were 9.7, 10.5, 13.6, and 18.0 per 1000 person-years among those receiving EFV/FTC/TDF, RPV/FTC/TDF, or EVG/COBI/FTC/TDF, or all HIV patients, respectively. Corresponding values for IRs of fracture were 3.4, 3.6, 7.2, and 4.4 per 1000 person-years, respectively. Renal adverse outcomes with EFV/FTC/TDF were significantly less frequent than with EVG/COBI/FTC/TDF (IRD -3.96; 95% CI: -7.31, -1.06). No IRR differences were identified for the renal analysis. Fractures with EFV/FTC/TDF were significantly less frequent than with EVG/COBI/FTC/TDF (IRR 0.47; 95% CI: 0.27, 0.81 and IRD -3.85; 95% CI: -5.02, -2.78). In this large real-world database, observed IRs for renal adverse outcomes with TDF-containing STRs were lower

Cost-effectiveness analysis of tenofovir disoproxil fumarate for treatment of chronic hepatitis B in China.

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Ke, Weixia; Zhang, Chi; Liu, Li; Gao, Yanhui; Yao, Zhenjiang; Ye, Xiaohua; Zhou, Shudong; Yang, Yi

2016-11-01

Tenofovir disoproxil fumarate (TDF) is newly available for treatment of chronic hepatitis B patients in China. To date, no study has been conducted to examine the cost-effectiveness of this treatment. The aim of this study was to estimate the cost-effectiveness of TDF versus four oral nucleos(t)ide analogs [lamivudine (LAM), adefovir (ADV), telbivudine (LdT), and entecavir (ETV)] and from a pharmacoeconomic perspective to assess current drug pricing for TDF. Based on Chinese healthcare perspectives, a Markov model was applied to simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for five different monotherapy strategies. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: directly using ETV + ADV) were separately considered for treatment of patients refractory to monotherapy. Model parameters (including disease transition, cost, and utility) were obtained from previous Chinese population studies. Both branded and generic drugs were separately analyzed. Study model uncertainties were assessed by one-way and probabilistic sensitivity analyses. Two-way sensitivity analysis was used to explore uncertainties between efficacy and price of TDF. In the base-case analysis, the lowest lifetime cost and the best cost-effectiveness ratio were obtained by ETV, which was considered the reference treatment. LAM, ADV, and LdT treatments had significantly greater costs and lower efficacies. Compared to ETV, TDF was more effective but also more expensive. The incremental cost-effectiveness ratios of TDF versus ETV were much higher than the willing-to-pay threshold of $20,466 US dollars (USD) per QALY gained (3 × gross domestic product per capita of China, 2014). TDF would be the most cost-effective strategy if the annual cost did not exceed $2260 USD and $1600 USD for branded and generic drugs, respectively. For Chinese chronic hepatitis B patients, ETV is still the most cost

Tenofovir alafenamide (TAF) treatment of HBV, what are the unanswered questions?

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Viganò, Mauro; Loglio, Alessandro; Grossi, Glenda; Lampertico, Pietro

2018-02-01

Tenofovir disoproxil fumarate (TDF), an ester prodrug of tenofovir (TFV), is one of the recommended drugs for chronic hepatitis B (CHB) patients. However, reduced kidney function and loss of bone mineral density have been reported in some CHB patients treated with TDF. Consequent to these safety issues, tenofovir alafenamide (TAF) [Vemlidy®], a phosphonate prodrug of TFV, was developed for the treatment of CHB patients. Areas covered: The favourable pharmacological profile of TAF allows a marked reduction in dosage (25 mg/day) thus reducing systemic exposure to tenofovir and improving the bone and renal safety, keeping however the same virological efficacy, compared to TDF 300 mg/day. In two ongoing 96-week phase III trials in mainly treatment-naive HBeAg-positive or -negative patients, TAF showed similar viral suppression but was associated with significantly higher alanine aminotransferase normalization rates and more favourable renal and bone safety compared to TDF. In a 48-week TAF switch study enrolling patients treated with TDF for 96 weeks, glomerular, tubular and bone safety parameters rapidly improved while virological suppression was maintained. Expert commentary: Waiting long-term large scale clinical practice studies aimed to confirm these advantages, TAF represents an helpful treatment option for both naïve and TDF-exposed CHB patients.

Efficacy and safety of tenofovir in chronic hepatitis B: Australian real world experience.

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Lovett, Grace C; Nguyen, Tin; Iser, David M; Holmes, Jacinta A; Chen, Robert; Demediuk, Barbara; Shaw, Gideon; Bell, Sally J; Desmond, Paul V; Thompson, Alexander J

2017-01-08

To evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting. We performed a retrospective analysis of treatment outcomes among treatment-naïve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent's Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate (TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemical response, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus (HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA < 20 IU/mL. Secondary efficacy endpoints included rates of biochemical response, and HB e antigen (HBeAg)/HB surface antigen loss and seroconversion over time. Ninety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo (range 3-114). Mean age was 46 (24-78) years, 64 (70%) were male and 77 (84%) were of Asian origin. 55 (60%) patients were treatment-naïve and 62 patients (67%) were HBeAg-negative. Complete virological suppression was achieved by 45/65 (71%) patients at 12 mo, 37/46 (80%) at 24 mo and 25/28 (89%) at 36 mo. Partial virological response (HBV DNA 20-2000 IU/mL) was achieved by 89/92 (96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level (OR = 0.897, 95%CI

A Validated Stability Indicating RP-HPLC Method for the Determination of Emtricitabine, Tenofovir Disoproxil Fumarate, Elvitegravir and Cobicistat in Pharmaceutical Dosage Form

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Runja, Chinnalalaiah; Ravi Kumar, Pigili; Avanapu, Srinivasa Rao

2016-01-01

A new simple, rapid stability indicating assay method has been developed and validated for the determination of emtricitabine, tenofovir disoproxil fumarate, elvitegravir and cobicistat using reverse-phase high-performance liquid chromatography in their pharmaceutical dosage form. The chromatographic separation was performed on an ODS column (250 × 4.6 mm, 5 µm) using mobile phase A (potassium dihydrogen orthophosphate, pH adjusted to 2.5) and mobile phase B (acetonitrile) in the ratio of 55:45% v/v at a flow rate of 1 mL/min. The analytes were detected at 250 nm. The method was found to be linear in the concentration range of 2–12 µg/mL for EMT, 3–18 µg/mL for TNDF, 1.5–9 µg/mL for ELV and COB, with the coefficient value (R2) of >0.9990. The accuracy was measured via recovery studies and found to be acceptable, and the percentage recoveries were found in the range of 99.93–100.08 ± 0.5%. Forced degradation studies were also conducted, and the drugs were subjected to various stress conditions such as acid hydrolysis, base hydrolysis, oxidative, photolytic and thermal degradation. The proposed method was successfully validated and applied for the quantitative estimation of these drugs in both bulk and tablet dosage forms. PMID:26865655

Tenofovir and its potential in the treatment of hepatitis B virus

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Laura Reynaud

2009-02-01

Full Text Available Laura Reynaud, Maria Aurora Carleo, Maria Talamo, Guglielmo BorgiaDepartment of Public Medicine and Social Security – Section of Infectious Disease University of Naples “Federico II”, ItalyAbstract: Recent literature is reviewed about treatment of chronic hepatitis B virus (CHB, focusing on tenofovir disoproxil fumarate (TDF; Viread®, among the nucleotide and nucleoside analogs. TDF pharmacokinetics and pharmacodynamics, activity in respect of hepatitis B virus (HBV multi-drug-resistant mutations, efficacy in treatment-naïve and treatment-experienced patients, and side effects are described. The most predictive response factors to TDF therapy are discussed and all available combination therapies to optimize clinical outcome in the various patient profiles are analyzed, such as compensated and/or decompensated cirrhotic patients. The use of TDF in pregnancy, and prophylaxis after exposure to HBV and post-liver transplantation are also evaluated.Keywords: HBV, chronic hepatitis B, tenofovir, antiviral therapy

Maternal Tenofovir Disoproxil Fumarate Use During Pregnancy Is Not Associated With Adverse Perinatal Outcomes Among HIV-infected East African Women: A Prospective Study.

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Pintye, Jillian; Baeten, Jared M; Celum, Connie; Mugo, Nelly; Ngure, Kenneth; Were, Edwin; Bukusi, Elizabeth A; John-Stewart, Grace; Heffron, Renee A

2017-12-19

Tenofovir disoproxil fumarate (TDF) is commonly used in antiretroviral treatment (ART) and pre-exposure prophylaxis regimens. We evaluated the relationship between adverse perinatal outcomes and prenatal TDF use. Longitudinal data were analyzed from human immunodeficiency virus (HIV)-infected women who became pregnant during 2 HIV prevention studies conducted among HIV-serodiscordant couples in Kenya and Uganda. Pregnancies included were singleton, not terminated by an induced abortion, and had documented 3-drug ART use. Multivariate generalized estimating equation models were used to determine the association of prenatal TDF and perinatal outcomes. The most frequent ART regimens were TDF/3TC/EFV (39%) and AZT/3TC/NVP (34%); 49% of pregnancies had prenatal TDF exposure and 6% used a protease inhibitor. Neonatal death, preterm birth, and pregnancy loss occurred in 2%, 8%, and 12% of pregnancies, respectively. No differences were observed between pregnancies with and without exposure to TDF in the frequency of pregnancy loss (adjusted prevalence rate ratio [aPRR] 1.19, P = .8) or neonatal death (aPRR 0.68, P = .6). Preterm birth occurred less frequently among pregnancies exposed to TDF (aPRR, 0.34, P = .02). Maternal TDF use did not adversely affect perinatal outcomes. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Neurological syndrome in an HIV-prevention trial participant randomized to daily tenofovir disoproxil fumarate (300 mg and emtricitabine (200 mg in Bondo, Kenya

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Owino F

2013-11-01

Full Text Available Fredrick Owino,1 Justin Mandala,2 Julie Ambia,3 Kawango Agot,1 Lut Van Damme2 1Impact Research and Development Organization, Kisumu, Kenya; 2Department of Global Health, Population, and Nutrition, FHI 360, Washington, DC, USA; 3KAVI-Institute of Clinical Research, University of Nairobi, Nairobi, Kenya Abstract: Side effects of antiretroviral drug use by HIV-positive patients have been extensively studied; however, there are limited data on the side effects of antiretroviral drugs used as an HIV prophylaxis among healthy, HIV-negative individuals. Here we report on an unusual neuropathy in a 24-year-old participant in the FEM-PrEP trial. This was a Phase III randomized, double blind, placebo-controlled trial to test the safety and effectiveness of tenofovir disoproxil fumarate (300 mg and emtricitabine (200 mg (TDF-FTC to prevent HIV. At the eighth week of taking TDF-FTC with moderate adherence, the participant complained of mild paresthesiae, numbness, and a tingling sensation in her upper limbs that was associated with pain and cold. After an additional 4 days, she developed a disabling weakness of her upper limbs and tremors in her hands. The study product was discontinued, and within 2 weeks she was free of all symptoms. One month after restarting the drug, she complained of posture-dependent numbness of her upper limbs. Results of clinical and neurological exams, laboratory tests, and magnetic resonance imaging are described here. Keywords: pre-exposure prophylaxis, toxic neuropathy, NRTI

A case study of chewed Truvada® for PrEP maintaining protective drug levels as measured by a novel urine tenofovir assay.

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Lalley-Chareczko, Linden; Clark, Devon; Zuppa, Athena F; Moorthy, Ganesh; Conyngham, Caitlin; Mounzer, Karam; Koenig, Helen

2017-01-01

Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF; Truvada ® ) given as pre-exposure prophylaxis (PrEP) successfully blocks HIV when taken once daily prior to potential HIV exposure. A 22-year-old male reported difficulty swallowing FTC/TDF for PrEP and subsequently began chewing the FTC/TDF tablets. Monthly urine samples assessed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated tenofovir levels >1,000 ng/ml, indicative of protection from HIV acquisition, over a 48-week period. Data from observational studies of HIV-positive patients details the successful treatment of HIV using crushed FTC/TDF delivered via feeding and gastronomy tubes while small, randomized trials of healthy volunteers demonstrate bioequivalence between whole and crushed FTC/TDF.

Tenofovir disoproxil fumarate monotherapy for nucleos(tide analogue-naïve and nucleos(tide analogue-experienced chronic hepatitis B patients

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Sang Kyung Jung

2015-03-01

Full Text Available Background/AimsThis study investigated the antiviral effects of tenofovir disoproxil fumarate (TDF monotherapy in nucleos(tide analogue (NA-naive and NA-experienced chronic hepatitis B (CHB patients.MethodsCHB patients treated with TDF monotherapy (300 mg/day for ≥12 weeks between December 2012 and July 2014 at a single center were retrospectively enrolled. Clinical, biochemical, and virological parameters were assessed every 12 weeks.ResultsIn total, 136 patients (median age 49 years, 96 males, 94 HBeAg positive, and 51 with liver cirrhosis were included. Sixty-two patients were nucleos(tide (NA-naïve, and 74 patients had prior NA therapy (NA-exp group, and 31 patients in the NA-exp group had lamivudine (LAM-resistance (LAM-R group. The baseline serum hepatitis B virus (HBV DNA level was 4.9±2.3 log IU/mL (mean±SD, and was higher in the NA-naïve group than in the NA-exp and LAM-R groups (5.9±2.0 log IU/mL vs 3.9±2.0 log IU/mL vs 4.2±1.7 log IU/mL, P<0.01. The complete virological response (CVR rate at week 48 in the NA-naïve group (71.4% did not differ significantly from those in the NA-exp (71.3% and LAM-R (66.1% groups. In multivariate analysis, baseline serum HBV DNA was the only predictive factor for a CVR at week 48 (hazard ratio, 0.809; 95% confidence interval, 0.729-0.898, while the CVR rate did not differ with the NA experience.ConclusionsTDF monotherapy was effective for CHB treatment irrespective of prior NA treatment or LAM resistance. Baseline serum HBV DNA was the independent predictive factor for a CVR.

Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial.

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Orkin, Chloe; Molina, Jean-Michel; Negredo, Eugenia; Arribas, José R; Gathe, Joseph; Eron, Joseph J; Van Landuyt, Erika; Lathouwers, Erkki; Hufkens, Veerle; Petrovic, Romana; Vanveggel, Simon; Opsomer, Magda

2018-01-01

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

Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration

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Soo-Yon Rhee

2017-04-01

Full Text Available Tenofovir disoproxil fumarate (TDF genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT mutations selected in individuals with VF on such a regimen is not known. To identify TDF regimen-associated mutations (TRAMs, we compared the proportion of each RT mutation in 2873 individuals with VF on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-naïve individuals. To identify TRAMs specifically associated with TDF-selection pressure, we compared the proportion of each TRAM to its proportion in a cohort of 5805 individuals with VF on a first-line thymidine analog-containing regimen. We identified 83 TRAMs including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12 – A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F – were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. These 12 TDF-selected TRAMs will be important for monitoring TDF-associated transmitted drug-resistance and for determining the extent of reduced TDF susceptibility in individuals with VF on a TDF-containing regimen.

MTN-001: randomized pharmacokinetic cross-over study comparing tenofovir vaginal gel and oral tablets in vaginal tissue and other compartments.

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Craig W Hendrix

Full Text Available Oral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP for human immunodeficiency virus (HIV infection have demonstrated variable efficacy in men and women prompting assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development.MTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design.We enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel [40 mg], or both. Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001. Vaginal tissue tenofovir diphosphate was quantifiable in ≥90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ≥130-fold higher with vaginal compared to oral dosing (p<0.001. Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03.Compared to oral dosing, vaginal dosing achieved much lower serum concentrations and much higher vaginal tissue concentrations. Even allowing for 100-fold concentration differences due to poor adherence or less frequent prescribed dosing, vaginal dosing of tenofovir should provide higher active site concentrations and theoretically greater PrEP efficacy than oral dosing; randomized topical dosing PrEP trials to the contrary indicates that factors beyond tenofovir

Role of tenofovir alafenamide (TAF) in the treatment and prophylaxis of HIV and HBV infections.

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De Clercq, Erik

2018-07-01

Tenofovir (TFV) is the cornerstone of the treatment and prophylaxis of HIV infections. It has been routinely used in its prodrug form TDF (tenofovir disoproxil fumarate) combined with emtricitabine ((-)FTC) and other antiretroviral agents. TDF has now been replaced by TAF (tenofovir alafenamide) which allows better uptake by the lymphoid tissue. In combination with elvitegravir (E), cobicistat (C), emtricitabine (F), TAF can be advocated as an STR (single tablet regimen, Genvoya®) for the treatment of HIV infections. In this combination, E and C may in the future be replaced by bictegravir. The prophylaxis of HIV infection is momentarily based upon Truvada®, the combination of F with TDF, which in the future may also be replaced by TAF. TAF (Vemlidy®) has also replaced TDF (Viread®) for the treatment of hepatitis B virus (HBV) infections. Both TDF and TAF offer little or no risk for virus-drug resistance. As compared to TDF, TAF limits the risk for nephrotoxicity and loss of bone mineral density. What remains to be settled, however, before the universal use of TAF could be recommended, is its safety during pregnancy and its applicability in the treatment of tuberculosis, in combination with rifampicin. Copyright © 2017 Elsevier Inc. All rights reserved.

Maraviroc/raltegravir simplification strategy following 6 months of quadruple therapy with tenofovir/emtricitabine/maraviroc/raltegravir in treatment-naive HIV patients.

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Pradat, Pierre; Durant, Jacques; Brochier, Corinne; Trabaud, Mary-Anne; Cottalorda-Dufayard, Jacqueline; Izopet, Jacques; Raffi, François; Lucht, Frédéric; Gagnieu, Marie-Claude; Gatey, Caroline; Jacomet, Christine; Vassallo, Matteo; Dellamonica, Pierre; Cotte, Laurent

2016-11-01

We assessed the virological efficacy of a 6 month maraviroc/raltegravir simplification strategy following 6 months of quadruple therapy combining tenofovir disoproxil fumarate/emtricitabine with maraviroc/raltegravir. HIV-1-infected naive patients were enrolled in an open label, single-arm, Phase 2 trial. All patients received maraviroc 300 mg twice daily, raltegravir 400 mg twice daily and tenofovir/emtricitabine for 24 weeks. Patients with stable HIV-RNA HIV-RNA HIV-RNA was 4.3 log copies/mL. All patients had CCR5-tropic viruses by genotropism and phenotropism assays. All but one patient had an HIV-RNA < 50 copies/mL at W24 and entered the simplification phase. Virological success was maintained at W48 in 88% (90% CI 79%-97%) of patients. N155H mutation was detected at failure in one patient. No tropism switch was observed. Raltegravir and maraviroc plasma exposure were satisfactory in 92% and 79% of 41 samples from 21 patients. Five severe adverse events (SAEs) were observed up to W48; none was related to the study drugs. Four patients presented grade 3 AEs; none was related to the study. No grade 4 AE was observed. No patient died. Maraviroc/raltegravir maintenance therapy following a 6 month induction phase with maraviroc/raltegravir/tenofovir/emtricitabine was well tolerated and maintained virological efficacy in these carefully selected patients. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Rare emergence of drug resistance in HIV-1 treatment-naïve patients receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide for 144 weeks.

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Margot, Nicolas; Cox, Stephanie; Das, Moupali; McCallister, Scott; Miller, Michael D; Callebaut, Christian

2018-06-01

The single tablet regimen (STR) composed of elvitegravir (E), cobicistat (C), emtricitabine (F), and tenofovir alafenamide (TAF) (E/C/F/TAF) was compared to the STR composed of E, C, F, and tenofovir disoproxil fumarate (TDF) (E/C/F/TDF) in 2 phase 3 studies in 1733 HIV-1 infected treatment-naïve adults. Superior efficacy of E/C/F/TAF compared to E/C/F/TDF was demonstrated at Week 144 with 84% treatment success compared to 80%, respectively, along with significantly better outcomes of bone and renal safety. Analyze the emergence of HIV-1 resistance in treatment-naïve adults receiving E/C/F/TAF for 144 weeks. We conducted an integrated resistance analysis of the 2 Phase 3 studies, comprising pretreatment HIV-1 sequencing for all participants (N = 1733) and post-baseline HIV-1 resistance analysis for participants with virologic failure (HIV-1 RNA ≥400 copies/mL). Primary resistance-associated mutations (RAMs) were observed pre-treatment in 7.4% (NRTI-RAMs), 18.1% (NNRTI-RAMs), and 3.3% (PI-RAMs) of enrolled subjects. Baseline HIV-1 subtype or pre-existing RAMs did not affect E/C/F/TAF treatment response at week 144. Virologic failure resistance analyses were conducted for 28/866 (3.2%) and 30/867 (3.5%) patients in the E/C/F/TAF and E/C/F/TDF arms, respectively. Over the 3-year study, the rate of resistance emergence remained low at 1.4% in each group (12/866 in E/C/F/TAF; 12/867 in E/C/F/TDF). Resistant virus emerged in 24 patients who developed resistance to antiretrovirals in the regimens (E/C/F/TAF: M184V/I [1.3%], INSTI-RAMs [0.9%], K65R/N [0.2%]; E/C/F/TDF: M184V/I [1.0%], INSTI-RAMs [0.9%], K65R/N [0.5%]). Resistance emergence was rare (1.4%) with similar patterns of emergent mutations in both groups. M184V/I was the most prevalent RAM (1.2% overall). Copyright © 2018 Elsevier B.V. All rights reserved.

Formulation development and optimization of Lamivudine 300 mg and Tenofovir Disoproxil Fumarate (TDF 300 mg FDC tablets by D-optimal mixture design

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Prosper Tibalinda

2016-12-01

Full Text Available The usage of fixed dose combination (FDC tablets of Lamivudine and Tenofovir Disoproxil Fumarate (TDF is increasing due to increased incidences of HIV/Hepatitis B and HIV/TB co-infections. This is likely to increase the financial crisis due to limited resources for funding procurement of ready-made products from the pharmaceuticals manufacturing leading countries. Therefore, production of local oral tablets containing Lamivudine and TDF FDC is inevitable. Lamivudine 300 mg/TDF 300 mg tablets were developed and optimized by D-optimal mixture design and produced by direct compression technique. Twenty trial formulations with independent variables, including PVP-CL 1–12.00%, PVP-K30 1–10.00%, starch-1500 2.5–12.5% and Avicel-PH102 2–19.25% were prepared by direct compression technique. The formulations were assessed on assay, dissolution, friability, weight variation and disintegration time. It was found that assay ranged from 98.13–101.95% for Lamivudine, 98.25–102.84 for TDF, both were within the in-house assay specification of 95 to 105%. Dissolution at single point was above 80% for Lamivudine 93.96–100.55% and 95.85–103.15% for TDF, disintegration time was between 1.92–66.33 min and friability 0.06–12.56%. Out of twenty formulation trials, eight formulations had all parameters in proven acceptable range. On optimization, one formulation with independent variables, PVP-CL 5.67%, PVP-K30 1.00%, Starch-1500 5.76% was selected. The optimized formulation was comparable to the reference product on the market with similarity factor (f2 and difference factor (f1 within the acceptable range for both Lamivudine and TDF.

Antiviral and immunological effects of tenofovir microbicide in vaginal herpes simplex virus 2 infection.

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Vibholm, Line; Reinert, Line S; Søgaard, Ole S; Paludan, Søren R; Østergaard, Lars; Tolstrup, Martin; Melchjorsen, Jesper

2012-11-01

The anti-HIV microbicide, tenofovir (TFV) gel, has been shown to decrease HIV-1 acquisition by 39% and reduce herpes simplex virus 2 (HSV-2) transmission by 51%. We evaluated the effect of a 1% TFV gel on genital HSV-2 infection in a mouse vaginal challenge model. In vitro plaque assays and luminex multiplex bead analysis were used, respectively, to measure postinfection vaginal viral shedding (day 1) and cytokine secretion (day 2). To further investigate the anti-HSV-2 properties, we evaluated the direct antiviral effect of TFV and the oral prodrug tenofovir disoproxil fumerate (TDF) in cell culture. Compared to placebo-treated mice, TFV-treated mice had significantly lower clinical scores, developed later genital lesions, and showed reduced vaginal viral shedding. Furthermore, the levels of IFN-γ, IL-2, TNF-α, and other cytokines were altered in the vaginal fluid following topical tenofovir treatment and subsequent HSV-2 challenge. Finally, we found that both TFV and TDF inhibited HSV-2 infection in vitro; TDF showed a 50-fold greater potency than TFV. In conclusion, we confirmed that the microbicide TFV had direct anti-HSV-2 effects in a murine vaginal challenge model. Therefore, this model would be suitable for evaluating present and future microbicide candidates. Furthermore, the present study warrants further investigation of TDF in microbicides.

Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir.

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J Gerardo García-Lerma

2008-02-01

Full Text Available In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission.We used a repeat-exposure macaque model with 14 weekly rectal virus challenges. Three drug treatments were given once daily, each to a different group of six rhesus macaques. Group 1 was treated subcutaneously with a human-equivalent dose of emtricitabine (FTC, group 2 received orally the human-equivalent dosing of both FTC and tenofovir-disoproxil fumarate (TDF, and group 3 received subcutaneously a similar dosing of FTC and a higher dose of tenofovir. A fourth group of six rhesus macaques (group 4 received intermittently a PrEP regimen similar to group 3 only 2 h before and 24 h after each weekly virus challenge. Results were compared to 18 control macaques that did not receive any drug treatment. The risk of infection in macaques treated in groups 1 and 2 was 3.8- and 7.8-fold lower than in untreated macaques (p = 0.02 and p = 0.008, respectively. All six macaques in group 3 were protected. Breakthrough infections had blunted acute viremias; drug resistance was seen in two of six animals. All six animals in group 4 that received intermittent PrEP were protected.This model suggests that single drugs for daily PrEP can be protective but a combination of antiretroviral drugs may be required to increase the level of protection. Short but potent intermittent PrEP can provide protection comparable to that of daily PrEP in this SHIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising PrEP modalities.

Validation and implementation of liquid chromatographic-mass spectrometric (LC-MS) methods for the quantification of tenofovir prodrugs.

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Hummert, Pamela; Parsons, Teresa L; Ensign, Laura M; Hoang, Thuy; Marzinke, Mark A

2018-04-15

The nucleotide reverse transcriptase inhibitor tenofovir (TFV) is widely administered in a disoproxil prodrug form (tenofovir disoproxil fumarate, TDF) for HIV management and prevention. Recently, novel prodrugs tenofovir alafenamide fumarate (TAF) and hexadecyloxypropyl tenofovir (CMX157) have been pursued for HIV treatment while minimizing adverse effects associated with systemic TFV exposure. Dynamic and sensitive bioanalytical tools are required to characterize the pharmacokinetics of these prodrugs in systemic circulation. Two parallel methods have been developed, one to combinatorially quantify TAF and TFV, and a second method for CMX157 quantification, in plasma. K 2 EDTA plasma was spiked with TAF and TFV, or CMX157. Following the addition of isotopically labeled internal standards and sample extraction via solid phase extraction (TAF and TFV) or protein precipitation (CMX157), samples were subjected to liquid chromatographic-tandem mass spectrometric (LC-MS/MS) analysis. For TAF and TFV, separation occurred using a Zorbax Eclipse Plus C18 Narrow Bore RR, 2.1 × 50 mm, 3.5 μm column and analytes were detected on an API5000 mass analyzer; CMX157 was separated using a Kinetex C8, 2.1 × 50 mm, 2.6 μm column and quantified using an API4500 mass spectrometer. Methods were validated according to FDA Bioanalytical Method Validation guidelines. Analytical methods: were optimized for the multiplexed monitoring of TAF and TFV, and CMX157 in plasma. The lower limits of quantification (LLOQs) for TAF, TFV, and CMX157 were 0.03, 1.0, and 0.25 ng/mL, respectively. Calibration curves were generated via weighted linear regression of standards. Intra- and inter-assay precision and accuracy studies demonstrated %CVs ≤ 14.4% and %DEVs ≤ ± 7.95%, respectively. Stability and matrix effects studies were also performed. All results were acceptable and in accordance with the recommended guidelines for bioanalytical methods. Assays were also

Clinical Outcomes of Virologically-Suppressed Patients with Pre-existing HIV-1 Drug Resistance Mutations Switching to Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in the SPIRIT Study.

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Porter, Danielle P; Toma, Jonathan; Tan, Yuping; Solberg, Owen; Cai, Suqin; Kulkarni, Rima; Andreatta, Kristen; Lie, Yolanda; Chuck, Susan K; Palella, Frank; Miller, Michael D; White, Kirsten L

2016-02-01

Antiretroviral regimen switching may be considered for HIV-1-infected, virologically-suppressed patients to enable treatment simplification or improve tolerability, but should be guided by knowledge of pre-existing drug resistance. The current study examined the impact of pre-existing drug resistance mutations on virologic outcomes among virologically-suppressed patients switching to Rilpivirine (RPV)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF). SPIRIT was a phase 3b study evaluating the safety and efficacy of switching to RPV/FTC/TDF in virologically-suppressed HIV-1-infected patients. Pre-existing drug resistance at baseline was determined by proviral DNA genotyping for 51 RPV/FTC/TDF-treated patients with known mutations by historical RNA genotype and matched controls and compared with clinical outcome at Week 48. Drug resistance mutations in protease or reverse transcriptase were detected in 62.7% of patients by historical RNA genotype and in 68.6% by proviral DNA genotyping at baseline. Proviral DNA sequencing detected 89% of occurrences of NRTI and NNRTI resistance-associated mutations reported by historical genotype. Mutations potentially affecting RPV activity, including E138A/G/K/Q, Y181C, and H221Y, were detected in isolates from 11 patients by one or both assays. None of the patients with single mutants had virologic failure through Week 48. One patient with pre-existing Y181Y/C and M184I by proviral DNA genotyping experienced virologic failure. Nineteen patients with K103N present by historical genotype were confirmed by proviral DNA sequencing and 18/19 remained virologically-suppressed. Virologic success rates were high among virologically-suppressed patients with pre-existing NRTI and NNRTI resistance-associated mutations who switched to RPV/FTC/TDF in the SPIRIT study. While plasma RNA genotyping remains preferred, proviral DNA genotyping may provide additional value in virologically-suppressed patients for whom historical resistance

Research

African Journals Online (AJOL)

abp

2017-09-05

Sep 5, 2017 ... HIV-infected patients aged ≥ 18 years, who received either stavudine or zidovudine or tenofovir disoproxil fumarate-based regimens. Using systematic ... not last long on them due to new possible side effects [9]. Studies ... these limitations, designing strategies aimed at prolonging the use of the original ...

Oral and Vaginal Tenofovir for Genital Herpes Simplex Virus Type 2 Shedding in Immunocompetent Women: A Double-Blind, Randomized, Cross-over Trial.

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Bender Ignacio, Rachel A; Perti, Tara; Magaret, Amalia S; Rajagopal, Sharanya; Stevens, Claire E; Huang, Meei-Li; Selke, Stacy; Johnston, Christine; Marrazzo, Jeanne; Wald, Anna

2015-12-15

Tenofovir is a potent anti-human immunodeficiency virus (HIV) agent that decreased risk of herpes simplex virus type 2 (HSV-2) acquisition in HIV pre-exposure prophylaxis trials. Whether tenofovir has utility in established HSV-2 disease is unclear. We randomized immunocompetent women with symptomatic HSV-2 infection to oral tenofovir disoproxil fumarate (TDF)/placebo vaginal gel, oral placebo/tenofovir (TFV) vaginal gel, or double placebo (ratio 2:2:1) in a one-way cross-over trial. Women collected genital swabs twice daily for HSV PCR during 4-week lead-in and 5-week treatment phases. The primary intent-to-treat end point was within-person comparison of genital HSV shedding and lesion rates. 64 women completed the lead-in phase and were randomized. Neither TDF nor TFV gel decreased overall shedding or lesion rate in the primary analysis; TFV gel decreased quantity of HSV DNA by -0.50 (-0.86-0.13) log10 copies/mL. In the per-protocol analysis, TDF reduced shedding (relative risk [RR] = 0.74, P = .006) and lesion rates (RR = 0.75, P = .032); quantity of virus shed decreased by 0.41 log10 copies/mL. Oral TDF modestly decreased HSV shedding and lesion rate, and quantity of virus shed when used consistently. Vaginal TFV gel decreased quantity of virus shed by 60%. In contrast to effects on HSV-2 acquisition, tenofovir is unlikely to provide clinically meaningful reductions in the frequency of HSV shedding or genital lesions. NCT01448616. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Pharmaceutical characterization of novel tenofovir liposomal formulations for enhanced oral drug delivery: in vitro pharmaceutics and Caco-2 permeability investigations

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Spinks CB

2017-02-01

Full Text Available Crystal B Spinks,1 Ahmed S Zidan,2,3 Mansoor A Khan,4 Muhammad J Habib,1 Patrick J Faustino2 1Department of Pharmaceutical Sciences, School of Pharmacy, Howard University, Washington, DC, 2Division of Product Quality Research, Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA; 3Faculty of Pharmacy, Zagazig University, Zagazig, Egypt; 4Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, College Station, TX, USA Abstract: Tenofovir, currently marketed as the prodrug tenofovir disoproxil fumarate, is used clinically to treat patients with HIV/AIDS. The oral bioavailability of tenofovir is relatively low, limiting its clinical effectiveness. Encapsulation of tenofovir within modified long-circulating liposomes would deliver this hydrophilic anti-HIV drug to the reticuloendothelial system for better therapeutic efficacy. The objectives of the current study were to prepare and pharmaceutically characterize model liposomal tenofovir formulations in an attempt to improve their bioavailability. The entrapment process was performed using film hydration method, and the formulations were characterized in terms of encapsulation efficiency and Caco-2 permeability. An efficient reverse-phase high-performance liquid chromatography method was developed and validated for tenofovir quantitation in both in vitro liposomal formulations and Caco-2 permeability samples. Separation was achieved isocratically on a Waters Symmetry C8 column using 10 mM Na2PO4/acetonitrile pH 7.4 (95:5 v/v. The flow rate was 1 mL/min with a 12 min elution time. Injection volume was 10 µL with ultraviolet detection at 270 nm. The method was validated according to United States Pharmacopeial Convention category I requirements. The obtained result showed that tenofovir encapsulation within the prepared liposomes was dependent on the employed amount of the positive charge-imparting agent. The obtained results indicated that

Characteristics of foot fractures in HIV-infected patients previously treated with tenofovir versus non-tenofovir-containing highly active antiretroviral therapy

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Horizon AA

2011-06-01

Full Text Available Arash A Horizon1, Robert J Joseph2, Qiming Liao3, Steven T Ross3, Gary E Pakes31Center for Rheumatology, 2Surgical Podiatry, Los Angeles, CA, USA; 3GlaxoSmithKline, Research Triangle Park, NC, USASummary: In a retrospective case series study, medical records were evaluated for all male patients infected with human immunodeficiency virus (HIV diagnosed over a one-year period with foot fractures (n = 30 confirmed by magnetic resonance imaging at a Los Angeles outpatient private practice rheumatology clinic. Proportionally more patients had received tenofovir prefracture (17 [57%] than those who had not (13 [43%]. At fracture diagnosis, these two groups were similar in median age (49 versus 48 years, HIV-1 RNA (both 1.7 log10 copies/mL, CD4 count (300 versus 364/mm3, time between HIV diagnosis and foot fracture (both 17 years, family history of degenerative bone disease (24% versus 23%, prevalence of malabsorption syndrome, renal failure, calcium deficiency, or vitamin D deficiency, and concurrent use of bisphosphonates, calcitonin, and diuretics. However, more tenofovir-treated patients had osteoporosis (35% versus 8%, stress-type fractures (53% versus 31%, concurrent fractures (12% versus 0%, wasting syndrome (29% versus 15%, truncal obesity (18% versus 8%, smoked cigarettes (more than one pack/day for more than one year; 35% versus 8%, dual energy X-ray absorptiometry (DEXA T scores <–2.4 (denoting osteoporosis at the femur (24% versus 9% and spine (47% versus 36%, and had received protease inhibitors (71% versus 46%, non-nucleoside reverse transcriptase inhibitors (24% versus 0%, prednisone (24% versus 0%, testosterone (47% versus 23%, and teriparatide (29% versus 8%. Median time from tenofovir initiation until fracture was 2.57 (range 1.17–5.69 years. In conclusion, more foot fractures were observed in tenofovir-treated patients than in non-tenofovir-treated patients with HIV infection. Comorbidities and/or coadministered drugs may have

Tenofovir therapy in chronic hepatitis B infection: 48-week results from Izmir Province, Turkey

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Şükran Köse

2012-09-01

Full Text Available Objectives: The goal of therapy in chronic hepatitis B infection (CHB is to impede liver injury by suppressing viral replication.The study was aimed to determine the efficacy of tenofovir (TDF in CHB infection for 48 weeks.Materials and methods: We retrospectively analyzed the data of 45 CHB patients treated by tenofovir. The patientswere divided into two groups based on their hepatitis B e antigen status (HBeAg. Those who were eligible to therapyreceived TDF 300 mg once daily for 48 weeks. Serum alanine aminotransferase levels (ALT, hepatitis B virus DNA (HBVDNA, and viral serological markers were checked at three-month intervals. Liver biopsy scores were determined in allpatients.Results: The mean age ± standard deviation (SD was 35.8 ± 17.0 years, 26 (57.8 % were male, and seven patients(15.5% were treatment-experienced by a nucleos(tide analogue before TDF. HBeAg was positive in 17 (37.8% patients.At week 48 among HBeAg positive (HBeAg + patients’ biochemical and virological response rates at month-3, -6 and-12 were 64.7%, and 100%, 70.6%, and 94.1%, and 88.2%, and 64.7%, respectively. The serological response in HBeAg+ patients was 29.4%. For HBeAg negative (HBeAg - patients; biochemical, and virological response rates were 64.3%,and 96.4% at month 3; 82.1%, and 96.4% at month 6; and 100%, and 85.7% at month 12, respectively. At week 48 bothgroups had significant virological response (p<0.001.Conclusion: Treatment in CHB with TDF leads to HBV DNA suppression without evident resistance for 48-week, and iswell tolerated. J Microbiol Infect Dis 2012; 2(3: 87-92Key words: Hepatitis B, chronic, tenofovir disoproxil

Effect of Food on the Steady-State Pharmacokinetics of Tenofovir and Emtricitabine plus Efavirenz in Ugandan Adults

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Mohammed Lamorde

2012-01-01

Full Text Available We investigated the effect of food on the steady-state pharmacokinetics of a proprietary fixed-dose combination (FDC tablet containing tenofovir disoproxil fumarate (TDF/emtricitabine/efavirenz. Fifteen Ugandan HIV-1 patients at steady-state dosing with TDF/emtricitabine/efavirenz were admitted for 24-hour intensive pharmacokinetic sampling after dosing in the fasting state. Blood sampling was repeated seven days later with TDF/emtricitabine/efavirenz administered with food (19 g fat. Drug concentrations in plasma were determined by liquid chromatography and tandem mass spectrometry. Geometric mean ratios (GMRs and confidence intervals (CIs of parameters were calculated (reference, fasting. For efavirenz, GMRs (90% CIs for Cmax, AUC0-24, and C24 were 1.47 (1.24–1.75, 1.13 (1.03–1.23, and 1.01 (0.91–1.11, respectively. Corresponding GMRs were 1.04 (0.84–1.27, 1.19 (1.10–1.29, and 0.99 (0.82–1.19 for tenofovir, 0.83 (0.76–0.92, 0.87 (0.78–0.97, and 0.91 (0.73–1.14 for emtricitabine. Stable patients may take the FDC without meal restrictions. The FDC should be taken without food by patients experiencing central nervous system toxicities.

Biphasic Elimination of Tenofovir Diphosphate and Nonlinear Pharmacokinetics of Zidovudine Triphosphate in a Microdosing Study

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Chen, Jianmeng; Flexner, Charles; Liberman, Rosa G.; Skipper, Paul L.; Louissaint, Nicolette; Tannenbaum, Steven R.; Hendrix, Craig; Fuchs, Edward

2012-01-01

Objective Phase 0 studies can provide initial pharmacokinetics (PK) data in humans and help to facilitate early drug development, but their predictive value for standard dosing is controversial. To evaluate the prediction of microdosing for active intracellular drug metabolites, we compared the PK profile of two antiretroviral drugs, zidovudine (ZDV) and tenofovir (TFV), in microdose and standard dosing regimens. Study Design We administered a microdose (100 μg) of 14C-labeled drug (ZDV or tenofovir disoproxil fumarate (TDF)) with or without a standard unlabelled dose (300 mg) to healthy volunteers. Both the parent drug in plasma and the active metabolite, ZDV-triphosphate (ZDV-TP) or TFV-diphosphate (TFV-DP) in PBMCs and CD4+ cells were measured by AMS. Results The intracellular ZDV-TP concentration increased less than proportionally over the dose range studied (100 μg to 300 mg), while the intracellular TFV-DP PK were linear over the same dose range. ZDV-TP concentrations were lower in CD4+ cells versus total peripheral blood mononuclear cells (PBMCs), while TFV-DP concentrations were not different in CD4+ cells and PBMCs. Conclusion Our data were consistent with a rate-limiting step in the intracellular phosphorylation of ZDV but not TFV. AMS shows promise for predicting the PK of active intracellular metabolites of nucleosides, but nonlinearity of PK may be seen with some drugs. PMID:23187888

New approaches in the management of chronic hepatitis B: role of tenofovir

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Jurriën GP Reijnders

2009-04-01

Full Text Available Jurriën GP Reijnders, Harry LA JanssenDepartment of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, The NetherlandsAbstract: In the field of HIV management, tenofovir disoproxil fumarate (TDF plays a pivotal role and has been demonstrated to be a safe and well-tolerated antiviral agent. Recent data showed the efficacy of TDF in the treatment of chronically hepatitis B virus (HBV-infected patients. TDF was superior to adefovir dipivoxil (ADV in both nucleos(tide-naïve HBeAg-positive and HBeAg-negative HBV patients, and appeared to be one of the most potent antiviral agents so far. In addition, several reports showed that TDF was also effective in the nucleos(tide-experienced population, although conflicting results have been presented concerning patients with genotypic resistance to ADV. TDF seems to have a good resistance profile as well. The rtA194T mutation in association with lamivudine resistance may confer resistance to TDF, although both in vivo and in vitro studies regarding this mutation demonstrate conflicting results. As treatment with TDF may be associated with nephrotoxicity, all TDF-treated patients should be monitored for renal function at baseline and periodically thereafter. While the relative roles of interferon vs nucleos(tide analogues (NA as initial anti-HBV therapy remains unclear, TDF will probably become one of the key factors in HBV management both as first-choice NA for nucleos(tide-naïve patients and as rescue therapy for nucleos(tide-experienced patients.Keywords: hepatitis B, antiviral therapy, tenofovir, HBV

Fixed dose darunavir boosted with cobicistat combined with emtricitabine and tenofovir alafenamide fumarate.

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Cevik, Muge; Orkin, Chloe

2018-07-01

In an era when virological efficacy approaches 100%, novel antiretroviral (ARV) therapies must deliver better tolerability, safety, and convenient coformulated regimens. We review the phase II and III clinical data on the fixed dose combination (FDC) darunavir (DRV) 800mg / cobicistat (COBI/C) 150 mg / emtricitabine (F/FTC) 200 mg / tenofovir alafenamide fumarate (TAF) 10mg (D/C/F/TAF) for the treatment of HIV-1 infection. In an exploratory phase II study, D/C/F/TAF FDC demonstrated similar virological efficacy to darunavir/cobicistat FDC + F /tenofovir disoproxil fumarate (TDF) FDC in treatment-naive HIV-1-infected individuals with favorable bone and renal outcomes. These findings led to two subsequent international phase III double-blind randomized controlled trials; AMBER and EMERALD. In the (treatment naïve) AMBER study, D/C/F/TAF FDC was noninferior to component regimen F/TDF + darunavir/cobicistat with favorable bone and renal outcomes at week 48. In the EMERALD study (switch study for virologically suppressed patients), D/C/F/TAF showed noninferior efficacy to F/TDF and boosted protease inhibitor (bPI) regimen at week 48 also with favorable renal and bone outcomes. No virological failure was observed, and no resistance to TDF or darunavir emerged in either study. In clinical trials, D/C/F/TAF FDC demonstrated excellent, noninferior virological efficacy, maintained a high genetic barrier and conferred the additional safety benefits of TAF. As the first one pill, once daily, protease inhibitor-based regimen, D/C/F/TAF FDC offers a new option for the treatment of HIV infection.

Mucosal effects of tenofovir 1% gel.

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Hladik, Florian; Burgener, Adam; Ballweber, Lamar; Gottardo, Raphael; Vojtech, Lucia; Fourati, Slim; Dai, James Y; Cameron, Mark J; Strobl, Johanna; Hughes, Sean M; Hoesley, Craig; Andrew, Philip; Johnson, Sherri; Piper, Jeanna; Friend, David R; Ball, T Blake; Cranston, Ross D; Mayer, Kenneth H; McElrath, M Juliana; McGowan, Ian

2015-02-03

Tenofovir gel is being evaluated for vaginal and rectal pre-exposure prophylaxis against HIV transmission. Because this is a new prevention strategy, we broadly assessed its effects on the mucosa. In MTN-007, a phase-1, randomized, double-blinded rectal microbicide trial, we used systems genomics/proteomics to determine the effect of tenofovir 1% gel, nonoxynol-9 2% gel, placebo gel or no treatment on rectal biopsies (15 subjects/arm). We also treated primary vaginal epithelial cells from four healthy women with tenofovir in vitro. After seven days of administration, tenofovir 1% gel had broad-ranging effects on the rectal mucosa, which were more pronounced than, but different from, those of the detergent nonoxynol-9. Tenofovir suppressed anti-inflammatory mediators, increased T cell densities, caused mitochondrial dysfunction, altered regulatory pathways of cell differentiation and survival, and stimulated epithelial cell proliferation. The breadth of mucosal changes induced by tenofovir indicates that its safety over longer-term topical use should be carefully monitored.

Uptake of tenofovir-based antiretroviral therapy among HIV-HBV-coinfected patients in the EuroSIDA study

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Peters, Lars; Mocroft, Amanda; Grint, Daniel

2018-01-01

BACKGROUND: According to guidelines all HIV/HBV co-infected patients should receive tenofovir-based combination antiretroviral therapy (cART). We aimed to investigate uptake and outcomes of tenofovir-based cART among HIV/HBV patients in the EuroSIDA study. METHODS: All HBsAg+ patients followed up...

Brief Report: Efficacy and Safety of Switching to Coformulated Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide (E/C/F/TAF) in Virologically Suppressed Women.

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Hodder, Sally; Squires, Kathleen; Kityo, Cissy; Hagins, Debbie; Avihingsanon, Anchalee; Kido, Anna; Jiang, Shuping; Kulkarni, Rima; Cheng, Andrew; Cao, Huyen

2018-06-01

The integrase inhibitor regimen [elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (TDF)] demonstrated superior efficacy when compared with a protease inhibitor regimen [ritonavir-boosted atazanavir (ATV + RTV) and FTC/TDF] in 575 treatment-naive women at week 48. We investigated the efficacy, safety, and tolerability of switching to a TAF-based, single-tablet regimen containing elvitegravir, cobicistat, FTC, and tenofovir alafenamide (E/C/F/TAF) versus remaining on ATV + RTV plus FTC/TDF. After completing the initial randomized, blinded phase, virologically suppressed (HIV-1 RNA TAF versus remaining on their current regimen. The primary end point was proportion of participants with plasma HIV-1 RNA TAF and 53 to remain on ATV + RTV plus FTC/TDF. At week 48, virologic suppression was maintained in 150 (94%) of women on E/C/F/TAF and 46 (87%) on ATV + RTV plus FTC/TDF [difference 7.5% (95% confidence interval -1.2% to 19.4%)], demonstrating noninferiority of E/C/F/TAF to ATV + RTV and FTC/TDF. Incidence of AEs was similar between groups; study drug-related AEs were more common with E/C/F/TAF (11% versus 4%). Switching to E/C/F/TAF was noninferior to continuing ATV + RTV plus FTC/TDF in maintaining virologic suppression and was well tolerated at 48 weeks.

HIV disease progression among women following seroconversion during a tenofovir-based HIV prevention trial.

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Sharon A Riddler

Full Text Available Little is known regarding HIV disease outcomes among individuals who become infected with HIV while receiving antiretroviral medications for prevention. We compared HIV disease parameters among women who seroconverted while receiving tenofovir-containing oral or vaginal pre-exposure prophylaxis (PrEP to placebo.Participants with HIV seroconversion in a randomized placebo-controlled trial of oral tenofovir, oral tenofovir/emtricitabine, and vaginal tenofovir gel (MTN-003 were followed in a longitudinal cohort study (MTN-015. The effect of oral and vaginal tenofovir-containing PrEP on HIV disease progression was compared to placebo using linear mixed effects and Cox proportional hazard models, as appropriate. Additional analyses were performed to compare the outcomes among participants with detectable tenofovir or emtricitabine in plasma at the first quarterly visit in MTN-003.A total of 224 participants were included in the analysis; 93% from South Africa and 94% clade C virus. No differences in HIV RNA at steady state or the trajectory over 12 months were observed for each active arm compared to placebo; tenofovir gel recipients had higher CD4+ T cell counts (722 vs 596 cells/mm3; p = 0.02 at 90 days after estimated HIV seroconversion and higher average rates of change over 12 months compared to placebo (-181 vs -92 cells/mm3 per year; p = 0.08. With a median follow-up of 31 months, no significant differences were observed for time to CD4+ T cell count ≤350 cells/mm3, or the composite endpoint of CD4+ T cells ≤350 cells/mm3, initiation of antiretroviral therapy or death for each active arm compared to placebo. Additionally, there were no significant differences in the HIV RNA or CD4+ T cell counts at baseline, the change to month 12, or any disease progression outcomes among participants with oral drug detected and no oral drug detected compared to placebo.No clinically significant differences in HIV seroconversion outcomes were observed

Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial

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Mulligan, Kathleen; Glidden, David V.; Anderson, Peter L.; Liu, Albert; McMahan, Vanessa; Gonzales, Pedro; Ramirez-Cardich, Maria Esther; Namwongprom, Sirianong; Chodacki, Piotr; de Mendonca, Laura Maria Carvalo; Wang, Furong; Lama, Javier R.; Chariyalertsak, Suwat; Guanira, Juan Vicente; Buchbinder, Susan; Bekker, Linda-Gail; Schechter, Mauro; Veloso, Valdilea G.; Grant, Robert M.; Vargas, Lorena; Sanchez, Jorge; Mai, Chiang; Saokhieo, Pongpun; Murphy, Kerry; Gilmore, Hailey; Holland, Sally; Faber, Elizabeth; Duda, John; Bewerunge, Linda; Batist, Elizabeth; Hoskin, Christine; Brown, Ben; de Janeiro, Rio; Beppu-Yoshida, Carina; da Costa, Marcellus Dias; Assis de Jesus, Sergio Carlos; Grangeiro da Silva, Jose Roberto; Millan, Roberta; de Siqueira Hoagland, Brenda Regina; Martinez Fernandes, Nilo; da Silva Freitas, Lucilene; Grinsztejn, Beatriz; Pilotto, Jose; Bushman, Lane; Zheng, Jia-Hua; Anthony Guida, Louis; Kline, Brandon; Goicochea, Pedro; Manzo, Jonathan; Hance, Robert; McConnell, Jeff; Defechereux, Patricia; Levy, Vivian; Robles, Malu; Postle, Brian; Burns, David; Rooney, James

2015-01-01

Background. Daily preexposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) decreases the risk of human immunodeficiency virus (HIV) acquisition. Initiation of TDF decreases bone mineral density (BMD) in HIV-infected people. We report the effect of FTC/TDF on BMD in HIV-seronegative men who have sex with men and in transgender women. Methods. Dual-energy X-ray absorptiometry was performed at baseline and 24-week intervals in a substudy of iPrEx, a randomized, double-blind, placebo-controlled trial of FTC/TDF PrEP. Plasma and intracellular tenofovir concentrations were measured in participants randomized to FTC/TDF. Results. In 498 participants (247 FTC/TDF, 251 placebo), BMD in those randomized to FTC/TDF decreased modestly but statistically significantly by 24 weeks in the spine (net difference, −0.91% [95% confidence interval {CI}, −1.44% to −.38%]; P = .001) and hip (−0.61% [95% CI, −.96% to −.27%], P = .001). Changes within each subsequent 24-week interval were not statistically significant. Changes in BMD by week 24 correlated inversely with intracellular tenofovir diphosphate (TFV-DP), which was detected in 53% of those randomized to FTC/TDF. Net BMD loss by week 24 in participants with TFV-DP levels indicative of consistent dosing averaged −1.42% ± 29% and −0.85% ± 19% in the spine and hip, respectively (P < .001 vs placebo). Spine BMD tended to rebound following discontinuation of FTC/TDF. There were no differences in fractures (P = .62) or incidence of low BMD. Conclusions. In HIV-uninfected persons, FTC/TDF PrEP was associated with small but statistically significant decreases in BMD by week 24 that inversely correlated with TFV-DP, with more stable BMD thereafter. Clinical Trials Registration. NCT00458393. PMID:25908682

77 FR 15110 - Antiviral Drugs Advisory Committee; Notice of Meeting

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2012-03-14

.../phone line to learn about possible modifications before coming to the meeting. Agenda: The committee.../tenofovir disoproxil fumarate) Tablet, submitted by Gilead Sciences, Inc. The supplemental application...

K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism.

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Atsuko Hachiya

2011-01-01

Full Text Available HIV-1 carrying the "Q151M complex" reverse transcriptase (RT mutations (A62V/V75I/F77L/F116Y/Q151M, or Q151Mc is resistant to many FDA-approved nucleoside RT inhibitors (NRTIs, but has been considered susceptible to tenofovir disoproxil fumarate (TFV-DF or TDF. We have isolated from a TFV-DF-treated HIV patient a Q151Mc-containing clinical isolate with high phenotypic resistance to TFV-DF. Analysis of the genotypic and phenotypic testing over the course of this patient's therapy lead us to hypothesize that TFV-DF resistance emerged upon appearance of the previously unreported K70Q mutation in the Q151Mc background. Virological analysis showed that HIV with only K70Q was not significantly resistant to TFV-DF. However, addition of K70Q to the Q151Mc background significantly enhanced resistance to several approved NRTIs, and also resulted in high-level (10-fold resistance to TFV-DF. Biochemical experiments established that the increased resistance to tenofovir is not the result of enhanced excision, as K70Q/Q151Mc RT exhibited diminished, rather than enhanced ATP-based primer unblocking activity. Pre-steady state kinetic analysis of the recombinant enzymes demonstrated that addition of the K70Q mutation selectively decreases the binding of tenofovir-diphosphate (TFV-DP, resulting in reduced incorporation of TFV into the nascent DNA chain. Molecular dynamics simulations suggest that changes in the hydrogen bonding pattern in the polymerase active site of K70Q/Q151Mc RT may contribute to the observed changes in binding and incorporation of TFV-DP. The novel pattern of TFV-resistance may help adjust therapeutic strategies for NRTI-experienced patients with multi-drug resistant (MDR mutations.

Renal impairment in HIV-infected patients initiating tenofovir-containing antiretroviral therapy regimens in a Primary Healthcare Setting in South Africa.

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Kamkuemah, Monika; Kaplan, Richard; Bekker, Linda-Gail; Little, Francesca; Myer, Landon

2015-04-01

Long-term use of tenofovir disoproxil fumarate is associated with declines in glomerular function and chronic kidney disease in HIV-infected patients. We aimed to assess the prevalence and incidence of renal impairment in a primary care setting in sub-Saharan Africa. We analysed data from 1092 HIV-infected patients initiating tenofovir at a primary care clinic in Cape Town, South Africa. Renal function was assessed for the first 12 months on ART by estimating glomerular filtration rate (eGFR) calculated using the Cockroft-Gault equation categorised into normal, mild, moderate and severe reduction in renal function based on values >90, 60-89, 30-59 and <30 ml/min/1.73 m(2) , respectively. Associations were assessed using logistic regression, and average GFR trajectory over time was modelled using linear mixed-effects models. The cohort consisted of 62% women; median age was 34 years (IQR 29; 41 years). The majority had normal renal function pre-ART (79%), 19% had mildly reduced GFR, and 2% had moderate renal impairment. Older age, more advanced WHO stage and anaemia were independently associated with prevalent renal impairment. On average, estimated glomerular function improved over the first year on tenofovir [1.10 ml/min/1.73 m(2) average increase over 12 months (95% CI: 0.80; 1.40)]. Male gender, anaemia and immunosuppression (WHO Stage III/IV and CD4 cell counts <100 cells/mm(3) ) were associated with lower average eGFR levels over time. Overall, 3% developed eGFR <50 ml/min/1.73 m(2) during this period. Serum creatinine tests conducted before 4 months on ART had low predictive value for predicting change in eGFR after a year on ART. Generally, renal function improved in HIV-infected adults initiating ART in this primary healthcare setting during the first year on ART. While monitoring of renal function is recommended in the first 4 months on ART, renal impairment appears uncommon during the first 12 months of tenofovir-containing ART in primary

Analysis of drug-drug interactions among patients receiving antiretroviral regimens using data from a large open-source prescription database.

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Patel, Nimish; Borg, Peter; Haubrich, Richard; McNicholl, Ian

2018-06-14

Results of a study of contraindicated concomitant medication use among recipients of preferred antiretroviral therapy (ART) regimens are reported. A retrospective study was conducted to evaluate concomitant medication use in a cohort of previously treatment-naive, human immunodeficiency virus (HIV)-infected U.S. patients prescribed preferred ART regimens during the period April 2014-March 2015. Data were obtained from a proprietary longitudinal prescription database; elements retrieved included age, sex, and prescription data. The outcome of interest was the frequency of drug-drug interactions (DDIs) associated with concomitant use of contraindicated medications. Data on 25,919 unique treatment-naive patients who used a preferred ART regimen were collected. Overall, there were 384 instances in which a contraindicated medication was dispensed for concurrent use with a recommended ART regimen. Rates of contraindicated concomitant medication use differed significantly by ART regimen; the highest rate (3.2%) was for darunavir plus ritonavir plus emtricitabine-tenofovir disoproxil fumarate (DRV plus RTV plus FTC/TDF), followed by elvitegravir-cobicistat-emtricitabine-tenofovir disoproxil fumarate (EVG/c/FTC/TDF)(2.8%). The highest frequencies of DDIs were associated with ART regimens that included a pharmacoenhancing agent: DRV plus RTV plus FTC/TDF (3.2%) and EVG/c/FTC/TDF (2.8%). In a large population of treatment-naive HIV-infected patients, ART regimens that contained a pharmacoenhancing agent were involved most frequently in contraindicated medication-related DDIs. All of the DDIs could have been avoided by using therapeutic alternatives within the same class not associated with a DDI. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Fate of the antiretroviral drug tenofovir in agricultural soil

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Al-Rajab, Abdul Jabbar; Sabourin, Lyne; Chapman, Ralph; Lapen, David R.; Topp, Edward, E-mail: ed.topp@agr.gc.ca [Agriculture and Agri-Food Canada, London, ON, N5V 4T3 (Canada)

2010-10-15

Tenofovir (9-(R)-(2-phosphonylmethoxypropyl)-adenine) is an antiretroviral drug widely used for the treatment of human immunodeficiency virus (HIV-1) and Hepatitis B virus (HBV) infections. Tenofovir is extensively and rapidly excreted unchanged in the urine. In the expectation that tenofovir could potentially reach agricultural lands through the application of municipal biosolids or wastewater, and in the absence of any environmental fate data, we evaluated its persistence in selected agricultural soils. Less than 10% of [adenine-8-{sup 14}C]-tenofovir added to soils varying widely in texture (sand, loam, clay loam) was mineralized in a 2-month incubation under laboratory conditions. Tenofovir was less readily extractable from clay soils than from a loam or a sandy loam soil. Radioactive residues of tenofovir were removed from the soil extractable fraction with DT{sub 50}s ranging from 24 {+-} 2 to 67 + 22 days (first order kinetic model) or 44 + 9 to 127 + 55 days (zero order model). No extractable transformation products were detectable by HPLC. Tenofovir mineralization in the loam soil increased with temperature (range 4 {sup o}C to 30 {sup o}C), and did not occur in autoclaved soil, suggesting a microbial basis. Mineralization rates increased with soil moisture content, ranging from air-dried to saturated. In summary, tenofovir was relatively persistent in soils, there were no extractable transformation products detected, and the response of [adenine-8-{sup 14}C]-tenofovir mineralization to soil temperature and heat sterilization indicated that the molecule was biodegraded by aerobic microorganisms. Sorption isotherms with dewatered biosolids suggested that tenofovir residues could potentially partition into the particulate fraction during sewage treatment.

Fanconi syndrome and chronic renal failure in a chronic hepatitis B monoinfected patient treated with tenofovir

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Pedro Magalhães-Costa

Full Text Available Tenofovir disoproxil fumarate (TDF is one of the first-line treatment options in chronic hepatitis B (CHB. Despite its efficacy in suppressing viral load and a high resistance barrier, long life maintenance therapy is required. Registration studies demonstrated TDF to be a safe drug. However, post-marketing experience reported cases of serious nephrotoxicity associated with hypophosphatemia, osteomalacia and, even more recently, Fanconi syndrome associated with TDF therapy in CHB monoinfected patients. Here the authors report a case of a 40 year-old male, with a CHB monoinfection, that, three years after TDF therapy, developed a progressive chronic kidney disease with a serious hypophosphatemia and a secondary osteomalacia that was manifested by bone pain and multiple bone fractures. Further investigational analyses unveiled a proximal renal tubular dysfunction, which fulfilled most of the diagnostic criteria for a Fanconi syndrome. After TDF withdrawal and oral supplementation with phosphate and calcitriol, his renal function stabilized (despite not returning to normal, proximal renal tubular dysfunction abnormalities resolved as well as osteomalacia. In conclusion, physicians should be aware that, in CHB monoinfected patients under TDF therapy, serious renal damage is possible and preventable by timely monitoring serum creatinine and phosphate.

Nonalbumin proteinuria predominates in biopsy-proven tenofovir nephrotoxicity.

Science.gov (United States)

Sise, Meghan E; Hirsch, Jamie S; Canetta, Pietro A; Herlitz, Leal; Mohan, Sumit

2015-05-15

Tenofovir disoproxil fumarate (TDF) nephrotoxicity is characterized by proximal renal tubular injury and dysmorphic mitochondria resulting in proteinuria, orthoglycemic glycosuria, and other markers of proximal tubular dysfunction. The objective of this study was to determine the pattern of proteinuria in patients with biopsy-proven TDF nephrotoxicity. Retrospective chart review. Patients with biopsy-proven TDF nephrotoxicity were identified and their medical charts and biopsy reports were reviewed. Comparison was made with HIV-infected patients not on TDF who underwent kidney biopsy. We identified 43 biopsy-proven cases of TDF nephrotoxicity; mean age 54.7 ± 0.4 years, 53% men, 42% whites. Thirty-seven cases reported proteinuria by dipstick of which only 60% had at least 2+ proteinuria. Twenty-seven patients had urine protein quantified by either 24-h collection or spot urine protein-to-creatinine ratio; median proteinuria was 1742 mg/day [interquartile range (IQR) 1200-2000 mg] and 1667 mg/g creatinine (IQR 851-1967 mg/g), respectively. Ten patients had concurrent urinary albumin measured, with a median 236 mg/g creatinine (IQR 137-343 mg/g). The mean urine albumin-to-urine protein ratio (uAPR) was 0.17 (IQR 0.14-0.19), confirming that TDF nephrotoxicity is primarily associated with nonalbumin proteinuria. Control cases had a uAPR of 0.65 (IQR 0.55-0.79) P < 0.001. Histopathology showed the predominance of proximal tubular injury with characteristic mitochondrial abnormalities. In the largest published cohort of patients with biopsy-proven TDF nephrotoxicity, we show that low uAPR is a reliable feature of this disease. Because of the predominance of nonalbumin proteinuria, dipstick urinalysis may be unreliable in TDF nephrotoxicity.

Development of High Performance Thin Layer Chromatography for ...

African Journals Online (AJOL)

are likely to be found on the market, especially in developing countries. ... was a deuterium lamp emitting a continuous UV spectrum in the range 200– ... disoproxil fumarate. Table 1. Summary of response function of lamivudine and tenofovir ...

Chronic Kidney Disease and Antiretroviral Therapy in HIV-Positive Individuals

DEFF Research Database (Denmark)

Achhra, Amit C; Nugent, Melinda; Mocroft, Amanda

2016-01-01

Chronic kidney disease (CKD) has emerged as an important health concern in HIV-positive individuals. Preventing long-term kidney toxicity from an antiretroviral therapy is therefore critical. Selected antiretroviral agents, especially tenofovir disoproxil fumarate (TDF) and some ritonavir-boosted...

Tenofovir-related nephrotoxicity: case report and review of the literature.

Science.gov (United States)

James, Christopher W; Steinhaus, Mary C; Szabo, Susan; Dressier, Robert M

2004-03-01

Tenofovir is a nucleotide reverse transcriptase inhibitor for treatment of human immunodeficiency virus (HIV) infection. Several cases of renal failure associated with tenofovir therapy recently have been reported. A 54-year-old man with HIV experienced decreasing renal function and Fanconi's syndrome secondary to tenofovir therapy. His condition gradually improved after discontinuation of the drug. The available medical literature for reported cases of tenofovir-related nephrotoxicity indicates that this complication is apparently rare. However, our case report and literature review underscore the importance of monitoring renal function when treating patients with any nucleotide reverse transcriptase inhibitor.

A qualitative study of provider thoughts on implementing pre-exposure prophylaxis (PrEP) in clinical settings to prevent HIV infection

OpenAIRE

Morin, Stephen; Arnold, EA; Hazelton, P; Lane, T; Christopoulos, KA; Galindo, GR; Steward, WT; Morin, SF

2012-01-01

Background: A recent clinical trial demonstrated that a daily dose tenofovir disoproxil fumarate and emtricitabrine (TDF-FTC) can reduce HIV acquisition among men who have sex with men (MSM) and transgender (TG) women by 44%, and up to 90% if taken daily.

Pharmacokinetics of Tenofovir Alafenamide When Co-administered With Other HIV Antiretrovirals.

Science.gov (United States)

Begley, Rebecca; Das, Moupali; Zhong, Lijie; Ling, John; Kearney, Brian P; Custodio, Joseph M

2018-04-10

Tenofovir alafenamide (TAF), a prodrug of the nucleotide analogue tenofovir (TFV), is an antiretroviral (ARV) agent approved either as a complete regimen (elvitegravir/cobicistat/emtricitabine (F)/tenofovir alafenamide (TAF), rilpivirine/F/TAF, bictegravir/F/TAF), or for use with other ARVs (F/TAF), for treatment of HIV. TAF is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters. Disposition of TAF may be altered by co-medications that can inhibit or induce P-gp or BCRP transporters. The effects of ARVs on the pharmacokinetics (PK) of TAF were evaluated in 3 studies. Healthy participants received TAF administered alone or with rilpivirine (RPV) in study 1; with dolutegravir (DTG), ritonavir boosted atazanavir (ATV+RTV), lopinavir (LPV/RTV), or darunavir (DRV+RTV) in study 2; and with the pharmacokinetic enhancer cobicistat (COBI), or efavirenz (EFV) in study 3. Across the three studies, 98 participants received treatment with TAF and a coadministered agent (n=10-34/cohort). All study treatments were well tolerated. TAF and TFV exposures were unaffected following co-administration with RPV and DTG. Co-administration with Pgp/BCRP inhibitors such as COBI or PI based regimens (ATV+RTV, LPV/r or DRV+RTV) resulted in a range of 6% to 183% increases in TAF and 105% to 316% increases in TFV exposure, while co-administration with a Pgp inducer, EFV, resulted in a 15% to 24% decrease in TAF and TFV exposure. Evaluation of the drug interaction between TAF and other commonly prescribed boosted and unboosted ARVs provides characterization of the susceptibility of TAF and/or TFV PK to inhibitors or inducers of Pgp/BCRP transporters.

Drug kinetics release from Eudragit – Tenofovir@SiOC tablets

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Tamayo, A., E-mail: aitanath@icv.csic.es [Ceramics and Glass Institute, CSIC, Madrid (Spain); Mazo, M.A. [Ceramics and Glass Institute, CSIC, Madrid (Spain); Veiga, M.D.; Ruiz-Caro, R.; Notario-Pérez, F. [Dpt. Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Madrid (Spain); Rubio, J. [Ceramics and Glass Institute, CSIC, Madrid (Spain)

2017-06-01

A novel drug release system has been obtained in form of tablets from Eudragit® RS and tenofovir loaded on porous silicon oxycarbide glasses (SiOC). Active carbon (AC) and mesoporous silica (MCM-41) have also been used for comparative purposes. The porous silicon oxycarbide presents a bimodal mesopore size distribution that is maintained after functionalization with amino groups. We have studied the adsorption kinetics and adsorption equilibrium when the materials are loaded with tenofovir and, in all cases, pseudo-second order kinetics and Langmuir isotherm have been revealed as the most representative models describing the kinetic and thermodynamic parameters. Besides, the tenofovir adsorption on these materials turns out to be a favorable process. In vitro release of tenofovir has been studied in simulated vaginal medium by applying different release models. Continuous tenofovir release for > 20 days has been obtained for the SiOC material functionalized with amine groups. We concluded that the drug release occurs in two steps that involve a drug diffusion step through the material pores and diffusion through the swollen polymer. The interactions between the tenofovir drug and de amine groups of the functionalized silicon oxycarbide also play an important role in the release process. - Highlights: • Kinetic and thermodinamic parameters of the adsorption of tenofovir on porous substrates have been obtained. • Sustained release of TFV for > 20 days in SVF when it is supported on SiOC and manufactured as Eudragit®RS-containing tablets. • Release described by a two-step process involving diffusion through SiOC matrix and subsequent diffusion through the polymer.

Model Linking Plasma and Intracellular Tenofovir/Emtricitabine with Deoxynucleoside Triphosphates.

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Xinhui Chen

Full Text Available The coformulation of the nucleos(tide analogs (NA tenofovir (TFV disoproxil fumarate (TDF and emtricitabine (FTC is approved for HIV-infection treatment and prevention. Plasma TFV and FTC undergo complicated hybrid processes to form, accumulate, and retain as their active intracellular anabolites: TFV-diphosphate (TFV-DP and FTC-triphosphate (FTC-TP. Such complexities manifest in nonlinear intracellular pharmacokinetics (PK. In target cells, TFV-DP/FTC-TP compete with endogenous deoxynucleoside triphosphates (dNTP at the active site of HIV reverse transcriptase, underscoring the importance of analog:dNTP ratios for antiviral efficacy. However, NA such as TFV and FTC have the potential to disturb the dNTP pool, which could augment or reduce their efficacies. We conducted a pharmacokinetics-pharmacodynamics (PKPD study among forty subjects receiving daily TDF/FTC (300 mg/200 mg from the first-dose to pharmacological intracellular steady-state (30 days. TFV/FTC in plasma, TFV-DP/FTC-TP and dNTPs in peripheral blood mononuclear cells (PBMC were quantified using validated LC/MS/MS methodologies. Concentration-time data were analyzed using nonlinear mixed effects modeling (NONMEM. Formations and the accumulation of intracellular TFV-DP/FTC-TP was driven by plasma TFV/FTC, which was described by a hybrid of first-order formation and saturation. An indirect response link model described the interplay between TFV-DP/FTC-TP and the dNTP pool change. The EC50 (interindividual variability, (%CV of TFV-DP and FTC-TP on the inhibition of deoxyadenosine triphosphate (dATP and deoxycytidine triphosphate (dCTP production were 1020 fmol/106 cells (130% and 44.4 pmol/106 cells (82.5%, resulting in (90% prediction interval 11% (0.45%, 53% and 14% (2.6%, 35% reductions. Model simulations of analog:dNTP molar ratios using IPERGAY dosing suggested that FTC significantly contributes to the protective effect of preexposure prophylaxis (PrEP. Simulation

Tenofovir alafenamide (TAF) does not deplete mitochondrial DNA in human T-cell lines at intracellular concentrations exceeding clinically relevant drug exposures.

Science.gov (United States)

Stray, Kirsten M; Park, Yeojin; Babusis, Darius; Callebaut, Christian; Cihlar, Tomas; Ray, Adrian S; Perron, Michel

2017-04-01

HIV-infected patients treated with certain nucleoside reverse transcriptase inhibitors (NRTIs) have experienced adverse effects due to drug-related mitochondrial toxicity. Tenofovir alafenamide (TAF) is a novel prodrug of the NRTI tenofovir (TFV) with an improved safety profile compared to tenofovir disoproxil fumarate (TDF). Prior in vitro studies have demonstrated that the parent nucleotide TFV has no significant effects on mtDNA synthesis. This study investigated whether clinically relevant TAF and TDF exposures affect mtDNA content in human lymphocytes. First, activated or resting peripheral blood mononuclear cells (PBMCs), as well as MT-2 and Jurkat T-cell lines, were continuously treated with ddC for 10 days to establish their susceptibility to mtDNA depletion. PBMCs had low sensitivity to NRTI-mediated mtDNA depletion in vitro. In contrast, ddC treatment of rapidly dividing MT-2 and Jurkat cells resulted in a dose-dependent decrease in mtDNA. Therefore, these two T-cell lines were selected for evaluating TAF and TDF treatment effects. MT-2 and Jurkat cells were pulse-treated with TAF or TDF every 24 h for 10 days to mimic pharmacologically relevant drug exposures. Pulse treatment of cells with 3.3 μM TAF or 1.1 μM TDF for 10 days resulted in 2- to 7-fold greater steady-state intracellular TFV-diphosphate (TFV-DP) levels than those observed clinically in TAF- or TDF-treated patients. At these concentrations, no significant TAF- (106.7% and 84.1% of control; p = 0.77 and 0.12 for MT-2 and Jurkat, respectively) or TDF- (100.6% and 91.0% of control; p = 0.91 and 0.37, respectively) associated reduction in mtDNA content was observed compared with untreated control cells. This study demonstrates that, despite delivering higher intracellular levels of TFV-DP than TDF, TAF does not inhibit mtDNA synthesis in vitro at concentrations exceeding the clinically relevant intracellular drug exposures. Thus, TAF has a low potential for mitochondrial toxicity in

MARCH HIV ISSUE 1-16

African Journals Online (AJOL)

impo

2005-03-01

Mar 1, 2005 ... therapeutic options. Members of this class under development include both new molecules and new formulations of existing approved drugs. Tenofovir disoproxil ... of these adenosine derivatives may be antagonistic in vivo. Co- ..... for future research and being involved in report findings. The positions are ...

Renal outcomes in patients initiated on tenofovir disoproxil fumarate-based antiretroviral therapy at a community health centre in Malawi.

Science.gov (United States)

Chikwapulo, Bongani; Ngwira, Bagrey; Sagno, Jean Baptiste; Evans, Rhys

2018-01-01

Tenofovir-based antiretroviral therapy (TDF ART) is the first-line regimen for human immunodeficiency virus (HIV) in Africa. However, contemporary data on nephrotoxicity are lacking. We determined the renal outcomes of patients commenced on TDF ART in Malawi. ART-naïve patients initiated on TDF ART at a community health centre between 1 July 2013 and 31 December 2015 were included. The estimated glomerular filtration rate (eGFR, Cockcroft-Gault) was recorded at the initiation of therapy and over 18 months thereafter. The prevalence of renal impairment at ART initiation (eGFR age: 32 years; 317 [72.2%] female) were included. Twenty-one (4.8%) patients had renal impairment at ART initiation; eGFR improved in all during follow-up. Nephrotoxicity occurred in 17 (4.0%) patients with eGFR > 50 ml/min at baseline, predominantly within the first six months of therapy. Increasing age and diastolic hypertension (>100 mmHg) were independent risk factors for nephrotoxicity development. The prevalence of kidney disease at ART initiation was 4.8% and nephrotoxicity occurred in 4.0%. Some eGFR decline may have been due to weight gain. Targeted monitoring of kidney function six months after TDF initiation should be considered in Malawi.

The risks of concurrent treatment with tenofovir and aminoglycosides ...

African Journals Online (AJOL)

The risks of concurrent treatment with tenofovir and aminoglycosides in patients with HIV-associated tuberculosis. C Kenyon, N Wearne, R Burton, G Meintjes. Abstract. The South African public sector antiretroviral treatment (ART) guidelines have recently been changed to include tenofovir in the first-line regimen.1 ...

Acute Liver Toxicity due to Efavirenz/Emtricitabine/Tenofovir

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Rashmee Patil

2015-01-01

Full Text Available The fixed-dose combination of Efavirenz/Emtricitabine/Tenofovir is a first-line agent for the treatment of HIV; however few cases have reported hepatotoxicity associated with the drug. We report a case of Efavirenz/Emtricitabine/Tenofovir-associated hepatotoxicity presenting mainly with hepatocellular injury characterized by extremely elevated aminotransferase levels, which resolved without acute liver failure or need for liver transplant referral.

Tenofovir treatment in an unselected cohort of highly antiretroviral experienced HIV positive patients

DEFF Research Database (Denmark)

Lerbaek, Anne; Kristiansen, Thomas B; Katzenstein, Terese L

2004-01-01

The aim of the present study was to explore the treatment effect of tenofovir as implemented in clinical practice. Data are presented on 34 patients. 11 patients had tenofovir added to a stable anti-retroviral treatment (ART) and 23 patients had drugs other than tenofovir. CD4 counts, HIV......-RNA levels and genotypic resistance were determined at baseline and after 3 and 6 months. After initiation of tenofovir treatment, a mean decrease in HIV-RNA for all 34 patients was observed (-0.43 log1o copies/ml (+/- 1.22) and -0.49 log10 copies/ml (+/- 1.36) after 3 and 6 months, respectively, (p = 0...... initiation of tenofovir treatment, no significant increases in CD4 count were observed. All new NRTI-associated mutations could be explained by the background treatment. In conclusion, we observed a significant decrease in HIV-RNA only when tenofovir was prescribed, in conjunction with other anti...

The Safety of Tenofovir-Emtricitabine for HIV Pre-Exposure Prophylaxis (PrEP) in Individuals With Active Hepatitis B.

Science.gov (United States)

Solomon, Marc M; Schechter, Mauro; Liu, Albert Y; McMahan, Vanessa M; Guanira, Juan V; Hance, Robert J; Chariyalertsak, Suwat; Mayer, Kenneth H; Grant, Robert M

2016-03-01

Pre-exposure prophylaxis (PrEP) with daily oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) prevents HIV infection. The safety and feasibility of HIV PrEP in the setting of hepatitis B virus (HBV) infection were evaluated. The Iniciativa Profilaxis Pre-Exposición study randomized 2499 HIV-negative men and transgender women who have sex with men to once-daily oral FTC/TDF versus placebo. Hepatitis serologies and transaminases were obtained at screening and at the time PrEP was discontinued. HBV DNA was assessed by polymerase chain reaction, and drug resistance was assessed by population sequencing. Vaccination was offered to individuals susceptible to HBV infection. Of the 2499 participants, 12 (0.5%; including 6 randomized to FTC/TDF) had chronic HBV infection. After stopping FTC/TDF, 5 of the 6 participants in the active arm had liver function tests performed at follow-up. Liver function tests remained within normal limits at post-stop visits except for a grade 1 elevation in 1 participant at post-stop week 12 (alanine aminotransferase = 90, aspartate aminotransferase = 61). There was no evidence of hepatic flares. Polymerase chain reaction of stored samples showed that 2 participants in the active arm had evidence of acute HBV infection at enrollment. Both had evidence of grade 4 transaminase elevations with subsequent resolution. Overall, there was no evidence of TDF or FTC resistance among tested genotypes. Of 1633 eligible for vaccination, 1587 (97.2%) received at least 1 vaccine; 1383 (84.7%) completed the series. PrEP can be safely provided to individuals with HBV infection if there is no evidence of cirrhosis or substantial transaminase elevation. HBV vaccination rates at screening were low globally, despite recommendations for its use, yet uptake and efficacy were high when offered.

Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel.

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Martin Cranage

2008-08-01

Full Text Available The rectum is particularly vulnerable to HIV transmission having only a single protective layer of columnar epithelium overlying tissue rich in activated lymphoid cells; thus, unprotected anal intercourse in both women and men carries a higher risk of infection than other sexual routes. In the absence of effective prophylactic vaccines, increasing attention is being given to the use of microbicides and preventative antiretroviral (ARV drugs. To prevent mucosal transmission of HIV, a microbicide/ARV should ideally act locally at and near the virus portal of entry. As part of an integrated rectal microbicide development programme, we have evaluated rectal application of the nucleotide reverse transcriptase (RT inhibitor tenofovir (PMPA, 9-[(R-2-(phosphonomethoxy propyl] adenine monohydrate, a drug licensed for therapeutic use, for protective efficacy against rectal challenge with simian immunodeficiency virus (SIV in a well-established and standardised macaque model.A total of 20 purpose-bred Indian rhesus macaques were used to evaluate the protective efficacy of topical tenofovir. Nine animals received 1% tenofovir gel per rectum up to 2 h prior to virus challenge, four macaques received placebo gel, and four macaques remained untreated. In addition, three macaques were given tenofovir gel 2 h after virus challenge. Following intrarectal instillation of 20 median rectal infectious doses (MID50 of a noncloned, virulent stock of SIVmac251/32H, all animals were analysed for virus infection, by virus isolation from peripheral blood mononuclear cells (PBMC, quantitative proviral DNA load in PBMC, plasma viral RNA (vRNA load by sensitive quantitative competitive (qc RT-PCR, and presence of SIV-specific serum antibodies by ELISA. We report here a significant protective effect (p = 0.003; Fisher exact probability test wherein eight of nine macaques given tenofovir per rectum up to 2 h prior to virus challenge were protected from infection (n = 6 or had

Bone scintigraphy and tenofovir-induced osteomalacia in chronic hepatitis B

International Nuclear Information System (INIS)

Hoe, Alex khoo cheen; Feng, Lee Yeong

2017-01-01

Tenofovir, used in the treatment of chronic hepatitis B and HIV, is known for its side effects on the kidneys and bones. We share interesting images of a patient with tenofovir-induced osteomalacia on Technetium-99 m hydroxymethyelene (Tc-99 m HDP) bone scintigraphy. Pattern recognition of this bone scintigraphy and correlation with the clinical history is essential to avoid misdiagnosis

Bone scintigraphy and tenofovir-induced osteomalacia in chronic hepatitis B

Energy Technology Data Exchange (ETDEWEB)

Hoe, Alex khoo cheen; Feng, Lee Yeong [Dept. of Nuclear Medicine, Penang Hospital, Georgetown (Malaysia)

2017-06-15

Tenofovir, used in the treatment of chronic hepatitis B and HIV, is known for its side effects on the kidneys and bones. We share interesting images of a patient with tenofovir-induced osteomalacia on Technetium-99 m hydroxymethyelene (Tc-99 m HDP) bone scintigraphy. Pattern recognition of this bone scintigraphy and correlation with the clinical history is essential to avoid misdiagnosis.

In vitro and ex vivo testing of tenofovir shows it is effective as an HIV-1 microbicide.

Directory of Open Access Journals (Sweden)

Lisa C Rohan

2010-02-01

Full Text Available Tenofovir gel has entered into clinical trials for use as a topical microbicide to prevent HIV-1 infection but has no published data regarding pre-clinical testing using in vitro and ex vivo models. To validate our findings with on-going clinical trial results, we evaluated topical tenofovir gel for safety and efficacy. We also modeled systemic application of tenofovir for efficacy.Formulation assessment of tenofovir gel included osmolality, viscosity, in vitro release, and permeability testing. Safety was evaluated by measuring the effect on the viability of vaginal flora, PBMCs, epithelial cells, and ectocervical and colorectal explant tissues. For efficacy testing, PBMCs were cultured with tenofovir or vehicle control gels and HIV-1 representing subtypes A, B, and C. Additionally, polarized ectocervical and colorectal explant cultures were treated apically with either gel. Tenofovir was added basolaterally to simulate systemic application. All tissues were challenged with HIV-1 applied apically. Infection was assessed by measuring p24 by ELISA on collected supernatants and immunohistochemistry for ectocervical explants. Formulation testing showed the tenofovir and vehicle control gels were >10 times isosmolar. Permeability through ectocervical tissue was variable but in all cases the receptor compartment drug concentration reached levels that inhibit HIV-1 infection in vitro. The gels were non-toxic toward vaginal flora, PBMCs, or epithelial cells. A transient reduction in epithelial monolayer integrity and epithelial fracture for ectocervical and colorectal explants was noted and likely due to the hyperosmolar nature of the formulation. Tenofovir gel prevented HIV-1 infection of PBMCs regardless of HIV-1 subtype. Topical and systemic tenofovir were effective at preventing HIV-1 infection of explant cultures.These studies provide a mechanism for pre-clinical prediction of safety and efficacy of formulated microbicides. Tenofovir was effective

Patents and profits: A disparity of manufacturing margins in the tenofovir value chain.

Science.gov (United States)

Walwyn, David

2013-03-01

Registered in 2001, tenofovir disoproxil fumarate (TDF) has quickly become a mainstay of first line regimens for the treatment of HIV. Initially only available in developed countries at a cost of US$5 000 per person per year (ppy), Gilead's Access Programme (GAP) has extended the use of the product to 2.4 million patients in low and middle income countries. The programme has two components: distribution of the branded product at reduced prices and licensing partnerships with generic manufacturers. The licensing partnerships now supply 75% of the market by volume, at a treatment cost of US$57 ppy (1% of the branded cost). From Gilead's perspective, GAP must be considered a huge success. It has enabled the company to maintain high prices in developed countries whilst reducing its input costs and deflecting criticism of its failure to provide essential medicines for the poor, hence risking the possibility of compulsory licensing. Over the period 2001 to 2011, TDF in its various forms has generated for Gilead more than US$31 billion revenue at a gross margin of 80%, equivalent to a gross profit of US$25 billion. Analysis of the TDF value chain, from preparation of the active pharmaceutical ingredient (API) to sale of the formulated product, shows that manufacturing margins are highly skewed in favour of the originator, with the latter's profit being US$3.2 billion vs. US$4 million for API manufacturers and US$39 million for formulators (2011). The data argues for a more rational approach to drug pricing including possible regulation in developed countries and more sustainable margins for the generic producers.

Hypophosphatemic osteomalacia associated with tenofovir: a multidisciplinary approach is required.

Directory of Open Access Journals (Sweden)

Giuseppe Vittorio De Socio

2012-05-01

Full Text Available Tenofovir is widely used as first-line treatment of HIV infection, although its use is sometimes complicated by a reversible proximal renal tubulopathy. We report the case of a 45-year-old woman with chronic HIV infection and personality disorder, who after 12 months of tenofovir, complained of fatigue, diffuse bone pain and gait disturbances. The elevated level of alkaline phosphatase, hypophosphatemia and inappropriate phosphaturia suggested the diagnosis of hypophosphatemic osteomalacia secondary to proximal renal tubulopathy. A dual-energy x-ray absorptiometry showed a bone mineral density below the expected range for age (lumbar spine Z-score -3.3, femoral neck Z-score -2.1. A whole body 99mTc-methylene diphosphonate bone scan showed multiple areas of increased focal activity in the lumbar and thoracic spine and in sacroiliac and hip joints consistent with pseudo-fractures. Two months after tenofovir discontinuation and administration of vitamin D and phosphate, osteomalacia-related symptoms disappeared. Eleven months later, bone and mineral metabolism data were normal and bone scintigraphy did not show any pathological findings. This report highlights the importance of considering the diagnosis of osteomalacia in patients treated with tenofovir and emphasizes the need for monitoring alkaline phosphatase, blood and urinary phosphate and creatinine, especially in patients with risk factors for bone disease.

Tenofovir treatment in an unselected cohort of highly antiretroviral experienced HIV positive patients

DEFF Research Database (Denmark)

Lerbaek, A; Kristiansen, Thomas Birk; Katzenstein, TL

2004-01-01

Tenofovir treatment in an unselected cohort of highly antiretroviral experienced HIV positive patients.Lerbaek A, Kristiansen TB, Katzenstein TL, Mathiesen L, Gerstoft J, Nielsen C, Larsen K, Nielsen JO, Obel N, Laursen AL, Nielsen SD. Department of Infectious Diseases, Hvidovre Hospital......, HIV-RNA levels and genotypic resistance were determined at baseline and after 3 and 6 months. After initiation of tenofovir treatment, a mean decrease in HIV-RNA for all 34 patients was observed (-0.43 log1o copies/ml (+/- 1.22) and -0.49 log10 copies/ml (+/- 1.36) after 3 and 6 months, respectively......, respectively). After initiation of tenofovir treatment, no significant increases in CD4 count were observed. All new NRTI-associated mutations could be explained by the background treatment. In conclusion, we observed a significant decrease in HIV-RNA only when tenofovir was prescribed, in conjunction...

Segmented polyurethane intravaginal rings for the sustained combined delivery of antiretroviral agents dapivirine and tenofovir.

Science.gov (United States)

Johnson, Todd J; Gupta, Kavita M; Fabian, Judit; Albright, Theodore H; Kiser, Patrick F

2010-02-19

Dual segment polyurethane intravaginal rings (IVRs) were fabricated to enable sustained release of antiretroviral agents dapivirine and tenofovir to prevent the male to female sexual transmission of the human immunodeficiency virus. Due to the contrasting hydrophilicity of the two drugs, dapivirine and tenofovir were separately formulated into polymers with matching hydrophilicity via solvent casting and hot melt extrusion. The resultant drug loaded rods were then joined together to form dual segment IVRs. Compression testing of the IVRs revealed that they are mechanically comparable to the widely accepted NuvaRing IVR. Physical characterization of the individual IVR segments using wide angle X-ray scattering and differential scanning calorimetry determined that dapivirine and tenofovir are amorphous and crystalline within their polymeric segments, respectively. In vitro release of tenofovir from the dual segment IVR was sustained over 30 days while dapivirine exhibited linear release over the time period. A 90 day accelerated stability study confirmed that dapivirine and tenofovir are stable in the IVR formulation. Altogether, these results suggest that multisegment polyurethane IVRs are an attractive formulation for the sustained vaginal delivery of drugs with contrasting hydrophilicity such as dapivirine and tenofovir. 2009 Elsevier B.V. All rights reserved.

Daily oral emtricitabine/tenofovir preexposure prophylaxis and herpes simplex virus type 2 among men who have sex with men.

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Julia L Marcus

Full Text Available In addition to protecting against HIV acquisition, antiretroviral preexposure prophylaxis (PrEP using topical 1% tenofovir gel reduced Herpes simplex virus type 2 (HSV-2 acquisition by 51% among women in the CAPRISA 004 study. We examined the effect of daily oral emtricitabine/tenofovir (FTC/TDF PrEP on HSV-2 seroincidence and ulcer occurrence among men who have sex with men (MSM in the iPrEx trial.HSV-2 serum testing was performed at screening and every six months. Among HSV-2-seronegative individuals, we used Cox regression models to estimate hazard ratios (HRs of HSV-2 seroincidence associated with randomization to FTC/TDF. We used multiple imputation and Cox regression to estimate HRs for HSV-2 seroincidence accounting for drug exposure. We assessed ulcer occurrence among participants with prevalent or incident HSV-2 infection.Of the 2,499 participants, 1383 (55.3% tested HSV-2-seronegative at baseline, 892 (35.7% tested positive, 223 (8.9% had indeterminate tests, and one test was not done. Of the 1,347 HSV-2-seronegative participants with follow-up, 125 (9.3% had incident HSV-2 infection (5.9 per 100 person-years. Compared with participants receiving placebo, there was no difference in HSV-2 seroincidence among participants receiving FTC/TDF (HR 1.1, 95% CI: 0.8-1.5; P = 0.64 or among participants receiving FTC/TDF with a concentration of tenofovir diphosphate >16 per million viable cells (HR 1.0, 95% CI: 0.3-3.5; P = 0.95. Among participants with HSV-2 infection, the proportion with ≥1 moderate or severe ulcer adverse event was twice as high in the placebo vs. active arm (5.9% vs. 2.9%, P = 0.02, but there were no differences in the proportions with ≥1 clinical examination during which perianal or groin ulcers were identified.Tenofovir in daily oral FTC/TDF PrEP may reduce the occurrence of ulcers in individuals with HSV-2 infection but does not protect against HSV-2 incidence among MSM.

Strong relationship between oral dose and tenofovir hair levels in a randomized trial: hair as a potential adherence measure for pre-exposure prophylaxis (PrEP.

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Albert Y Liu

Full Text Available Pre-exposure prophylaxis (PrEP trials using tenofovir-based regimens have demonstrated that high levels of adherence are required to evaluate efficacy; the incorporation of objective biomarkers of adherence in trial design has been essential to interpretation, given the inaccuracy of self-report. Antiretroviral measurements in scalp hair have been useful as a marker of long-term exposure in the HIV treatment setting, and hair samples are relatively easy and inexpensive to collect, transport, and store for analysis. To evaluate the relationship between dose and tenofovir concentrations in hair, we examined the dose proportionality of tenofovir in hair in healthy, HIV-uninfected adults.A phase I, crossover pharmacokinetic study was performed in 24 HIV-negative adults receiving directly-observed oral tenofovir tablets administered 2, 4, and 7 doses/week for 6 weeks, with a ≥3-week break between periods. Small samples of hair were collected after each six-week period and analyzed for tenofovir concentrations. Geometric-mean-ratios compared levels between each pair of dosing conditions. Intensive plasma pharmacokinetic studies were performed during the daily-dosing period to calculate areas-under-the-time-concentration curves (AUCs.Over 90% of doses were observed per protocol. Median tenofovir concentrations in hair increased monotonically with dose. A log-linear relationship was seen between dose and hair levels, with an estimated 76% (95% CI 60-93% increase in hair level per 2-fold dose increase. Tenofovir plasma AUCs modestly predicted drug concentrations in hair.This study found a strong linear relationship between frequency of dosing and tenofovir levels in scalp hair. The analysis of quantitative drug levels in hair has the potential to improve adherence measurement in the PrEP field and may be helpful in determining exposure thresholds for protection and explaining failures in PrEP trials. Hair measures for adherence monitoring may also

Efficacy and safety on tenofovire therapy in patients with hepatitis B viral infections resistent to lamivudin

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Katanić N.

2015-01-01

Full Text Available Chronic viral hepatitis B (CHB still represents a significant world health problem despite obligatory and worldwide immunization against infections of viral hepatitis B. In some patients with chronic viral hepatitis B infections, in the natural course of the disease, progression towards cirhossis and hepatocellular carcinoma is primarily targeted by antiviral CHB therapy stopping further progression of the disease. Today on the market there exist two classes of pharmnaceutical drugs for treatment of CHB: a immunomodulatory therapy with conventional interferon alpha (INF and PEGylated interferon alpha-2a, b and oral antiviral therapy with nucleos( tide analogues. Lamivudine was for quite a period the only medicament available on our market for the treatment of HVB and in most of our patients led to the development of resistance. As of two years ago, a new oral analogue from the group of nucleotides is being registered in Serbia for market use: tenofovir disoproxil (TDF. In our work we have analysed 69 patients with chronic viral hepatitis B treated in the Clinic for Infectious and Tropical Diseases KCS Belgrade in the period between years 2012 and 2014. All patients involved in this reasearch were previously treated with LAM, and on subsequent development of resistance to LAM, TDF was used. TDF showed an excellent efficacy, a high resistance barrier and very few unwanted side effects over several years of treatment. Our experience with the use of this drug does not pertain to and acount for its long term use, in view of its brief availability on our market.

Dynamics of immune reconstitution and activation markers in HIV+ treatment-naïve patients treated with raltegravir, tenofovir disoproxil fumarate and emtricitabine.

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Nicholas T Funderburg

Full Text Available The dynamics of CD4+ T cell reconstitution and changes in immune activation and inflammation in HIV-1 disease following initiation of antiretroviral therapy (ART are incompletely defined and their underlying mechanisms poorly understood.Thirty-nine treatment-naïve patients were treated with raltegravir, tenofovir DF and emtricitabine. Immunologic and inflammatory indices were examined in persons with sustained virologic control during 48 weeks of therapy.Initiation of ART increased CD4+ T cell numbers and decreased activation and cell cycle entry among CD4+ and CD8+ T cell subsets, and attenuated markers of coagulation (D-dimer levels and inflammation (IL-6 and TNFr1. These indices decayed at different rates and almost all remained elevated above levels measured in HIV-seronegatives through 48 weeks of viral control. Greater first and second phase CD4+ T cell restoration was related to lower T cell activation and cell cycling at baseline, to their decay with treatment, and to baseline levels of selected inflammatory indices, but less so to their changes on therapy.ART initiation results in dynamic changes in viral replication, T cell restoration, and indices of immune activation, inflammation, and coagulation. These findings suggest that determinants of T cell activation/cycling and inflammation/coagulation may have distinguishable impact on immune homeostasis.Clinicaltrials.gov NCT00660972.

Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya.

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Brooks, Katherine; Diero, Lameck; DeLong, Allison; Balamane, Maya; Reitsma, Marissa; Kemboi, Emmanuel; Orido, Millicent; Emonyi, Wilfred; Coetzer, Mia; Hogan, Joseph; Kantor, Rami

2016-01-01

Tenofovir-based first-line antiretroviral therapy (ART) is recommended globally. To evaluate the impact of its incorporation into the World Health Organization (WHO) guidelines, we examined treatment failure and drug resistance among a cohort of patients on tenofovir-based first-line ART at the Academic Model Providing Access to Healthcare, a large HIV treatment programme in western Kenya. We determined viral load (VL), drug resistance and their correlates in patients on ≥six months of tenofovir-based first-line ART. Based on enrolled patients' characteristics, we described these measures in those with (prior ART group) and without (tenofovir-only group) prior non-tenofovir-based first-line ART using Wilcoxon rank sum and Fisher's exact tests. Among 333 participants (55% female; median age 41 years; median CD4 336 cells/µL), detectable (>40 copies/mL) VL was found in 18%, and VL>1000 copies/mL (WHO threshold) in 10%. Virologic failure at both thresholds was significantly higher in 217 participants in the tenofovir-only group compared with 116 in the prior ART group using both cut-offs (24% vs. 7% with VL>40 copies/mL; 15% vs. 1% with VL>1000 copies/mL). Failure in the tenofovir-only group was associated with lower CD4 values and advanced WHO stage. In 35 available genotypes from 51 participants in the tenofovir-only group with VL>40 copies/mL (69% subtype A), any resistance was found in 89% and dual-class resistance in 83%. Tenofovir signature mutation K65R occurred in 71% (17/24) of the patients infected with subtype A. Patients with K65R had significantly lower CD4 values, higher WHO stage and more resistance mutations. In this Kenyan cohort, tenofovir-based first-line ART resulted in good (90%) virologic suppression including high suppression (99%) after switch from non-tenofovir-based ART. Lower virologic suppression (85%) and high observed resistance levels (89%) in the tenofovir-only group impact future treatment options, support recommendations for

Changes in estimated glomerular filtration rate over time in South African HIV-1-infected patients receiving tenofovir: a retrospective cohort study

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De Waal, Reneé; Cohen, Karen; Fox, Matthew P; Stinson, Kathryn; Maartens, Gary; Boulle, Andrew; Igumbor, Ehimario U; Davies, Mary-Ann

2017-01-01

Abstract Introduction: Tenofovir has been associated with decline in kidney function, but in patients with low baseline kidney function, improvements over time have been reported. Additionally, the magnitude and trajectory of estimated glomerular filtration rate (eGFR) changes may differ according to how eGFR is calculated. We described changes in eGFR over time, and the incidence of, and risk factors for, kidney toxicity, in a South African cohort. Methods: We included antiretroviral-naïve patients ≥16 years old who started tenofovir-containing antiretroviral therapy (ART) between 2002 and 2013. We calculated eGFR using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockcroft-Gault equations. We described changes in eGFR from ART initiation using linear mixed effects regression. We described the incidence of eGFR <30 mL/min on treatment, and identified associations with low eGFR using Cox regression. Results: We included 15156 patients with median age of 35.4 years (IQR 29.9–42.0), median CD4 cell count of 168 cells/µL (IQR 83–243), and median eGFR (MDRD) of 98.6 mL/min (IQR 84.4–115.6). Median duration of follow up on tenofovir was 12.9 months (IQR 5.1–23.3). Amongst those with a baseline and subsequent eGFR  available, mean eGFR change from baseline at 12 months was −4.4 mL/min (95% CI −4.9 to −4.0), −2.3 (−2.5 to −2.1), and 0.6 (0.04 to 1.2) in those with baseline eGFR ≥90 mL/min; and 11.9 mL/min (11.0 to 12.7), 14.6 (13.5 to 15.7), and 11.0 (10.3 to 11.7) in those with baseline eGFR <90 mL/min, according to the MDRD, CKD-EPI (n = 11 112), and Cockcroft-Gault (n = 9 283) equations, respectively. Overall, 292 (1.9%) patients developed eGFR <30 mL/min. Significant associations with low eGFR included older age, baseline eGFR <60 mL/min, CD4 count <200 cells/µL, body weight <60 kg, and concomitant protease inhibitor use. Conclusions: Patients on

Comparing genotoxic signatures in cord blood cells from neonates exposed in utero to zidovudine or tenofovir.

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Vivanti, Alexandre; Soheili, Tayebeh S; Cuccuini, Wendy; Luce, Sonia; Mandelbrot, Laurent; Lechenadec, Jerome; Cordier, Anne-Gael; Azria, Elie; Soulier, Jean; Cavazzana, Marina; Blanche, Stéphane; André-Schmutz, Isabelle

2015-07-17

Zidovudine and tenofovir are the two main nucleos(t)ide analogs used to prevent mother-to-child transmission of HIV. In vitro, both drugs bind to and integrate into human DNA and inhibit telomerase. The objective of the present study was to assess the genotoxic effects of either zidovudine or tenofovir-based combination therapies on cord blood cells in newborns exposed in utero. We compared the aneuploid rate and the gene expression profiles in cord blood samples from newborns exposed either to zidovudine or tenofovir-based combination therapies during pregnancy and from unexposed controls (n = 8, 9, and 8, respectively). The aneuploidy rate was measured on the cord blood T-cell karyotype. Gene expression profiles of cord blood T cells and hematopoietic stem and progenitor cells were determined with microarrays, analyzed in a gene set enrichment analysis and confirmed by real-time quantitative PCRs. Aneuploidy was more frequent in the zidovudine-exposed group (26.3%) than in the tenofovir-exposed group (14.2%) or in controls (13.3%; P < 0.05 for both). The transcription of genes involved in DNA repair, telomere maintenance, nucleotide metabolism, DNA/RNA synthesis, and the cell cycle was deregulated in samples from both the zidovudine and the tenofovir-exposed groups. Although tenofovir has a lower clastogenic impact than zidovudine, gene expression profiling showed that both drugs alter the transcription of DNA repair and telomere maintenance genes.

Bone scintigraphy and secondary osteomalacia due to nephrotoxicity in a chronic hepatitis B patient treated with tenofovir.

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Gómez Martinez, M V; Gallardo, F G; Pirogova, T; García-Samaniego, J

2014-01-01

Tenofovir is a nucleotide analogue used for the treatment of chronic hepatitis B and HIV infection. The safety of tenofovir is high but it has been described that tenofovir produces tubular toxicity and Fanconi's syndrome in some HIV-infected patients. To our knowledge this is the first documented case of bone involvement in Fanconi's syndrome in a patient treated with tenofovir for chronic hepatitis B without HIV coinfection. Bone scintigraphy has proven to be very useful for the diagnosis of secondary osteomalacia. Normalization of the bone scan after the withdrawal of the drug and the decline in alkaline phosphatase and phosphate serum levels reinforce the cause-effect relationship. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother-infant pairs.

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Waitt, Catriona; Olagunju, Adeniyi; Nakalema, Shadia; Kyohaire, Isabella; Owen, Andrew; Lamorde, Mohammed; Khoo, Saye

2018-04-01

Breast milk transfer of first-line ART from mother to infant is not fully understood. To determine the concentrations of lamivudine, emtricitabine and tenofovir in maternal blood, breast milk and infant blood from breastfeeding mother-infant pairs. Intensive pharmacokinetic sampling of maternal dried blood spots (DBS), dried breast milk spots (DBMS) and infant DBS from 30 Ugandan and 29 Nigerian mothers receiving first-line ART and their infants was conducted. DBS and DBMS were collected pre-dose and at 5-6 timepoints up to 12 h following observed dosing. Infant DBS were sampled twice during this period. Lamivudine, emtricitabine and tenofovir were quantified using LC-MS/MS, with non-compartmental analysis to calculate key pharmacokinetic parameters. Peak concentrations in breast milk from women taking lamivudine and emtricitabine occurred later than in plasma (4-8 h compared with 2 h for lamivudine and 2-4 h for emtricitabine). Consequently, the milk-to-plasma (M:P) ratio of lamivudine taken once daily was 0.95 (0.82-1.15) for AUC0-12, whereas for AUC12-20 this was 3.04 (2.87-4.16). Lamivudine was detectable in 36% (14/39) of infants [median 17.7 (16.3-22.7) ng/mL]. For 200 mg of emtricitabine once daily, the median M:P ratio was 3.01 (2.06-3.38). Three infants (19%) had measurable emtricitabine [median 18.5 (17.6-20.8) ng/mL]. For 300 mg of tenofovir once daily, the median M:P ratio was 0.015 (0-0.03) and no infant had measurable tenofovir concentrations. Emtricitabine and lamivudine accumulate in breast milk and were detected in breastfeeding infants. In contrast, tenofovir penetrates the breast milk to a small degree, but is undetectable in breastfeeding infants.

In vitro activity of 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy]-pyrimidine against multidrug-resistant hepatitis B virus mutants

Czech Academy of Sciences Publication Activity Database

Brunelle, M. N.; Lucifora, J.; Neyts, J.; Villet, S.; Holý, Antonín; Trepo, C.; Zoulim, F.

2007-01-01

Roč. 51, č. 6 (2007), s. 2240-2243 ISSN 0066-4804 R&D Projects: GA MŠk 1M0508; GA AV ČR 1QS400550501 Grant - others:ViRgil(XE) LSHM-CT-2004-503359; Descartes Prize(XE) HPAW-CT-2002-9001 Institutional research plan: CEZ:AV0Z40550506 Keywords : tenofovir-disoproxil-fumarate * adefovir dipivoxil * lamivudine * entecavir * nucleoside Subject RIV: CC - Organic Chemistry Impact factor: 4.390, year: 2007

Long-term treatment with tenofovir in Asian-American chronic hepatitis B patients is associated with abnormal renal phosphate handling.

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Tien, Connie; Xu, Jason J; Chan, Linda S; Chang, Mimi; Lim, Carolina; Lee, Sue; Huh, Brian; Shinada, Shuntaro; Bae, Ho S; Fong, Tse-Ling

2015-02-01

Increased risk of defective urinary phosphate reabsorption and osteoporosis has been reported in HIV and chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF). Goals of this study were to evaluate the prevalence of renal phosphate wasting and abnormal bone mineral density in CHB patients taking TDF compared to CHB patients treated with entecavir (ETV) and untreated CHB patients. This is a cross-sectional study of 146 consecutive Asian-American CHB patients who were treatment naïve (n = 60) or treated with either TDF (n = 42) or ETV (n = 44). Proximal tubular handling of phosphate was assessed by the maximal rate of tubular reabsorption of phosphate (TmPO4) divided by glomerular filtration rate (GFR) (TmPO4/GFR). Bone mineral density (BMD) was measured using dual X-ray absorptiometry. TmPO4/GFR was similar among CHB patients treated with TDF compared to untreated patients and patients taking ETV. However, among patients treated with ≥18 months of TDF or ETV, prevalence of abnormal TmPO4/GFR was higher among patients treated with TDF compared to ETV (48.5 % (16/33) vs. 12.5 % (3/24), p = 0.005). Overall prevalence of osteoporosis in this cohort of CHB patients was 14 %, with no significant difference between the three groups. Renal phosphate handling did not correlate with osteoporosis. Chronic hepatitis B patients treated with ≥18 months of TDF experienced an increased risk of proximal tubular dysfunction. TDF did not increase the risk of osteoporosis. Longitudinal studies are needed to confirm these findings.

Efficacy of Tenofovir 1% Vaginal Gel in Reducing the Risk of HIV-1 and HSV-2 Infection

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Christopher McConville

2014-01-01

Full Text Available Human Immunodeficiency Virus (HIV is a retrovirus that can result in rare opportunistic infections occurring in humans. The onset of these infections is known as Acquired Immune Deficiency Syndrome (AIDS. Sexual transmission is responsible for the majority of infections 1, resulting in transmission of HIV due to infected semen or vaginal and cervical secretions containing infected lymphocytes. HIV microbicides are formulations of chemical or biological agents that can be applied to the vagina or rectum with the intention of reducing the acquisition of HIV. Tenofovir is an NRTI that is phosphorylated by adenylate kinase to tenofovir diphosphate, which in turn competes with deoxyadeosine 5′-triphosphate for incorporation into newly synthesized HIV DNA. Once incorporated, tenofovir diphosphate results in chain termination, thus inhibiting viral replication. Tenofovir has been formulated into a range of vaginal formulations, such as rings, tablets gels and films. It has been shown to safe and effective in numerous animal models, while demonstrating safety and acceptability in numerous human trials. The most encouraging results came from the CAPRISA 004 clinical trial which demonstrated that a 1% Tenofovir vaginal gel reduced HIV infection by approximately 39%.

Impact of Small Body Weight on Tenofovir-Associated Renal Dysfunction in HIV-Infected Patients: A Retrospective Cohort Study of Japanese Patients

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Nishijima, Takeshi; Komatsu, Hirokazu; Gatanaga, Hiroyuki; Aoki, Takahiro; Watanabe, Koji; Kinai, Ei; Honda, Haruhito; Tanuma, Junko; Yazaki, Hirohisa; Tsukada, Kunihisa; Honda, Miwako; Teruya, Katsuji; Kikuchi, Yoshimi; Oka, Shinichi

2011-01-01

Background Treatment with tenofovir is sometimes associated with renal dysfunction. Limited information is available on this side effect in patients with small body weight, although the use of tenofovir will spread rapidly in Asia and Africa, where patients are likely to be of smaller body weight. Methods In a single-center cohort, Japanese patients with HIV infection who started tenofovir-containing antiretroviral therapy were retrospectively analyzed. The incidence of tenofovir-associated renal dysfunction, defined as more than 25% decrement of estimated glomerular filtration rate (eGFR) from the baseline, was determined. The effects of small body weight and body mass index (BMI) on tenofovir-associated renal dysfunction, respectively, were estimated in univariate and multivariate Cox hazards models as the primary exposure. Other possible risk factors were evaluated by univariate analysis and those found significant were entered into the multivariate analysis. Results The median weight of 495 patients was 63 kg. Tenofovir-related renal dysfunction occurred in 97 (19.6%) patients (incidence: 10.5 per 100 person-years). Univariate analysis showed that the incidence of tenofovir-related renal dysfunction was significantly associated with smaller body weight and BMI, respectively (per 5 kg decrement, HR = 1.23; 95% CI, 1.10–1.37; pdecrement, HR = 1.14; 95% CI, 1.05–1.23; p = 0.001). Old age, high baseline eGFR, low serum creatinine, low CD4 count, high HIV viral load, concurrent nephrotoxic drugs, hepatitis C infection, and current smoking were also associated with tenofovir-related renal dysfunction. Multivariate analysis identified small body weight as a significant risk (adjusted HR = 1.13; 95% CI, 1.01–1.27; p = 0.039), while small BMI had marginal significance (adjusted HR = 1.07; 95% CI 1.00–1.16; p = 0.058). Conclusion The incidence of tenofovir-associated renal dysfunction in Japanese patients was high. Small body weight

Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother–infant pairs

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Waitt, Catriona; Olagunju, Adeniyi; Nakalema, Shadia; Kyohaire, Isabella; Owen, Andrew; Lamorde, Mohammed; Khoo, Saye

2018-01-01

Abstract Background Breast milk transfer of first-line ART from mother to infant is not fully understood. Objectives To determine the concentrations of lamivudine, emtricitabine and tenofovir in maternal blood, breast milk and infant blood from breastfeeding mother–infant pairs. Methods Intensive pharmacokinetic sampling of maternal dried blood spots (DBS), dried breast milk spots (DBMS) and infant DBS from 30 Ugandan and 29 Nigerian mothers receiving first-line ART and their infants was conducted. DBS and DBMS were collected pre-dose and at 5–6 timepoints up to 12 h following observed dosing. Infant DBS were sampled twice during this period. Lamivudine, emtricitabine and tenofovir were quantified using LC-MS/MS, with non-compartmental analysis to calculate key pharmacokinetic parameters. Results Peak concentrations in breast milk from women taking lamivudine and emtricitabine occurred later than in plasma (4–8 h compared with 2 h for lamivudine and 2–4 h for emtricitabine). Consequently, the milk-to-plasma (M:P) ratio of lamivudine taken once daily was 0.95 (0.82–1.15) for AUC0–12, whereas for AUC12–20 this was 3.04 (2.87–4.16). Lamivudine was detectable in 36% (14/39) of infants [median 17.7 (16.3–22.7) ng/mL]. For 200 mg of emtricitabine once daily, the median M:P ratio was 3.01 (2.06–3.38). Three infants (19%) had measurable emtricitabine [median 18.5 (17.6–20.8) ng/mL]. For 300 mg of tenofovir once daily, the median M:P ratio was 0.015 (0–0.03) and no infant had measurable tenofovir concentrations. Conclusions Emtricitabine and lamivudine accumulate in breast milk and were detected in breastfeeding infants. In contrast, tenofovir penetrates the breast milk to a small degree, but is undetectable in breastfeeding infants. PMID:29309634

Gateways to clinical trials.

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Tomillero, A; Moral, M A

2009-05-01

(-)-Gossypol; Abacavir sulfate/lamivudine, ACAM-1000, ACE-011, Agomelatine, AGS-004, Alemtuzumab, Alvocidib hydrochloride, AMG-317, Amlodipine, Aripiprazole, Atazanavir sulfate, Azacitidine; Becatecarin, Belinostat, Bevacizumab, BMS-387032, BMS-690514, Bortezomib; Casopitant mesylate, Cetuximab, Choline fenofibrate, CK-1827452, Clofarabine, Conivaptan hydrochloride; Dabigatran etexilate, DADMe-Immucillin-H, Darbepoetin alfa, Darunavir, Dasatinib, DC-WT1, Decitabine, Deferasirox, Degarelix acetate, Denenicokin, Denosumab, Dienogest, Duloxetine hydrochloride; Ecogramostim, Eculizumab, Edoxaban tosilate, Elacytarabine, Elesclomol, Eltrombopag olamine, Enfuvirtide, Enzastaurin hydrochloride, Eribulin mesilate, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone, Etravirine; Flibanserin, Fludarabine, Fondaparinux sodium, Fosamprenavir calcium; Gefitinib, Genistein; I-131-L19-SIP, Idrabiotaparinux sodium, Imatinib mesylate, IMGN-901, Ipilimumab; Laromustine, Lenalidomide, Liposomal cisplatin, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Lopinavir/ritonavir; Maraviroc, MDV-3100, Mecasermin rinfabate, MP-470, Mycophenolic acid sodium salt; Naproxcinod, NB-002, Nesiritide, Nilotinib hydrochloride monohydrate, NK-012; Palonosetron hydrochloride, Panobinostat, Pegfilgrastim, Peginterferon alfa-2a, Pitavastatin calcium, PL-3994, Plerixafor hydrochloride, Plitidepsin, PM-10450; Raltegravir potassium, Recombinant human soluble thrombomodulin, ReoT3D, RHAMM R3 peptide, Rivaroxaban, Romiplostim, Rosuvastatin calcium, Rozrolimupab; Sabarubicin hydrochloride, Salinosporamide A, Sirolimus-eluting stent, Smallpox (Vaccinia) Vaccine, Live, Sorafenib; Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Teriparatide, Tipifarnib, Tipranavir, Trabectedin, Trifluridine/TPI; Vardenafil hydrochloride hydrate, Vinflunine, Volociximab, Vorinostat; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziprasidone hydrochloride, Zoledronic acid monohydrate

Population Pharmacokinetics of Tenofovir in Human Immunodeficiency Virus-Infected Patients Taking Highly Active Antiretroviral Therapy

OpenAIRE

Jullien, Vincent; Tréluyer, Jean-Marc; Rey, Elisabeth; Jaffray, Patrick; Krivine, Anne; Moachon, Laurence; Lillo-Le Louet, Agnès; Lescoat, Anne; Dupin, Nicolas; Salmon, Dominique; Pons, Gérard; Urien, Saïk

2005-01-01

The influence of renal function on tenofovir pharmacokinetics was investigated in 193 human immunodeficiency virus (HIV)-infected patients by the use of a population approach performed with the nonlinear mixed effects modeling program NONMEM. Tenofovir pharmacokinetics was well described by a two-compartment open model in which the absorption and the distribution rate constants are equal. Typical population estimates of apparent central distribution volume (Vc/F), peripheral distribution volu...

Atazanavir exposure is effective during pregnancy regardless of tenofovir use

NARCIS (Netherlands)

Colbers, A.; Hawkins, D.; Hidalgo-Tenorio, C.; Ende, M. van der; Gingelmaier, A.; Weizsacker, K.; Kabeya, K.; Taylor, G.; Rockstroh, J.; Lambert, J.; Molto, J.; Wyen, C.; Sadiq, S.T.; Ivanovic, J.; Giaquinto, C.; Burger, D.M.

2015-01-01

BACKGROUND: We studied the effect of pregnancy on atazanavir pharmacokinetics in the presence and absence of tenofovir. METHODS: This was a non-randomized, open-label, multicentre Phase IV study in HIV-infected pregnant women recruited from European HIV treatment centres. HIV-infected pregnant women

A randomized trial to assess anti-HIV activity in female genital tract secretions and soluble mucosal immunity following application of 1% tenofovir gel.

Directory of Open Access Journals (Sweden)

Marla J Keller

2011-01-01

Full Text Available Preclinical and early phase clinical microbicide studies have not consistently predicted the outcome of efficacy trials. To address this gap, candidate biomarkers of microbicide pharmacodynamics and safety were evaluated in a double-blind, placebo-controlled trial of tenofovir gel, the first microbicide to demonstrate significant protection against HIV acquisition.30 women were randomized to apply a single daily dose of tenofovir or placebo gel for 14 consecutive days. Anti-HIV activity was measured in cervicovaginal lavage (CVL on Days 0, 3, 7, 14 and 21 by luciferase assay as a surrogate marker of pharmacodynamics. Endogenous activity against E. coli and HSV-2 and concentrations of immune mediators were quantified in CVL as candidate biomarkers of safety. Tenofovir levels were measured in CVL and blood.A significant increase in anti-HIV activity was detected in CVL from women who applied tenofovir gel compared to their endogenous anti-HIV activity in genital tract secretions on Day 0 and compared to activity in CVL from women in the placebo group. The activity correlated significantly with CVL concentration of tenofovir (r = 0.6, p<0.001 and fit a sigmoid E(max pharmacodynamic model. Anti-HIV activity in CVL from women who applied tenofovir persisted when virus was introduced in semen, whereas endogenous anti-HIV activity decreased. Tenofovir did not trigger an inflammatory response or induce sustained loss in endogenous antimicrobial activity or immune mediators.Tenofovir gel had no deleterious impact on soluble mucosal immunity. The increased anti-HIV activity in CVL, which persisted in the presence of semen and correlated with tenofovir concentration, is consistent with the efficacy observed in a recent clinical trial. These results promote quantified CVL anti-HIV activity as a surrogate of tissue pharmacodynamics and as a potential biomarker of adherence to product. This simple, feasible and inexpensive bioassay may promote the development

WHO antiretroviral therapy guidelines 2010 and impact of tenofovir on chronic kidney disease in Vietnamese HIV-infected patients.

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Daisuke Mizushima

Full Text Available OBJECTIVE: The 2010 WHO antiretroviral therapy (ART guidelines have resulted in increased tenofovir use. Little is known about tenofovir-induced chronic kidney disease (CKD in HIV-infected Vietnamese with mean body weight of 55 kg. We evaluated the prevalence and risk factors of CKD in this country. DESIGN: Cross-sectional study was performed. METHODS: Clinical data on HIV-infected Vietnamese cohort were collected twice a year. To evaluate the prevalence of CKD, serum creatinine was measured in 771 patients in October 2011 and April 2012. CKD was defined as creatinine clearance less than 60 ml/min at both time points. Multivariate logistic regression was used to determine the factors associated with CKD. RESULTS: Tenofovir use increased in Vietnam from 11.9% in April 2011 to 40.3% in April 2012. CKD was diagnosed in 7.3%, of which 7% was considered moderate and 0.3% was severe. Multivariate analysis of October-2011 data identified age per year-increase (OR: 1.229, 95%CI, 1.170-1.291, body weight per 1 kg-decrement (1.286, 1.193-1.386, and tenofovir use (2.715, 1.028-7.168 as risk factors for CKD. CONCLUSIONS: Older age, low body weight and tenofovir use were independent risk factors for CKD in Vietnam. Further longitudinal study is required to evaluate the impact of TDF on renal function in Vietnam and other countries with small-body weight patients.

Predictive value of serum ALT and T-cell receptor beta variable chain for HBeAg seroconversion in chronic hepatitis B patients during tenofovir treatment.

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Yang, Jiezuan; Yan, Dong; Guo, Renyong; Chen, Jiajia; Li, Yongtao; Fan, Jun; Fu, Xuyan; Yao, Xinsheng; Diao, Hongyan; Li, Lanjuan

2017-03-01

Effective antiviral therapy plays a key role in slowing the progression of chronic hepatitis B (CHB). Identification of serum indices, including hepatitis B e antigen (HBeAg) expression and seroconversion, will facilitate evaluation of the efficacy of antiviral therapy in HBeAg-positive CHB patients. The biochemical, serological, virological parameters, and the frequency of circulating CD4CD25 regulatory T cell (Treg) in 32 patients were measured at baseline and every 12 weeks during 96 weeks of tenofovir disoproxil fumarate (TDF) treatment. The relationship between the hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and Treg and alanine aminotransferase (ALT) levels was analyzed, respectively. The molecular profiles of T-cell receptor beta variable chain (TRBV) were determined using gene melting spectral pattern. For the seroconverted 12 patients, ALT declined to normal levels by week 24 and remained at this level in subsequent treatment; moreover, the predictive cutoff value of ALT for HBeAg seroconversion (SC) was 41.5 U/L at week 24. The positive correlation between HBV DNA and Treg and ALT was significant in SC patients, but not in non-SC patients. Six TRBV families (BV3, BV11, BV12, BV14, BV20, and BV24) were predominantly expressed in SC patients at baseline. The decline of ALT could be used to predict HBeAg seroconversion for CHB patients during TDF treatment. In addition, the profile of Tregs and TRBVs may be associated with HBeAg seroconversion and could also be a potential indicator for predicting HBeAg SC and treatment outcome for CHB patients.

Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy.

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Etiebet, Mary-Ann A; Shepherd, James; Nowak, Rebecca G; Charurat, Man; Chang, Harry; Ajayi, Samuel; Elegba, Olufunmilayo; Ndembi, Nicaise; Abimiku, Alashle; Carr, Jean K; Eyzaguirre, Lindsay M; Blattner, William A

2013-02-20

In resource-limited settings, HIV-1 drug resistance testing to guide antiretroviral therapy (ART) selection is unavailable. We retrospectively conducted genotypic analysis on archived samples from Nigerian patients who received targeted viral load testing to confirm treatment failure and report their drug resistance mutation patterns. Stored plasma from 349 adult patients on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens was assayed for HIV-1 RNA viral load, and samples with more than 1000 copies/ml were sequenced in the pol gene. Analysis for resistance mutations utilized the IAS-US 2011 Drug Resistance Mutation list. One hundred and seventy-five samples were genotyped; the majority of the subtypes were G (42.9%) and CRF02_AG (33.7%). Patients were on ART for a median of 27 months. 90% had the M184V/I mutation, 62% had at least one thymidine analog mutation, and 14% had the K65R mutation. 97% had an NNRTI resistance mutation and 47% had at least two etravirine-associated mutations. In multivariate analysis tenofovir-based regimens were less likely to have at least three nucleoside reverse transcriptase inhibitor (NRTI) mutations after adjusting for subtype, previous ART, CD4, and HIV viral load [P < 0.001, odds ratio (OR) 0.04]. 70% of patients on tenofovir-based regimens had at least two susceptible NRTIs to include in a second-line regimen compared with 40% on zidovudine-based regimens (P = 0.04, OR = 3.4). At recognition of treatment failure, patients on tenofovir-based first-line regimens had fewer NRTI drug-resistant mutations and more active NRTI drugs available for second-line regimens. These findings can inform strategies for ART regimen sequencing to optimize long-term HIV treatment outcomes in low-resource settings.

Development and validation of reversed-phase HPLC gradient method for the estimation of efavirenz in plasma.

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Shweta Gupta

Full Text Available Efavirenz is an anti-viral agent of non-nucleoside reverse transcriptase inhibitor category used as a part of highly active retroviral therapy for the treatment of infections of human immune deficiency virus type-1. A simple, sensitive and rapid reversed-phase high performance liquid chromatographic gradient method was developed and validated for the determination of efavirenz in plasma. The method was developed with high performance liquid chromatography using Waters X-Terra Shield, RP18 50 x 4.6 mm, 3.5 μm column and a mobile phase consisting of phosphate buffer pH 3.5 and Acetonitrile. The elute was monitored with the UV-Visible detector at 260 nm with a flow rate of 1.5 mL/min. Tenofovir disoproxil fumarate was used as internal standard. The method was validated for linearity, precision, accuracy, specificity, robustness and data obtained were statistically analyzed. Calibration curve was found to be linear over the concentration range of 1-300 μg/mL. The retention times of efavirenz and tenofovir disoproxil fumarate (internal standard were 5.941 min and 4.356 min respectively. The regression coefficient value was found to be 0.999. The limit of detection and the limit of quantification obtained were 0.03 and 0.1 μg/mL respectively. The developed HPLC method can be useful for quantitative pharmacokinetic parameters determination of efavirenz in plasma.

Tenofovir-Based Highly Active Antiretroviral Therapy Is Associated with Superior CD4 T Cells Repopulation Compared to Zidovudine-Based HAART in HIV 1 Infected Adults

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Vitus Sambo Badii

2018-01-01

Full Text Available Tenofovir-based highly active antiretroviral therapy (HAART is one of the preferred first-line therapies in the management of HIV 1 infection. Ghana has since 2014 adopted this recommendation; however there is paucity of scientific data that reflects the safety and efficacy of the tenofovir-based therapy compared to zidovudine in the Ghanaian health system. This study sought to assess the comparative immune reconstitution potential between tenofovir and zidovudine-based HAART regimens, which includes lamivudine and efavirenz in combination therapy. It also aimed to investigate the adverse drug reactions/events (ADREs associated with pharmacotherapy with these agents in a total of 106 HAART naïve HIV patients. The study included 80 patients in the tenofovir cohort while 26 patients were on the zidovudine regimen. The occurrence of HIV comorbidities profile was assessed at diagnosis and throughout the study period. The baseline CD4 T cells count of the participants was also assessed at diagnosis and repeated at a median period of five months (range 4–6 months, after commencing treatment with either tenofovir- or zidovudine-based HAART. After five months of the HAART, the tenofovir cohort recorded higher CD4 T cell count change from baseline compared to the zidovudine cohort (p<0.0001. The patients on the tenofovir-based HAART and female sex however appeared to be associated with more multiple ADREs.

Coformulated bictegravir, Emtricitabine (F), tenofovir alafenamide (TAF) after initial treatment with bictegravir or dolutegravir plus F/TAF.

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Sax, Paul E; Dejesus, Edwin; Crofoot, Gordon; Ward, Douglas; Benson, Paul; Dretler, Robin; Mills, Anthony; Brinson, Cynthia; Wei, Xuelian; Collins, Sean E; Cheng, Andrew

2018-05-22

: A phase 2, randomized, active-controlled study of initial antiretroviral therapy with bictegravir or dolutegravir in combination with emtricitabine and tenofovir alafenamide showed excellent efficacy. After 60 weeks of blinded treatment, participants switched to a single tablet regimen of bictegravir, emtricitabine and tenofovir alafenamide. Switching maintained viral suppression in all participants who chose to remain on the study through at least 12 weeks in the open-label phase, was safe and well tolerated.

The antiviral drug tenofovir, an inhibitor of Pannexin-1-mediated ATP release, prevents liver and skin fibrosis by downregulating adenosine levels in the liver and skin.

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Jessica L Feig

Full Text Available Fibrosing diseases are a leading cause of morbidity and mortality worldwide and, therefore, there is a need for safe and effective antifibrotic therapies. Adenosine, generated extracellularly by the dephosphorylation of adenine nucleotides, ligates specific receptors which play a critical role in development of hepatic and dermal fibrosis. Results of recent clinical trials indicate that tenofovir, a widely used antiviral agent, reverses hepatic fibrosis/cirrhosis in patients with chronic hepatitis B infection. Belonging to the class of acyclic nucleoside phosphonates, tenofovir is an analogue of AMP. We tested the hypothesis that tenofovir has direct antifibrotic effects in vivo by interfering with adenosine pathways of fibrosis using two distinct models of adenosine and A2AR-mediated fibrosis.Thioacetamide (100mg/kg IP-treated mice were treated with vehicle, or tenofovir (75mg/kg, SubQ (n = 5-10. Bleomycin (0.25U, SubQ-treated mice were treated with vehicle or tenofovir (75mg/kg, IP (n = 5-10. Adenosine levels were determined by HPLC, and ATP release was quantitated as luciferase-dependent bioluminescence. Skin breaking strength was analysed and H&E and picrosirus red-stained slides were imaged. Pannexin-1expression was knocked down following retroviral-mediated expression of of Pannexin-1-specific or scrambled siRNA.Treatment of mice with tenofovir diminished adenosine release from the skin of bleomycin-treated mice and the liver of thioacetamide-treated mice, models of diffuse skin fibrosis and hepatic cirrhosis, respectively. More importantly, tenofovir treatment diminished skin and liver fibrosis in these models. Tenofovir diminished extracellular adenosine concentrations by inhibiting, in a dose-dependent fashion, cellular ATP release but not in cells lacking Pannexin-1.These studies suggest that tenofovir, a widely used antiviral agent, could be useful in the treatment of fibrosing diseases.

Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis.

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Chan, Philip A; Huang, Austin; Kantor, Rami

2012-10-15

Tenofovir-containing regimens have demonstrated potential efficacy as pre-exposure prophylaxis (PrEP) in preventing HIV-1 infection. Transmitted drug resistance mutations associated with tenofovir, specifically the reverse transcriptase (RT) mutation K65R, may impact the effectiveness of PrEP. The worldwide prevalence of transmitted tenofovir resistance in different HIV-1 subtypes is unknown. Sequences from treatment-naïve studies and databases were aggregated and analyzed by Stanford Database tools and as per the International AIDS Society (IAS-USA) resistance criteria. RT sequences were collected from GenBank, the Stanford HIV Sequence Database and the Los Alamos HIV Sequence Database. Sequences underwent rigorous quality control measures. Tenofovir-associated resistance mutations included K65R, K70E, T69-insertion and ≥3 thymidine analogue mutations (TAMs), inclusive of M41L or L210W. A total of 19,823 sequences were evaluated across diverse HIV-1 subtypes (Subtype A: 1549 sequences, B: 9783, C: 3198, D: 483, F: 372, G: 594, H: 41, J: 69, K: 239, CRF01_AE: 1797 and CRF02_AG: 1698). Overall, tenofovir resistance prevalence was 0.4% (n=77/19,823, 95% confidence interval or CI: 0.3 to 0.5). K65R was found in 20 sequences (0.1%, 95% CI: 0.06 to 0.15). Differences in the prevalence of K65R between HIV-1 subtypes were not statistically significant. K70E and ≥3 TAMs were found in 0.015% (95% CI: 0.004 to 0.04) and 0.27% (95% CI: 0.2 to 0.4) of sequences, respectively. Prevalence of transmitted K65R and other tenofovir resistance mutations across diverse HIV-1 subtypes and recombinants is low, suggesting minimal effect on tenofovir-containing PrEP regimens.

The history of antiretrovirals: key discoveries over the past 25 years.

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De Clercq, Erik

2009-09-01

Within 25 years after zidovudine (3'-azido-2',3'-dideoxythymidine, AZT) was first described as an inhibitor of HIV replication, 25 anti-HIV drugs have been formally approved for clinical use in the treatment of HIV infections: seven nucleoside reverse transcriptase inhibitors (NRTIs): zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine; one nucleotide reverse transcriptase inhibitor (NtRTI): tenofovir [in its oral prodrug form: tenofovir disoproxil fumarate (TDF)]; four non-nucleoside reverse transcriptase inhibitors (NNRTIs): nevirapine, delavirdine, efavirenz and etravirine; ten protease inhibitors (PIs): saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir and darunavir; one fusion inhibitor (FI): enfuvirtide; one co-receptor inhibitor (CRI): maraviroc and one integrase inhibitor (INI): raltegravir. These compounds are used in various drug combination (some at fixed dose) regimens so as to achieve the highest possible benefit and tolerability, and to diminish the risk of virus-drug resistance development. (c) 2009 John Wiley & Sons, Ltd.

Adipocytes Impair Efficacy of Antiretroviral Therapy

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Couturier, Jacob; Winchester, Lee C.; Suliburk, James W.; Wilkerson, Gregory K.; Podany, Anthony T.; Agarwal, Neeti; Chua, Corrine Ying Xuan; Nehete, Pramod N.; Nehete, Bharti P.; Grattoni, Alessandro; Sastry, K. Jagannadha; Fletcher, Courtney V.; Lake, Jordan E.; Balasubramanyan, Ashok; Lewis, Dorothy E.

2018-01-01

Adequate distribution of antiretroviral drugs to infected cells in HIV patients is critical for viral suppression. In humans and primates, HIV- and SIV-infected CD4 T cells in adipose tissues have recently been identified as reservoirs for infectious virus. To better characterize adipose tissue as a pharmacological sanctuary for HIV-infected cells, in vitro experiments were conducted to assess antiretroviral drug efficacy in the presence of adipocytes, and drug penetration in adipose tissue cells (stromal-vascular-fraction cells and mature adipocytes) was examined in treated humans and monkeys. Co-culture experiments between HIV-1-infected CD4 T cells and primary human adipocytes showed that adipocytes consistently reduced the antiviral efficacy of the nucleotide reverse transcriptase inhibitor tenofovir and its prodrug forms tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). In HIV-infected persons, LC-MS/MS analysis of intracellular lysates derived from adipose tissue stromal-vascular-fraction cells or mature adipocytes suggested that integrase inhibitors penetrate adipose tissue, whereas penetration of nucleoside/nucleotide reverse transcriptase inhibitors such as TDF, emtricitabine, abacavir, and lamivudine is restricted. The limited distribution and functions of key antiretroviral drugs within fat depots may contribute to viral persistence in adipose tissue. PMID:29630975

Randomized Controlled Trial of Daily Text Messages to Support Adherence to Preexposure Prophylaxis in Individuals at Risk for Human Immunodeficiency Virus: The TAPIR Study.

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Moore, David J; Jain, Sonia; Dubé, Michael P; Daar, Eric S; Sun, Xiaoying; Young, Jason; Corado, Katya; Ellorin, Eric; Milam, Joel; Collins, Deborah; Blumenthal, Jill; Best, Brookie M; Anderson, Peter; Haubrich, Richard; Morris, Sheldon R

2018-05-02

Adherence is critical for efficacy of tenofovir disoproxil fumarate/emtricitabine (FTC) as preexposure prophylaxis (PrEP). Between February 2013 and February 2016, 398 men who have sex with men and transgender women were randomized 1:1 to receive individualized texting for adherence building (iTAB) or standard care (SoC) for 48 weeks. The primary endpoint was dried blood spot (DBS) tenofovir diphosphate (TFV-DP) concentrations at both week 12 and the last on-drug visit of >719 fmol/punch (ie, adequate adherence). Secondary outcomes included DBS TFV-DP concentrations of >1246 fmol/punch (ie, near-perfect adherence) and plasma FTC >350 ng/mL (consistent with dosing within the past 24 hours). Concentrations >719 fmol/punch of TFV-DP were found in 88.6% of participants at week 12 and 82.5% at week 48. For the primary endpoint, the study arms did not differ (72.0% in iTAB and 69.2% in SoC; P > .05). For the secondary composite endpoint of >1246 fmol/punch the iTAB arm was superior to SoC (33.5% vs 24.8%; P = .06), reaching statistical significance when adjusting for age (odds ratio, 1.56 [95% confidence interval, 1.00-2.42]; P .05). Automated text messaging is a low-burden tool that improves durability of near-perfect PrEP adherence. NCT01761643.

Hypophosphatemic osteomalacia associated with tenofovir: a multidisciplinary approach is required.

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Giuseppe Vittorio De Socio

2012-01-01

Full Text Available

Tenofovir is widely used as first-line treatment of HIV infection, although its use is sometimes complicated by a reversible proximal renal tubulopathy.

We report the case of a 45-year-old woman with chronic HIV infection and personality disorder, who after 12 months of tenofovir, complained of fatigue, diffuse bone pain and gait disturbances. The elevated level of alkaline phosphatase, hypophosphatemia and inappropriate phosphaturia suggested the diagnosis of hypophosphatemic osteomalacia secondary to proximal renal tubulopathy. A dual-energy x-ray absorptiometry showed a bone mineral density below the expected range for age (lumbar spine Z-score -3.3, femoral neck Z-score -2.1. A whole body ^99mTc-methylene diphosphonate bone scan showed multiple areas of increased focal activity in the lumbar and thoracic spine and in sacroiliac and hip joints consistent with pseudo-fractures. Two months after tenofovir discontinuation and administration of vitamin D and phosphate, osteomalacia-related symptoms disappeared. Eleven months later, bone and mineral metabolism data were normal and bone

Vibrational Spectroscopic Studies of Tenofovir Using Density Functional Theory Method

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G. R. Ramkumaar

2013-01-01

Full Text Available A systematic vibrational spectroscopic assignment and analysis of tenofovir has been carried out by using FTIR and FT-Raman spectral data. The vibrational analysis was aided by electronic structure calculations—hybrid density functional methods (B3LYP/6-311++G(d,p, B3LYP/6-31G(d,p, and B3PW91/6-31G(d,p. Molecular equilibrium geometries, electronic energies, IR intensities, and harmonic vibrational frequencies have been computed. The assignments proposed based on the experimental IR and Raman spectra have been reviewed and complete assignment of the observed spectra have been proposed. UV-visible spectrum of the compound was also recorded and the electronic properties such as HOMO and LUMO energies and were determined by time-dependent DFT (TD-DFT method. The geometrical, thermodynamical parameters, and absorption wavelengths were compared with the experimental data. The B3LYP/6-311++G(d,p-, B3LYP/6-31G(d,p-, and B3PW91/6-31G(d,p-based NMR calculation procedure was also done. It was used to assign the 13C and 1H NMR chemical shift of tenofovir.

Stable Caloric Intake and Continued Virologic Suppression for HIV-Positive Antiretroviral Treatment-Experienced Women After Switching to a Single-Tablet Regimen of Emtricitabine, Rilpivirine, and Tenofovir Disoproxil Fumarate.

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Menezes, Prema; Mollan, Katie; Hoffman, Erin; Xie, Zimeng; Wills, Jennifer; Marcus, Cheryl; Rublein, John; Hudgens, Michael; Eron, Joseph J

2018-05-02

Benefits of switching to a single-tablet regimen (STR) of emtricitabine/rilpivirine/tenofovir (FTC/RPV/TDF) in virologically suppressed antiretroviral treatment (ART) experienced HIV-positive women include pregnancy category B rating and lack of clinically significant drug interactions between RPV and oral contraceptives. Unfortunately, studies involving switching to FTC/RPV/TDF enrolled fewer than 25% women. We undertook this 48-week study to assess the ability of virologically suppressed HIV-positive women switching to RPV STR to remain virologically suppressed and comply with the caloric intake requirement. HIV-positive women on ART with viral load phone calls on randomly chosen dates. For each 3-day food diary, the daily median caloric intake and median value for each macronutrient consumed concurrent with FTC/RPV/TDF were computed. Medication adherence was measured using a visual analog scale. We enrolled 33 women, 73% of whom were African American. At week 48, virologic suppression (HIV RNA phone call. Median kcal intake (food diary) did not change significantly from baseline (684 kcal) to week 48 (820 kcal); median change 102 kcal, p = .15. Women who reported noncompliance with a ≥400 kcal meal did not experience virologic failure. Significant concordance between caloric adherence and virologic suppression was not detected. Our study demonstrated that HIV-positive women who switched to STR FTC/RPV/TDF continued to experience virologic suppression and were readily able to comply with the recommended caloric intake requirement.

Pregnancy and infant outcomes among HIV-infected women taking long-term ART with and without tenofovir in the DART trial.

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Diana M Gibb

Full Text Available Few data have described long-term outcomes for infants born to HIV-infected African women taking antiretroviral therapy (ART in pregnancy. This is particularly true for World Health Organization (WHO-recommended tenofovir-containing first-line regimens, which are increasingly used and known to cause renal and bone toxicities; concerns have been raised about potential toxicity in babies due to in utero tenofovir exposure.Pregnancy outcome and maternal/infant ART were collected in Ugandan/Zimbabwean HIV-infected women initiating ART during The Development of AntiRetroviral Therapy in Africa (DART trial, which compared routine laboratory monitoring (CD4; toxicity versus clinically driven monitoring. Women were followed 15 January 2003 to 28 September 2009. Infant feeding, clinical status, and biochemistry/haematology results were collected in a separate infant study. Effect of in utero ART exposure on infant growth was analysed using random effects models. 382 pregnancies occurred in 302/1,867 (16% women (4.4/100 woman-years [95% CI 4.0-4.9]. 226/390 (58% outcomes were live-births, 27 (7% stillbirths (≥22 wk, and 137 (35% terminations/miscarriages (0.4. Of 219 surviving infants, 182 (83% enrolled in the follow-up study; median (interquartile range [IQR] age at last visit was 25 (12-38 months. From mothers' ART, 62/9/111 infants had no/20%-89%/≥90% in utero tenofovir exposure; most were also zidovudine/lamivudine exposed. All 172 infants tested were HIV-negative (ten untested. Only 73/182(40% infants were breast-fed for median 94 (IQR 75-212 days. Overall, 14 infants died at median (IQR age 9 (3-23 months, giving 5% 12-month mortality; six of 14 were HIV-uninfected; eight untested infants died of respiratory infection (three, sepsis (two, burns (one, measles (one, unknown (one. During follow-up, no bone fractures were reported to have occurred; 12/368 creatinines and seven out of 305 phosphates were grade one (16 or two (three in 14 children

Pregnancy and infant outcomes among HIV-infected women taking long-term ART with and without tenofovir in the DART trial.

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Gibb, Diana M; Kizito, Hilda; Russell, Elizabeth C; Chidziva, Ennie; Zalwango, Eva; Nalumenya, Ruth; Spyer, Moira; Tumukunde, Dinah; Nathoo, Kusum; Munderi, Paula; Kyomugisha, Hope; Hakim, James; Grosskurth, Heiner; Gilks, Charles F; Walker, A Sarah; Musoke, Phillipa

2012-01-01

Few data have described long-term outcomes for infants born to HIV-infected African women taking antiretroviral therapy (ART) in pregnancy. This is particularly true for World Health Organization (WHO)-recommended tenofovir-containing first-line regimens, which are increasingly used and known to cause renal and bone toxicities; concerns have been raised about potential toxicity in babies due to in utero tenofovir exposure. Pregnancy outcome and maternal/infant ART were collected in Ugandan/Zimbabwean HIV-infected women initiating ART during The Development of AntiRetroviral Therapy in Africa (DART) trial, which compared routine laboratory monitoring (CD4; toxicity) versus clinically driven monitoring. Women were followed 15 January 2003 to 28 September 2009. Infant feeding, clinical status, and biochemistry/haematology results were collected in a separate infant study. Effect of in utero ART exposure on infant growth was analysed using random effects models. 382 pregnancies occurred in 302/1,867 (16%) women (4.4/100 woman-years [95% CI 4.0-4.9]). 226/390 (58%) outcomes were live-births, 27 (7%) stillbirths (≥22 wk), and 137 (35%) terminations/miscarriages (0.4). Of 219 surviving infants, 182 (83%) enrolled in the follow-up study; median (interquartile range [IQR]) age at last visit was 25 (12-38) months. From mothers' ART, 62/9/111 infants had no/20%-89%/≥90% in utero tenofovir exposure; most were also zidovudine/lamivudine exposed. All 172 infants tested were HIV-negative (ten untested). Only 73/182(40%) infants were breast-fed for median 94 (IQR 75-212) days. Overall, 14 infants died at median (IQR) age 9 (3-23) months, giving 5% 12-month mortality; six of 14 were HIV-uninfected; eight untested infants died of respiratory infection (three), sepsis (two), burns (one), measles (one), unknown (one). During follow-up, no bone fractures were reported to have occurred; 12/368 creatinines and seven out of 305 phosphates were grade one (16) or two (three) in 14

[Tenofovir and entecavir for chronic hepatitis B infection treatment: a single-center experience

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Fabio Tarsetti

2015-12-01

DISCUSSION: Tenofovir seems to exert a better viral replication inhibition (though not statistically significant and to show transaminases improvement in comparison with entecavir, which, in turn, results more effective in HBeAg/HBsAg seroconversion. Both drugs have a high safety profile in terms of side effects. [Article in Italian

Efavirenz, tenofovir and emtricitabine combined with first-line tuberculosis treatment in tuberculosis-HIV-coinfected Tanzanian patients: a pharmacokinetic and safety study.

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Semvua, Hadija H; Mtabho, Charles M; Fillekes, Quirine; van den Boogaard, Jossy; Kisonga, Riziki M; Mleoh, Liberate; Ndaro, Arnold; Kisanga, Elton R; van der Ven, Andre; Aarnoutse, Rob E; Kibiki, Gibson S; Boeree, Martin J; Burger, David M

2013-01-01

To evaluate the effect of rifampicin-based tuberculosis (TB) treatment on the pharmacokinetics of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet, and vice versa, in Tanzanian TB-HIV-coinfected patients. This was a Phase II open-label multiple dose pharmacokinetic and safety study. This study was conducted in TB-HIV-coinfected Tanzanian patients who started TB treatment (rifampicin/isoniazid/pyrazinamide/ethambutol) at week 1 to week 8 and continued with rifampicin and isoniazid for another 16 weeks. Antiretroviral treatment (ART) of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet was started at week 4 after initiation of TB treatment. A 24-h pharmacokinetic sampling curve was recorded at week 8 (with TB treatment) and week 28 (ART alone). For TB drugs, blood samples at 2 and 5 h post-dose were taken at week 3 (TB treatment alone) and week 8 (with ART). A total of 25 patients (56% male) completed the study; 21 had evaluable pharmacokinetic profiles. The area under the concentration-time curve 0-24 h post-dose of efavirenz, tenofovir and emtricitabine were slightly higher when these drugs were coadministered with TB drugs; geometric mean ratios (90% CI) were 1.08 (0.90, 1.30), 1.13 (0.93, 1.38) and 1.05 (0.85, 1.29), respectively. For TB drugs, equivalence was suggested for peak plasma concentrations when administered with and without efavirenz/tenofovir/emtricitabine. Adverse events were mostly mild and no serious adverse events or drug discontinuations were reported. Coadministration of efavirenz, tenofovir and emtricitabine with a standard first-line TB treatment regimen did not significantly alter the pharmacokinetic parameters of these drugs and was tolerated well by Tanzanian TB patients who are coinfected with HIV.

Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study

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Stellbrink, Hans-Jürgen; Orkin, Chloe; Arribas, Jose Ramon

2010-01-01

Abacavir-lamivudine and tenofovir DF-emtricitabine fixed-dose combinations are commonly used as first-line antiretroviral therapies. However, few studies have comprehensively compared their relative safety profiles.......Abacavir-lamivudine and tenofovir DF-emtricitabine fixed-dose combinations are commonly used as first-line antiretroviral therapies. However, few studies have comprehensively compared their relative safety profiles....

An update on the use of Atripla® in the treatment of HIV in the United States

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Michael A Horberg

2010-06-01

Full Text Available Michael A Horberg1, Daniel B Klein21HIV Interregional Initiative, Kaiser Permanente, Oakland, California, USA; 2Department of Infectious Diseases, Kaiser Permanente Hayward Medical Center, Hayward, California, USAAbstract: Atripla® (Gilead Sciences Inc, Foster City, CA, USA and Bristol-Myers Squibb, New York City, NY, USA is a coformulated single pill composed of efavirenz, emtricitabine, and tenofovir disoproxil, intended as a once-daily potent combination antiretroviral therapeutic agent. Its efficacy is equivalent to the 3 component drugs taken in a combination as single medications. The coformulated antiretroviral regimen can be quite effective in patients whose human immunodeficiency virus is sensitive to all 3 components of Atripla. However, women at risk of pregnancy, already pregnant, or nursing mothers should not take Atripla, due to the teratogenic potential of the efavirenz moiety. Adverse effects are similar to those seen with the constituent medications, including potential central nervous system effects and renal toxicity. Since its US Food and Drug administration approval, prescriptions for Atripla have increased steadily.Keywords: tenofovir, efavirenz, emtricitabine, antiretroviral therapy

Laboratory evaluation of three regimens of treatment of chronic hepatitis B: Tenofovir, entecavir and combination of lamivudine and adefovir

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Rajeswari Jayakumar

2012-01-01

Full Text Available Background: Chronic hepatitis B is a disease of concern due to its life-threatening complications like cirrhosis, and hepatocellular carcinoma (HCC in 20-40% of patients. There are about 400 million people affected worldwide with HBV, and over 300,000 die every year from HBV-related diseases. Oral antivirals like lamivudine, adefovir, entecavir, and tenofovir are commonly used to treat chronic hepatitis B. In this study, we tried to evaluate the comparative efficacy of these drugs alone and in combination. Materials and Methods: Chronic hepatitis B patients with HBV-DNA more than 10 4 Copies/mL irrespective of their HBeAg status (n=60 were enrolled in a prospective study. 21, 20, and 19 patients were treated with lamivudine (100 mg/day plus adefovir (10 mg/day combination entecavir monotherapy (0.5 mg/day and tenofovir monotherapy (300 mg/day, respectively and were followed up for 24 weeks with their virological, serological, and biochemical markers measured at 12 and 24 weeks. Results: After 24 weeks of treatment, there was no significant difference between the 3 groups in suppressing HBV-DNA to undetectable levels. The median decrease in HBV-DNA levels from baseline was better with tenofovir and entecavir monotherapies than lamivudine and adefovir combination, which was statistically significant. There was no significant difference between the 3 groups in HBsAg and HBeAg seroconversion and normalization of biochemical parameters. Conclusion: Entecavir and tenofovir monotherapy were found to be more effective than lamivudine plus adefovir combination in reducing the HBV-DNA levels. However, lamivudine plus adefovir combination was not too inferior, especially when cost of treatment was taken into consideration.

Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection.

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Walmsley, Sharon L; Antela, Antonio; Clumeck, Nathan; Duiculescu, Dan; Eberhard, Andrea; Gutiérrez, Felix; Hocqueloux, Laurent; Maggiolo, Franco; Sandkovsky, Uriel; Granier, Catherine; Pappa, Keith; Wynne, Brian; Min, Sherene; Nichols, Garrett

2013-11-07

Dolutegravir (S/GSK1349572), a once-daily, unboosted integrase inhibitor, was recently approved in the United States for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral agents. Dolutegravir, in combination with abacavir-lamivudine, may provide a simplified regimen. We conducted a randomized, double-blind, phase 3 study involving adult participants who had not received previous therapy for HIV-1 infection and who had an HIV-1 RNA level of 1000 copies per milliliter or more. Participants were randomly assigned to dolutegravir at a dose of 50 mg plus abacavir-lamivudine once daily (DTG-ABC-3TC group) or combination therapy with efavirenz-tenofovir disoproxil fumarate (DF)-emtricitabine once daily (EFV-TDF-FTC group). The primary end point was the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter at week 48. Secondary end points included the time to viral suppression, the change from baseline in CD4+ T-cell count, safety, and viral resistance. A total of 833 participants received at least one dose of study drug. At week 48, the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (88% vs. 81%, P=0.003), thus meeting the criterion for superiority. The DTG-ABC-3TC group had a shorter median time to viral suppression than did the EFV-TDF-FTC group (28 vs. 84 days, Pdreams, anxiety, dizziness, and somnolence) were significantly more common in the EFV-TDF-FTC group, whereas insomnia was reported more frequently in the DTG-ABC-3TC group. No participants in the DTG-ABC-3TC group had detectable antiviral resistance; one tenofovir DF-associated mutation and four efavirenz-associated mutations were detected in participants with virologic failure in the EFV-TDF-FTC group. Dolutegravir plus abacavir-lamivudine had a better safety profile and was more effective

Gateways to clinical trials.

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Bayés, M; Rabasseda, X; Prous, J R

2005-04-01

extract, synthetic human secretin; Taxus, telavancin hydrochloride, telithromycin, temoporfin, tenofovir disoproxil fumarate, tenofovir disoproxil fumarate/emtricitabine, teriparatide, testosterone gel, TG-1024, tirapazamine, travoprost, travoprost/timolol; Valdecoxib, valganciclovir hydrochloride, voriconazole; Ximelagatran.

Cumulative Antiretroviral Exposure Measured in Hair Is Not Associated With Measures of HIV Persistence or Inflammation Among Individuals on Suppressive ART.

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Gandhi, Monica; Gandhi, Rajesh T; Stefanescu, Andrei; Bosch, Ronald J; Cyktor, Joshua C; Horng, Howard; Louie, Alexander; Phung, Nhi; Eron, Joseph J; Hogg, Evelyn; Macatangay, Bernard J C; Hensel, Christopher; Fletcher, Courtney V; Mellors, John W; McMahon, Deborah K

2018-06-20

Data on the relationship of antiretroviral exposure to measures of human immunodeficiency virus (HIV) persistence are limited. To address this gap, multiple viral, immunologic, and pharmacologic measures were analyzed from individuals with sustained virologic suppression on therapy (median 7 years) in the AIDS Clinical Trials Group A5321 cohort. Among 110 participants on tenofovir-(TFV)-disoproxil-fumarate (TDF)/emtricitabine (FTC)-containing regimens, we found no significant correlation between hair concentrations of individual antiretrovirals (ARVs) in the regimen and measures of HIV persistence (plasma HIV-1 RNA by single copy assay, cell-associated-DNA, cell-associated RNA) or soluble markers of inflammation. These findings suggest that higher systemic ARV exposure may not impact HIV persistence or inflammation.

Pre-exposure Prophylaxis Against Human Immunodeficiency Virus

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Güle ÇINAR

2018-03-01

Full Text Available According to the Center for Disease Control and Prevention (CDC, there were 2.1 million new human immunodeficiency virus (HIV cases reported worldwide in 2015, which shows that siginificant work needs to be done to prevent the transmission of HIV. Research to date has focused mainly on high-risk men who have sex with men, but many women around the world are also at a high risk for HIV transmissions. In studies conducted, the incidence of HIV infection in high-risk individuals decreases over 90% when high-risk individuals use pre-exposure prophylaxis (PreP HIV, tenofovir disoproxil fumarate-emtricitabine (TDF-FTC safely. Current data and studies on pre-exposure prophylaxis were discussed in this review.

Effects on vitamin D, bone and the kidney of switching from fixed-dose tenofovir disoproxil fumarate/emtricitabine/efavirenz to darunavir/ritonavir monotherapy: a randomized, controlled trial (MIDAS).

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Hamzah, Lisa; Tiraboschi, Juan M; Iveson, Helen; Toby, Martina; Mant, Christine; Cason, John; Burling, Keith; Wandolo, Emily; Jendrulek, Isabelle; Taylor, Chris; Ibrahim, Fowzia; Kulasegaram, Ranjababu; Teague, Alastair; Post, Frank A; Fox, Julie

2016-01-01

Efavirenz (EFV) has been associated with reductions in vitamin D (25[OH]D) and tenofovir (TDF) with increased bone turnover, reductions in bone mineral density (BMD) and renal tubular dysfunction. We hypothesized that switching from fixed-dose TDF/emtricitabine (FTC)/EFV to darunavir/ritonavir monotherapy (DRV/r) might increase 25(OH)D and BMD, and improve renal tubular function. Subjects with HIV RNA <50 copies/ml on TDF/FTC/EFV for ≥6 months were randomized 1:1 to ongoing TDF/FTC/EFV or DRV/r (800/100 mg once daily) for 48 weeks. The primary end point was change from baseline in 25(OH)D at week 48. Secondary end points included changes in BMD, bone turnover markers and renal tubular function. A total of 64 subjects (86% male, 66% white, mean [sd] CD4(+) T-cell count 537.3 [191.5]/mm(3)) were analysed. After adjustment for baseline 25(OH)D and demographics, at week 48 DRV/r monotherapy was associated with a +3.6 (95% CI 0.6, 6.6) ng/ml increase in 25(OH)D compared to TDF/FTC/EFV (P=0.02). DRV/r monotherapy was associated with an increase in BMD (+2.9% versus -0.003% at the neck of femur and +2.6% versus +0.008% at the lumbar spine for DRV/r versus TDF/FTC/EFV; P<0.05 for all) and reductions in bone biomarkers compared with those remaining on TDF/FTC/EFV. No significant difference in renal tubular function was observed. Reasons for discontinuation in the DRV/r arm included side effects (n=4) and viral load rebound (n=3), all of which resolved with DRV/r discontinuation or regimen intensification. Switching from TDF/FTC/EFV to DRV/r in patients with suppressed HIV RNA resulted in significant improvements in 25(OH)D and bone biomarkers, and a 2-3% increase in BMD.

Virological responses to lamivudine or emtricitabine when combined with tenofovir and a protease inhibitor in treatment-naïve HIV-1-infected patients in the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort.

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Rokx, C; Gras, L; van de Vijver, Damc; Verbon, A; Rijnders, Bja

2016-09-01

Lamivudine (3TC) and emtricitabine (FTC) are considered interchangeable in recommended tenofovir disoproxil-fumarate (TDF)-containing combination antiretroviral therapies (cARTs). This statement of equivalence has not been systematically studied. We compared the treatment responses to 3TC and FTC combined with TDF in boosted protease inhibitor (PI)-based cART for HIV-1-infected patients. An observational study in the AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort was carried out between 2002 and 2013. Virological failure rates, time to HIV RNA suppression treatment failure were analysed using multivariable logistic regression and Cox proportional hazard models. Sensitivity analyses included propensity score-adjusted models. A total of 1582 ART-naïve HIV-1-infected patients initiated 3TC or FTC with TDF and ritonavir-boosted darunavir (29.6%), atazanavir (41.5%), lopinavir (27.1%) or another PI (1.8%). Week 48 virological failure rates on 3TC and FTC were comparable (8.9% and 5.6%, respectively; P = 0.208). The multivariable adjusted odds ratio of virological failure when using 3TC instead of FTC with TDF in PI-based cART was 0.75 [95% confidence interval (CI) 0.32-1.79; P = 0.51]. Propensity score-adjusted models showed comparable results. The adjusted hazard ratio (HR) for treatment failure of 3TC compared with FTC was 1.15 (95% CI 0.58-2.27) within 240 weeks after cART initiation. The time to two consecutive HIV RNA measurements treatment failure after suppression treatment-naïve HIV-1-infected patients starting either 3TC/TDF or FTC/TDF and a ritonavir-boosted PI. © 2016 British HIV Association.

Bone Health and Impact of Tenofovir Treatment in Men with Hepatitis-B Related Chronic Liver Disease.

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Sajith, Kattiparambil G; Kapoor, Nitin; Shetty, Sahana; Goel, Ashish; Zachariah, Uday; Eapen, Chundamannil E; Paul, Thomas V

2018-03-01

Chronic Liver Disease (CLD) has been shown to have an adverse impact on bone health. Hepatitis-B related CLD and its treatment with tenofovir may have additional effects on skeleton. To study the impact of HBV related CLD and its treatment with Tenofovir on bone health in Indian subjects. This cross sectional study included men (18-60 years) and comprised of three groups: Group-1 was treatment naïve HBV related CLD ( n  = 79), Group-2 those with HBV related CLD on tenofovir for at least 1 year ( n  = 136), Group-3 age, sex and Body Mass Index (BMI) matched healthy controls ( n  = 58). Bone biochemistry and Bone Mineral Density (BMD) at spine, Femoral Neck (FN) and forearm were studied. Independent t -test or ANOVA was used to compare the means of continuous variables and chi-square test for categorical variables. Multiple logistic regression was used to assess the factors causing Low Bone Mass (LBM) at FN. A significantly greater proportion ( P  CLD (group 1 and group 2) had vitamin D deficiency (CLD than controls. The prevalence of LBM was higher in group 1 at the spine (31%) and forearm (18.4%) when compared to controls (8.1% and 7.8% respectively) ( P  10,000 IU/ml) emerged as significant risk factors for LBM at FN. The impact of hepatitis-B related CLD as well as its treatment on bone health is significant. Bone health need to be periodically evaluated in these subjects especially in older men who are lean and have a higher viral load.

In Silico and in Vitro Screening for P-Glycoprotein Interaction with Tenofovir, Darunavir, and Dapivirine: An Antiretroviral Drug Combination for Topical Prevention of Colorectal HIV Transmission.

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Swedrowska, Magda; Jamshidi, Shirin; Kumar, Abhinav; Kelly, Charles; Rahman, Khondaker Miraz; Forbes, Ben

2017-08-07

The aim of the study was to use in silico and in vitro techniques to evaluate whether a triple formulation of antiretroviral drugs (tenofovir, darunavir, and dapivirine) interacted with P-glycoprotein (P-gp) or exhibited any other permeability-altering drug-drug interactions in the colorectal mucosa. Potential drug interactions with P-gp were screened initially using molecular docking, followed by molecular dynamics simulations to analyze the identified drug-transporter interaction more mechanistically. The transport of tenofovir, darunavir, and dapivirine was investigated in the Caco-2 cell models and colorectal tissue, and their apparent permeability coefficient (P app ), efflux ratio (ER), and the effect of transporter inhibitors were evaluated. In silico, dapivirine and darunavir showed strong affinity for P-gp with similar free energy of binding; dapivirine exhibiting a ΔG PB value -38.24 kcal/mol, darunavir a ΔG PB value -36.84 kcal/mol. The rank order of permeability of the compounds in vitro was tenofovir dapivirine. The P app for tenofovir in Caco-2 cell monolayers was 0.10 ± 0.02 × 10 -6 cm/s, ER = 1. For dapivirine, P app was 32.2 ± 3.7 × 10 -6 cm/s, but the ER = 1.3 was lower than anticipated based on the in silico findings. Neither tenofovir nor dapivirine transport was influenced by P-gp inhibitors. The absorptive permeability of darunavir (P app = 6.4 ± 0.9 × 10 -6 cm/s) was concentration dependent with ER = 6.3, which was reduced by verapamil to 1.2. Administration of the drugs in combination did not alter their permeability compared to administration as single agents. In conclusion, in silico modeling, cell culture, and tissue-based assays showed that tenofovir does not interact with P-gp and is poorly permeable, consistent with a paracellular transport mechanism. In silico modeling predicted that darunavir and dapivirine were P-gp substrates, but only darunavir showed P-gp-dependent permeability in the biological models, illustrating that

Long-term exposure to tenofovir continuously decrease renal function in HIV-1-infected patients with low body weight: results from 10 years of follow-up.

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Nishijima, Takeshi; Kawasaki, Yohei; Tanaka, Noriko; Mizushima, Daisuke; Aoki, Takahiro; Watanabe, Koji; Kinai, Ei; Honda, Haruhito; Yazaki, Hirohisa; Tanuma, Junko; Tsukada, Kunihisa; Teruya, Katsuji; Kikuchi, Yoshimi; Gatanaga, Hiroyuki; Oka, Shinichi

2014-08-24

To investigate the effect of long-term tenofovir disoproxil fumarate (TDF) use on renal function, especially in patients with low body weight who are vulnerable to TDF nephrotoxicity. A single-center, observational study in Tokyo, Japan. We performed a 10 years cohort study of 792 HIV-1-infected patients. The effect of long-term TDF use on estimated glomerular filtration rate (eGFR) was investigated on treatment-naive patients who started TDF-containing antiretroviral therapy (n = 422) and those who started abacavir-containing antiretroviral therapy as control (n = 370). Three renal endpoints were examined by the logistic regression model: decrement in eGFR of higher than 10 ml/min per 1.73 m relative to the baseline, more than 25% decrement in eGFR, and eGFR lower than 60 ml/min per 1.73 m at least 3 months apart. The loss in eGFR was estimated using linear mixed models for repeated measures. The median weight at baseline was 63 kg. TDF use increased the risk of all three renal outcomes compared with the control group: higher than 10 ml/min per 1.73 m decrement in eGFR [adjusted odds ratio (OR) = 2.1, 95% confidence interval (CI) 1.45-3.14, P decrement (adjusted OR = 2.1, 95% CI 1.50-2.90, P < 0.001), and eGFR lower than 60 ml/min per 1.73 m at least 3 months apart (adjusted OR = 3.9, 95% CI 1.62-9.36, P = 0.002). The cumulative mean loss relative to the control after 1, 2, 3, 4, and 5 years of TDF exposure was -3.8, -3.6, -5.5, -6.6, and -10.3 ml/min per 1.73 m, respectively, indicating that the loss in eGFR increased over time (P < 0.001). In this cohort of patients with low body weight, TDF exposure increased the risk of renal dysfunction. Furthermore, the loss in eGFR relative to the control increased continuously up to 5 years.

Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection

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Pedersen Niels C

2007-04-01

Full Text Available Abstract Background We reported previously on the emergence and clinical implications of simian immunodeficiency virus (SIVmac251 mutants with a K65R mutation in reverse transcriptase (RT, and the role of CD8+ cell-mediated immune responses in suppressing viremia during tenofovir therapy. Because of significant sequence differences between SIV and HIV-1 RT that affect drug susceptibilities and mutational patterns, it is unclear to what extent findings with SIV can be extrapolated to HIV-1 RT. Accordingly, to model HIV-1 RT responses, 12 macaques were inoculated with RT-SHIV, a chimeric SIV containing HIV-1 RT, and started on prolonged tenofovir therapy 5 months later. Results The early virologic response to tenofovir correlated with baseline viral RNA levels and expression of the MHC class I allele Mamu-A*01. For all animals, sensitive real-time PCR assays detected the transient emergence of K70E RT mutants within 4 weeks of therapy, which were then replaced by K65R mutants within 12 weeks of therapy. For most animals, the occurrence of these mutations preceded a partial rebound of plasma viremia to levels that remained on average 10-fold below baseline values. One animal eventually suppressed K65R viremia to undetectable levels for more than 4 years; sequential experiments using CD8+ cell depletion and tenofovir interruption demonstrated that both CD8+ cells and continued tenofovir therapy were required for sustained suppression of viremia. Conclusion This is the first evidence that tenofovir therapy can select directly for K70E viral mutants in vivo. The observations on the clinical implications of the K65R RT-SHIV mutants were consistent with those of SIVmac251, and suggest that for persons infected with K65R HIV-1 both immune-mediated and drug-dependent antiviral activities play a role in controlling viremia. These findings suggest also that even in the presence of K65R virus, continuation of tenofovir treatment as part of HAART may be

Bone mineral density and inflammatory and bone biomarkers after darunavir-ritonavir combined with either raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults with HIV-1: a substudy of the NEAT001/ANRS143 randomised trial.

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Bernardino, Jose I; Mocroft, Amanda; Mallon, Patrick W; Wallet, Cedrick; Gerstoft, Jan; Russell, Charlotte; Reiss, Peter; Katlama, Christine; De Wit, Stephane; Richert, Laura; Babiker, Abdel; Buño, Antonio; Castagna, Antonella; Girard, Pierre-Marie; Chene, Genevieve; Raffi, Francois; Arribas, Jose R

2015-11-01

lumbar spine was greater in the standard group than in the NtRTI-sparing group (mean percentage change -2.49% vs -1.00%, mean percentage difference -1.49, 95% CI -2.94 to -0.04; p=0.046). Total hip bone mineral density loss was similarly greater at week 48 in the standard group than in the NtRTI-sparing group (mean percentage change -3.30% vs -0.73%; mean percentage difference -2.57, 95% CI -3.75 to -1.35; pfractures occurred during the trial (two in the NtRTI-sparing group and five in the standard group). A raltegravir-based regimen was associated with significantly less loss of bone mineral density than a standard regimen containing tenofovir disoproxil fumarate, and might be a treatment option for patients at high risk of osteopenia or osteoporosis who are not suitable for NtRTIs such as abacavir or tenofovir alafenamide. The European Union Sixth Framework Programme, Inserm-ANRS, Ministerio de Sanidad y Asuntos Sociales de España, Gilead Sciences, Janssen Pharmaceuticals, and Merck Laboratories. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development and validation of an assay for the simultaneous determination of zidovudine, abacavir, emtricitabine, lamivudine, tenofovir and ribavirin in human plasma using liquid chromatography-tandem mass spectrometry.

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Kromdijk, W; Pereira, S A; Rosing, H; Mulder, J W; Beijnen, J H; Huitema, A D R

2013-03-01

This paper describes the development and validation of an assay for the simultaneous quantification of the antiviral and antiretroviral drugs zidovudine, abacavir, emtricitabine, lamivudine, tenofovir and ribavirin in human plasma using liquid chromatography coupled to tandem mass spectrometry. Sample pretreatment consisted of protein precipitation with 0.1% (v/v) formic acid in methanol, evaporation and reconstitution. Chromatographic separation was performed on a Synergy Polar reversed phase C18 column (150 mm × 2.0 mm ID, particle size 4 μm) using a stepwise gradient with 0.1% (v/v) formic acid in water and 0.1% (v/v) formic acid in methanol at a flow rate of 300 μL/min. A triple quadrupole mass spectrometer operating in the positive ionization mode was used for drug detection and quantification. Isotopically labeled zidovudine, lamivudine, tenofovir and ribavirin were used as internal standards. The method was validated over a clinical range of 20-2500 ng/mL for zidovudine, lamivudine and tenofovir, 4-500 ng/mL for abacavir and emtricitabine and 160-20,000 ng/mL for ribavirin. The inter and intra-assay accuracies and precisions were between -8.47% and 14.2% for zidovudine, emtricitabine and ribavirin. For abacavir, lamivudine and tenofovir, the inter and intra-assay accuracies and precisions at the lower limit of quantification were between -11.0% and 18.3%, whereas at all other levels these accuracies and precisions were between -11.7% and 12.0%. The described method is suitable for the determination of zidovudine, abacavir, emtricitabine, lamivudine, tenofovir and ribavirin in human plasma in clinical practice to monitor plasma concentrations in selected cases to optimize therapy. Copyright © 2013. Published by Elsevier B.V.

HIV-HBV coinfection in Southern Africa and the effect of lamivudine- versus tenofovir-containing cART on HBV outcomes

NARCIS (Netherlands)

Hamers, Raph L.; Zaaijer, Hans L.; Wallis, Carole L.; Siwale, Margaret; Ive, Prudence; Botes, Mariette E.; Sigaloff, Kim C. E.; Hoepelman, Andy I. M.; Stevens, Wendy S.; Rinke de Wit, Tobias F.

2013-01-01

This study assessed HIV-hepatitis B virus (HBV) coinfection in southern Africa in terms of prevalence, viral characteristics, occult HBV, and the effect of lamivudine- versus tenofovir-containing first-line combination antiretroviral treatment (cART) on HBV-related outcomes. A multicenter

The Vaginal Acquisition and Dissemination of HIV-1 Infection in a Novel Transgenic Mouse Model Is Facilitated by Coinfection with Herpes Simplex Virus 2 and Is Inhibited by Microbicide Treatment.

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Seay, Kieran; Khajoueinejad, Nazanin; Zheng, Jian Hua; Kiser, Patrick; Ochsenbauer, Christina; Kappes, John C; Herold, Betsy; Goldstein, Harris

2015-09-01

Epidemiological studies have demonstrated that herpes simplex virus 2 (HSV-2) infection significantly increases the risk of HIV-1 acquisition, thereby contributing to the expanding HIV-1 epidemic. To investigate whether HSV-2 infection directly facilitates mucosal HIV-1 acquisition, we used our transgenic hCD4/R5/cT1 mouse model which circumvents major entry and transcription blocks preventing murine HIV-1 infection by targeting transgenic expression of human CD4, CCR5, and cyclin T1 genes to CD4(+) T cells and myeloid-committed cells. Productive infection of mucosal leukocytes, predominantly CD4(+) T cells, was detected in all hCD4/R5/cT1 mice intravaginally challenged with an HIV-1 infectious molecular clone, HIV-Du151.2env-NLuc, which expresses an env gene (C.Du151.2) cloned from an acute heterosexually infected woman and a NanoLuc luciferase reporter gene. Lower genital tract HIV-1 infection after HIV-Du151.2env-NLuc intravaginal challenge was increased ~4-fold in hCD4/R5/cT1 mice coinfected with HSV-2. Furthermore, HIV-1 dissemination to draining lymph nodes was detected only in HSV-2-coinfected mice. HSV-2 infection stimulated local infiltration and activation of CD4(+) T cells and dendritic cells, likely contributing to the enhanced HIV-1 infection and dissemination in HSV-2-coinfected mice. We then used this model to demonstrate that a novel gel containing tenofovir disoproxil fumarate (TDF), the more potent prodrug of tenofovir (TFV), but not the TFV microbicide gel utilized in the recent CAPRISA 004, VOICE (Vaginal and Oral Interventions to Control the Epidemic), and FACTS 001 clinical trials, was effective as preexposure prophylaxis (PrEP) to completely prevent vaginal HIV-1 infection in almost half of HSV-2-coinfected mice. These results also support utilization of hCD4/R5/cT1 mice as a highly reproducible immunocompetent preclinical model to evaluate HIV-1 acquisition across the female genital tract. Multiple epidemiological studies have reported that

Aminotransferase elevation in HIV/hepatitis B virus co-infected patients treated with two active hepatitis B virus drugs.

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Jain, Mamta K; Parekh, Nimisha K; Hester, Jill; Lee, William M

2006-12-01

Discerning drug hepatotoxicity from viral hepatitis flares remains an ongoing problem unique to patients coinfected with HIV and hepatitis B (HBV). We present three such coinfected patients who have been on two anti-HBV agents, lamivudine and tenofovir disoproxil fumarate simultaneously, as part of highly active antiretroviral therapy (HAART). All three developed significant aminotransferase elevations 6-12 weeks after initiation of HAART despite being on two active HBV drugs. Two of the three patients were initially thought to have drug-related hepatotoxicity from HIV medications. It seems more likely that all three patients demonstrated hepatitis B reactivation of differing severity as the result of varying degrees of immune recovery. Distinguishing clearly between drug-related hepatotoxicity and hepatitis reactivation may be difficult but is important as their clinical management differs.

Peg-interferon plus nucleotide analogue treatment versus no treatment in patients with chronic hepatitis B with a low viral load: a randomised controlled, open-label trial.

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de Niet, Annikki; Jansen, Louis; Stelma, Femke; Willemse, Sophie B; Kuiken, Sjoerd D; Weijer, Sebastiaan; van Nieuwkerk, Carin M J; Zaaijer, Hans L; Molenkamp, Richard; Takkenberg, R Bart; Koot, Maarten; Verheij, Joanne; Beuers, Ulrich; Reesink, Hendrik W

2017-08-01

Antiviral treatment is currently not recommended for patients with chronic hepatitis B with a low viral load. However, they might benefit from acquiring a functional cure (hepatitis B surface antigen [HBsAg] loss with or without formation of antibodies against hepatitis B surface antigen [anti-HBs]). We assessed HBsAg loss during peg-interferon-alfa-2a (peg-IFN) and nucleotide analogue combination therapy in patients with chronic hepatitis B with a low viral load. In this randomised controlled, open-label trial, patients were enrolled from the Academic Medical Center (AMC), Amsterdam, Netherlands. Eligible patients were HBsAg positive and hepatitis B e antigen (HBeAg) negative for more than 6 months, could be treatment naive or treatment experienced, and had alanine aminotransferase (ALT) concentrations less than 5 × upper limit of normal (ULN). Participants were randomly assigned (1:1:1) by a computerised randomisation programme (ALEA Randomisation Service) to receive peg-IFN 180 μg/week plus adefovir 10 mg/day, peg-IFN 180 μg/week plus tenofovir disoproxil fumarate 245 mg/day, or no treatment for 48 weeks. The primary endpoint was the proportion of patients with serum HBsAg loss among those who received at least one dose of study drug or had at least one study visit (modified intention-to-treat population [mITT]). All patients have finished the initial study of 72 weeks and will be observed for up to 5 years of follow-up. This study is registered with ClinicalTrials.gov, number NCT00973219. Between Aug 4, 2009, and Oct 17, 2013, 167 patients were screened for enrolment, of whom 151 were randomly assigned (52 to peg-IFN plus adefovir, 51 to peg-IFN plus tenofovir, and 48 to no treatment). 46 participants in the peg-IFN plus adefovir group, 45 in the peg-IFN plus tenofovir group, and 43 in the no treatment group began treatment or observation and were included in the mITT population. At week 72, two (4%) patients in the peg-IFN plus adefovir group and two (4

Nephrotoxicity during tenofovir treatment: a three-year follow-up study in a Brazilian reference clinic

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Lauro Ferreira da Silva Pinto Neto

2016-01-01

Full Text Available In this study, 275 patients in use of tenofovir were retrospectively followed-up for three years to evaluate risk factors involved in impaired renal function. Analysis of variance (ANOVA and Tukey's test were used to verify any differences in creatinine levels and estimated clearance at 0, 6, 12, 24 and 36 months, adjusting for the co-variables sex, skin color, age >50 years, arterial hypertension, diabetes and the use of the ritonavir-boosted protease inhibitors (PI/r lopinavir/r or atazanavir/r. The software package STATISTICA 10® was used for statistical analysis. The patients’ mean age was 43.2 ± 10.7 years. Systemic arterial hypertension (SAH and diabetes were found in 20.4% and 8.7% of the patients, respectively. Overall, 96.7% were on tenofovir associated with lamivudine (TDF + 3TC, 39.3% on lopinavir/r, 29.8% on efavirenz, and 17.6% on atazanavir/r. There was a statistically significant difference in estimated creatinine clearance at 24 months, when the co-variables male (F = 3.95; p = 0.048, SAH (F = 6.964; p = 0.009, and age over 50 years (F = 45.81; p < 0.001 were taken into consideration. Analysis of the co-variable use of atazanavir/r showed a tendency toward an increased risk over time (F = 2.437; p = 0.063; however, no significant time interaction was seen. At 36-month, a statistically significant difference was found for age over 50 years, (F = 32.02; p < 0.05 and there was a significant time-by-sex interaction (F = 3.117; p = 0.0149. TDF was discontinued in 12 patients, one because of a femoral neck fracture (0.7% and 11 due to nephrotoxicity (4%. Of these latter cases, 9/11 patients were also using protease inhibitors. These data strongly alert that tenofovir use should be individualized with careful attention to renal function especially in male patients, over 50 years, with SAH, and probably those on ATV/r.

Approaches to tenofovir and abacavir drug shortages in South Africa: A guide for clinicians

Directory of Open Access Journals (Sweden)

Laurie Schowalter

2012-06-01

Full Text Available Shortages of the nucleoside reverse transcriptase inhibitors (NRTI abacavir and tenofovir have been reported recently at health facilities across South Africa. The Society issued the following clinical advice to healthcare providers experiencing shortages on 29 March 2012. These recommendations are intended only as a guide to clinical therapy, based on expert consensus and best available evidence. Treatment decisions for patients should be made by their responsible clinicians, with due consideration for individual circumstances. S Afr J HIV Med 2012;13(2:56-57.

Efavirenz, tenofovir and emtricitabine combined with first-line tuberculosis treatment in tuberculosis-HIV-coinfected Tanzanian patients: a pharmacokinetic and safety study

NARCIS (Netherlands)

Semvua, H.H.; Mtabho, C.M.; Fillekes, Q.; Boogaard, J. van den; Kisonga, R.M.; Mleoh, L.; Ndaro, A.; Kisanga, E.R.; Ven, A. van der; Aarnoutse, R.E.; Kibiki, G.S.; Boeree, M.J.; Burger, D.M.

2013-01-01

BACKGROUND: To evaluate the effect of rifampicin-based tuberculosis (TB) treatment on the pharmacokinetics of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet, and vice versa, in Tanzanian TB-HIV-coinfected patients. METHODS: This was a Phase II open-label multiple dose

Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study

DEFF Research Database (Denmark)

Stellbrink, Hans-Jürgen; Orkin, Chloe; Arribas, Jose Ramon

2010-01-01

Abacavir-lamivudine and tenofovir DF-emtricitabine fixed-dose combinations are commonly used as first-line antiretroviral therapies. However, few studies have comprehensively compared their relative safety profiles....

Recommendations for evaluation and management of bone disease in HIV.

Science.gov (United States)

Brown, Todd T; Hoy, Jennifer; Borderi, Marco; Guaraldi, Giovanni; Renjifo, Boris; Vescini, Fabio; Yin, Michael T; Powderly, William G

2015-04-15

Thirty-four human immunodeficiency virus (HIV) specialists from 16 countries contributed to this project, whose primary aim was to provide guidance on the screening, diagnosis, and monitoring of bone disease in HIV-infected patients. Four clinically important questions in bone disease management were identified, and recommendations, based on literature review and expert opinion, were agreed upon. Risk of fragility fracture should be assessed primarily using the Fracture Risk Assessment Tool (FRAX), without dual-energy X-ray absorptiometry (DXA), in all HIV-infected men aged 40-49 years and HIV-infected premenopausal women aged ≥40 years. DXA should be performed in men aged ≥50 years, postmenopausal women, patients with a history of fragility fracture, patients receiving chronic glucocorticoid treatment, and patients at high risk of falls. In resource-limited settings, FRAX without bone mineral density can be substituted for DXA. Guidelines for antiretroviral therapy should be followed; adjustment should avoid tenofovir disoproxil fumarate or boosted protease inhibitors in at-risk patients. Dietary and lifestyle management strategies for high-risk patients should be employed and antiosteoporosis treatment initiated. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Pre-exposure Prophylaxis Use by Breastfeeding HIV-Uninfected Women: A Prospective Short-Term Study of Antiretroviral Excretion in Breast Milk and Infant Absorption.

Directory of Open Access Journals (Sweden)

Kenneth K Mugwanya

2016-09-01

Full Text Available As pre-exposure prophylaxis (PrEP becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking PrEP. We investigated whether tenofovir and emtricitabine are excreted into breast milk and then absorbed by the breastfeeding infant in clinically significant concentrations when used as PrEP by lactating women.We conducted a prospective short-term, open-label study of daily oral emtricitabine-tenofovir disoproxil fumarate PrEP among 50 HIV-uninfected breastfeeding African mother-infant pairs between 1-24 wk postpartum (ClinicalTrials.gov Identifier: NCT02776748. The primary goal was to quantify the steady-state concentrations of tenofovir and emtricitabine in infant plasma ingested via breastfeeding. PrEP was administered to women through daily directly observed therapy (DOT for ten consecutive days and then discontinued thereafter. Non-fasting peak and trough samples of maternal plasma and breast milk were obtained at drug concentration steady states on days 7 and 10, and a single infant plasma sample was obtained on day 7. Peak blood and breast milk samples were obtained 1-2 h after the maternal DOT PrEP dose, while maternal trough samples were obtained at the end of the PrEP dosing interval (i.e., 23 to 24 h after maternal DOT PrEP dose. Tenofovir and emtricitabine concentrations were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS assays. Of the 50 mother-infant pairs enrolled, 48% were ≤12 wk and 52% were 13-24 wk postpartum, and median maternal age was 25 y (interquartile range [IQR] 22-28. During study follow-up, the median (IQR daily reported frequency of infant breastfeeding was 15 times (12 to 18 overall, 16 (14 to 19 for the ≤12 weeks, and 14 (12 to 17 for the 13-24 wk infant age groups. Overall, median (IQR time-averaged peak concentrations in breast milk were 3.2 ng/mL (2.3 to 4.7 for tenofovir and 212.5 ng/mL (140.0 to 405.0 for

Topical tenofovir protects against vaginal simian HIV infection in macaques coinfected with Chlamydia trachomatis and Trichomonas vaginalis.

Science.gov (United States)

Makarova, Natalia; Henning, Tara; Taylor, Andrew; Dinh, Chuong; Lipscomb, Jonathan; Aubert, Rachael; Hanson, Debra; Phillips, Christi; Papp, John; Mitchell, James; McNicholl, Janet; Garcia-Lerma, Gerardo J; Heneine, Walid; Kersh, Ellen; Dobard, Charles

2017-03-27

Chlamydia trachomatis and Trichomonas vaginalis, two prevalent sexually transmitted infections, are known to increase HIV risk in women and could potentially diminish preexposure prophylaxis efficacy, particularly for topical interventions that rely on local protection. We investigated in macaques whether coinfection with Chlamydia trachomatis/Trichomonas vaginalis reduces protection by vaginal tenofovir (TFV) gel. Vaginal TFV gel dosing previously shown to provide 100 or 74% protection when applied either 30 min or 3 days before simian HIV(SHIV) challenge was assessed in pigtailed macaques coinfected with Chlamydia trachomatis/Trichomonas vaginalis and challenged twice weekly with SHIV162p3 for up to 10 weeks (two menstrual cycles). Three groups of six macaques received either placebo or 1% TFV gel 30 min or 3 days before each SHIV challenge. We additionally assessed TFV and TFV diphosphate concentrations in plasma and vaginal tissues in Chlamydia trachomatis/Trichomonas vaginalis coinfected (n = 4) and uninfected (n = 4) macaques. Chlamydia trachomatis/Trichomonas vaginalis coinfections were maintained during the SHIV challenge period. All macaques that received placebo gel were SHIV infected after a median of seven challenges (one menstrual cycle). In contrast, no infections were observed in macaques treated with TFV gel 30 min before SHIV challenge (P vaginal lymphocytes were significantly higher in Chlamydia trachomatis/Trichomonas vaginalis coinfected compared with Chlamydia trachomatis/Trichomonas vaginalis uninfected macaques. Our findings in this model suggest that Chlamydia trachomatis/Trichomonas vaginalis coinfection may have little or no impact on the efficacy of highly effective topical TFV modalities and highlight a significant modulation of TFV pharmacokinetics.

Switch to Rilpivirine/Emtricitabine/Tenofovir Single-Tablet Regimen of Human Immunodeficiency Virus-1 RNA-Suppressed Patients, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales CO3 Aquitaine Cohort, 2012-2014.

Science.gov (United States)

Cazanave, Charles; Reigadas, Sandrine; Mazubert, Cyril; Bellecave, Pantxika; Hessamfar, Mojgan; Le Marec, Fabien; Lazaro, Estibaliz; Peytavin, Gilles; Bruyand, Mathias; Fleury, Hervé; Dabis, François; Neau, Didier

2015-01-01

Background.  The purpose of this study was to assess the efficacy and tolerability of combined antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-1 virologically suppressed patients who switched to rilpivirine (RPV)/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) as a single-tablet regimen (STR). Methods.  A retrospective multicenter cohort study was performed between September 2012 and February 2014 in Bordeaux University Hospital-affiliated clinics. Patients with a plasma HIV viral load (VL) lower than 50 copies/mL and switching to STR were evaluated at baseline, 3, 6, 9, and 12 months from switch time (M3, M6, M9, M12) for VL and other biological parameters. Change from baseline in CD4 cell counts was evaluated at M6 and M12. Virological failure (VF) was defined as 2 consecutive VL >50 copies/mL. Results.  Three hundred four patients were included in the analysis. Single-tablet regimen switch was proposed to 116 patients with adverse events, mostly efavirenz (EFV)-based (n = 59), and to 224 patients for cART simplification. Thirty of 196 patients with available genotype resistance test results displayed virus with ≥1 drug resistance mutation on reverse-transcriptase gene. After 12 months of follow-up, 93.4% (95.5% confidence interval, 89.9-96.2) of patients remained virologically suppressed. There was no significant change in CD4 cell count. During the study period, 5 patients experienced VF, one of them harboring RPV resistance mutation. Clinical cART tolerability improved in 79 patients overall (29.9%) at M6, especially neurological symptoms related to EFV. Fasting serum lipid profiles improved, but a significant estimated glomerular function rate decrease (-11 mL/min/1.73 m(2); P < 10(-4)) was observed. Conclusions.  Overall, virologic suppression was maintained in patients after switching to RPV/TDF/ FTC. This STR strategy was associated with improved tolerability.

Antiretroviral resistance at virological failure in the NEAT 001/ANRS 143 trial: raltegravir plus darunavir/ritonavir or tenofovir/emtricitabine plus darunavir/ritonavir as first-line ART

NARCIS (Netherlands)

Lambert-Niclot, S.; George, E. C.; Pozniak, A.; White, E.; Schwimmer, C.; Jessen, H.; Johnson, M.; Dunn, D.; Perno, C. F.; Clotet, B.; Plettenberg, A.; Blaxhult, A.; Palmisano, L.; Wittkop, L.; Calvez, V.; Marcelin, A. G.; Raffi, F.; Dedes, Nikos; Chêne, Geneviève; Richert, Laura; Allavena, Clotilde; Raffi, François; Autran, Brigitte; Antinori, Andrea; Bucciardini, Raff Aella; Vella, Stefano; Horban, Andrzej; Arribas, Jose; Babiker, Abdel G.; Boffito, Marta; Pillay, Deenan; Pozniak, Anton; Franquet, Xavier; Schwarze, Siegfried; Grarup, Jesper; Fischer, Aurélie; Wallet, Cédrick; Diallo, Alpha; Molina, Jean-Michel; Saillard, Juliette; Moecklinghoff, Christiane; Stellbrink, Hans-Jürgen; van Leeuwen, Remko; Gatell, Jose; Sandstrom, Eric; Flepp, Markus; Ewings, Fiona; George, Elizabeth C.; Hudson, Fleur; Pearce, Gillian; Quercia, Romina; Rogatto, Felipe; Leavitt, Randi; Nguyen, Bach-Yen; Goebel, Frank; Marcotullio, Simone; Kaur, Navrup; Sasieni, Peter; Spencer-Drake, Christina; Peto, Tim; Miller, Veronica; Arnault, Fabien; Boucherie, Céline; Jean, Delphine; Paniego, Virginie; Paraina, Felasoa; Rouch, Elodie; Schwimmer, Christine; Soussi, Malika; Taieb, Audrey; Termote, Monique; Touzeau, Guillaume; Cursley, Adam; Dodds, Wendy; Hoppe, Anne; Kummeling, Ischa; Pacciarini, Filippo; Paton, Nick; Russell, Charlotte; Taylor, Kay; Ward, Denise; Aagaard, Bitten; Eid, Marius; Gey, Daniela; Jensen, Birgitte Gram; Jakobsen, Marie-Louise; Jansson, Per O.; Jensen, Karoline; Joensen, Zillah Maria; Larsen, Ellen Moseholm; Pahl, Christiane; Pearson, Mary; Nielsen, Birgit Riis; Reilev, Søren Stentoft; Christ, Ilse; Lathouwers, Desiree; Manting, Corry; Mendy, Bienvenu Yves; Metro, Annie; Couffin-Cadiergues, Sandrine; Knellwolf, Anne-Laure; Palmisiano, Lucia; Aznar, Esther; Barea, Cristina; Cotarelo, Manuel; Esteban, Herminia; Girbau, Iciar; Moyano, Beatriz; Ramirez, Miriam; Saiz, Carmen; Sanchez, Isabel; Yllescas, Maria; Binelli, Andrea; Colasanti, Valentina; Massella, Maurizio; Anagnostou, Olga; Gioukari, Vicky; Touloumi, Giota; Schmied, Brigitte; Rieger, Armin; Vetter, Norbert; de Wit, Stephane; Florence, Eric; Vandekerckhove, Linos; Gerstoft, Jan; Mathiesen, Lars; Katlama, Christine; Cabie, Andre; Cheret, Antoine; Dupon, Michel; Ghosn, Jade; Girard, Pierre-Marie; Goujard, Cécile; Lévy, Yves; Morlat, Philippe; Neau, Didier; Obadia, Martine; Perre, Philippe; Piroth, Lionel; Reynes, Jacques; Tattevin, Pierre; Ragnaud, Jean Marie; Weiss, Laurence; Yazdan, Yazdanpanah; Yeni, Patrick; Zucman, David; Behrens, Georg; Esser, Stefan; Fätkenheuer, Gerd; Hoffmann, Christian; Jessen, Heiko; Rockstroh, Jürgen; Schmidt, Reinhold; Stephan, Christoph; Unger, Stefan; Hatzakis, Angelos; Daikos, George L.; Papadopoulos, Antonios; Skoutelis, Athamasios; Banhegyi, Denes; Mallon, Paddy; Mulcahy, Fiona; Andreoni, Massimo; Bonora, Stefano; Castelli, Francesco; Monforte, Antonella D.'Arminio; Di Perri, Giovanni; Galli, Massimo; Lazzarin, Adriano; Mazzotta, Francesco; Carlo, Torti; Vullo, Vincenzo; Prins, Jan; Richter, Clemens; Verhagen, Dominique; van Eeden, Arne; Doroana, Manuela; Antunes, Francisco; Maltez, Fernando; Sarmento-Castro, Rui; Garcia, Juan Gonzalez; Aldeguer, José López; Clotet, Bonaventura; Domingo, Pere; Gatell, Jose M.; Knobel, Hernando; Marquez, Manuel; Miralles, Martin Pilar; Portilla, Joaquin; Soriano, Vicente; Tellez, Maria-Jesus; Thalme, Anders; Blaxhult, Anders; Gisslen, Magnus; Winston, Alan; Fox, Julie; Gompels, Mark; Herieka, Elbushra; Johnson, Margaret; Leen, Clifford; Teague, Alastair; Williams, Ian; Boyd, Mark Alastair; Møller, Nina Friis; Larsen, Ellen Frøsig Moseholm; Le Moing, Vincent; Wit, Ferdinand W. N. M.; Kowalska, Justyna; Berenguer, Juan; Moreno, Santiago; Müller, Nicolas J.; Török, Estée; Post, Frank; Angus, Brian; Calvez, Vincent; Boucher, Charles; Collins, Simon; Dunn, David; Lambert, Sidonie; Marcelin, Anne-Geneviève; Perno, Carlo Federico; White, Ellen; Ammassari, Adriana; Stoehr, Wolgang; Schmidt, Reinhold Ernst; Odermarsky, Michal; Smith, Colette; Thiébaut, Rodolphe; de La Serna, Jose Ignacio Bernardino; Castagna, Antonella; Furrer, Hans-Jackob; Mocroft, Amanda; Reiss, Peter; Bucciardini, Raffaella; Fragola, Vincenzo; Lauriola, Marco; Murri, Rita; Nieuwkerk, Pythia; Spire, Bruno; Volny-Anne, Alain; West, Brian; Amieva, Hélène; Llibre Codina, Josep Maria; Braggion, Marco; Focà, Emanuele

2016-01-01

To describe the pattern of drug resistance at virological failure in the NEAT001/ANRS143 trial (first-line treatment with ritonavir-boosted darunavir plus either tenofovir/emtricitabine or raltegravir). Genotypic testing was performed at baseline for reverse transcriptase (RT) and protease genes and

Efficacy and safety of rilpivirine (TMC278) versus efavirenz at 48 weeks in treatment-naive HIV-1-infected patients: pooled results from the phase 3 double-blind randomized ECHO and THRIVE Trials.

Science.gov (United States)

Cohen, Calvin J; Molina, Jean-Michel; Cahn, Pedro; Clotet, Bonaventura; Fourie, Jan; Grinsztejn, Beatriz; Wu, Hao; Johnson, Margaret A; Saag, Michael; Supparatpinyo, Khuanchai; Crauwels, Herta; Lefebvre, Eric; Rimsky, Laurence T; Vanveggel, Simon; Williams, Peter; Boven, Katia

2012-05-01

Pooled analysis of phase 3, double-blind, double-dummy ECHO and THRIVE trials comparing rilpivirine (TMC278) and efavirenz. Treatment-naive HIV-1-infected adults were randomized 1:1 to rilpivirine 25 mg once daily or efavirenz 600 mg once daily, with background tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) (ECHO) or TDF/FTC, zidovudine/lamivudine, or abacavir/lamivudine (THRIVE). The primary endpoint was confirmed response [viral load effects on virologic failure were more apparent with rilpivirine. CD4 cell count increased over time in both groups. Rilpivirine compared with efavirenz gave smaller incidences of adverse events leading to discontinuation (3% vs. 8%, respectively), treatment-related grade 2-4 adverse events (16% vs. 31%), rash (3% vs. 14%), dizziness (8% vs. 26%), abnormal dreams/nightmares (8% vs. 13%), and grade 2-4 lipid abnormalities. At week 48, rilpivirine 25 mg once daily and efavirenz 600 mg once daily had comparable response rates. Rilpivirine had more virologic failures and improved tolerability versus efavirenz.

The future of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection.

Science.gov (United States)

Özdener, Ayşe Elif; Park, Tae Eun; Kalabalik, Julie; Gupta, Rachna

2017-05-01

People at high risk for HIV acquisition should be offered pre-exposure prophylaxis (PrEP). Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) is currently the only medication recommended for pre-exposure prophylaxis (PrEP) by the Centers for Disease Control and Prevention (CDC) in people at high risk for HIV acquisition. This article will review medications currently under investigation and the future landscape of PrEP therapy. Areas covered: This article will review clinical trials that have investigated nontraditional regimens of TDF/FTC, antiretroviral agents from different drug classes such as integrase strand transfer inhibitors (INSTI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) as potential PrEP therapies. Expert commentary: Currently, there are several investigational drugs in the pipeline for PrEP against HIV infection. Increased utilization of PrEP therapy depends on provider identification of people at high risk for HIV transmission. Advances in PrEP development will expand options and access for people and reduce the risk of HIV acquisition.

Release of Tenofovir from Carrageenan-Based Vaginal Suppositories

Directory of Open Access Journals (Sweden)

Toral Zaveri

2014-07-01

Full Text Available Microbicides are an active area of research for HIV prevention, being developed as a woman-initiated method of prevention during unprotected coitus. Along with safety and efficacy, assessing and improving compliance is a major area of research in microbicide development. We have produced microbicide prototypes in the form of semisoft vaginal suppositories prepared from carrageenan and conducted both qualitative and quantitative studies using these prototypes to determine the physical properties that drive acceptability and possibly adherence. In order to ensure that the suppositories function as effective drug delivery vehicles, we have conducted in vitro dissolution studies in water, vaginal simulant fluid (VSF and semen simulant fluid (SSF with suppositories loaded with the antiretroviral drug, tenofovir (TFV. TFV was released via diffusion and matrix erosion in water or by diffusion out of the matrix in VSF and SSF. Diffusion studies were conducted in two different volumes of VSF and SSF. The volume of VSF/SSF into which TFV diffused and the size of the suppositories determined the rate of diffusion from the suppositories. About 45%–50% of the encapsulated TFV diffused out of the suppositories within the first two hours, irrespective of suppository size, diffusion medium (VSF/SSF and the volume of medium. Prior work indicates that a short waiting period between insertion and coitus is highly desired by women; present data suggest our microbicide prototypes have rapid initial release followed by a slow release curve over the first 24 h.

Pre-Exposure Prophylaxis for HIV Prevention: Safety Concerns.

Science.gov (United States)

Tetteh, Raymond A; Yankey, Barbara A; Nartey, Edmund T; Lartey, Margaret; Leufkens, Hubert G M; Dodoo, Alexander N O

2017-04-01

Available evidence supports the efficacy of pre-exposure prophylaxis (PrEP) in decreasing the incidence of human immunodeficiency virus (HIV) infection among high-risk individuals, especially when used in combination with other behavioural preventive methods. Safety concerns about PrEP present challenges in the implementation and use of PrEP. The aim of this review is to discuss safety concerns observed in completed clinical trials on the use of PrEP. We performed a literature search on PrEP in PubMed, global advocacy for HIV prevention (Aids Vaccine Advocacy Coalition) database, clinical trials registry " http://www.clinicaltrials.gov " and scholar.google, using combination search terms 'pre-exposure prophylaxis', 'safety concerns in the use of pre-exposure prophylaxis', 'truvada use as PrEP', 'guidelines for PrEP use', 'HIV pre-exposure prophylaxis' and 'tenofovir' to identify clinical trials and literature on PrEP. We present findings associated with safety issues on the use of PrEP based on a review of 11 clinical trials on PrEP with results on safety and efficacy as at April 2016. We also reviewed findings from routine real-life practice reports. The pharmacological intervention for PrEP was tenofovir disoproxil fumarate/emtricitabine in a combined form as Truvada ® or tenofovir as a single entity. Both products are efficacious for PrEP and seem to have a good safety profile. Regular monitoring is recommended to prevent long-term toxic effects. The main adverse effects observed with PrEP are gastrointestinal related; basically mild to moderate nausea, vomiting and diarrhea. Other adverse drug effects worth monitoring are liver enzymes, renal function and bone mineral density. PrEP as an intervention to reduce HIV transmission appears to have a safe benefit-risk profile in clinical trials. It is recommended for widespread use but adherence monitoring and real-world safety surveillance are critical in the post-marketing phase to ensure that the benefits

Switch from unboosted protease inhibitor to a single-tablet regimen containing rilpivirine improves cholesterol and triglycerides.

Science.gov (United States)

Di Biagio, Antonio; Riccardi, Niccolò; Taramasso, Lucia; Capetti, Amedeo; Cenderello, Giovanni; Signori, Alessio; Vitiello, Paola; Guerra, Michele; de Socio, Giuseppe Vittorio; Cassola, Giovanni; Quirino, Tiziano; Viscoli, Claudio

2016-11-01

This study aimed to evaluate the efficacy, tolerability and potential savings of combined antiretroviral therapy (cART) simplification from an unboosted protease inhibitor (PI) regimen with atazanavir or fosamprenavir to a single-tablet regimen (STR) based on rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) among HIV-1-infected patients with HIV-1 RNA triglycerides, bilirubin, glycaemia, creatinine and physical examination were performed at baseline and at scheduled follow-up. All patient costs were calculated and were estimated for 52 weeks of therapy. Fifty-one patients were enrolled [28 male (54.9%)]. At baseline, 30 patients (58.8%) were treated with FTC/TDF, 20 (39.2%) with abacavir/lamivudine and 1 (2.0%) with lamivudine/zidovudine. Thirty-three patients (64.7%) received atazanavir. All patients maintained HIV-RNA triglycerides decreased from 124 mg/dL (range, 39-625) at enrolment to 108.7 mg/dL (range, 39-561) at study end (P = 0.25). At baseline, mean cholesterol was 172.8 ± 38.1 mg/dL and decreased to 161.9 ± 38.6 mg/dL (P = 0.038); likewise, median total bilirubin decreased from 1.07 mg/dL (range, 0.2-4.7) to 0.6 mg/dL (range, 0.13-3.1) (P triglycerides, cholesterol and cART-related costs. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Efficacy and safety of emtricitabine/tenofovir alafenamide (FTC/TAF) vs. emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) as a backbone for treatment of HIV-1 infection in virologically suppressed adults: subgroup analysis by third agent of a randomized, double-blind, active-controlled phase 3 trial.

Science.gov (United States)

Post, Frank A; Yazdanpanah, Yazdan; Schembri, Gabriel; Lazzarin, Adriano; Reynes, Jacques; Maggiolo, Franco; Yan, Mingjin; Abram, Michael E; Tran-Muchowski, Cecilia; Cheng, Andrew; Rhee, Martin S

2017-05-01

FTC/TAF was shown to be noninferior to FTC/TDF with advantages in markers of renal and bone safety. To evaluate the efficacy and safety of switching to FTC/TAF from FTC/TDF by third agent (boosted protease inhibitor [PI] vs. unboosted third agent). We conducted a 48-week subgroup analysis based on third agent from a randomized, double blind study in virologically suppressed adults on a FTC/TDF-containing regimen who switched to FTC/TAF vs. continued FTC/TDF while remaining on the same third agent. We randomized (1:1) 663 participants to either switch to FTC/TAF (N = 333) or continue FTC/TDF (N = 330), each with baseline third agent stratifying by class of third agent in the prior treatment regimen (boosted PI 46%, unboosted third agent 54%). At week 48, significant differences in renal biomarkers and bone mineral density were observed favoring FTC/TAF over FTC/TDF (p TAF arm in those who received boosted PI vs. unboosted third agents. At week 48, virologic success rates were similar between treatment groups for those who received a boosted PI (FTC/TAF 92%, FTC/TDF 93%) and for those who received an unboosted third agent (97% vs. 93%). In virologically suppressed patients switching to FTC/TAF from FTC/TDF, high rates of virologic suppression were maintained, while renal and bone safety parameters improved, regardless of whether participants were receiving a boosted PI or an unboosted third agent. FTC/TAF offers safety advantages over FTC/TDF and can be an important option as an NRTI backbone given with a variety of third agents.

Hepatitis B Virus (HBV) Load Response to 2 Antiviral Regimens, Tenofovir/Lamivudine and Lamivudine, in HIV/ HBV-Coinfected Pregnant Women in Guangxi, China: The Tenofovir in Pregnancy (TiP) Study.

Science.gov (United States)

Wang, Liming; Wiener, Jeffrey; Bulterys, Marc; Wei, Xiaoyu; Chen, Lili; Liu, Wei; Liang, Shujia; Shepard, Colin; Wang, Linhong; Wang, Ailing; Zhang, Fujie; Kourtis, Athena P

2016-12-01

 There is limited information on antiviral therapy for hepatitis B virus (HBV) infection among pregnant women coinfected with human immunodeficiency virus (HIV) and HBV.  A phase 2 randomized, controlled trial of a regimen containing tenofovir (TDF)/lamivudine (3TC) and a regimen containing 3TC in HIV/HBV-coinfected pregnant women in China. The HBV virological response was compared in study arms.  The median decline in the HBV DNA level was 2.60 log 10 copies/mL in the TDF/3TC arm and 2.24 log 10 copies/mL in the 3TC arm (P = .41). All women achieved HBV DNA levels of <6 log 10 copies/mL at delivery.  Initiation of either regimen led to achievement of HBV DNA levels below the threshold associated with perinatal HBV transmission.  NCT01125696. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

A STUDY OF DYSLIPIDAEMIA IN HIV PATIENTS RECEIVING HAART

Directory of Open Access Journals (Sweden)

Chepuri Venkata Ravikumar

2018-02-01

Full Text Available BACKGROUND Human Immunodeficiency Virus (HIV was discovered in 1986 in Chennai (India amongst female sex workers by Dr. Suniti Solomon. Since then, HIV has spread to all parts of the country from the high-risk group to the antepartum population in many states at an alarming rate. The prevalence of dyslipidaemia and other risk factors for cardiovascular disease is significant in HIV/AIDS patients receiving highly active antiretroviral therapy (HAART, ranging from 20% to 80%. In view of the high prevalence of dyslipidaemia and the increased risk for cardiovascular diseases among patients with HIV/AIDS, this is a matter of concern for public health. MATERIALS AND METHODS 143 patients who had been receiving HAART for a minimum of two years from Rajiv Gandhi Institute of Medical Sciences, Kadapa, during the period of January 2015 to September 2016 were studied. They were divided into 4 regimens groups 1 TEL (Tenofovir, Efavirenz, Lamivudine 2 TLAR (Tenofovir, Lamivudine, Atazanavir, Ritonavir 3 ZLE (Zidovudine, Lamivudine, Efavirenz 4 ZLN (Zidovudine, Lamivudine, Nevirapine. Detailed history, demographic data, anthropometric measurements, serum lipid profile obtained and analysed. RESULTS Out of 143 patients, 90 (62.9% were males and 53 (37.1% were females. 68 (47.6% were in the 30-39 years age group accounted for maximum percentage of groups. Based on BMI only 3 (2.1% were obese, 24 (16.8% were of overweight. WaistHip ratio was abnormal in 117 (81.8% and 26 (18.2% were normal. The mean values for patients on TEL regimen are TC is 195.4 mg%, LDL 122.1 mg%, HDL 34.96 mg%, TG 194.02 mg% and TC/HDL is 5.5714. In patients treated with TLAR regimen the mean values of TC are 172.15 mg%, LDL 99.15 mg %, HDL 36.35 mg%, TG 183.35 mg% and TC/HDL is 4.8. In patients treated with ZLE regimen, TC is 201.64 mg%, LDL 123.27 mg%, HDL 35.68 mg%, TG 212.27 mg% and TC/HDL is 5.6364. In patients treated with ZLN regimen, TC is 162.1 mg%, LDL 91.94 mg%, HDL 35.98 mg%, TG

HIV Prevention: Opportunities and Challenges.

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Marrazzo, Jeanne M

Preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)-based regimens has been shown to be effective in preventing acquisition of HIV infection, with protective efficacy being dependent on adherence to treatment. Data from the PROUD (Preexposure Option for Reducing HIV in the UK) and IPERGAY (Action to Prevent Risk Exposure By and For Gay Men) studies, the later of which employed event-driven PrEP, showed a high rate of protective efficacy of PrEP with TDF and emtricitabine among men who have sex with men. Data from the ASPIRE (A Study to Prevent Infection With a Ring for Extended Use) study of a dapivirine vaginal ring showed a moderate rate of protective efficacy among women older than 21 years. Ongoing investigations are examining long-acting PrEP modalities and combination PrEP and contraception products. This article summarizes a presentation by Jeanne M. Marrazzo, MD, MPH, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Washington, DC, in April 2016.

Multiple Sclerosis and Subsequent Human Immunodeficiency Virus Infection: A Case with the Rare Comorbidity, Focus on Novel Treatment Issues and Review of the Literature.

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Skarlis, Charalampos; Gontika, Maria; Katsavos, Serafeim; Velonakis, Giorgios; Toulas, Panagiotis; Anagnostouli, Maria

2017-01-01

The comorbidity between Multiple Sclerosis (MS) and Human Immunodeficiency Virus (HIV) infection is particularly rare. Only a few cases of comorbidity of Clinically Definite(CD)-MS and HIV have been documented worldwide, while the potential beneficial role of antiretroviral therapy regarding MS activity has long been an area of debate. We present a 36-year old male, bearing a diagnosis of CD-MS for twelve years. He had been treated for ten years with interferon-beta-1b, when he voluntarily discontinued therapy, claiming clinical stability. One year later he was diagnosed positive for HIV and he started and continued only on efavirenz/emricitabine/tenofovir-disoproxil fumarate (ATRIPLA®), remaining relapse-free until today. This fact, in combination with the unique pharmaceutical composition of the drug, which contains a component similar to a newly-approved agent for MS, dimethyl fumarate, prompted us to review the literature regarding this rare comorbidity and to suggest that the role of the antiretroviral therapy should be further explored in MS. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

A week 48 randomized phase 3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naïve HIV-1 patients.

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Eron, Joseph J; Orkin, Chloe; Gallant, Joel; Molina, Jean-Michel; Negredo, Eugenia; Antinori, Andrea; Mills, Anthony; Reynes, Jacques; Van Landuyt, Erika; Lathouwers, Erkki; Hufkens, Veerle; Jezorwski, John; Vanveggel, Simon; Opsomer, Magda

2018-04-19

To investigate efficacy and safety of a single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg vs. darunavir/cobicistat plus emtricitabine/tenofovir disoproxyl fumarate (TDF) (control) in antiretroviral-treatment-naïve, HIV-1-infected adults. Phase-3, randomized, active-controlled, double-blind, international, multicenter, noninferiority study (NCT02431247). Seven hundred and twenty-five participants were randomized (1 : 1) to D/C/F/TAF (362) or control (363). The primary objective was to demonstrate noninferiority of D/C/F/TAF vs. control for percentage viral load less than 50 copies/ml (FDA-snapshot analysis) at 48 weeks (10% margin). At week 48, D/C/F/TAF was noninferior to control (91.4 vs. 88.4% achieved viral load TAF/TDF resistance were observed in either group. Only one patient (D/C/F/TAF) developed M184I/V conferring resistance to emtricitabine. Incidences of grades 3 and 4 adverse events (5 vs. 6%), serious adverse events (5 vs. 6%) and adverse event-related discontinuations (2 vs. 4%) were low and similar between groups. Mean decrease in urine protein/creatinine ratio was greater with D/C/F/TAF than control (-22.42 vs. -10.34 mg/g, P = 0.033). Mean percentage change in bone mineral density with D/C/F/TAF vs. control was 0.21 vs. -2.73%, P TAF achieved a high virologic suppression rate (91.4%) and was noninferior to darunavir/cobicistat with F/TDF. D/C/F/TAF also demonstrated the bone and renal safety advantages of TAF in combination with darunavir/cobicistat.

Higher risk of renal impairment associated with tenofovir use amongst people living with HIV in India: a comparative cohort analysis between Western India and United Kingdom.

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Pujari, Sanjay N; Smith, Colette; Makane, Abhimanyu; Youle, Mike; Johnson, Margaret; Bele, Vivek; Joshi, Kedar; Dabhade, Digamber; Bhagani, Sanjay

2014-03-29

Data on the renal safety of Tenofovir (TDF) in Low and Middle Income Countries (LMICs) is scarce. We compared development of various forms of renal impairment with use of TDF-containing antiretroviral therapy (ART) between a cohort from the Institute of Infectious Diseases (IID) Pune, Western India and the Royal Free Hospital (RFH) London, UK. This is a retrospective analysis of change in estimated glomerular filtration rates (eGFRs) at 6, 12 and 24 months post TDF initiation using the Modification of Diet in Renal Disease (MDRD) equation. In people living with Human Immunodeficiency virus (PLHIV) with pre-TDF eGFR > 90 ml/min/1.73 m2 time to development of and factors associated with progression to eGFR  90 ml/min/1.73 m2 PLHIV at IID were more likely to develop an eGFR < 60 ml/min/1.73 m2 (aHR = 7.6 [95% CI 3.4, 17.4] p < 0.0001) and had a faster rate of progression estimated using Kaplan Meier methods. Risk factors included age (per 10 years older: aHR = 2.21 [1.6, 3.0] p < 0.0001) and receiving concomitant ritonavir boosted Protease Inhibitor (PI/r) (aHR = 2.4 [1.2, 4.8] p = 0.01). There is higher frequency of treatment limiting renal impairment events amongst PLHIV receiving TDF in Western India. As TDF scale up progresses, programs need to develop capacity for monitoring and treatment of renal impairment associated with TDF.

Durable protection from vaginal simian-human immunodeficiency virus infection in macaques by tenofovir gel and its relationship to drug levels in tissue.

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Dobard, Charles; Sharma, Sunita; Martin, Amy; Pau, Chou-Pong; Holder, Angela; Kuklenyik, Zsuzsanna; Lipscomb, Jonathan; Hanson, Debra L; Smith, James; Novembre, Francis J; García-Lerma, J Gerardo; Heneine, Walid

2012-01-01

A vaginal gel containing 1% tenofovir (TFV) was found to be safe and effective in reducing HIV infection in women when used pericoitally. Because of the long intracellular half-life of TFV and high drug exposure in vaginal tissues, we hypothesized that a vaginal gel containing TFV may provide long-lasting protection. Here, we performed delayed-challenge experiments and showed that vaginal 1% TFV gel protected 4/6 macaques against vaginal simian-human immunodeficiency virus (SHIV) exposures occurring 3 days after gel application, demonstrating long-lasting protection. Despite continued gel dosing postinfection, neither breakthrough infection had evidence of drug resistance by ultrasensitive testing of SHIV in plasma and vaginal lavage. Analysis of the active intracellular tenofovir diphosphate (TFV-DP) in vaginal lymphocytes collected 4 h to 3 days after gel dosing persistently showed high TFV-DP levels (median, 1,810 fmol/10(6) cells) between 4 and 24 h that exceed the 95% inhibitory concentration (IC(95)), reflecting rapid accumulation and long persistence. In contrast to those in peripheral blood mononuclear cells (PBMCs) following oral dosing, TFV-DP levels in vaginal lymphocytes decreased approximately 7-fold by 3 days, exhibiting a much higher rate of decay. We observed a strong correlation between intracellular TFV-DP in vaginal lymphocytes, in vitro antiviral activity, and in vivo protection, suggesting that TFV-DP above the in vitro IC(95) in vaginal lymphocytes is a good predictor of high efficacy. Data from this model reveal an extended window of protection by TFV gel that supports coitus-independent use. The identification of protective TFV-DP concentrations in vaginal lymphocytes may facilitate the evaluation of improved delivery methods of topical TFV and inform clinical studies.

Assessment of Oral Fluid HIV Test Performance in an HIV Pre-Exposure Prophylaxis Trial in Bangkok, Thailand.

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Pravan Suntharasamai

Full Text Available Rapid easy-to-use HIV tests offer opportunities to increase HIV testing among populations at risk of infection. We used the OraQuick Rapid HIV-1/2 antibody test (OraQuick in the Bangkok Tenofovir Study, an HIV pre-exposure prophylaxis trial among people who inject drugs.The Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial. We tested participants' oral fluid for HIV using OraQuick monthly and blood using a nucleic-acid amplification test (NAAT every 3 months. We used Kaplan-Meier methods to estimate the duration from a positive HIV NAAT until the mid-point between the last non-reactive and first reactive oral fluid test and proportional hazards to examine factors associated with the time until the test was reactive.We screened 3678 people for HIV using OraQuick. Among 447 with reactive results, 436 (97.5% were confirmed HIV-infected, 10 (2.2% HIV-uninfected, and one (0.2% had indeterminate results. Two participants with non-reactive OraQuick results were, in fact, HIV-infected at screening yielding 99.5% sensitivity, 99.7% specificity, a 97.8% positive predictive value, and a 99.9% negative predictive value. Participants receiving tenofovir took longer to develop a reactive OraQuick (191.8 days than participants receiving placebo (16.8 days (p = 0.02 and participants infected with HIV CRF01_AE developed a reactive OraQuick earlier than participants infected with other subtypes (p = 0.04.The oral fluid HIV test performed well at screening, suggesting it can be used when rapid results and non-invasive tools are preferred. However, participants receiving tenofovir took longer to develop a reactive oral fluid test result than those receiving placebo. Thus, among people using pre-exposure prophylaxis, a blood-based HIV test may be an appropriate choice.ClinicalTrials.gov NCT00119106.

Limited SHIV env diversification in macaques failing oral antiretroviral pre-exposure prophylaxis.

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Zheng, Qi; Ruone, Susan; Switzer, William M; Heneine, Walid; García-Lerma, J Gerardo

2012-05-09

Pre-exposure prophylaxis (PrEP) with daily Truvada [a combination of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF)] is a novel HIV prevention strategy recently found to prevent HIV transmission among men who have sex with men and heterosexual couples. Acute infection in adherent persons who fail PrEP will inevitably occur under concurrent antiretroviral therapy, thus raising questions regarding the potential impact of PrEP on early viral dynamics. We investigated viral evolution dynamics in a macaque model of PrEP consisting of repeated rectal exposures to SHIV162P3 in the presence of PrEP. Four macaques were infected during daily or intermittent PrEP with FTC or FTC/TDF, and five were untreated controls. SHIV env sequence evolution was monitored by single genome amplification with phylogenetic and sequence analysis. Mean nucleotide divergence from transmitted founder viruses calculated 17 weeks (range = 12-20) post peak viremia was significantly lower in PrEP failures than in control animals (7.2 × 10-3 compared to 1.6 × 10-2 nucleotide substitutions per site per year, respectively, p diversification during early infection might enhance immune control by slowing the selection of escape mutants.

Which HIV patients should be screened for osteoporosis: an international perspective.

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Alvarez, Elena; Belloso, Waldo H; Boyd, Mark A; Inkaya, Ahmet Ç; Hsieh, Evelyn; Kambugu, Andrew; Kaminski, Greg; Martinez, Esteban; Stellbrink, Hans-Jürgen; Walmsley, Sharon; Brown, Todd T; Mallon, Patrick W G

2016-05-01

This review provides international insights into the real-world clinical approach to screening for bone mineral density (BMD) and osteoporosis in people living with HIV (PLWH) using opinions from HIV physicians from key regions around the world. Although a significant proportion of PLWH are aged over 50, the relative importance of low BMD to clinical care differs significantly between countries and regions, based on factors such as the population at risk, access to adequate screening resources, and physicians' knowledge. Generally, management of osteoporosis in PLWH follows similar principals as for the general population, with risk factors for fracture combined with measurement of BMD by dual energy X-ray absorptiometry in algorithms such as Fracture Risk Assessment Tool, designed to provide an overall risk estimation. Although in most regions age is considered among the most important factors contributing to low BMD and fractures, considerable country and region-specific factors become apparent, such as malnutrition, inactivity and impact of comorbidities, substance abuse, and increasing use of tenofovir disoproxil fumarate. These opinions highlight the diversity that still exists in the approach to the long-term management of PLWH and highlight challenges facing development of consensus guidelines that can be effectively implemented worldwide.

Synergistic activity profile of griffithsin in combination with tenofovir, maraviroc and enfuvirtide against HIV-1 clade C

International Nuclear Information System (INIS)

Ferir, Geoffrey; Palmer, Kenneth E.; Schols, Dominique

2011-01-01

Griffithsin (GRFT) is possibly the most potent anti-HIV peptide found in natural sources. Due to its potent and broad-spectrum antiviral activity and unique safety profile it has great potential as topical microbicide component. Here, we evaluated various combinations of GRFT against HIV-1 clade B and clade C isolates in primary peripheral blood mononuclear cells (PBMCs) and in CD4 + MT-4 cells. In all combinations tested, GRFT showed synergistic activity profile with tenofovir, maraviroc and enfuvirtide based on the median effect principle with combination indices (CI) varying between 0.34 and 0.79 at the calculated EC 95 level. Furthermore, the different glycosylation patterns on the viral envelope of clade B and clade C gp120 had no observable effect on the synergistic interactions. Overall, we can conclude that the evaluated two-drug combination increases their antiviral potency and supports further clinical investigations in pre-exposure prophylaxis for GRFT combinations in the context of HIV-1 clade C infection.

Interactions of Tenofovir, Lamivudine, Abacavir and Didanosine in Primary Human Cells

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Saye H. Khoo

2011-06-01

Full Text Available Certain triple nucleoside/tide reverse transcriptase inhibitor (NRTI regimens containing tenofovir (TDF have been associated with rapid early treatment failure. The mechanism is unknown, but may be at the level of drug transport. We measured the lipophilicity of the drugs [3H]-lamivudine (3TC, -didanosine (ddI, -TDF and -ABC. Peripheral blood mononuclear cells (PBMCs were used to evaluate drug–drug interactions at the level of drug transport. PBMCs were measured for the expression of P-glycoprotein (P-gp, multidrug resistance-associated protein-1 (MRP-1 and breast cancer resistance protein (BCRP by flow cytometry. The rank order of the lipophilicity of the drugs were ABC>>>3TC³ddI>TDF. The accumulation of [3H]-3TC, -ddI and -TDF were temperature sensitive (suggesting facilitated transport, in contrast to [3H]-ABC. ABC reduced the accumulation of [3H]-3TC, and cell fractionation experiments suggested this was mainly in membrane-bound [3H]-3TC. ABC/TDF and ABC/ddI increased the accumulation of [3H]-3TC and 3TC/TDF also increased the accumulation of [3H]-TDF. In contrast, none of the NRTI/NtRTI incubations (alone or in combination altered the accumulation of [3H]-ABC and -ddI. PBMC expression of P-gp, MRP1 and BCRP were detected, but none correlated with the accumulation of the drugs. The high failure rates seen with TDF, ABC and 3TC are not fully explained by an interaction at transporter level.

Tenofovir alafenamide demonstrates broad cross-genotype activity against wild-type HBV clinical isolates and maintains susceptibility to drug-resistant HBV isolates in vitro.

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Liu, Yang; Miller, Michael D; Kitrinos, Kathryn M

2017-03-01

Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir (TFV). This study evaluated the antiviral activity of TAF against wild-type genotype A-H HBV clinical isolates as well as adefovir-resistant, lamivudine-resistant, and entecavir-resistant HBV isolates. Full length HBV genomes or the polymerase/reverse transcriptase (pol/RT) region from treatment-naïve patients infected with HBV genotypes A-H were amplified and cloned into an expression vector under the control of a CMV promoter. In addition, 11 drug resistant HBV constructs were created by site-directed mutagenesis of a full length genotype D construct. Activity of TAF was measured by transfection of each construct into HepG2 cells and assessment of HBV DNA levels following treatment across a range of TAF concentrations. TAF activity in vitro was similar against wild-type genotype A-H HBV clinical isolates. All lamivudine- and entecavir-resistant isolates and 4/5 adefovir-resistant isolates were found to be sensitive to inhibition by TAF in vitro as compared to the wild-type isolate. The adefovir-resistant isolate rtA181V + rtN236T exhibited low-level reduced susceptibility to TAF. TAF is similarly active in vitro against wild-type genotype A-H HBV clinical isolates. The TAF sensitivity results for all drug-resistant isolates are consistent with what has been observed with the parent drug TFV. The in vitro cell-based HBV phenotyping assay results support the use of TAF in treatment of HBV infected subjects with diverse HBV genotypes, in both treatment-naive and treatment-experienced HBV infected patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Antiviral activity of tenofovir against Cauliflower mosaic virus and its metabolism in Brassica pekinensis plants.

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Spak, Josef; Votruba, Ivan; Pavingerová, Daniela; Holý, Antonín; Spaková, Vlastimila; Petrzik, Karel

2011-11-01

The antiviral effect of the acyclic nucleoside phosphonate tenofovir (R)-PMPA on double-stranded DNA Cauliflower mosaic virus (CaMV) in Brassica pekinensis plants grown in vitro on liquid medium was evaluated. Double antibody sandwich ELISA and PCR were used for relative quantification of viral protein and detecting nucleic acid in plants. (R)-PMPA at concentrations of 25 and 50 mg/l significantly reduced CaMV titers in plants within 6-9 weeks to levels detectable neither by ELISA nor by PCR. Virus-free plants were obtained after 3-month cultivation of meristem tips on semisolid medium containing 50 mg/l (R)-PMPA and their regeneration to whole plants in the greenhouse. Studying the metabolism of (R)-PMPA in B. pekinensis revealed that mono- and diphosphate, structural analogs of NDP and/or NTP, are the only metabolites formed. The data indicate very low substrate activity of the enzymes toward (R)-PMPA as substrate. The extent of phosphorylation in the plant's leaves represents only 4.5% of applied labeled (R)-PMPA. In roots, we detected no radioactive peaks of phosphorylated metabolites of (R)-PMPAp or (R)-PMPApp. Copyright © 2011 Elsevier B.V. All rights reserved.

Improvement of Tenofovir vaginal release from hydrophilic matrices through drug granulation with hydrophobic polymers.

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Notario-Pérez, Fernando; Martín-Illana, Araceli; Cazorla-Luna, Raúl; Ruiz-Caro, Roberto; Peña, Juan; Veiga, María-Dolores

2018-05-30

Sustained-release vaginal microbicides hold out great hope for the prevention of sexual transmission of HIV from men to women. Tenofovir (TFV) -an antiretroviral drug- sustained-release vaginal compacts combining two release control systems (by drug-loading granules with hydrophobic polymers and incorporating them in a hydrophilic matrix) are proposed in this work as a possible microbicide. The polymers used for the drug granules are Eudragit® RS (ERS), an acrylic derivative, and Zein, a maize protein. The hydrophilic matrix is composed of a mixture of hydroxypropylmethyl cellulose (HPMC) and chitosan (CH). The thermal, microscopic, spectrophotometric and X-ray diffraction analysis showed that the drug was not altered during the granulation process. Studies of TFV release, swelling and ex vivo mucoadhesion were subsequently performed on simulated vaginal fluid. The formulation whereby TFV is granulated using twice its weight in ERS, and then including these granules in a matrix in which the CH predominates over HPMC, allows the sustained release of TFV for 144 h, mucoadhesion to the vaginal mucosa for 150 h and a moderate swelling, making it the most suitable formulation of all those studied. These compacts would therefore offer women protection against the sexual acquisition of HIV. Copyright © 2018 Elsevier B.V. All rights reserved.

A Phase 1 Randomized, Open Label, Rectal Safety, Acceptability, Pharmacokinetic, and Pharmacodynamic Study of Three Formulations of Tenofovir 1% Gel (the CHARM-01 Study.

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Ian Mcgowan

Full Text Available The CHARM-01 study characterized the safety, acceptability, pharmacokinetics (PK, and pharmacodynamics (PD of three tenofovir (TFV gels for rectal application. The vaginal formulation (VF gel was previously used in the CAPRISA 004 and VOICE vaginal microbicide Phase 2B trials and the RMP-02/MTN-006 Phase 1 rectal safety study. The reduced glycerin VF (RGVF gel was used in the MTN-007 Phase 1 rectal microbicide trial and is currently being evaluated in the MTN-017 Phase 2 rectal microbicide trial. A third rectal specific formulation (RF gel was also evaluated in the CHARM-01 study.Participants received 4 mL of the three TFV gels in a blinded, crossover design: seven daily doses of RGVF, seven daily doses of RF, and six daily doses of placebo followed by one dose of VF, in a randomized sequence. Safety, acceptability, compartmental PK, and explant PD were monitored throughout the trial.All three gels were found to be safe and acceptable. RF and RGVF PK were not significantly different. Median mucosal mononuclear cell (MMC TFV-DP trended toward higher values for RF compared to RGVF (1136 and 320 fmol/106 cells respectively. Use of each gel in vivo was associated with significant inhibition of ex vivo colorectal tissue HIV infection. There was also a significant negative correlation between the tissue levels of TFV, tissue TFV-DP, MMC TFV-DP, rectal fluid TFV, and explant HIV-1 infection.All three formulations were found to be safe and acceptable. However, the safety profile of the VF gel was only based on exposure to one dose whereas participants received seven doses of the RGVF and RF gels. There was a trend towards higher tissue MMC levels of TFV-DP associated with use of the RF gel. Use of all gels was associated with significant inhibition of ex vivo tissue HIV infection.ClinicalTrials.gov NCT01575405.

Formulation and Optimization of Eudragit RS PO-Tenofovir Nanocarriers Using Box-Behnken Experimental Design

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Kefilwe Matlhola

2015-01-01

Full Text Available The objective of present study was to develop an optimized polymeric nanoparticle system for the antiretroviral drug tenofovir. A modified nanoprecipitation method was used to prepare Eudragit RS PO nanoparticles of the drug. The effect of amount of polymer, surfactant concentration, and sonication time on particle size, particle distribution, encapsulation efficiency (EE, and zeta potential were assessed and optimized utilizing a three-factor, three-level Box-Behnken Design (BBD of experiment. Fifteen formulations of nanoparticles were prepared as per BBD and evaluated for particle size, polydispersity index (PDI, EE, and zeta potential. The results showed that the measured mean particle sizes were in the range of 233 to 499 nm, PDI ranged from 0.094 to 0.153, average zeta potential ranged from −19.9 to −45.8 mV, and EE ranged between 98 and 99%. The optimized formulation was characterized for in vitro drug release and structural characterization. The mean particle size of this formulation was 233 nm with a PDI of 0.0107. It had a high EE of 98% and average zeta potential of −35 mV, an indication of particle stability. The FTIR showed some noncovalent interactions between the drug and polymer but a sustained release was observed in vitro for up to 80 hours.

Implications of HIV PrEP Trials Results

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Anton, Peter; Fletcher, Courtney V.; DeGruttola, Victor; McGowan, Ian; Becker, Stephen; Zwerski, Sheryl; Burns, David

2011-01-01

Abstract Six randomized clinical trials have been implemented to examine the efficacy of tenofovir disoproxil fumarate (TDF) and/or TDF/emtricitabine (TDF/FTC) as preexposure prophylaxis for HIV-1 infection (PrEP). Although largely complementary, the six trials have many similar features. As the earliest results become available, an urgent question may arise regarding whether changes should be made in the conduct of the other trials. To consider this in advance, a Consultation on the Implications of HIV Pre-Exposure Prophylaxis (PrEP) Trials Results sponsored by the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Bill and Melinda Gates Foundation (BMGF) was held on January 29, 2010, at the Natcher Conference Center, NIH, Bethesda, MD. Participants included basic scientists, clinical researchers (including investigators performing the current PrEP trials), and representatives from the U.S. Food and Drug Administration (FDA) and the agencies sponsoring the trials: the U.S. Centers for Disease Control and Prevention (CDC), the U.S. Agency for International Development (USAID), the BMGF, and the U.S. NIH. We report here a summary of the presentations and highlights of salient discussion topics from this workshop. PMID:20969483

HIV pre-exposure prophylaxis: Exploring the potential for expanding the role of pharmacists in public health.

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Okoro, Olihe; Hillman, Lisa

2018-05-19

The study objectives were to a) assess knowledge and experience; b) describe perceptions and attitudes; and c) identify training needs of community-based pharmacists regarding HIV pre-exposure prophylaxis (PrEP). This was a cross-sectional survey study. The survey was administered online to pharmacists practicing in a community setting in the state of Minnesota. Measures included knowledge of and experience with HIV PrEP, perceptions and attitudes towards pharmacists' involvement, and HIV PrEP-specific training needs for pharmacists. With a survey response rate of approximately 13% (n = 347), most respondents (76.4%) agreed that HIV PrEP can be beneficial in high-risk populations. Forty-six percent of respondents were not aware of U.S. Food and Drug Administration approval of emtricitabine and tenofovir disoproxil fumarate for PrEP. Most respondents (71.1%) were "not at all familiar" with Centers for Disease Control and Prevention guidelines for PrEP. Twenty-one percent of respondents had sufficient knowledge to counsel patients on PrEP. Experience with counseling on PrEP (21.8%), having dispensed PrEP in the last 2 years (33.1%), fewer years in practice (≤10 years), location of practice site (urban or suburban), and having received HIV continuing education in the last 2 years (33.0%) were associated with more knowledge of HIV PrEP. Top concerns with counseling were knowledge about the medication and behavior modification. The most frequently indicated primary concerns with implementing PrEP initiatives were identifying appropriate candidates and patient adherence. As pharmacists' roles continue to expand, relevant content in pharmacy education and requisite training (including continuing education) are critical to addressing knowledge gaps and competencies that will enable pharmacists engage more effectively in public health efforts such as HIV prevention. Published by Elsevier Inc.

The Safety of Tenofovir–Emtricitabine for HIV Pre-Exposure Prophylaxis (PrEP) in Individuals With Active Hepatitis B

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Schechter, Mauro; Liu, Albert Y.; McManhan, Vanessa M.; Guanira, Juan V.; Hance, Robert J.; Chariyalertsak, Suwat; Mayer, Kenneth H.; Grant, Robert M.

2016-01-01

Background: Pre-exposure prophylaxis (PrEP) with daily oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) prevents HIV infection. The safety and feasibility of HIV PrEP in the setting of hepatitis B virus (HBV) infection were evaluated. Methods: The Iniciativa Profilaxis Pre-Exposición study randomized 2499 HIV-negative men and transgender women who have sex with men to once-daily oral FTC/TDF versus placebo. Hepatitis serologies and transaminases were obtained at screening and at the time PrEP was discontinued. HBV DNA was assessed by polymerase chain reaction, and drug resistance was assessed by population sequencing. Vaccination was offered to individuals susceptible to HBV infection. Results: Of the 2499 participants, 12 (0.5%; including 6 randomized to FTC/TDF) had chronic HBV infection. After stopping FTC/TDF, 5 of the 6 participants in the active arm had liver function tests performed at follow-up. Liver function tests remained within normal limits at post-stop visits except for a grade 1 elevation in 1 participant at post-stop week 12 (alanine aminotransferase = 90, aspartate aminotransferase = 61). There was no evidence of hepatic flares. Polymerase chain reaction of stored samples showed that 2 participants in the active arm had evidence of acute HBV infection at enrollment. Both had evidence of grade 4 transaminase elevations with subsequent resolution. Overall, there was no evidence of TDF or FTC resistance among tested genotypes. Of 1633 eligible for vaccination, 1587 (97.2%) received at least 1 vaccine; 1383 (84.7%) completed the series. Conclusions: PrEP can be safely provided to individuals with HBV infection if there is no evidence of cirrhosis or substantial transaminase elevation. HBV vaccination rates at screening were low globally, despite recommendations for its use, yet uptake and efficacy were high when offered. PMID:26413853

Antiretroviral Drug Activity in Macaques Infected during Pre-Exposure Prophylaxis Has a Transient Effect on Cell-Associated SHIV DNA Reservoirs.

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Mian-Er Cong

Full Text Available Pre-exposure prophylaxis (PrEP with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF is a novel HIV prevention strategy. Suboptimal PrEP adherence and HIV infection creates an opportunity for continued antiretroviral drug activity during undiagnosed infection. We previously showed that macaques infected with SHIV during PrEP with FTC/TDF display reduced acute plasma viremias and limited virus diversity. We investigated the effect of PrEP on acute SHIV DNA dynamics and on the size of the persistent virus reservoir in lymphoid tissues.Cell-associated SHIV DNA levels in PBMCs were measured in 8 macaques infected during PrEP with FTC/TDF or single-agent TAF and was compared to those seen in untreated infections (n = 10. PrEP breakthrough infections continued treatment with 1-2 weekly drug doses to model suboptimal drug exposure during undiagnosed HIV infection in humans. SHIV DNA was also measured in lymphoid tissues collected from FTC/TDF PrEP breakthroughs after 1 year of infection.Compared to untreated controls, PrEP infections had reduced plasma RNA viremias both at peak and throughout weeks 1-12 (p<0.005. SHIV DNA levels were also reduced at peak and during the first 12 weeks of infection (p<0.043 but not throughout weeks 12-20. At 1 year, SHIV DNA reservoirs in lymphoid tissues were similar in size among macaques that received PrEP or placebo.Antiviral drug activity due to PrEP limits acute SHIV replication but has only a transient effect on cell-associated SHIV DNA levels. Our model suggests that suboptimal drug exposure in persons that are taking PrEP and become infected with HIV may not be sufficient to reduce the pool of HIV-infected cells, and that treatment intensification may be needed to sustain potential virological benefits from the PrEP regimen.

Preexposure Prophylaxis for HIV Infection among African Women

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Van Damme, Lut; Corneli, Amy; Ahmed, Khatija; Agot, Kawango; Lombaard, Johan; Kapiga, Saidi; Malahleha, Mookho; Owino, Fredrick; Manongi, Rachel; Onyango, Jacob; Temu, Lucky; Monedi, Modie Constance; Mak’Oketch, Paul; Makanda, Mankalimeng; Reblin, Ilse; Makatu, Shumani Elsie; Saylor, Lisa; Kiernan, Haddie; Kirkendale, Stella; Wong, Christina; Grant, Robert; Kashuba, Angela; Nanda, Kavita; Mandala, Justin; Fransen, Katrien; Deese, Jennifer; Crucitti, Tania; Mastro, Timothy D.; Taylor, Douglas

2013-01-01

BACKGROUND Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus (HIV) infection in some trials but not in others. METHODS In this randomized, double-blind, placebo-controlled trial, we assigned 2120 HIV-negative women in Kenya, South Africa, and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine (TDF–FTC) or placebo once daily. The primary objective was to assess the effectiveness of TDF–FTC in preventing HIV acquisition and to evaluate safety. RESULTS HIV infections occurred in 33 women in the TDF–FTC group (incidence rate, 4.7 per 100 person-years) and in 35 in the placebo group (incidence rate, 5.0 per 100 person-years), for an estimated hazard ratio in the TDF-FTC group of 0.94 (95% confidence interval, 0.59 to 1.52; P = 0.81). The proportions of women with nausea, vomiting, or elevated alanine aminotransferase levels were significantly higher in the TDF–FTC group (P = 0.04, P<0.001, and P = 0.03, respectively). Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF–FTC group (4.7%) than in the placebo group (3.0%, P = 0.051). Less than 40% of the HIV-uninfected women in the TDF–FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion. The study was stopped early, on April 18, 2011, because of lack of efficacy. CONCLUSIONS Prophylaxis with TDF–FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects, as compared with placebo. Despite substantial counseling efforts, drug adherence appeared to be low. (Supported by the U.S. Agency for International Development and others; FEM-PrEP ClinicalTrials.gov number, NCT00625404.) PMID:22784040

Simultaneous determination and validation of emtricitabine, rilpivirine and tenofovir from biological samples using LC and CE methods.

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Gumustas, Mehmet; Caglayan, Mehmet Gokhan; Onur, Feyyaz; Ozkan, Sibel A

2018-04-01

A combination of antiretroviral agents is frequently used in effective treatment of the human immunodeficiency virus infection. In this study, two different separation methods are presented for the simultaneous determination of emtricitabine, rilpivirine and tenofovir from raw materials and urine samples. Developed liquid chromatography and capillary electrophoresis methods were thoroughly optimized for high analytical performances. Optimization of multiple variables at the same time by performing a minimum number of experiments was achieved by the Box-Behnken design, which is an experimental design in response surface methodology, in capillary electrophoresis. The results of the experimental design ensure minimum analysis time with well-separated analytes. Separation conditions, such as different stationary phases, pH level, organic modifiers and temperatures in liquid chromatography method, were also optimized. In particular, among stationary phases, the core-shell column especially enhanced the effectiveness of separation in liquid chromatography. Both methods were fully validated and applied to real samples. The main advantage of the developed methods is the separation of the drug combination in a short time with high efficiency and without any time-consuming steps. Copyright © 2017 John Wiley & Sons, Ltd.

Associations between plasma tenofovir concentration and renal function markers in HIV-infected women

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Mwila Mulubwa

2016-07-01

Objective: To investigate the correlation between plasma tenofovir (TFV concentration and certain renal function markers in HIV-infected women on TDF antiretroviral therapy (ART.These markers were also compared to a HIV-uninfected control group. Methods: HIV-infected women (n = 30 on TDF-based ART were matched with 30 controls forage and body mass index. Renal markers analysed were estimated glomerular filtration rate (eGFR, creatinine clearance (CrCl, serum creatinine, albuminuria, glucosuria, serum urea, serum uric acid, urine sodium and maximum tubular reabsorption of phosphate. Baseline eGFR and CrCl data were obtained retrospectively for the HIV-infected women. Plasma TFV was assayed using a validated HPLC-MS/MS method. Step wise regression, Mann–Whitney test, unpaired and paired t-tests were applied in the statistical analyses. Results: TFV concentration was independently associated with albuminuria (adjusted r2 = 0.339; p = 0.001 in HIV-infected women. In the adjusted (weight analysis, eGFR (p = 0.038,CrCl (p = 0.032 and albuminuria (p = 0.048 were significantly higher in HIV-infected compared to the uninfected women, but eGFR was abnormally high in HIV-infected women. Both eGFR (p < 0.001 and CrCl (p = 0.008 increased from baseline to follow-up in HIV-infected women. Conclusion: Plasma TFV concentration was associated with increased albuminuria in HIV infected women in this sub-study. Both eGFR and CrCl were increased in HIV-infected women from baseline. These findings should be confirmed in larger studies, and hyperfiltration in HIV-infected women warrants further investigation.

High levels of adherence to a rectal microbicide gel and to oral Pre-Exposure Prophylaxis (PrEP) achieved in MTN-017 among men who have sex with men (MSM) and transgender women.

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Carballo-Diéguez, Alex; Balán, Ivan C; Brown, William; Giguere, Rebecca; Dolezal, Curtis; Leu, Cheng-Shiun; Marzinke, Mark A; Hendrix, Craig W; Piper, Jeanna M; Richardson, Barbra A; Grossman, Cynthia; Johnson, Sherri; Gomez, Kailazarid; Horn, Stephanie; Kunjara Na Ayudhya, Ratiya Pamela; Patterson, Karen; Jacobson, Cindy; Bekker, Linda-Gail; Chariyalertsak, Suwat; Chitwarakorn, Anupong; Gonzales, Pedro; Holtz, Timothy H; Liu, Albert; Mayer, Kenneth H; Zorrilla, Carmen; Lama, Javier; McGowan, Ian; Cranston, Ross D

2017-01-01

Trials to assess microbicide safety require strict adherence to prescribed regimens. If adherence is suboptimal, safety cannot be adequately assessed. MTN-017 was a phase 2, randomized sequence, open-label, expanded safety and acceptability crossover study comparing 1) daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), 2) daily use of reduced-glycerin 1% tenofovir (RG-TFV) gel applied rectally, and 3) RG-TFV gel applied before and after receptive anal intercourse (RAI)-if participants had no RAI in a week, they were asked to use two doses of gel within 24 hours. Product use was assessed by mixed methods including unused product return count, text messaging reports, and qualitative plasma TFV pharmacokinetic (PK) results. Convergence interviews engaged participants in determining the most accurate number of doses used based on product count and text messaging reports. Client-centered adherence counseling was also used. Participants (N = 187) were men who have sex with men and transgender women enrolled in the United States (42%), Thailand (29%), Peru (19%) and South Africa (10%). Mean age was 31.4 years (range 18-64 years). Based on convergence interviews, over an 8-week period, 94% of participants had ≥80% adherence to daily tablet, 41% having perfect adherence; 83% had ≥80% adherence to daily gel, 29% having perfect adherence; and 93% had ≥80% adherence to twice-weekly use during the RAI-associated gel regimen, 75% having perfect adherence and 77% having ≥80% adherence to gel use before and after RAI. Only 4.4% of all daily product PK results were undetectable and unexpected (TFV concentrations <0.31 ng/mL) given self-reported product use near sampling date. The mixed methods adherence measurement indicated high adherence to product use in all three regimens. Adherence to RAI-associated rectal gel use was as high as adherence to daily oral PrEP. A rectal microbicide gel, if efficacious, could be an alternative for individuals uninterested in

High levels of adherence to a rectal microbicide gel and to oral Pre-Exposure Prophylaxis (PrEP achieved in MTN-017 among men who have sex with men (MSM and transgender women.

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Alex Carballo-Diéguez

Full Text Available Trials to assess microbicide safety require strict adherence to prescribed regimens. If adherence is suboptimal, safety cannot be adequately assessed. MTN-017 was a phase 2, randomized sequence, open-label, expanded safety and acceptability crossover study comparing 1 daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, 2 daily use of reduced-glycerin 1% tenofovir (RG-TFV gel applied rectally, and 3 RG-TFV gel applied before and after receptive anal intercourse (RAI-if participants had no RAI in a week, they were asked to use two doses of gel within 24 hours. Product use was assessed by mixed methods including unused product return count, text messaging reports, and qualitative plasma TFV pharmacokinetic (PK results. Convergence interviews engaged participants in determining the most accurate number of doses used based on product count and text messaging reports. Client-centered adherence counseling was also used. Participants (N = 187 were men who have sex with men and transgender women enrolled in the United States (42%, Thailand (29%, Peru (19% and South Africa (10%. Mean age was 31.4 years (range 18-64 years. Based on convergence interviews, over an 8-week period, 94% of participants had ≥80% adherence to daily tablet, 41% having perfect adherence; 83% had ≥80% adherence to daily gel, 29% having perfect adherence; and 93% had ≥80% adherence to twice-weekly use during the RAI-associated gel regimen, 75% having perfect adherence and 77% having ≥80% adherence to gel use before and after RAI. Only 4.4% of all daily product PK results were undetectable and unexpected (TFV concentrations <0.31 ng/mL given self-reported product use near sampling date. The mixed methods adherence measurement indicated high adherence to product use in all three regimens. Adherence to RAI-associated rectal gel use was as high as adherence to daily oral PrEP. A rectal microbicide gel, if efficacious, could be an alternative for individuals

Economic evaluation of treatments for chronic hepatitis B

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Astrid Wiens

Full Text Available The aim of this study was to conduct a cost-utility study of adefovir, entecavir, interferon alpha, pegylated interferon alpha, lamivudine and tenofovir for chronic hepatitis B in the context of Brazilian Public Health Care System. A systematic review was carried out for efficacy and safety. Another review was performed to collect utility data and transition probabilities between health states. A Markov model was developed in a time horizon of 40 years with annual cycles for three groups of: HBeAg positive, HBeAg negative, and all patients. These strategies were compared to a fourth group that received no treatment. Discount rates of 5% were applied and sensitivity analyses were performed. Tenofovir offered the best cost-utility ratio for the three evaluated models: U$397, U$385 and U$384 (per QALY, respectively, for HBeAg positive, negative, and all patients. All other strategies were completely dominated because they showed higher costs and lower effectiveness than tenofovir. The sequence of cost-utility in the three models was: tenofovir, entecavir, lamivudine, adefovir, telbivudine, pegylated interferon alpha, and interferon alpha. In the sensitivity analysis, adefovir showed lower cost-utility than telbivudine in some situations. The study has some limitations, primarily related to the creation of scenarios and modeling. In this study, tenofovir presented the best cost-utility ratio. The results obtained in this study will be valuable in decision-making and in the review of the clinical protocol, mainly involving the allocation of available resources for health care.

Adherence and acceptability in MTN 001: A randomized cross-over trial of daily oral and topical tenofovir for HIV prevention in women

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Minnis, Alexandra M.; Gandham, Sharavi; Richardson, Barbra A.; Guddera, Vijayanand; Chen, Beatrice A.; Salata, Robert; Nakabiito, Clemensia; Hoesley, Craig; Justman, Jessica; Soto-Torres, Lydia; Patterson, Karen; Gomez, Kailazarid; Hendrix, Craig

2012-01-01

We compared adherence to and acceptability of daily topical and oral formulations of tenofovir (TFV) used as pre-exposure prophylaxis (PrEP) for HIV prevention among women in South Africa, Uganda and the United States. 144 sexually active, HIV-uninfected women participated in a cross-over study of three regimens: oral tablet, vaginal gel, or both. We tested for differences in adherence and evaluated product acceptability. Self-reported adherence for all regimens was high (94%), but serum TFV concentrations indicated only 64% of participants used tablets consistently. Most women in the U.S. (72%) favored tablets over gel; while preferences varied at the African sites (42% preferred gel and 40% tablets). Findings indicate a role for oral and vaginal PrEP formulations and highlight the importance of integrating pharmacokinetics-based adherence assessment in future trials. Biomedical HIV prevention interventions should consider geographic and cultural experience with product formulations, partner involvement, and sexual health benefits that ultimately influence use. PMID:23065145

Participant experiences and facilitators and barriers to pill use among men who have sex with men in the iPrEx pre-exposure prophylaxis trial in San Francisco.

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Gilmore, Hailey J; Liu, Albert; Koester, Kimberly Ann; Amico, K Rivet; McMahan, Vanessa; Goicochea, Pedro; Vargas, Lorena; Lubensky, David; Buchbinder, Susan; Grant, Robert

2013-10-01

In 2010, the iPrEx study demonstrated efficacy of daily emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) pre-exposure prophylaxis (PrEP) in reducing HIV acquisition among men who have sex with men. Adherence to study product was critical for PrEP efficacy, and varied considerably, with FTC/TDF detection rates highest in the United States. We conducted a qualitative study to gain insights into the experiences of iPrEx participants in San Francisco (SF) where there was high confirmed adherence, to understand individual and contextual factors influencing study product use in this community. In 2009 and 2011, we conducted focus groups and in-depth interviews in 36 and 16 SF iPrEx participants, respectively. Qualitative analyses indicate that participants joined the study out of altruism. They had a clear understanding of study product use, and pill taking was facilitated by establishing or building on an existing routine. Participants valued healthcare provided by the study and relationships with staff, whom they perceived as nonjudgmental, and found client-centered counseling to be an important part of the PrEP package. This facilitated pill taking and accurate reporting of missed doses. Adherence barriers included changes in routine, side effects/intercurrent illnesses, and stress. Future PrEP adherence interventions should leverage existing routines and establish client-centered relationships/ environments to support pill taking and promote accurate reporting.

Synergy against drug-resistant HIV-1 with the microbicide antiretrovirals, dapivirine and tenofovir, in combination.

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Schader, Susan M; Colby-Germinario, Susan P; Schachter, Jordana R; Xu, Hongtao; Wainberg, Mark A

2011-08-24

To evaluate the candidate antiretroviral microbicide compounds, dapivirine (DAP) and tenofovir (TFV), alone and in combination against the transmission of wild-type and nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 from different subtypes. We determined single-drug efficacy of the RTIs, DAP and TFV, against subtype B and non-B wild-type and NNRTI-resistant HIV-1 in vitro. To assess breadth of activity, compounds were tested alone and in combination against wild-type and NNRTI-resistant subtype C primary HIV-1 isolates and complimentary clonal HIV-1 from subtypes B, C and CRF02_AG to control for viral variation. Early infection was quantified by counting light units emitted from TZM-bl cells less than 48-h postinfection. Combination ratios were based on drug inhibitory concentrations (IC(50)s) and combined effects were determined by calculating combination indices. Both candidate microbicide antiretrovirals demonstrated potent anti-NNRTI-resistant HIV-1 activity in vitro, albeit the combination protected better than the single-drug treatments. Of particular interest, the DAP with TFV combination exhibited synergy (50% combination index, CI(50) = 0.567) against subtype C NNRTI-resistant HIV-1, whereas additivity (CI(50) = 0.987) was observed against the wild-type counterpart from the same patient. The effect was not compounded by the presence of subdominant viral fractions, as experiments using complimentary clonal subtype C wild-type (CI(50) = 0.968) and NNRTI-resistant (CI(50) = 0.672) HIV-1, in lieu of the patient quasispecies, gave similar results. This study supports the notion that antiretroviral drug combinations may retain antiviral activity against some drug-resistant HIV-1 despite subtype classification and quasispecies diversity.

Optimization of tenofovir release from mucoadhesive vaginal tablets by polymer combination to prevent sexual transmission of HIV.

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Notario-Pérez, Fernando; Cazorla-Luna, Raúl; Martín-Illana, Araceli; Ruiz-Caro, Roberto; Tamayo, Aitana; Rubio, Juan; Veiga, María-Dolores

2018-01-01

The use of sustained-release mucoadhesive vaginal tablets of antiretroviral drugs as microbicidal formulations can be an effective strategy for reducing the sexual transmission of HIV from men to women, which is a main problem particularly in low- and middle-income countries. Different polymers (hydroxypropylmethyl cellulose (HPMC), chitosan, guar gum and Eudragit ® RS) have proven some good features for this purpose. At this work, these polymers have been combined in pairs in different proportions to enhance the advantages offered by each one individually. The in vitro release of tenofovir from the matrices, ex vivo mucoadhesive capacity (evaluated on vaginal mucosa) and the degree of swelling in simulated vaginal fluid have been assessed. A multimodal pore size distribution is observed in porosimetry studies -carried out with swelling witnesses-, due to the contribution of polymers with different swelling behaviour to the pore formation, and it is corroborated by scanning electron microscopy. X-ray diffraction technique confirms the changes in crystallinity of the formulation after swelling. We can report that the combination of HPMC and chitosan in the same formulation may be useful for the prevention of sexual transmission of HIV, since tablets can be obtained that remain adhered to the vaginal mucosa for 96h, so the drug is released in a sustained manner for 72h. When the formulation contains more chitosan than HPMC the swelling is moderate, making it more comfortable for women to apply. Copyright © 2017. Published by Elsevier Ltd.

Influence of Chitosan Swelling Behaviour on Controlled Release of Tenofovir from Mucoadhesive Vaginal Systems for Prevention of Sexual Transmission of HIV

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Notario-Pérez, Fernando; Martín-Illana, Araceli; Cazorla-Luna, Raúl; Ruiz-Caro, Roberto; Bedoya, Luis-Miguel; Tamayo, Aitana; Rubio, Juan; Veiga, María-Dolores

2017-01-01

The main challenges facing efforts to prevent the transmission of human immunodeficiency virus (HIV) are the lack of access to sexual education services and sexual violence against young women and girls. Vaginal formulations for the prevention of sexually transmitted infections are currently gaining importance in drug development. Vaginal mucoadhesive tablets can be developed by including natural polymers that have good binding capacity with mucosal tissues, such as chitosan or guar gum, semisynthetic polymers such as hydroxypropylmethyl cellulose, or synthetic polymers such as Eudragit® RS. This paper assesses the potential of chitosan for the development of sustained-release vaginal tablets of Tenofovir and compares it with different polymers. The parameters assessed were the permanence time of the bioadhesion—determined ex vivo using bovine vaginal mucosa as substrate—the drug release profiles from the formulation to the medium (simulated vaginal fluid), and swelling profiles in the same medium. Chitosan can be said to allow the manufacture of tablets that remain adhered to the vaginal mucosa and release the drug in a sustained way, with low toxicity and moderate swelling that ensures the comfort of the patient and may be useful for the prevention of sexual transmission of HIV. PMID:28230790

Influence of Chitosan Swelling Behaviour on Controlled Release of Tenofovir from Mucoadhesive Vaginal Systems for Prevention of Sexual Transmission of HIV.

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Notario-Pérez, Fernando; Martín-Illana, Araceli; Cazorla-Luna, Raúl; Ruiz-Caro, Roberto; Bedoya, Luis-Miguel; Tamayo, Aitana; Rubio, Juan; Veiga, María-Dolores

2017-02-21

The main challenges facing efforts to prevent the transmission of human immunodeficiency virus (HIV) are the lack of access to sexual education services and sexual violence against young women and girls. Vaginal formulations for the prevention of sexually transmitted infections are currently gaining importance in drug development. Vaginal mucoadhesive tablets can be developed by including natural polymers that have good binding capacity with mucosal tissues, such as chitosan or guar gum, semisynthetic polymers such as hydroxypropylmethyl cellulose, or synthetic polymers such as Eudragit ® RS. This paper assesses the potential of chitosan for the development of sustained-release vaginal tablets of Tenofovir and compares it with different polymers. The parameters assessed were the permanence time of the bioadhesion-determined ex vivo using bovine vaginal mucosa as substrate-the drug release profiles from the formulation to the medium (simulated vaginal fluid), and swelling profiles in the same medium. Chitosan can be said to allow the manufacture of tablets that remain adhered to the vaginal mucosa and release the drug in a sustained way, with low toxicity and moderate swelling that ensures the comfort of the patient and may be useful for the prevention of sexual transmission of HIV.

Electronic warfare receivers and receiving systems

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Poisel, Richard A

2014-01-01

Receivers systems are considered the core of electronic warfare (EW) intercept systems. Without them, the fundamental purpose of such systems is null and void. This book considers the major elements that make up receiver systems and the receivers that go in them.This resource provides system design engineers with techniques for design and development of EW receivers for modern modulations (spread spectrum) in addition to receivers for older, common modulation formats. Each major module in these receivers is considered in detail. Design information is included as well as performance tradeoffs o

Scaling up the 2010 World Health Organization HIV Treatment Guidelines in resource-limited settings: a model-based analysis.

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Rochelle P Walensky

2010-12-01

Full Text Available The new 2010 World Health Organization (WHO HIV treatment guidelines recommend earlier antiretroviral therapy (ART initiation (CD4<350 cells/µl instead of CD4<200 cells/µl, multiple sequential ART regimens, and replacement of first-line stavudine with tenofovir. This paper considers what to do first in resource-limited settings where immediate implementation of all of the WHO recommendations is not feasible.We use a mathematical model and local input data to project clinical and economic outcomes in a South African HIV-infected cohort (mean age = 32.8 y, mean CD4 = 375/µl. For the reference strategy, we assume that all patients initiate stavudine-based ART with WHO stage III/IV disease and receive one line of ART (stavudine/WHO/one-line. We rank-in survival, cost-effectiveness, and equity terms-all 12 possible combinations of the following: (1 stavudine replacement with tenofovir, (2 ART initiation (by WHO stage, CD4<200 cells/µl, or CD4<350 cells/µl, and (3 one or two regimens, or lines, of available ART. Projected life expectancy for the reference strategy is 99.0 mo. Considering each of the guideline components separately, 5-y survival is maximized with ART initiation at CD4<350 cells/µl (stavudine/<350/µl/one-line, 87% survival compared with stavudine/WHO/two-lines (66% and tenofovir/WHO/one-line (66%. The greatest life expectancies are achieved via the following stepwise programmatic additions: stavudine/<350/µl/one-line (124.3 mo, stavudine/<350/µl/two-lines (177.6 mo, and tenofovir/<350/µl/two-lines (193.6 mo. Three program combinations are economically efficient: stavudine/<350/µl/one-line (cost-effectiveness ratio, US$610/years of life saved [YLS], tenofovir/<350/µl/one-line (US$1,140/YLS, and tenofovir/<350/µl/two-lines (US$2,370/YLS.In settings where immediate implementation of all of the new WHO treatment guidelines is not feasible, ART initiation at CD4<350 cells/µl provides the greatest short- and long

Costo-efectividad de dos terapias antivirales para Hepatitis B crónica en el Perú: Entecavir y tenofovir

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Rafael Bolaños-Díaz

Full Text Available RESUMEN Objetivos Comparar en términos de costo-efectividad a entecavir (ETV y tenofovir (TDF en el tratamiento del virus de la hepatitis B (HBV en hospitales públicos del Perú. Materiales y métodos Estructuramos un modelo de Markov, definimos la efectividad en años de vida ajustados a calidad (AVAC. Incluimos los costos directos del tratamiento en soles desde la perspectiva del Ministerio de Salud del Perú. Calculamos la relación entre costo y efectividad incrementales (ICER. Realizamos análisis de sensibilidad determinístico y probabilístico, considerando un rango de disponibilidad de pago (WTP desde uno hasta tres veces el producto bruto interno (PBI per-cápita, y el beneficio monetario neto (BMN o ICER en el caso del análisis de tornado. Resultados El tratamiento con TDF es más efectivo y menos costoso que ETV. El ETV tuvo un costo por AVAC de S/ 4482, y de S/ 1526 para TDF. El TDF mantiene un BMN progresivamente mayor conforme aumenta la WTP. La tasa de descuento fue la única variable con efecto significativo en la incertidumbre del modelo. Conclusiones El tratamiento con TDF es más costo-efectivo que ETV en hospitales públicos del Perú.

Phototoxicity free quantum dot-based niosome formulation for controlled drug release and its monitoring

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Kumar, Sunil; Kang, T. W.; Bala, Suman; Kamboj, Sunil; Jeon, H. C.

2018-04-01

A novel niosomes-based system composed of Hypromellose (HPMC) functionalized fluorescent, biocompatible ZnS:Mn quantum dots (QDs), and anti-HIV drug Tenofovir disoproxil fumarate (TDF) was designed. An appropriate ratio of surfactant Sorbitan Monostearate (SPAN-60) and cholesterol was used to obtain an optimal entrapment efficiency. Initially, after observing the successful interaction of HPMC with SPAN-60, the noisome formulation including (QDs + drug) and HPMC-coated QDs was synthesized by a wet chemical route and characterized by X-ray diffraction (XRD), Transmission electron microscope (TEM) and Selected Electron Diffraction (SAED). Secondly, (QDs + drug) loaded niosome formulations were studied by varying the ratio of SPAN-60 and cholesterol. Multiple studies were done to characterize the shape, size, viscosity, colloidal stability, and entrapment efficiency of (QDs + drug) loaded niosomes. Lastly, pH-dependent (QDs + drug) release profiles were studied by a spectroscopic technique considering the pH of the human gastrointestinal region to obtain the formulation stability of (QDs + drug) release from the niosome vesicles. These studies also include pH-dependent photo-stability measurements based on laser-induced multiphoton excitation technique in the Infrared region. The multiphoton time-resolved studies were completed to avoid the UV induced phototoxicity in the drug delivery modules. Current studies on the formulation of niosomes-based (QDs + drug) system laid a foundation to make a complete phototoxicity free system for tracking controlled drug release and its imaging.

Risk factors and co-morbidities associated with changes in renal function among antiretroviral treatment-naïve adults in South Africa: A chart review.

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Assaram, Shirelle; Mashamba-Thompson, Tivani P; Magula, Nombulelo P

2018-01-01

Our systematic scoping review has demonstrated a research gap in antiretroviral treatment (ART) nephrotoxicity as well as in the long-term outcomes of renal function for patients on ART in South Africa. Bearing in mind the high prevalence of human immunodeficiency virus (HIV) in South Africa, this is of great concern. To determine the risk factors and co-morbidities associated with changes in renal function in HIV-infected adults in South Africa. We conducted a retrospective study of 350 ART-naïve adult patients attending the King Edward VIII HIV clinic, Durban, South Africa. Data were collected at baseline (pre-ART) and at six, 12, 18 and 24 months on ART. Renal function was assessed in the 24-month period using the Modification of Diet in Renal Disease equation and was categorised into normal renal function (estimated glomerular filtration rate [eGFR] ≥ 60), moderate renal impairment (eGFR 30-59), severe renal impairment (eGFR 15-29) and kidney failure (eGFR 0.05. The vast majority of patients were initiated on tenofovir disoproxil fumarate (TDF) (90.6%), in combination with lamivudine (3TC) (100%) and either efavirenz (EFV) (56.6%) or nevirapine (NVP) (43.4%). This study reports a low prevalence of baseline renal impairment in HIV-infected ART-naïve outpatients. An improvement in renal function after the commencement of ART has been demonstrated in this population. However, the long-term outcomes of patients with HIV-related renal disease are not known.

HIV Prevention After Discontinuing Pre-Exposure Prophylaxis: Conclusions From a Case Study

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Kai J. Jonas

2018-05-01

Full Text Available Pre-exposure prophylaxis (PrEP with tenofovir disoproxil fumarate in combination with emtricitabine (FTC is a highly effective form of HIV prevention. Endeavors of health-care providers and activists in many countries over the world are directed at making access to PrEP possible, or increasing PrEP use among men-who-have-sex-with-men (MSM. We argue while this effort is necessary, we also need to consider modes of HIV prevention after a period of PrEP use. PrEP uptake is not a one-way street, meaning that individuals may discontinue PrEP use, either voluntarily and involuntarily. Voluntary discontinued PrEP use in conjunction with decreased or no HIV risk exposure is unproblematic, but involuntary discontinuations with continuous high level of HIV risk exposure calls for tailored post-PrEP use HIV prevention. We present a case study of an MSM individual who discontinued PrEP for medical reasons (renal function and seroconverted soon afterward, to illustrate the need for tailored HIV prevention post-PrEP. Furthermore, we provide additional contexts of PrEP discontinuation leading to populations that are in need for post-PrEP types of HIV prevention. Subsequently, we present suggestions for modes of post-PrEP HIV prevention based on knowledge–communication–choice model. Community organization and health-care providers should consider and prepare their HIV prevention consulting protocols for such types of clients and add post-PrEP HIV prevention measures to their consulting offer.

Influence of Chitosan Swelling Behaviour on Controlled Release of Tenofovir from Mucoadhesive Vaginal Systems for Prevention of Sexual Transmission of HIV

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Fernando Notario-Pérez

2017-02-01

Full Text Available The main challenges facing efforts to prevent the transmission of human immunodeficiency virus (HIV are the lack of access to sexual education services and sexual violence against young women and girls. Vaginal formulations for the prevention of sexually transmitted infections are currently gaining importance in drug development. Vaginal mucoadhesive tablets can be developed by including natural polymers that have good binding capacity with mucosal tissues, such as chitosan or guar gum, semisynthetic polymers such as hydroxypropylmethyl cellulose, or synthetic polymers such as Eudragit® RS. This paper assesses the potential of chitosan for the development of sustained-release vaginal tablets of Tenofovir and compares it with different polymers. The parameters assessed were the permanence time of the bioadhesion—determined ex vivo using bovine vaginal mucosa as substrate—the drug release profiles from the formulation to the medium (simulated vaginal fluid, and swelling profiles in the same medium. Chitosan can be said to allow the manufacture of tablets that remain adhered to the vaginal mucosa and release the drug in a sustained way, with low toxicity and moderate swelling that ensures the comfort of the patient and may be useful for the prevention of sexual transmission of HIV.

Receiver gain function: the actual NMR receiver gain

OpenAIRE

Mo, Huaping; Harwood, John S.; Raftery, Daniel

2010-01-01

The observed NMR signal size depends on the receiver gain parameter. We propose a receiver gain function to characterize how much the raw FID is amplified by the receiver as a function of the receiver gain setting. Although the receiver is linear for a fixed gain setting, the actual gain of the receiver may differ from what the gain setting suggests. Nevertheless, for a given receiver, we demonstrate that the receiver gain function can be calibrated. Such a calibration enables accurate compar...

Books Received

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education. Books Received. Articles in Resonance – Journal of Science Education. Volume 1 Issue 1 January 1996 pp 118-118 Books Received. Books Received · More Details Fulltext PDF. Volume 1 Issue 2 February 1996 pp 120-120 Books Received. Books Received.

Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention.

Science.gov (United States)

Fowler, Mary G; Qin, Min; Fiscus, Susan A; Currier, Judith S; Flynn, Patricia M; Chipato, Tsungai; McIntyre, James; Gnanashanmugam, Devasena; Siberry, George K; Coletti, Anne S; Taha, Taha E; Klingman, Karin L; Martinson, Francis E; Owor, Maxensia; Violari, Avy; Moodley, Dhayendre; Theron, Gerhard B; Bhosale, Ramesh; Bobat, Raziya; Chi, Benjamin H; Strehlau, Renate; Mlay, Pendo; Loftis, Amy J; Browning, Renee; Fenton, Terence; Purdue, Lynette; Basar, Michael; Shapiro, David E; Mofenson, Lynne M

2016-11-03

zidovudine-based ART of very preterm delivery before 34 weeks (6.0% vs. 2.6%, P=0.04) and early infant death (4.4% vs. 0.6%, P=0.001), but there were no significant differences between tenofovir-based ART and zidovudine alone (P=0.10 and P=0.43). The rate of HIV-free survival was highest among infants whose mothers received zidovudine-based ART. Antenatal ART resulted in significantly lower rates of early HIV transmission than zidovudine alone but a higher risk of adverse maternal and neonatal outcomes. (Funded by the National Institutes of Health; PROMISE ClinicalTrials.gov numbers, NCT01061151 and NCT01253538 .).

The Female Genital Tract Microbiome Is Associated With Vaginal Antiretroviral Drug Concentrations in Human Immunodeficiency Virus-Infected Women on Antiretroviral Therapy.

Science.gov (United States)

Donahue Carlson, Renee; Sheth, Anandi N; Read, Timothy D; Frisch, Michael B; Mehta, C Christina; Martin, Amy; Haaland, Richard E; Patel, Anar S; Pau, Chou-Pong; Kraft, Colleen S; Ofotokun, Igho

2017-11-15

The female genital tract (FGT) microbiome may affect vaginal pH and other factors that influence drug movement into the vagina. We examined the relationship between the microbiome and antiretroviral concentrations in the FGT. Over one menstrual cycle, 20 human immunodeficiency virus (HIV)-infected women virologically suppressed on tenofovir (TFV) disoproxil fumarate/emtricitabine and ritonavir-boosted atazanavir (ATV) underwent serial paired cervicovaginal and plasma sampling for antiretroviral concentrations using high-performance liquid chromatography-tandem mass spectrometry. Analysis of 16S ribosomal RNA gene sequencing of cervicovaginal lavage clustered each participant visit into a unique microbiome community type (mCT). Participants were predominantly African American (95%), with a median age of 38 years. Cervicovaginal lavage sequencing (n = 109) resulted in a low-diversity mCT dominated by Lactobacillus (n = 40), and intermediate-diversity (n = 28) and high-diversity (n = 41) mCTs with abundance of anaerobic taxa. In multivariable models, geometric mean FGT:plasma ratios varied significantly by mCT for all 3 drugs. For both ATV and TFV, FGT:plasma was significantly lower in participant visits with high- and low-diversity mCT groups (all P < .02). For emtricitabine, FGT:plasma was significantly lower in participant visits with low- vs intermediate-diversity mCT groups (P = .002). Certain FGT mCTs are associated with decreased FGT antiretroviral concentrations. These findings are relevant for optimizing antiretrovirals used for biomedical HIV prevention in women. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

3D printed, controlled release, tritherapeutic tablet matrix for advanced anti-HIV-1 drug delivery.

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Siyawamwaya, Margaret; du Toit, Lisa C; Kumar, Pradeep; Choonara, Yahya E; Kondiah, Pierre P P D; Pillay, Viness

2018-04-12

A 3D-Bioplotter® was employed to 3D print (3DP) a humic acid-polyquaternium 10 (HA-PQ10) controlled release fixed dose combination (FDC) tablet comprising of the anti-HIV-1 drugs, efavirenz (EFV), tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Chemical interactions, surface morphology and mechanical strength of the FDC were ascertained. In vitro drug release studies were conducted in biorelevant media followed by in vivo study in the large white pigs, in comparison with a market formulation, Atripla®. In vitro-in vivo correlation of results was undertaken. EFV, TDF and FTC were successfully entrapped in the 24-layered rectangular prism-shaped 3DP FDC with a loading of ∼12.5 mg/6.3 mg/4 mg of EFV/TDF/FTC respectively per printed layer. Hydrogen bonding between the EFV/TDF/FTC and HA-PQ10 was detected which was indicative of possible drug solubility enhancement. The overall surface of the tablet exhibited a fibrilla structure and the 90° inner pattern was determined to be optimal for 3DP of the FDC. In vitro and in vivo drug release profiles from the 3DP FDC demonstrated that intestinal-targeted and controlled drug release was achieved. A 3DP FDC was successfully manufactured with the aid of a 3D-Bioplotter in a single step process. The versatile HA-PQ10 entrapped all drugs and achieved an enhanced relative bioavailability of EFV, TDF, and FTC compared to the market formulation for potentially enhanced HIV treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Antiretroviral pre-exposure prophylaxis prevents vaginal transmission of HIV-1 in humanized BLT mice.

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Paul W Denton

2008-01-01

Full Text Available Worldwide, vaginal transmission now accounts for more than half of newly acquired HIV-1 infections. Despite the urgency to develop and implement novel approaches capable of preventing HIV transmission, this process has been hindered by the lack of adequate small animal models for preclinical efficacy and safety testing. Given the importance of this route of transmission, we investigated the susceptibility of humanized mice to intravaginal HIV-1 infection.We show that the female reproductive tract of humanized bone marrow-liver-thymus (BLT mice is reconstituted with human CD4+ T and other relevant human cells, rendering these humanized mice susceptible to intravaginal infection by HIV-1. Effects of HIV-1 infection include CD4+ T cell depletion in gut-associated lymphoid tissue (GALT that closely mimics what is observed in HIV-1-infected humans. We also show that pre-exposure prophylaxis with antiretroviral drugs is a highly effective method for preventing vaginal HIV-1 transmission. Whereas 88% (7/8 of BLT mice inoculated vaginally with HIV-1 became infected, none of the animals (0/5 given pre-exposure prophylaxis of emtricitabine (FTC/tenofovir disoproxil fumarate (TDF showed evidence of infection (Chi square = 7.5, df = 1, p = 0.006.The fact that humanized BLT mice are susceptible to intravaginal infection makes this system an excellent candidate for preclinical evaluation of both microbicides and pre-exposure prophylactic regimens. The utility of humanized mice to study intravaginal HIV-1 transmission is particularly highlighted by the demonstration that pre-exposure prophylaxis can prevent intravaginal HIV-1 transmission in the BLT mouse model.

Systemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT mice.

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Paul W Denton

2010-01-01

Full Text Available Successful antiretroviral pre-exposure prophylaxis (PrEP for mucosal and intravenous HIV-1 transmission could reduce new infections among targeted high-risk populations including discordant couples, injection drug users, high-risk women and men who have sex with men. Targeted antiretroviral PrEP could be particularly effective at slowing the spread of HIV-1 if a single antiretroviral combination were found to be broadly protective across multiple routes of transmission. Therefore, we designed our in vivo preclinical study to systematically investigate whether rectal and intravenous HIV-1 transmission can be blocked by antiretrovirals administered systemically prior to HIV-1 exposure. We performed these studies using a highly relevant in vivo model of mucosal HIV-1 transmission, humanized Bone marrow/Liver/Thymus mice (BLT. BLT mice are susceptible to HIV-1 infection via three major physiological routes of viral transmission: vaginal, rectal and intravenous. Our results show that BLT mice given systemic antiretroviral PrEP are efficiently protected from HIV-1 infection regardless of the route of exposure. Specifically, systemic antiretroviral PrEP with emtricitabine and tenofovir disoproxil fumarate prevented both rectal (Chi square = 8.6, df = 1, p = 0.003 and intravenous (Chi square = 13, df = 1, p = 0.0003 HIV-1 transmission. Our results indicate that antiretroviral PrEP has the potential to be broadly effective at preventing new rectal or intravenous HIV transmissions in targeted high risk individuals. These in vivo preclinical findings provide strong experimental evidence supporting the potential clinical implementation of antiretroviral based pre-exposure prophylactic measures to prevent the spread of HIV/AIDS.

Factors influencing uptake of pre-exposure prophylaxis: some qualitative insights from an intervention study of men who have sex with men in China.

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Liu, Chunxing; Ding, Yingying; Ning, Zhen; Gao, Meiyang; Liu, Xing; Wong, Frank Y; He, Na

2018-02-01

Pre-exposure prophylaxis (PrEP) is a biomedical approach for preventing the acquisition of HIV in populations at substantial risk for HIV. However, its uptake among men who have sex with men (MSM) is low in China. The study aimed to identify factors that might influence MSM's uptake and use of PrEP. In-depth interviews were conducted with 32 self-identified MSM from a PrEP intervention study evaluating daily oral tenofovir disoproxil fumarate (TDF) to prevent HIV infection. Of these men, 11 were presently using the 'TDF' group; 8 from the 'change-over' group (i.e. initially used PrEP but subsequently quitted); and 13 from the non-user group. Data were analysed using thematic approach. Perception of low HIV risk, mistrust of the national PrEP program, and concerns of side effects were the main reasons for not wanting to use PrEP. Also, lack of main sexual partner's support, difficulties in adhering to the daily TDF regimen, and the inconvenient schedules in securing the medicine were the major reasons for not wanting to use or quitting the use of PrEP. On the other hand, perceived high HIV risk, beliefs in efficacy of PrEP, and worries of transmitting HIV to families were the major motives for PrEP uptake. Findings suggest that PrEP implementation strategies should first address issues including but not limited to accurate self-assessment of HIV risk, mistrust and limited knowledge about medical trials and PrEP, and ease of accessing PrEP.

Safety, adherence and acceptability of intermittent tenofovir/emtricitabine as HIV pre-exposure prophylaxis (PrEP among HIV-uninfected Ugandan volunteers living in HIV-serodiscordant relationships: a randomized, clinical trial.

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Freddie M Kibengo

Full Text Available BACKGROUND: Efficacy of oral pre-exposure prophylaxis (PrEP in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens. DESIGN: Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment. METHODS: Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS and self-report. Sexual activity data were collected via daily short text message (SMS and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT. RESULTS: Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100 for daily PrEP regimen, 91% (IQR: 73-97 for fixed intermittent dosing and 45% (IQR: 20-63 for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen. CONCLUSIONS: Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be

Effectiveness and Safety of Generic Fixed-Dose Combination of Tenofovir/Emtricitabine/Efavirenz in HIV-1-Infected Patients in Western India.

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Pujari, Sanjay; Dravid, Ameet; Gupte, Nikhil; Joshix, Kedar; Bele, Vivek

2008-08-20

To assess effectiveness and safety of a generic fixed-dose combination of tenofovir (TDF)/emtricitabine (FTC)/efavirenz (EFV) among HIV-1-infected patients in Western India. Antiretroviral (ARV)-naive and experienced (thymidine analog nucleoside reverse transcriptase inhibitor [tNRTI] replaced by TDF) patients were started on a regimen of 1 TDF/FTC/EFV pill once a day. They were followed clinically on a periodic basis, and viral loads and CD4 counts were measured at 6 and 12 months. Creatinine clearance was calculated at baseline and at 6 months and/or as clinically indicated. Effectiveness was defined as not having to discontinue the regimen due to failure or toxicity. One hundred forty-one patients who started TDF/FTC/EFV before 1 June 2007 were eligible. Of these, 130 (92.2%) and 44 (31.2%) had 6- and 12-months follow-up, respectively. Thirty-five percent of the patients were ARV-naive. Eleven patients discontinued treatment (4 for virologic failure, 1 for grade 3-4 central nervous system disturbances, 4 for grade 3-4 renal toxicity, and 2 for cost). Ninety-six percent of patients were virologically suppressed at 6 months. Frequency of TDF-associated grade 3-4 renal toxicity was 2.8%; however, 3 of these patients had comorbid conditions associated with renal dysfunction. A fixed-dose combination of generic TDF/FTC/EFV is effective in ARV-naive and experienced patients. Although frequency of severe renal toxicity was higher than has been reported in the literature, it was safe in patients with no comorbid renal conditions.

Emergence of Lamivudine-Resistant HBV during Antiretroviral Therapy Including Lamivudine for Patients Coinfected with HIV and HBV in China

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Li, Yijia; Zhu, Ting; Song, Xiaojing; Huang, Ying; Yang, Feifei; Guan, Shuo; Xie, Jing; Gohda, Jin; Hosoya, Noriaki; Kawana-Tachikawa, Ai; Liu, Wenjun; Gao, George Fu; Iwamoto, Aikichi; Li, Taisheng; Ishida, Takaomi

2015-01-01

In China, HIV-1-infected patients typically receive antiretroviral therapy (ART) that includes lamivudine (3TC) as a reverse-transcriptase inhibitor (RTI) (ART-3TC). Previous studies from certain developed countries have shown that, in ART-3TC, 3TC-resistant HBV progressively emerges at an annual rate of 15–20% in patients coinfected with HIV-1 and HBV. This scenario in China warrants investigation because >10% of all HIV-infected patients in China are HBV carriers. We measured the occurrence of 3TC-resistant HBV during ART-3TC for HIV-HBV coinfection and also tested the effect of tenofovir disoproxil fumarate (TDF) used as an additional RTI (ART-3TC/TDF) in a cohort study in China. We obtained 200 plasma samples collected from 50 Chinese patients coinfected with HIV-1 and HBV (positive for hepatitis B surface antigen) and examined them for the prevalence of 3TC-resistant HBV by directly sequencing PCR products that covered the HBV reverse-transcriptase gene. We divided the patients into ART-3TC and ART-3TC/TDF groups and compared the efficacy of treatment and incidence of drug-resistance mutation between the groups. HIV RNA and HBV DNA loads drastically decreased in both ART-3TC and ART-3TC/TDF groups. In the ART-3TC group, HBV breakthrough or insufficient suppression of HBV DNA loads was observed in 20% (10/50) of the patients after 96-week treatment, and 8 of these patients harbored 3TC-resistant mutants. By contrast, neither HBV breakthrough nor treatment failure was recorded in the ART-3TC/TDF group. All of the 3TC-resistant HBV mutants emerged from the cases in which HBV DNA loads were high at baseline. Our results clearly demonstrated that ART-3TC is associated with the emergence of 3TC-resistant HBV in patients coinfected with HIV-1 and HBV and that ART-3TC/TDF reduces HBV DNA loads to an undetectable level. These findings support the use of TDF-based treatment regimens for patients coinfected with HIV-1 and HBV. PMID:26288093

Expanded HIV pre-exposure prophylaxis (PrEP) implementation in communities in New South Wales, Australia (EPIC-NSW): design of an open label, single arm implementation trial.

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Zablotska, Iryna B; Selvey, Christine; Guy, Rebecca; Price, Karen; Holden, Jo; Schmidt, Heather-Marie; McNulty, Anna; Smith, David; Jin, Fengyi; Amin, Janaki; Cooper, David A; Grulich, Andrew E

2018-02-02

The New South Wales (NSW) HIV Strategy 2016-2020 aims for the virtual elimination of HIV transmission in NSW, Australia, by 2020. Despite high and increasing levels of HIV testing and treatment since 2012, the annual number of HIV diagnoses in NSW has remained generally unchanged. Pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV infection among gay and bisexual men (GBM) when taken appropriately. However, there have been no population-level studies that evaluate the impact of rapid PrEP scale-up in high-risk GBM. Expanded PrEP Implementation in Communities in NSW (EPIC-NSW) is a population-level evaluation of the rapid, targeted roll-out of PrEP to high-risk individuals. EPIC-NSW, is an open-label, single-arm, multi-centre prospective observational study of PrEP implementation and impact. Over 20 public and private clinics across urban and regional areas in NSW have participated in the rapid roll-out of PrEP, supported by strong community mobilization and PrEP promotion. The study began on 1 March 2016, aiming to enroll at least 3700 HIV negative people at high risk of HIV. This estimate took into consideration criteria for PrEP prescription in people at high risk for acquiring HIV as defined in the NSW PrEP guidelines. Study participants receive once daily co-formulated tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) and are followed for up to 24 months. Follow-up includes: testing for HIV at 1 month, HIV and other sexually transmissible infections three-monthly, HCV annually and monitoring of renal function six-monthly. Optional online behavioural surveys are conducted quarterly. The co-primary endpoints are (i) HIV diagnoses and incidence in the cohort and (ii) HIV diagnoses in NSW. EPIC-NSW is a population-based PrEP implementation trial which targets the entire estimated population of GBM at high risk for HIV infection in NSW. It will provide a unique opportunity to evaluate the population impact of PrEP on a concentrated HIV

Synergistic activity of tenofovir and nevirapine combinations released from polycaprolactone matrices for potential enhanced prevention of HIV infection through the vaginal route.

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Dang, Nhung T T; Sivakumaran, Haran; Harrich, David; Shaw, Paul N; Davis-Poynter, Nicholas; Coombes, Allan G A

2014-10-01

Polycaprolactone (PCL) matrices were simultaneously loaded with the antiviral agents, tenofovir (TFV) and nevirapine (NVP), in combination to provide synergistic activity in the prevention of HIV transmission through the vaginal route. TFV and NVP were incorporated in PCL matrices at theoretical loadings of 10%TFV-10% NVP, 5%TFV-5%NVP and 5%TFV-10%NVP, measured with respect to the PCL content of the matrices. Actual TFV loadings ranged from 2.1% to 4.2% equating to loading efficiencies of about 41-42%. The actual loadings of NVP were around half those of TFV (1.2-1.9%), resulting in loading efficiencies ranging from 17.2% to 23.5%. Approximately 80% of the initial content of TFV was released from the PCL matrices into simulated vaginal fluid (SVF) over a period of 30 days, which was almost double the cumulative release of NVP (40-45%). The release kinetics of both antivirals over 30 days were found to be described most satisfactorily by the Higuchi model. In vitro assay of release media containing combinations of TFV and NVP released from PCL matrices confirmed a potential synergistic/additive effect of the released antivirals on HIV-1 infection of HeLa cells. These findings indicate that PCL matrices loaded with combinations of TFV and NVP provide an effective strategy for the sustained vaginal delivery of antivirals with synergistic/additive activity. Copyright © 2014 Elsevier B.V. All rights reserved.

Switch from a ZDV/3TC-based regimen to a completely once daily (QD regimen of emtricitabine/tenofovir DF fixed dose combination plus a third QD agent (SONETT

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Arasteh K

2009-05-01

Full Text Available Abstract Objectives To assess the efficacy and safety of a treatment switch from a twice-daily (BID regimen containing zidovudine (ZDV and lamivudine (3TC plus a third agent to a once daily (QD regimen containing the fixed-dose combination of tenofovir DF/emtricitabine (TDF/FTC, Truvada® plus a divergent third QD agent in HIV-1 infected patients. Methods Prospective, 48-week, non-randomised, single-group, open-label, study. Fifty-one patients on stable ZDV/3TC-containing HAART, with HIV-1 RNA 50 cells/μl, were switched to TDF/FTC plus a third agent. Plasma HIV-1 RNA, CD4+ and CD8+ T-cell counts were assessed at baseline and weeks 4, 12, 24, 36 and 48 post-switch. Results During the 48-week study, 10 patients discontinued prematurely, including three due to adverse events (AEs. At week 48, plasma HIV-1 RNA was p Conclusions Results from this study support switching from a ZDV/3TC-containing HAART regimen to a completely QD regimen of TDF/FTC plus a third agent. Virologic and immunologic control are maintained, with apparent benefits in haemoglobin.

KNOWLEDGE MANAGEMENT AND COLLABORATION EFFECTS: SOUTH-SOUTH NGO COLLABORATION: A CASE STUDY ON THE BRAZILIAN INTERDISCIPLINARY AIDS ASSOCIATION

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Grace Keeney

2012-06-01

Full Text Available In June 2008, the Brazilian Interdisciplinary AIDS Association (ABIA and the Indian NGO SAHARA submitted a joint pre-grant opposition to the patent application of Tenofovir Disoproxil Fumarate in India. This joint action provides a pertinent case model of the potential effects of South-South cooperation between civil society groups. In this study, the aim sought to determine the practicality of the methodology and propositions developed in Resources, Knowledge and Influence: the Organizational Effects of Interorganizational Collaboration (Hardy et al., 2003 in predicting the types of collaboration effects that would result from the degree of “involvement” and “embeddedness” of a collaboration. Data collection came from archival research, participant observation research and interviews. Research tasks included an investigation on South-South Cooperation in the area of IP rights and AIDS, compiling an SLR on knowledge management and collaboration theories, creating a chronology of the collaboration and application of aforementioned methodology. Application included (1 implementation of codification methodology based on “involvement” and “embeddedness” and (2 identification of types of effects in collaboration - strategic, knowledge creation or political. During data analysis, these effects were compared with the aims of collaboration. Results were then tested against propositions (Hardy et al., 2003 of the relationship between involvement and embeddedness and the collaborative effects. Findings support three propositions: (1 Collaborations with high levels of involvement will be positively associated with the acquisition of distinctive resources, (2 Collaborations with high levels of involvement and high levels of embeddedness will be positively associated with the creation of knowledge, (3 Collaborations that are highly embedded will be positively associated with an increase of influence.

Improved Neuropsychological and Neurological Functioning Across Three Antiretroviral Regimens in Diverse Resource-Limited Settings: AIDS Clinical Trials Group Study A5199, the International Neurological Study

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Robertson, K.; Jiang, H.; Kumwenda, J.; Supparatpinyo, K.; Evans, S.; Campbell, T. B.; Price, R.; Tripathy, S.; Kumarasamy, N.; La Rosa, A.; Santos, B.; Silva, M. T.; Montano, S.; Kanyama, C.; Faesen, S.; Murphy, R.; Hall, C.; Marra, C. M.; Marcus, C.; Berzins, B.; Allen, R.; Housseinipour, M.; Amod, F.; Sanne, I.; Hakim, J.; Walawander, A.; Nair, A.

2012-01-01

Background. AIDS Clinical Trials Group (ACTG) A5199 compared the neurological and neuropsychological (NP) effects of 3 antiretroviral regimens in participants infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited settings. Methods. Participants from Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A (lamivudine-zidovudine plus efavirenz, n = 289), B (atazanavir, emtricitabine, and didanosine-EC, n = 293), and C (emtricitabine-tenofovir-disoproxil fumarate plus efavirenz, n = 278) as part of the ACTG PEARLS study (A5175). Standardized neurological and neuropsychological (NP) screening examinations (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks from February 2006 to May 2010. Associations with neurological and neuropsychological function were estimated from linear and logistic regression models using generalized estimating equations. Results. The median weeks on study was 168 (Q1 = 96, Q3 = 192) for the 860 participants. NP test scores improved (P  .10). Significant country effects were noted on all NP tests and neurological outcomes (P < .01). Conclusions. The study detected no significant differences in neuropsychological and neurological outcomes between randomized ART regimens. Significant improvement occurred in neurocognitive and neurological functioning over time after initiation of ARTs. The etiology of these improvements is likely multifactorial, reflecting reduced central nervous system HIV infection, better general health, and practice effects. This study suggests that treatment with either of the World Health Organization –recommended first-line antiretroviral regimens in resource-limited settings will improve neuropsychological functioning and reduce neurological dysfunction. Clinical trials registration.  NCT00096824. PMID:22661489

Recent advances in pre-exposure prophylaxis for HIV.

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Desai, Monica; Field, Nigel; Grant, Robert; McCormack, Sheena

2017-12-11

Although pre-exposure prophylaxis (PrEP)-the use of antiretroviral drugs by non-infected people to prevent the acquisition of HIV-is a promising preventive option, important public health questions remain. Daily oral emtricitabine (FTC)-tenofovir disoproxil fumarate (TDF) is highly efficacious in preventing the acquisition of HIV in people at risk as a result of a range of different types of sexual exposure. There is good evidence of efficacy in women and men, and when men who have sex with men use event based dosing. Studies have been conducted in several countries and epidemics. Because adherence to this treatment varies greatly there are questions about its public health benefit. Oral FTC-TDF is extremely safe, with minimal impact on kidney, bone, or pregnancy outcomes, and there is no evidence that its effectiveness has been reduced by risk compensation during open label and programmatic follow-up. It is too early to assess the impact of this treatment on the incidence of sexually transmitted infections (STIs) at a population level. Many challenges remain. Access to pre-exposure prophylaxis is limited and disparities exist, including those governed by race and sex. Different pricing and access models need to be explored to avoid further widening inequalities. The optimal combination prevention program needs to be defined, and this will depend on local epidemiology, service provision, and cost effectiveness. This review updates the evidence base for pre-exposure prophylaxis regarding its effectiveness, safety, and risk compensation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The science of being a study participant: FEM-PrEP participants' explanations for overreporting adherence to the study pills and for the whereabouts of unused pills.

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Corneli, Amy L; McKenna, Kevin; Perry, Brian; Ahmed, Khatija; Agot, Kawango; Malamatsho, Fulufhelo; Skhosana, Joseph; Odhiambo, Jacob; Van Damme, Lut

2015-04-15

FEM-PrEP was unable to determine whether once-daily, oral emtricitabine/tenofovir disoproxil fumarate reduces the risk of HIV acquisition among women because of low adherence. Self-reported adherence was high, and pill-count data suggested good adherence. Yet, drug concentrations revealed limited pill use. We conducted a follow-up study with former participants in Bondo, Kenya, and Pretoria, South Africa, to understand factors that had influenced overreporting of adherence and to learn the whereabouts of unused pills. Qualitative, semistructured interviews were conducted with 88 participants, and quantitative, audio computer-assisted self-interviews were conducted with 224 participants. We used thematic analysis and descriptive statistics to analyze the qualitative and quantitative data, respectively. In audio computer-assisted self-interviews, 31% (n = 70) said they had overreported adherence; the main reason was the belief that nonadherence would result in trial termination (69%, n = 48). A considerable percentage (35%, n = 78) acknowledged discarding unused pills. Few acknowledged giving their pills to someone else (4%, n = 10), and even fewer acknowledged giving them to someone with HIV (2%, n = 5). Many participants in the semistructured interviews said other participants had counted and removed pills from their bottles to appear adherent. Despite repeated messages that nonadherence would not upset staff, participants acknowledged several perceived negative consequences of reporting nonadherence, which made it difficult to report accurately. Uneasiness continued in the follow-up study, as many said they had not overreported during the trial. Efforts to improve self-reported measures should include identifying alternative methods for creating supportive environments that allow participants to feel comfortable reporting actual adherence.

Cost-Effectiveness of Single- Versus Generic Multiple-Tablet Regimens for Treatment of HIV-1 Infection in the United States.

Directory of Open Access Journals (Sweden)

Donna E Sweet

Full Text Available The possibility of incorporating generics into combination antiretroviral therapy and breaking apart once-daily single-tablet regimens (STRs, may result in less efficacious medications and/or more complex regimens with the expectation of marked monetary savings. A modeling approach that assesses the merits of such policies in terms of lifelong costs and health outcomes using adherence and effectiveness data from real-world U.S. settings.A comprehensive computer-based microsimulation model was developed to assess the lifetime health (life expectancy and quality adjusted life-years--QALYs and economic outcomes in HIV-1 infected patients initiating STRs compared with multiple-table regimens including generic medications where possible (gMTRs. The STRs considered included tenofovir disoproxil fumarate/emtricitabine and efavirenz or rilpivirine or elvitegravir/cobicistat. gMTRs substitutions included each counterpart to STRs, including generic lamivudine for emtricitabine and generic versus branded efavirenz.Life expectancy is estimated to be 1.301 years higher (discounted 0.619 QALY gain in HIV-1 patients initiating a single-tablet regimen in comparison to a generic-based multiple-table regimen. STRs were associated with an average increment of $26,547.43 per patient in medication and $1,824.09 in other medical costs due to longer survival which were partially offset by higher inpatients costs ($12,035.61 with gMTRs treatment. Overall, STRs presented incremental lifetime costs of $16,335.91 compared with gMTRs, resulting in an incremental cost-effectiveness ratio of $26,383.82 per QALY gained.STRs continue to represent good value for money under contemporary cost-effectiveness thresholds despite substantial price reductions of generic medications in the U. S.

Prevention of vaginal and rectal HIV transmission by antiretroviral combinations in humanized mice.

Directory of Open Access Journals (Sweden)

Philippe A Gallay

Full Text Available With more than 7,000 new HIV infections daily worldwide, there is an urgent need for non-vaccine biomedical prevention (nBP strategies that are safe, effective, and acceptable. Clinical trials have demonstrated that pre-exposure prophylaxis (PrEP with antiretrovirals (ARVs can be effective at preventing HIV infection. In contrast, other trials using the same ARVs failed to show consistent efficacy. Topical (vaginal and rectal dosing is a promising regimen for HIV PrEP as it leads to low systematic drug exposure. A series of titration studies were carried out in bone marrow/liver/thymus (BLT mice aimed at determining the adequate drug concentrations applied vaginally or rectally that offer protection against rectal or vaginal HIV challenge. The dose-response relationship of these agents was measured and showed that topical tenofovir disoproxil fumarate (TDF and emtricitabine (FTC can offer 100% protection against rectal or vaginal HIV challenges. From the challenge data, EC50 values of 4.6 μM for TDF and 0.6 μM for FTC for HIV vaginal administration and 6.1 μM TDF and 0.18 μM for FTC for rectal administration were obtained. These findings suggest that the BLT mouse model is highly suitable for studying the dose-response relationship in single and combination ARV studies of vaginal or rectal HIV exposure. Application of this sensitive HIV infection model to more complex binary and ternary ARV combinations, particularly where agents have different mechanisms of action, should allow selection of optimal ARV combinations to be advanced into pre-clinical and clinical development as nBP products.

Non-daily pre-exposure prophylaxis for HIV prevention

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Anderson, Peter L.; García-Lerma, J. Gerardo; Heneine, Walid

2015-01-01

Purpose of review To discuss non-daily pre-exposure prophylaxis (PrEP) modalities that may provide advantages compared with daily PrEP in cost and cumulative toxicity, but may have lower adherence forgiveness. Recent Findings Animal models have informed our understanding of early viral transmission events, which help guide event-driven PrEP dosing strategies. These models indicate early establishment of viral replication in rectal or cervicovaginal tissues, so event-driven PrEP should rapidly deliver high mucosal drug concentrations within hours of the potential exposure event. Macaque models have demonstrated the high biological efficacy for event-driven dosing of oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) against both vaginal and rectal virus transmission. In humans, the IPERGAY study demonstrated 86% efficacy for event-driven oral TDF/FTC dosing among men who have sex with men (MSM), while no similar efficacy data are available on women or heterosexual men. The HPTN 067 study showed that certain MSM populations adhere well to non-daily PrEP while other populations of women adhere more poorly to non-daily versus daily regimens. Pharmacokinetic studies following oral TDF/FTC dosing in humans, indicate that TFV-diphosphate (the active form of TFV) accumulates to higher concentrations in rectal versus cervicovaginal tissue but non-adherence in trials complicates the interpretation of differential mucosal drug concentrations. Summary Event-driven dosing for TFV-based PrEP has promise for HIV prevention in MSM. Future research of event-driven PrEP in women and heterosexual men should be guided by a better understanding of the importance of mucosal drug concentrations for PrEP efficacy and its sensitivity to adherence. PMID:26633641

The Pre-Exposure Prophylaxis-Stigma Paradox: Learning from Canada's First Wave of PrEP Users.

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Grace, Daniel; Jollimore, Jody; MacPherson, Paul; Strang, Matthew J P; Tan, Darrell H S

2018-01-01

With the emergence of daily oral tenofovir disoproxil fumarate and emtricitabine-based pre-exposure prophylaxis (PrEP) use in Canada, questions have emerged concerning the impacts of this HIV prevention tool on gay men's social and sexual lives. We conducted small focus groups and individual qualitative interviews with 16 gay men in Toronto who were part of the 'first wave' of Canadian PrEP users. Participants were on PrEP for at least one year as part of a demonstration project (November 2014-June 2016). These participants accessed PrEP before regulatory approval by Health Canada in February 2016. The mean age of participants was 37.6 years (SD 11.02); 94% completed secondary education, and 69% were white. Sex-stigma emerged as a complex theme in men's accounts of PrEP use across three overlapping domains: (1) PrEP-related stigma, including discussions of concealment and stigma from friends, family, and sexual partners, (2) PrEP as a perceived tool for combating HIV-related stigma, where some men said that they no longer discussed HIV status with sexual partners, and (3) PrEP as illuminating structural stigma, where it was attributed to unmasking stigma related to sex and sexuality. For some participants, PrEP has allowed for liberating sex and a self-described return to normalcy-normal, exciting, pleasurable sex that was no longer reliant on condom use. Paradoxically, some men said that PrEP use both led them to experience stigmatizing reactions within their social and sexual networks, while also helping to remove stigma, shame, and fear related to HIV, sexuality, and sex with gay men living with HIV.

Pre-exposure prophylaxis and antiretroviral resistance: HIV prevention at a cost?

Science.gov (United States)

Hurt, Christopher B; Eron, Joseph J; Cohen, Myron S

2011-12-01

Pre-exposure prophylaxis (PrEP), the use of antiretrovirals (ARVs) by human immunodeficiency virus (HIV)-uninfected individuals to prevent acquisition of the virus during high-risk sexual encounters, enjoyed its first 2 major successes with the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 and the Pre-Exposure Prophylaxis Initiative (iPrEx). These successes were buoyed by additional positive results from the TDF2 and Partners PrEP trials. Although no seroconverters in either arm of CAPRISA developed resistance to tenofovir, 2 participants in iPrEx with undetected, seronegative acute HIV infection were randomized to receive daily oral tenofovir-emtricitabine and resistance to emtricitabine was later discovered in both men. A similar case in the TDF2 study resulted in resistance to both ARVs. These cases prompted us to examine existing literature on the nature of resistance mutations elicited by ARVs used for PrEP. Here, we discuss the impact of signature mutations selected by PrEP, how rapidly these emerge with daily ARV exposure, and the individual-level and public health consequences of ARV resistance.

Regimen durability in HIV-infected children and adolescents initiating first-line ART in a large public sector HIV cohort in South Africa.

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Bonawitz, Rachael; Brennan, Alana T; Long, Lawrence; Heeren, Timothy; Maskew, Mhairi; Sanne, Ian; Fox, Matthew P

2018-04-15

In April 2010 tenofovir and abacavir replaced stavudine in public-sector first-line antiretroviral therapy (ART) for children under 20 years old in South Africa. The association of both abacavir and tenofovir with fewer side-effects and toxicities compared to stavudine could translate to increased durability of tenofovir or abacavir-based regimens. We evaluated changes over time in regimen durability for pediatric patients 3 to 19 years of age at 8 public sector clinics in Johannesburg, South Africa. Cohort analysis of treatment naïve, non-pregnant pediatric patients from 3 to 19 years old initiated on ART between April 2004-December 2013. First-line ART regimens before April 2010 consisted of stavudine or zidovudine with lamivudine and either efavirenz or nevirapine. Tenofovir and/or abacavir was substituted for stavudine after April 2010 in first-line ART. We evaluated the frequency and type of single-drug substitutions, treatment interruptions, and switches to second-line therapy. Fine and Gray competing risk regression models were used to evaluate the association of antiretroviral drug type with single-drug substitutions, treatment interruptions, and second-line switches in the first 24-months on treatment. 398 (15.3%) single-drug substitutions, 187 (7.2%) treatment interruptions and 86 (3.3%) switches to second-line therapy occurred among 2602 pediatric patients over 24-months on ART. Overall, the rate of single-drug substitutions started to increase in 2009, peaked in 2011 at 25%, then declined to 10% in 2013, well after the integration of tenofovir into pediatric regimens; no patients over the age of 3 were initiated on abacavir for first-line therapy. Competing risk regression models showed patients on zidovudine or stavudine had upwards of a 5-fold increase in single-drug substitution vs. patients initiated on tenofovir in the first 24-months on ART. Older adolescents also had a 2-3-fold increase in treatment interruptions and switches to second

Diversity receiver

NARCIS (Netherlands)

2005-01-01

The invention is directed to the reception of high rate radio signals (for example DVB-T signals) while the receiver is moving at a high speed (for example in or with a car). Two or more antennas (12, 16) are closely spaced and arranged behind each other in the direction of motion (v) for receiving

AIDS in the Third World: how to stop the HIV infection?

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De Clercq, E

2007-01-01

Of the 38.6 million people living with HIV/AIDS globally, almost 25 million (65%) live in sub-Saharan Africa. Preventive strategies and measures fall short, often simply because they are not available or are largely male-controlled. A preventive HIV vaccine is still far away; hence the drive to develop alternative prevention technologies, such as microbicides and oral pre-exposure prophylaxis, that could be female controlled. There are, at present, twenty-two anti-HIV drugs which have been formally licensed for clinical use in the treatment of HIV infections (AIDS): zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine, tenofovir, nevirapine, delavirdine, efavirenz, saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir, darunavir and enfuvirtide. These compounds, in combination, form the basis of HAART (highly active antiretroviral therapy), which has led to the development of a single daily pill existing of the combination of tenofovir disoproxil fumarate, emtricitabine and efavirenz, which has to be taken orally once daily for the treatment of AIDS. Beyond development of new drugs and clinical evaluation of existing medications, several companies within the pharmaceutical industry have established innovative policies that provide HIV medications at affordable prices in the least-developed countries. Reduced pricing is not alone a solution, and thus companies are actively working in partnership with the World Health Organization and other multinational groups to address roadblocks such as complex registration and procurement systems. Even in this period of successful anti-HIV therapy via HAART, a growing number of patients is cycling through the various remaining therapeutic options and are increasingly becoming dependent of the availability of newly developed anti-HIV agents. It is of concern that existing and future therapies will have to be effective against newly evolving

Cost-effectiveness of tenofovir instead of zidovudine for use in first-line antiretroviral therapy in settings without virological monitoring.

Directory of Open Access Journals (Sweden)

Viktor von Wyl

Full Text Available BACKGROUND: The most recent World Health Organization (WHO antiretroviral treatment guidelines recommend the inclusion of zidovudine (ZDV or tenofovir (TDF in first-line therapy. We conducted a cost-effectiveness analysis with emphasis on emerging patterns of drug resistance upon treatment failure and their impact on second-line therapy. METHODS: We used a stochastic simulation of a generalized HIV-1 epidemic in sub-Saharan Africa to compare two strategies for first-line combination antiretroviral treatment including lamivudine, nevirapine and either ZDV or TDF. Model input parameters were derived from literature and, for the simulation of resistance pathways, estimated from drug resistance data obtained after first-line treatment failure in settings without virological monitoring. Treatment failure and cost effectiveness were determined based on WHO definitions. Two scenarios with optimistic (no emergence; base and pessimistic (extensive emergence assumptions regarding occurrence of multidrug resistance patterns were tested. RESULTS: In the base scenario, cumulative proportions of treatment failure according to WHO criteria were higher among first-line ZDV users (median after six years 36% [95% simulation interval 32%; 39%] compared with first-line TDF users (31% [29%; 33%]. Consequently, a higher proportion initiated second-line therapy (including lamivudine, boosted protease inhibitors and either ZDV or TDF in the first-line ZDV user group 34% [31%; 37%] relative to first-line TDF users (30% [27%; 32%]. At the time of second-line initiation, a higher proportion (16% of first-line ZDV users harboured TDF-resistant HIV compared with ZDV-resistant viruses among first-line TDF users (0% and 6% in base and pessimistic scenarios, respectively. In the base scenario, the incremental cost effectiveness ratio with respect to quality adjusted life years (QALY was US$83 when TDF instead of ZDV was used in first-line therapy (pessimistic scenario: US$ 315

Solar energy receiver

Science.gov (United States)

Schwartz, Jacob

1978-01-01

An improved long-life design for solar energy receivers provides for greatly reduced thermally induced stress and permits the utilization of less expensive heat exchanger materials while maintaining receiver efficiencies in excess of 85% without undue expenditure of energy to circulate the working fluid. In one embodiment, the flow index for the receiver is first set as close as practical to a value such that the Graetz number yields the optimal heat transfer coefficient per unit of pumping energy, in this case, 6. The convective index for the receiver is then set as closely as practical to two times the flow index so as to obtain optimal efficiency per unit mass of material.

Highly Sensitive Optical Receivers

CERN Document Server

Schneider, Kerstin

2006-01-01

Highly Sensitive Optical Receivers primarily treats the circuit design of optical receivers with external photodiodes. Continuous-mode and burst-mode receivers are compared. The monograph first summarizes the basics of III/V photodetectors, transistor and noise models, bit-error rate, sensitivity and analog circuit design, thus enabling readers to understand the circuits described in the main part of the book. In order to cover the topic comprehensively, detailed descriptions of receivers for optical data communication in general and, in particular, optical burst-mode receivers in deep-sub-µm CMOS are presented. Numerous detailed and elaborate illustrations facilitate better understanding.

Receiver Test Selection Criteria

Science.gov (United States)

2015-03-12

The DOT requests that GPS manufacturers submit receivers for test in the following TWG categories: - Aviation (non-certified), cellular, general location/navigation, high precision, timing, networks, and space-based receivers - Each receiver should b...

Association of baseline vitamin D levels with clinical parameters and treatment outcomes in chronic hepatitis B.

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Chan, Henry Lik-Yuen; Elkhashab, Magdy; Trinh, Huy; Tak, Won Young; Ma, Xiaoli; Chuang, Wan-Long; Kim, Yoon Jun; Martins, Eduardo B; Lin, Lanjia; Dinh, Phillip; Charuworn, Prista; Foster, Graham R; Marcellin, Patrick

2015-11-01

The relationship between vitamin D levels and chronic hepatitis B (CHB) infection and treatment outcomes are poorly elucidated. We measured pre-treatment serum vitamin D (25-hydroxyvitamin D3; 25[OH]D3) levels and determined their association with clinical parameters and treatment outcomes in active CHB patients without advanced liver disease enrolled in a global clinical trial. Patients were randomly assigned to either 48 weeks of tenofovir disoproxil fumarate (TDF) plus peginterferon alfa-2a (PegIFN), TDF plus PegIFN for 16 weeks followed by TDF for 32 weeks, PegIFN for 48 weeks, or TDF for 120 weeks. Univariate and multivariate analyses were conducted to determine associations between vitamin D, baseline factors, and week 48 clinical outcome. Of 737 patients, 35% had insufficient (⩾20 but vitamin D levels. In univariate analysis, lower vitamin D levels were significantly associated with the following baseline parameters: younger age, lower uric acid levels, HBeAg-positive status, lower calcium levels, blood draw in winter or autumn, and HBV genotype D. On multivariate analysis, only HBV genotype, season of blood draw, calcium level, and age retained their association. High baseline level of vitamin D was associated with low HBV DNA, normal ALT and HBsAg at week 48 independent of treatment groups, but the association, with the exception of ALT, became statistically insignificant after adjusting for age, gender, HBeAg and HBV genotype. Abnormally low vitamin D levels are highly prevalent among untreated, active CHB patients. Baseline vitamin D levels are not associated with treatment outcomes, but were associated with normal ALT. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Pregnancy and contraceptive use among women participating in the FEM-PrEP trial.

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Callahan, Rebecca; Nanda, Kavita; Kapiga, Saidi; Malahleha, Mookho; Mandala, Justin; Ogada, Teresa; Van Damme, Lut; Taylor, Douglas

2015-02-01

Pregnancy among study participants remains a challenge for trials of new HIV prevention agents despite promotion and provision of contraception. We evaluated contraceptive use, pregnancy incidence, and study drug adherence by contraceptive method among women enrolled in the FEM-PrEP trial of once-daily oral tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) for HIV prevention. We required women to be using effective non-barrier contraception at enrollment. At each monthly follow-up visit, women were counseled on contraceptive use and tested for pregnancy. TDF-FTC adherence was determined by measuring plasma drug concentrations at 4-week intervals. We used Cox proportional hazards models to assess factors associated with incident pregnancy and multivariate logistic regression to examine the relationship between contraceptive method used at enrollment and TDF-FTC adherence. More than half of women were not using effective contraception before enrollment. Ninety-eight percent of these women adopted either injectable (55%) or oral (43%) contraceptives. The overall pregnancy rate was 9.6 per 100 woman-years. Among injectable users and new users of combined oral contraceptives (COCs), the rates were 1.6 and 35.1, respectively. New users of injectables had significantly greater odds of adhering to TDF-FTC than new COC users [odds ratio (95% confidence interval): 4.4 (1.7 to 11.6), P = 0.002], existing COC users [3.1 (1.3 to 7.3), P = 0.01], and existing injectable users [2.4 (1.1 to 5.6), P = 0.04]. Women using COCs during FEM-PrEP, particularly new adopters, were more likely to become pregnant and less likely to adhere to study product than injectable users. HIV prevention trials should consider requiring long-acting methods, including injectables, for study participation.

Incident AIDS or Death After Initiation of Human Immunodeficiency Virus Treatment Regimens Including Raltegravir or Efavirenz Among Adults in the United States.

Science.gov (United States)

Cole, Stephen R; Edwards, Jessie K; Hall, H Irene; Brookhart, M Alan; Mathews, W Christopher; Moore, Richard D; Crane, Heidi M; Kitahata, Mari M; Mugavero, Michael J; Saag, Michael S; Eron, Joseph J

2017-06-01

The long-term effectiveness of human immunodeficiency virus (HIV) treatments containing integrase inhibitors is unknown. We use observational data from the Centers for AIDS Research Network of Integrated Clinical Systems and the Centers for Disease Control and Prevention to estimate 4-year risk of AIDS and all-cause mortality among 415 patients starting a raltegravir regimen compared to 2646 starting an efavirenz regimen (both regimens include emtricitabine and tenofovir disoproxil fumarate). We account for confounding and selection bias as well as generalizability by standardization for measured variables, and present both observational intent-to-treat and per-protocol estimates. At treatment initiation, 12% of patients were female, 36% black, 13% Hispanic; median age was 37 years, CD4 count 321 cells/µL, and viral load 4.5 log10 copies/mL. Two hundred thirty-five patients incurred an AIDS-defining illness or died, and 741 patients left follow-up. After accounting for measured differences, the 4-year risk was similar among those starting both regimens (ie, intent-to treat hazard ratio [HR], 0.96 [95% confidence interval {CI}, .63-1.45]; risk difference, -0.9 [95% CI, -4.5 to 2.7]), as well as among those remaining on regimens (ie, per-protocol HR, 0.95 [95% CI, .59-1.54]; risk difference, -0.5 [95% CI, -3.8 to 2.9]). Raltegravir and efavirenz-based initial antiretroviral therapy have similar 4-year clinical effects. Vigilance regarding longer-term comparative effectiveness of HIV regimens using observational data is needed because large-scale experimental data are not forthcoming. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Pharmacological and clinical evidence of nevirapine immediate- and extended-release formulations

Directory of Open Access Journals (Sweden)

Ena J

2012-11-01

Full Text Available Javier Ena, Concepción Amador, Conxa Benito, Francisco PasquauHIV Unit, Hospital Marina Baixa, Villajoyosa, SpainAbstract: We reviewed the current information available on nevirapine immediate- and extended-release formulations and its role in single-dose and combination antiretroviral therapy. Nevirapine was approved in 1996 and was the first non-nucleoside reverse-transcriptase inhibitor available for the treatment of HIV-1 infection. Nevirapine has demonstrated good efficacy and a well-characterized safety profile. A major drawback is the low genetic barrier, allowing the emergence of resistance in the presence of single mutations in the reverse-transcriptase gene. This shortcoming is particularly relevant when nevirapine is administered in a single dose to prevent mother-to-child transmission of HIV-1 infection, compromising the efficacy of future non-nucleoside reverse transcriptase–inhibitor regimens. Studies published recently have probed the noninferiority of nevirapine compared to ritonavir-boosted atazanavir with both tenofovir disoproxil fumarate and emtricitabine in antiretroviral treatment–naïve patients. In 2011, a new formulation of nevirapine (nevirapine extended release that allowed once-daily dosing was approved by the Food and Drug Administration and by the European Medicines Agency. VERxVe, a study comparing nevirapine extended release with nevirapine immediate release in antiretroviral treatment–naïve patients, and TRANxITION, a study carried out in antiretroviral treatment–experienced patients who switched therapy from nevirapine immediate release to nevirapine extended release, provided data on the noninferiority of the new formulation of nevirapine compared with nevirapine immediate release in terms of efficacy and safety. Nevirapine extended release will further increase the durability and persistence of nevirapine-containing antiretroviral therapy, allowing once-daily dosing regimens.Keywords: nevirapine

A qualitative study of provider thoughts on implementing pre-exposure prophylaxis (PrEP in clinical settings to prevent HIV infection.

Directory of Open Access Journals (Sweden)

Emily A Arnold

Full Text Available A recent clinical trial demonstrated that a daily dose tenofovir disoproxil fumarate and emtricitabrine (TDF-FTC can reduce HIV acquisition among men who have sex with men (MSM and transgender (TG women by 44%, and up to 90% if taken daily. We explored how medical and service providers understand research results and plan to develop clinical protocols to prescribe, support and monitor adherence for patients on PrEP in the United States.Using referrals from our community collaborators and snowball sampling, we recruited 22 healthcare providers in San Francisco, Oakland, and Los Angeles for in-depth interviews from May-December 2011. The providers included primary care physicians seeing high numbers of MSM and TG women, HIV specialists, community health clinic providers, and public health officials. We analyzed interviews thematically to produce recommendations for setting policy around implementing PrEP. Interview topics included: assessing clinician impressions of PrEP and CDC guidance, considerations of cost, office capacity, dosing schedules, and following patients over time.Little or no demand for PrEP from patients was reported at the time of the interviews. Providers did not agree on the most appropriate patients for PrEP and believed that current models of care, which do not involve routine frequent office visits, were not well suited for prescribing PrEP. Providers detailed the need to build capacity and were concerned about monitoring side effects and adherence. PrEP was seen as potentially having impact on the epidemic but providers also noted that community education campaigns needed to be tailored to effectively reach specific vulnerable populations.While PrEP may be a novel and clinically compelling prevention intervention for MSM and TG women, it raises a number of important implementation challenges that would need to be addressed. Nonetheless, most providers expressed optimism that they eventually could prescribe and monitor Pr

A qualitative study of provider thoughts on implementing pre-exposure prophylaxis (PrEP) in clinical settings to prevent HIV infection.

Science.gov (United States)

Arnold, Emily A; Hazelton, Patrick; Lane, Tim; Christopoulos, Katerina A; Galindo, Gabriel R; Steward, Wayne T; Morin, Stephen F

2012-01-01

A recent clinical trial demonstrated that a daily dose tenofovir disoproxil fumarate and emtricitabrine (TDF-FTC) can reduce HIV acquisition among men who have sex with men (MSM) and transgender (TG) women by 44%, and up to 90% if taken daily. We explored how medical and service providers understand research results and plan to develop clinical protocols to prescribe, support and monitor adherence for patients on PrEP in the United States. Using referrals from our community collaborators and snowball sampling, we recruited 22 healthcare providers in San Francisco, Oakland, and Los Angeles for in-depth interviews from May-December 2011. The providers included primary care physicians seeing high numbers of MSM and TG women, HIV specialists, community health clinic providers, and public health officials. We analyzed interviews thematically to produce recommendations for setting policy around implementing PrEP. Interview topics included: assessing clinician impressions of PrEP and CDC guidance, considerations of cost, office capacity, dosing schedules, and following patients over time. Little or no demand for PrEP from patients was reported at the time of the interviews. Providers did not agree on the most appropriate patients for PrEP and believed that current models of care, which do not involve routine frequent office visits, were not well suited for prescribing PrEP. Providers detailed the need to build capacity and were concerned about monitoring side effects and adherence. PrEP was seen as potentially having impact on the epidemic but providers also noted that community education campaigns needed to be tailored to effectively reach specific vulnerable populations. While PrEP may be a novel and clinically compelling prevention intervention for MSM and TG women, it raises a number of important implementation challenges that would need to be addressed. Nonetheless, most providers expressed optimism that they eventually could prescribe and monitor PrEP in their

Risk Perception, Sexual Behaviors, and PrEP Adherence Among Substance-Using Men Who Have Sex with Men: a Qualitative Study.

Science.gov (United States)

Storholm, Erik D; Volk, Jonathan E; Marcus, Julia L; Silverberg, Michael J; Satre, Derek D

2017-08-01

The antiretroviral drug combination emtricitabine and tenofovir disoproxil fumarate (TDF/FTC) taken as pre-exposure prophylaxis (PrEP) is effective in preventing HIV infection, yet it also requires adherence and potentially decreases condom use. This study sought to examine these issues among a key population at risk of HIV infection, substance-using men who have sex with men (MSM). We conducted semi-structured interviews with an ethnically diverse sample of 30 young (aged 20-35) MSM prescribed PrEP within a large integrated healthcare system in San Francisco, who had reported recent drug use or hazardous drinking and one or more missed doses of PrEP. We explored participants' risk perception and sexual risk behavior, drug and alcohol use, and PrEP adherence in the context of substance use. Interviews were transcribed and coded using a directed content analysis approach to identify key categories and commonalities, and differences across participants. Salient subcategories included positive psychological effects of being on PrEP (e.g., decreased anxiety, feelings of empowerment), social effects (e.g., reduced HIV stigma), and reduction in overall perceptions of HIV risk. While overall reported use of condoms went down and many reported a brief period of increased condomless sex following PrEP initiation, others continued condom use with most of their sexual partners. Contextual factors influencing their decision to engage in condomless sex included how well they knew the partner and whether the partner was on PrEP or HIV antiretroviral treatment. Factors associated with poor adherence included disruptions in daily routine and use of alcohol and methamphetamine. PrEP-prescribing clinicians should support their patients in making informed decisions about condom use and identifying strategies to maximize adherence in the context of substance use.

Effect of gender and race on the week 48 findings in treatment-naïve, HIV-1-infected patients enrolled in the randomized, phase III trials ECHO and THRIVE.

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Hodder, S; Arasteh, K; De Wet, J; Gathe, J; Gold, J; Kumar, P; Mohapi, L; Short, W; Crauwels, H; Vanveggel, S; Boven, K

2012-08-01

A week 48 efficacy and safety analysis with respect to gender and race was conducted using pooled data from the phase III, double-blind, double-dummy efficacy comparison in treatment-naïve, HIV-infected subjects of TMC278 and efavirenz (ECHO) and TMC278 against HIV, in a once-daily regimen versus efavirenz (THRIVE) trials. Treatment-naïve, HIV-1-infected adults were randomized to receive rilpivirine (RPV; TMC278) 25 mg once a day (qd), or efavirenz (EFV) 600 mg qd, plus tenofovir/emtricitabine (ECHO) or tenofovir/emtricitabine, zidovudine/lamivudine or abacavir/lamivudine (THRIVE). A total of 1368 participants (76% male and 61% White, of those with available race data) were randomized and treated. No gender-related differences in response rate (percentage of patients with HIV-1 viral load dreams/nightmares were more frequent in men in both the EFV and RPV groups. Overall response rates were high for both RPV and EFV. No gender differences were observed. However, response rates were lower among Black patients, regardless of treatment group. Gender appeared to influence the incidence of gastrointestinal adverse events and abnormal dreams/nightmares for both treatments. © 2012 British HIV Association.

Oxidized lipoproteins are associated with markers of inflammation and immune activation in HIV-1 infection

Science.gov (United States)

Kelesidis, T; Jackson, N; McComsey, GA; Wang, X; Elashoff, D; Dube, MP; Brown, TT; Yang, OO; Stein, JH; Currier, JS

2016-01-01

Objective The pathogenesis of immune dysfunction in chronic HIV-1 infection is unclear, and a potential role for oxidized lipids has been suggested. We hypothesize that both oxidized low- and high-density lipoproteins (HDLox, LDLox) contribute to HIV-1 related immune dysfunction. Study In the AIDS Clinical Trials Group (ACTG) A5260, 234 HIV-infected antiretroviral therapy (ART)-naïve participants were randomized to receive tenofovir-emtricitabine plus protease inhibitors or raltegravir and had HIV-1 RNA lipoproteins may contribute to persistent immune activation on ART. PMID:27603288

Development and validation of a liquid chromatography-MS/MS method for simultaneous quantification of tenofovir and efavirenz in biological tissues and fluids.

Science.gov (United States)

Barreiros, Luisa; Cunha-Reis, Cassilda; Silva, Eduarda M P; Carvalho, Joana R B; das Neves, José; Sarmento, Bruno; Segundo, Marcela A

2017-03-20

Millions of people worldwide live with human immunodeficiency virus (HIV) infection thus justifying the continuous search for new prevention and treatment strategies, including topical microbicide products combining antiretroviral drugs (ARVs) such as tenofovir (TFV) and efavirenz (EFV). Therefore, the aim of this work was to develop and validate a high performance liquid chromatography method coupled to triple quadrupole-tandem mass spectrometry (HPLC-MS/MS) for the quantification of TFV and EFV in biological matrices (mouse vaginal tissue, vaginal lavage and blood plasma). Chromatographic separation was achieved using a reversed phase C18 column (3μm, 100×2.1mm) at 45°C and elution in gradient mode using a combination of 0.1% (v/v) formic acid in water and 0.1% (v/v) formic acid in acetonitrile at 0.35mLmin -1 . Total run time was 9min, with retention time of 2.8 and 4.1min for TFV and EFV, respectively. The MS was operated in positive ionization mode (ESI+) for TFV and in negative ionization mode (ESI-) for EFV detection. Data were acquired in selected reaction monitoring (SRM) mode and deuterated ARVs were employed as internal standards. Calibration curves were linear for ARV concentrations ranging from 4 to 500ngmL -1 with LOD and LOQ for both analytes ≤0.4 and ≤0.7ngmL -1 in sample extracts, respectively. The method was found to be specific, accurate (96.0-106.0% of nominal values) and precise (RSDfluids were ≥88.4%. Matrix effects were observed for EFV determination in tissue and plasma extracts but compensated by the use of deuterated internal standards. The proposed methodology was successfully applied to a pharmacokinetic study following intravaginal administration of both ARVs. Copyright © 2016 Elsevier B.V. All rights reserved.

Tenofovir use and renal insufficiency among pregnant and general adult population of HIV-infected, ART-naive individuals in Lilongwe, Malawi.

Directory of Open Access Journals (Sweden)

Derek C Johnson

Full Text Available BACKGROUND: The Malawian government recently changed its prevention of mother-to-child transmission (PMTCT regimen and plans to change its first-line antiretroviral therapy (ART regimen to Tenofovir(TDF/Lamivudine/Efavirenz as a fixed-dose combination tablet. Implementation could be challenging if baseline creatinine clearance (CrCl screening were required to assess renal function prior to TDF therapy. Our goal is to determine predictors of CrCl<50 ml/min among HIV-infected, ART-naïve individuals. METHODOLOGY: Data on HIV-infected, ART-naïve adults screened for enrollment into 5 HIV clinical trials in Lilongwe, Malawi were combined for a pooled analysis of predictors for CrCl<50 ml/min. CrCl was derived from the Cockroft-Gault equation. Multivariable logistic regression modeled the association of age, body mass index (BMI, hemoglobin, CD4 cell count <350 cells/mm(3, gender, and pregnancy with CrCl<50 ml/min. RESULTS: The analysis included 3508 patients with values for creatinine clearance. Most subjects were female (90.6% with a median age of 26 years (IQR 22-29. The median CD4 cell count was 444 (IQR 298.0-561.0, and 85.2% percent of women in our study were pregnant. Few patients had CrCl<50 ml/min (n = 38, 1.1%. A BMI less than 18.5 in non-pregnant females (OR = 8.87, 95% CI = 2.45-32.09 was associated with CrCl<50 ml/min. Hemoglobin level higher than 10 g/dL in males (OR = 0.69, 95% CI = 0.56-0.86 and non-pregnant females (OR = 0.21, 95% CI = 0.04-0.97 was protective against CrCl<50 ml/min. DISCUSSION: Our findings indicate few patients would be excluded from a TDF-based antiretroviral regimen, suggesting baseline creatinine clearance assessment may not be necessary for implementation. However, in ART settings individuals with low BMI or anemia could potentially be at increased risk for lower CrCl.

A flexible WLAN receiver

NARCIS (Netherlands)

Schiphorst, Roelof; Hoeksema, F.W.; Slump, Cornelis H.

2003-01-01

Flexible radio receivers are also called Software Defined Radios (SDRs) [1], [2]. The focus of our SDR project [3] is on designing the front end, from antenna to demodulation in bits, of a °exible, multi-standard WLAN receiver. We try to combine an instance of a (G)FSK receiver (Bluetooth) with an

ASTRID© - Advanced Solar Tubular ReceIver Design: A powerful tool for receiver design and optimization

Science.gov (United States)

Frantz, Cathy; Fritsch, Andreas; Uhlig, Ralf

2017-06-01

In solar tower power plants the receiver is one of the critical components. It converts the solar radiation into heat and must withstand high heat flux densities and high daily or even hourly gradients (due to passage of clouds). For this reason, the challenge during receiver design is to find a reasonable compromise between receiver efficiency, reliability, lifetime and cost. There is a strong interaction between the heliostat field, the receiver and the heat transfer fluid. Therefore, a proper receiver design needs to consider these components within the receiver optimization. There are several design and optimization tools for receivers, but most of them focus only on the receiver, ignoring the heliostat field and other parts of the plant. During the last years DLR developed the ASTRIDcode for tubular receiver concept simulation. The code comprises both a high and a low-detail model. The low-detail model utilizes a number of simplifications which allow the user to screen a high number of receiver concepts for optimization purposes. The high-detail model uses a FE model and is able to compute local absorber and salt temperatures with high accuracy. One key strength of the ASTRIDcode is its interface to a ray tracing software which simulates a realistic heat flux distributions on the receiver surface. The results generated by the ASTRIDcode have been validated by CFD simulations and measurement data.

GNSS Software Receiver for UAVs

DEFF Research Database (Denmark)

Olesen, Daniel Madelung; Jakobsen, Jakob; von Benzon, Hans-Henrik

2016-01-01

This paper describes the current activities of GPS/GNSS Software receiver development at DTU Space. GNSS Software receivers have received a great deal of attention in the last two decades and numerous implementations have already been presented. DTU Space has just recently started development of ...... of our own GNSS software-receiver targeted for mini UAV applications, and we will in in this paper present our current progress and briefly discuss the benefits of Software Receivers in relation to our research interests....

Solar advanced internal film receiver

International Nuclear Information System (INIS)

Torre Cabezas, M. de la

1990-01-01

In a Solar Central Internal Film Receiver, the heat absorbing fluid (a molten nitrate salt) flows in a thin film down over the non illuminated side of an absorber panel. Since the molten salt working fluid is not contained in complicated tube manifolds, the receiver design is simples than a conventional tube type-receiver resulting in a lower cost and a more reliable receiver. The Internal Film Receiver can be considered as an alternative to the Direct Absorption Receiver, in the event that the current problems of the last one can not be solved. It also describes here the test facility which will be used for its solar test, and the test plans foreseen. (Author) 17 refs

Customizable Digital Receivers for Radar

Science.gov (United States)

Moller, Delwyn; Heavey, Brandon; Sadowy, Gregory

2008-01-01

Compact, highly customizable digital receivers are being developed for the system described in 'Radar Interferometer for Topographic Mapping of Glaciers and Ice Sheets' (NPO-43962), NASA Tech Briefs, Vol. 31, No. 7 (August 2007), page 72. The receivers are required to operate in unison, sampling radar returns received by the antenna elements in a digital beam-forming (DBF) mode. The design of these receivers could also be adapted to commercial radar systems. At the time of reporting the information for this article, there were no commercially available digital receivers capable of satisfying all of the operational requirements and compact enough to be mounted directly on the antenna elements. A provided figure depicts the overall system of which the digital receivers are parts. Each digital receiver includes an analog-to-digital converter (ADC), a demultiplexer (DMUX), and a field-programmable gate array (FPGA). The ADC effects 10-bit band-pass sampling of input signals having frequencies up to 3.5 GHz. The input samples are demultiplexed at a user-selectable rate of 1:2 or 1:4, then buffered in part of the FPGA that functions as a first-in/first-out (FIFO) memory. Another part of the FPGA serves as a controller for the ADC, DMUX, and FIFO memory and as an interface between (1) the rest of the receiver and (2) a front-panel data port (FPDP) bus, which is an industry-standard parallel data bus that has a high data-rate capability and multichannel configuration suitable for DBF. Still other parts of the FPGA in each receiver perform signal-processing functions. The digital receivers can be configured to operate in a stand-alone mode, or in a multichannel mode as needed for DBF. The customizability of the receiver makes it applicable to a broad range of system architectures. The capability for operation of receivers in either a stand-alone or a DBF mode enables the use of the receivers in an unprecedentedly wide variety of radar systems.

Receiver Gain Modulation Circuit

Science.gov (United States)

Jones, Hollis; Racette, Paul; Walker, David; Gu, Dazhen

2011-01-01

A receiver gain modulation circuit (RGMC) was developed that modulates the power gain of the output of a radiometer receiver with a test signal. As the radiometer receiver switches between calibration noise references, the test signal is mixed with the calibrated noise and thus produces an ensemble set of measurements from which ensemble statistical analysis can be used to extract statistical information about the test signal. The RGMC is an enabling technology of the ensemble detector. As a key component for achieving ensemble detection and analysis, the RGMC has broad aeronautical and space applications. The RGMC can be used to test and develop new calibration algorithms, for example, to detect gain anomalies, and/or correct for slow drifts that affect climate-quality measurements over an accelerated time scale. A generalized approach to analyzing radiometer system designs yields a mathematical treatment of noise reference measurements in calibration algorithms. By treating the measurements from the different noise references as ensemble samples of the receiver state, i.e. receiver gain, a quantitative description of the non-stationary properties of the underlying receiver fluctuations can be derived. Excellent agreement has been obtained between model calculations and radiometric measurements. The mathematical formulation is equivalent to modulating the gain of a stable receiver with an externally generated signal and is the basis for ensemble detection and analysis (EDA). The concept of generating ensemble data sets using an ensemble detector is similar to the ensemble data sets generated as part of ensemble empirical mode decomposition (EEMD) with exception of a key distinguishing factor. EEMD adds noise to the signal under study whereas EDA mixes the signal with calibrated noise. It is mixing with calibrated noise that permits the measurement of temporal-functional variability of uncertainty in the underlying process. The RGMC permits the evaluation of EDA by

Communications receivers principles and design

CERN Document Server

Rohde, Ulrich L; Zahnd, Hans

2017-01-01

This thoroughly updated guide offers comprehensive explanations of the science behind today’s radio receivers along with practical guidance on designing, constructing, and maintaining real-world communications systems. You will explore system planning, antennas and antenna coupling, amplifiers and gain control, filters, mixers, demodulation, digital communication, and the latest software defined radio (SDR) technology. Written by a team of telecommunication experts, Communications Receivers: Principles and Design, Fourth Edition, features technical illustrations, schematic diagrams, and detailed examples. Coverage includes: • Basic radio considerations • Radio receiver characteristics • Receiver system planning • Receiver implementation considerations • RF and baseband techniques for Software-Defined Radios • Transceiver SDR considerations • Antennas and antenna coupling • Mixers • Frequency sources and control • Ancillary receiver circuits • Performance measurement

Fosamprenavir or atazanavir once daily boosted with ritonavir 100 mg, plus tenofovir/emtricitabine, for the initial treatment of HIV infection: 48-week results of ALERT

Directory of Open Access Journals (Sweden)

Ross Lisa L

2008-03-01

Full Text Available Abstract Background Once-daily (QD ritonavir 100 mg-boosted fosamprenavir 1400 mg (FPV/r100 or atazanavir 300 mg (ATV/r100, plus tenofovir/emtricitabine (TDF/FTC 300 mg/200 mg, have not been compared as initial antiretroviral treatment. To address this data gap, we conducted an open-label, multicenter 48-week study (ALERT in 106 antiretroviral-naïve, HIV-infected patients (median HIV-1 RNA 4.9 log10 copies/mL; CD4+ count 191 cells/mm3 randomly assigned to the FPV/r100 or ATV/r100 regimens. Results At baseline, the FPV/r100 or ATV/r100 arms were well-matched for HIV-1 RNA (median, 4.9 log10 copies/mL [both], CD4+ count (mean, 176 vs 205 cells/mm3. At week 48, intent-to-treat: missing/discontinuation = failure analysis showed similar responses to FPV/r100 and ATV/r100 (HIV-1 RNA 3, p = 0.398 [Wilcoxon rank sum test]. Fasting total/LDL/HDL-cholesterol changes-from-baseline were also similar, although week 48 median fasting triglycerides were higher with FPV/r100 (150 vs 131 mg/dL. FPV/r100-treated patients experienced fewer treatment-related grade 2–4 adverse events (15% vs 57%, with differences driven by ATV-related hyperbilirubinemia. Three patients discontinued TDF/FTC because their GFR decreased to Conclusion The all-QD regimens of FPV/r100 and ATV/r100, plus TDF/FTC, provided similar virologic, CD4+ response, and fasting total/LDL/HDL-cholesterol changes through 48 weeks. Fewer FPV/r100-treated patients experienced treatment-related grade 2–4 adverse events.

Cryogenic microwave channelized receiver

International Nuclear Information System (INIS)

Rauscher, C.; Pond, J.M.; Tait, G.B.

1996-01-01

The channelized receiver being presented demonstrates the use of high temperature superconductor technology in a microwave system setting where superconductor, microwave-monolithic-integrated-circuit, and hybrid-integrated-circuit components are united in one package and cooled to liquid-nitrogen temperatures. The receiver consists of a superconducting X-band four-channel demultiplexer with 100-MHz-wide channels, four commercial monolithically integrated mixers, and four custom-designed hybrid-circuit detectors containing heterostructure ramp diodes. The composite receiver unit has been integrated into the payload of the second-phase NRL high temperature superconductor space experiment (HTSSE-II). Prior to payload assembly, the response characteristics of the receiver were measured as functions of frequency, temperature, and drive levels. The article describes the circuitry, discusses the key issues related to design and implementation, and summarizes the experimental results

Bone mineral density changes among HIV-uninfected young adults in a randomised trial of pre-exposure prophylaxis with tenofovir-emtricitabine or placebo in Botswana.

Directory of Open Access Journals (Sweden)

Michael Kasonde

Full Text Available Tenofovir-emtricitabine (TDF-FTC pre-exposure prophylaxis (PrEP has been found to be effective for prevention of HIV infection in several clinical trials. Two studies of TDF PrEP among men who have sex with men showed slight bone mineral density (BMD loss. We investigated the effect of TDF and the interaction of TDF and hormonal contraception on BMD among HIV-uninfected African men and women.We evaluated the effects on BMD of using daily oral TDF-FTC compared to placebo among heterosexual men and women aged 18-29 years enrolled in the Botswana TDF2 PrEP study. Participants had BMD measurements at baseline and thereafter at 6-month intervals with dual-energy X-ray absorptiometry (DXA scans at the hip, spine, and forearm.A total of 220 participants (108 TDF-FTC, 112 placebo had baseline DXA BMD measurements at three anatomic sites. Fifteen (6.8% participants had low baseline BMD (z-score of 3.0% at any anatomic site at any time after baseline were significantly greater for the TDF-FTC treatment group [34/68 (50.0% TDF-FTC vs. 26/79 (32.9% placebo; p = 0.04]. There was a small but significant difference in the mean percent change in BMD from baseline for TDF-FTC versus placebo at all three sites at month 30 [forearm -0.84% (p = 0.01, spine -1.62% (p = 0.0002, hip -1.51% (p = 0.003].Use of TDF-FTC was associated with a small but statistically significant decrease in BMD at the forearm, hip and lumbar spine. A high percentage (6.8% of healthy Batswana young adults had abnormal baseline BMD Further evaluation is needed of the longer-term use of TDF in HIV-uninfected persons.ClinicalTrials.gov NCT00448669.

Impaired Urine Dilution Capability in HIV Stable Patients

Directory of Open Access Journals (Sweden)

Waldo H. Belloso

2014-01-01

Full Text Available Renal disease is a well-recognized complication among patients with HIV infection. Viral infection itself and the use of some antiretroviral drugs contribute to this condition. The thick ascending limb of Henle’s loop (TALH is the tubule segment where free water clearance is generated, determining along with glomerular filtration rate the kidney’s ability to dilute urine. Objective. We analyzed the function of the proximal tubule and TALH in patients with HIV infection receiving or not tenofovir-containing antiretroviral treatment in comparison with healthy seronegative controls, by applying a tubular physiological test, hyposaline infusion test (Chaimowitz’ test. Material & Methods. Chaimowitz’ test was performed on 20 HIV positive volunteers who had normal renal functional parameters. The control group included 10 healthy volunteers. Results. After the test, both HIV groups had a significant reduction of serum sodium and osmolarity compared with the control group. Free water clearance was lower and urine osmolarity was higher in both HIV+ groups. Proximal tubular function was normal in both studied groups. Conclusion. The present study documented that proximal tubule sodium reabsorption was preserved while free water clearance and maximal urine dilution capability were reduced in stable HIV patients treated or not with tenofovir.

'Chaos' in superregenerative receivers

International Nuclear Information System (INIS)

Commercon, Jean-Claude; Badard, Robert

2005-01-01

The superregenerative principle has been known since the early 1920s. The circuit is extremely simple and extremely sensitive. Today, superheterodyne receivers generally supplant superregenerative receivers in most applications because there are several undesirable characteristics: poor selectivity, reradiation, etc. Superregenerative receivers undergo a revival in recent papers for wireless systems, where low cost and very low power consumption are relevant: house/building meters (such as water, energy, gas counter), personal computer environment (keyboard, mouse), etc. Another drawback is the noise level which is higher than that of a well-designed superheterodyne receiver; without an antenna input signal, the output of the receiver hears in an earphone as a waterfall noise; this sound principally is the inherent input noise amplified and detected by the circuit; however, when the input noise is negligible with respect of an antenna input signal, we are faced to an other source of 'noise' self-generated by the superregenerative working. The main objective of this paper concerns this self-generated noise coming from an exponential growing followed by a re-injection process for which the final state is a function of the phase of the input signal

HLA alleles association with changes in bone mineral density in HIV-1-infected adults changing treatment to tenofovir-emtricitabine or abacavir-lamivudine.

Directory of Open Access Journals (Sweden)

Hila Haskelberg

Full Text Available There are limited data regarding the influence of human leukocyte antigen (HLA polymorphisms on reduced bone mineral density (BMD. We investigated the relationship between HLA supertypes and BMD in HIV-infected adults changing their existing treatment to tenofovir-emtricitabine (TDF-FTC or abacavir-lamivudine (ABC-3TC in the STEAL study.Lumbar spine and right hip BMD were measured by Dual-energy X-ray absorptiometry (DXA. HLA genotypes at the 2-digit level were classified into class I and II supertypes. Student's t-tests were used to test the association between HLA supertypes and changes in hip and spine BMD over 96 weeks for the whole cohort and stratified by randomised groups. The relationship between HLA supertypes and BMD was also assessed in the subgroup of participants that were naïve to both ABC and TDF at study entry.Class II supertypes were mainly associated with hip BMD change. Overall, compared to participants not carrying HLA-DQ3, participants expressing DQ3 had less bone loss over 96 weeks at both the hip and spine (hip: 0.003 vs. -0.006 g/cm2, 95%CI 0.002 to 0.017, p = 0.016; spine: 0.006 vs. -0.006 g/cm2, 95%CI 0.001 to 0.023, p = 0.041. In participants that were naïve to both ABC and TDF at baseline and randomised to TDF-FTC, DQ3 was significantly associated with less bone loss compared with those not carrying DQ3 (hip: 0.001 vs. -0.032 g/cm2; diff 0.033; 95%CI 0.017 to 0.049; p<0.001; spine: 0.007 vs. -0.023 g/cm2; diff 0.035; 95%CI 0.014 to 0.056; p = 0.001.In this cohort of HIV-infected adults, there was an association between bone status and HLA supertypes, particularly HLA-DQ3.Clinicaltrials.gov NCT00192634.

The stability of a terahertz receiver based on a superconducting integrated receiver

International Nuclear Information System (INIS)

Ozhegov, R V; Gorshkov, K N; Gol'tsman, G N; Kinev, N V; Koshelets, V P

2011-01-01

We present the results of stability testing of a terahertz radiometer based on a superconducting receiver with a SIS tunnel junction as the mixer and a flux-flow oscillator as the local oscillator. In the continuum mode, the receiver with a noise temperature of 95 K at 510 GHz measured over the intermediate frequency (IF) passband of 4-8 GHz offered a noise equivalent temperature difference of 10 ± 1 mK at an integration time of 1 s. We offer a method to significantly increase the integration time without the use of complex measurement equipment. The receiver observed a strong signal over a final detection bandwidth of 4 GHz and offered an Allan time of 5 s.

The stability of a terahertz receiver based on a superconducting integrated receiver

Energy Technology Data Exchange (ETDEWEB)

Ozhegov, R V; Gorshkov, K N; Gol' tsman, G N [Department of Physics, Moscow State Pedagogical University, Moscow 119992 (Russian Federation); Kinev, N V; Koshelets, V P, E-mail: Ozhegov@rplab.ru [Institute of Radio Engineering and Electronics, 125009 Moscow (Russian Federation)

2011-03-15

We present the results of stability testing of a terahertz radiometer based on a superconducting receiver with a SIS tunnel junction as the mixer and a flux-flow oscillator as the local oscillator. In the continuum mode, the receiver with a noise temperature of 95 K at 510 GHz measured over the intermediate frequency (IF) passband of 4-8 GHz offered a noise equivalent temperature difference of 10 {+-} 1 mK at an integration time of 1 s. We offer a method to significantly increase the integration time without the use of complex measurement equipment. The receiver observed a strong signal over a final detection bandwidth of 4 GHz and offered an Allan time of 5 s.

Ground receiving station (GRS) of UMS - receiving and processing the electromagnetic wave data from satellite

International Nuclear Information System (INIS)

Mohammad Syahmi Nordin; Fauziah Abdul Aziz

2007-01-01

The low resolution Automatic Picture Transmission (APT) data from the National Oceanic and Atmospheric Administration (NOAA) polar-orbiting satellites Advanced Very High Resolution Radiometer (AVHRR) is being received and recorded in real-time mode at ground receiving station in School of Science and Technology, Universiti Malaysia Sabah. The system is suitable for the developing and undeveloped countries in south and Southeast Asia and is said to be acceptable for engineering, agricultural, climatological and environmental applications. The system comprises a personal computer attached with a small APT receiver. The data transmission between the ground receiving station and NOAA satellites is using the electromagnetic wave. The relation for receiving and processing the electromagnetic wave in the transmission will be discussed. (Author)

Understanding Adherence to Daily and Intermittent Regimens of Oral HIV Pre-exposure Prophylaxis Among Men Who Have Sex with Men in Kenya

OpenAIRE

Mugo, Peter Mwangi; Sanders, Eduard J.; Mutua, Gaudensia; van der Elst, Elisabeth; Anzala, Omu; Barin, Burc; Bangsberg, David R.; Priddy, Frances H.; Haberer, Jessica E.

2014-01-01

A qualitative assessment of Kenyan men who have sex with men taking daily and intermittent oral HIV pre-exposure prophylaxis (PrEP) found stigma, sex work, mobility, and alcohol impacted adherence. We analyzed quantitative data from the same cohort to explore different definitions of intermittent adherence. Volunteers were randomized to daily emtricitabine/tenofovir or placebo, or intermittent (prescription: Mondays/Fridays/after sex, maximum 1 dose/day) emtricitabine/tenofovir or placebo (2:...

UWB delay and multiply receiver

Energy Technology Data Exchange (ETDEWEB)

Dallum, Gregory E.; Pratt, Garth C.; Haugen, Peter C.; Romero, Carlos E.

2013-09-10

An ultra-wideband (UWB) delay and multiply receiver is formed of a receive antenna; a variable gain attenuator connected to the receive antenna; a signal splitter connected to the variable gain attenuator; a multiplier having one input connected to an undelayed signal from the signal splitter and another input connected to a delayed signal from the signal splitter, the delay between the splitter signals being equal to the spacing between pulses from a transmitter whose pulses are being received by the receive antenna; a peak detection circuit connected to the output of the multiplier and connected to the variable gain attenuator to control the variable gain attenuator to maintain a constant amplitude output from the multiplier; and a digital output circuit connected to the output of the multiplier.

Wideband CMOS receivers

CERN Document Server

Oliveira, Luis

2015-01-01

This book demonstrates how to design a wideband receiver operating in current mode, in which the noise and non-linearity are reduced, implemented in a low cost single chip, using standard CMOS technology.  The authors present a solution to remove the transimpedance amplifier (TIA) block and connect directly the mixer’s output to a passive second-order continuous-time Σ∆ analog to digital converter (ADC), which operates in current-mode. These techniques enable the reduction of area, power consumption, and cost in modern CMOS receivers.

HIGH-EFFICIENCY INFRARED RECEIVER

Directory of Open Access Journals (Sweden)

A. K. Esman

2016-01-01

Full Text Available Recent research and development show promising use of high-performance solid-state receivers of the electromagnetic radiation. These receivers are based on the low-barrier Schottky diodes. The approach to the design of the receivers on the basis of delta-doped low-barrier Schottky diodes with beam leads without bias is especially actively developing because for uncooled receivers of the microwave radiation these diodes have virtually no competition. The purpose of this work is to improve the main parameters and characteristics that determine the practical relevance of the receivers of mid-infrared electromagnetic radiation at the operating room temperature by modifying the electrodes configuration of the diode and optimizing the distance between them. Proposed original design solution of the integrated receiver of mid-infrared radiation on the basis of the low-barrier Schottky diodes with beam leads allows to effectively adjust its main parameters and characteristics. Simulation of the electromagnetic characteristics of the proposed receiver by using the software package HFSS with the basic algorithm of a finite element method which implemented to calculate the behavior of electromagnetic fields on an arbitrary geometry with a predetermined material properties have shown that when the inner parts of the electrodes of the low-barrier Schottky diode is performed in the concentric elliptical convex-concave shape, it can be reduce the reflection losses to -57.75 dB and the standing wave ratio to 1.003 while increasing the directivity up to 23 at a wavelength of 6.09 μm. At this time, the rounded radii of the inner parts of the anode and cathode electrodes are equal 212 nm and 318 nm respectively and the gap setting between them is 106 nm. These parameters will improve the efficiency of the developed infrared optical-promising and electronic equipment for various purposes intended for work in the mid-infrared wavelength range. 

More Efficient Solar Thermal-Energy Receiver

Science.gov (United States)

Dustin, M. O.

1987-01-01

Thermal stresses and reradiation reduced. Improved design for solar thermal-energy receiver overcomes three major deficiencies of solar dynamic receivers described in literature. Concentrator and receiver part of solar-thermal-energy system. Receiver divided into radiation section and storage section. Concentrated solar radiation falls on boiling ends of heat pipes, which transmit heat to thermal-energy-storage medium. Receiver used in number of applications to produce thermal energy directly for use or to store thermal energy for subsequent use in heat engine.

Comparison of Attitudes Toward Death Between University Students Who Receive Nursing Education and Who Receive Religious Education.

Science.gov (United States)

Bakan, Ayse Berivan; Arli, Senay Karadag

2018-03-22

This study aims to compare attitudes toward death between university students who receive nursing education and who receive religious education. This study is cross-sectional in nature. It was conducted with the participation of 197 university students in a university located in the Eastern part of Turkey between June and August, 2017. Data were collected using the socio-demographic form and Turkish form of Death Attitudes Profile-Revised. Of all the students participating in the study, 52.8% received nursing education and 47.2% received religious education. It was found that majority of both groups had no education about death, or found the education they received insufficient. Besides, no significant differences were found between the students who received nursing education and who received religious education in terms of their attitudes toward death (p > 0.05). Results showed that students who received nursing education and who received religious education had similar attitudes toward death. In conclusion, the education given to students about the religious or health aspects of death in accordance with the curriculum seemed to have no effects on students' developing positive attitudes toward death.

Receiver-exciter controller design

Science.gov (United States)

Jansma, P. A.

1982-01-01

A description of the general design of both the block 3 and block 4 receiver-exciter controllers for the Deep Space Network (DSN) Mark IV-A System is presented along with the design approach. The controllers are designed to enable the receiver-exciter subsystem (RCV) to be configured, calibrated, initialized and operated from a central location via high level instructions. The RECs are designed to be operated under the control of the DMC subsystem. The instructions are in the form of standard subsystem blocks (SSBs) received via the local area network (LAN). The centralized control provided by RECs and other DSCC controllers in Mark IV-A is intended to reduce DSN operations costs from the Mark III era.

Dish/stirling hybrid-receiver

Science.gov (United States)

Mehos, Mark S.; Anselmo, Kenneth M.; Moreno, James B.; Andraka, Charles E.; Rawlinson, K. Scott; Corey, John; Bohn, Mark S.

2002-01-01

A hybrid high-temperature solar receiver is provided which comprises a solar heat-pipe-receiver including a front dome having a solar absorber surface for receiving concentrated solar energy, a heat pipe wick, a rear dome, a sidewall joining the front and the rear dome, and a vapor and a return liquid tube connecting to an engine, and a fossil fuel fired combustion system in radial integration with the sidewall for simultaneous operation with the solar heat pipe receiver, the combustion system comprising an air and fuel pre-mixer, an outer cooling jacket for tangentially introducing and cooling the mixture, a recuperator for preheating the mixture, a burner plenum having an inner and an outer wall, a porous cylindrical metal matrix burner firing radially inward facing a sodium vapor sink, the mixture ignited downstream of the matrix forming combustion products, an exhaust plenum, a fossil-fuel heat-input surface having an outer surface covered with a pin-fin array, the combustion products flowing through the array to give up additional heat to the receiver, and an inner surface covered with an extension of the heat-pipe wick, a pin-fin shroud sealed to the burner and exhaust plenums, an end seal, a flue-gas diversion tube and a flue-gas valve for use at off-design conditions to limit the temperature of the pre-heated air and fuel mixture, preventing pre-ignition.

Engineering a segmented dual-reservoir polyurethane intravaginal ring for simultaneous prevention of HIV transmission and unwanted pregnancy.

Directory of Open Access Journals (Sweden)

Justin T Clark

Full Text Available The HIV/AIDS pandemic and its impact on women prompt the investigation of prevention strategies to interrupt sexual transmission of HIV. Long-acting drug delivery systems that simultaneously protect womenfrom sexual transmission of HIV and unwanted pregnancy could be important tools in combating the pandemic. We describe the design, in silico, in vitro and in vivo evaluation of a dual-reservoir intravaginal ring that delivers the HIV-1 reverse transcriptase inhibitor tenofovir and the contraceptive levonorgestrel for 90 days. Two polyether urethanes with two different hard segment volume fractions were used to make coaxial extruded reservoir segments with a 100 µm thick rate controlling membrane and a diameter of 5.5 mm that contain 1.3 wt% levonorgestrel. A new mechanistic diffusion model accurately described the levonorgestrel burst release in early time points and pseudo-steady state behavior at later time points. As previously described, tenofovir was formulated as a glycerol paste and filled into a hydrophilic polyurethane, hollow tube reservoir that was melt-sealed by induction welding. These tenofovir-eluting segments and 2 cm long coaxially extruded levonorgestrel eluting segments were joined by induction welding to form rings that released an average of 7.5 mg tenofovir and 21 µg levonorgestrel per day in vitro for 90 days. Levonorgestrel segments placed intravaginally in rabbits resulted in sustained, dose-dependent levels of levonorgestrel in plasma and cervical tissue for 90 days. Polyurethane caps placed between segments successfully prevented diffusion of levonorgestrel into the tenofovir-releasing segment during storage.Hydrated rings endured between 152 N and 354 N tensile load before failure during uniaxial extension testing. In summary, this system represents a significant advance in vaginal drug delivery technology, and is the first in a new class of long-acting multipurpose prevention drug delivery systems.

Nevirapine, sodium concentration and HIV-1 RNA in breast milk and plasma among HIV-infected women receiving short-course antiretroviral prophylaxis

DEFF Research Database (Denmark)

Salado-Rasmussen, Kirsten; Theilgaard, Zahra Persson; Chiduo, Mercy G.

2015-01-01

and breast milk after intrapartum single-dose nevirapine combined with either 1-week tail of Combivir (zidovudine/lamivudine) or single-dose Truvada (tenofovir/emtricitabine). Methods Maternal plasma and bilateral breast milk samples were collected between April 2008 and April 2011 at 1, 4 and 6 weeks...... postpartum from HIV-infected Tanzanian women. Moreover, plasma samples were collected at delivery from mother and infant. Results HIV-1 RNA was quantified in 1,212 breast milk samples from 273 women. At delivery, 96% of the women and 99% of the infants had detectable nevirapine in plasma with a median...... (interquartile range, IQR) of 1.5 μg/mL (0.75–2.20 μg/mL) and 1.04 μg/mL (0.39–1.71 μg/mL), respectively (P women had detectable nevirapine in plasma and breast milk, with a median (IQR) of 0.13 μg/mL (0.13–0.39 μg/mL) and 0.22 μg/mL (0.13–0.34 μg...

Differences in Lipid Measurements by Antiretroviral Regimen Exposure in Cohorts from Asia and Australia

Directory of Open Access Journals (Sweden)

Amit C. Achhra

2012-01-01

Full Text Available We explored the mean differences in routinely measured lipids (total cholesterol, triglycerides, and high-density lipoprotein cholesterol according to exposure to different combination antiretroviral regimens in Asian (n=2051 and Australian (predominantly Caucasian, n=794 cohorts. The regimen was defined as at least 3 antiretroviral drugs with at least 2 nucleoside-reverse transcriptases (NRTIs and either of at least one protease inhibitor (PI or non-nucleoside-reverse transcriptases (NNRTIs. We categorised cART regimens as: NRTIs as tenofovir based or not; NNRTIs as nevirapine or efavirenz (but not both; and PI as atazanavir based or not. We found that the impact of various antiretroviral regimens on lipids in Asian and Australian cohorts was only different by cohort for total cholesterol (P for interaction between regimen and cohort: 0.05. The differences in total cholesterol were however small and unlikely to be of clinical significance. Overall, tenofovir with nevirapine or atazanavir was associated with the most favorable lipids, while the PI regimens without tenofovir and atazanavir were associated with least favorable lipids. We conclude that the impact of various ART regimens on lipids is largely similar in Asian and Australian cohorts and that the newer drugs such as tenofovir and atazanavir are likely to provide similar benefit in terms of lipid profiles in both populations.

49 CFR 393.88 - Television receivers.

Science.gov (United States)

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false Television receivers. 393.88 Section 393.88... NECESSARY FOR SAFE OPERATION Miscellaneous Parts and Accessories § 393.88 Television receivers. Any motor vehicle equipped with a television viewer, screen or other means of visually receiving a television...

21 CFR 1020.10 - Television receivers.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Television receivers. 1020.10 Section 1020.10 Food...) RADIOLOGICAL HEALTH PERFORMANCE STANDARDS FOR IONIZING RADIATION EMITTING PRODUCTS § 1020.10 Television receivers. (a) Applicability. The provisions of this section are applicable to television receivers...

Reasons for receiving or not receiving HPV vaccination in primary schoolgirls in Tanzania: a case control study.

Science.gov (United States)

Watson-Jones, Deborah; Tomlin, Keith; Remes, Pieter; Baisley, Kathy; Ponsiano, Riziki; Soteli, Selephina; de Sanjosé, Silvia; Changalucha, John; Kapiga, Saidi; Hayes, Richard J

2012-01-01

There are few data on factors influencing human papillomavirus (HPV) vaccination uptake in sub-Saharan Africa. We examined the characteristics of receivers and non-receivers of HPV vaccination in Tanzania and identified reasons for not receiving the vaccine. We conducted a case control study of HPV vaccine receivers and non-receivers within a phase IV cluster-randomised trial of HPV vaccination in 134 primary schools in Tanzania. Girls who failed to receive vaccine (pupil cases) and their parents/guardians (adult cases) and girls who received dose 1 (pupil controls) of the quadrivalent vaccine (Gardasil™) and their parents/guardians (adult controls) were enrolled from 39 schools in a 1∶1 ratio and interviewed about cervical cancer, HPV vaccine knowledge and reasons why they might have received or not received the vaccine. Conditional logistic regression was used to determine factors independently associated with not receiving HPV vaccine. We interviewed 159 pupil/adult cases and 245 pupil/adult controls. Adult-factors independently associated with a daughter being a case were older age, owning fewer household items, not attending a school meeting about HPV vaccine, and not knowing anyone with cancer. Pupil-factors for being a case included having a non-positive opinion about the school de-worming programme, poor knowledge about the location of the cervix, and not knowing that a vaccine could prevent cervical cancer. Reasons for actively refusing vaccination included concerns about side effects and infertility. Most adult and pupil cases reported that they would accept the HPV vaccine if it were offered again (97% and 93% respectively). Sensitisation messages, especially targeted at older and poorer parents, knowledge retention and parent meetings are critical for vaccine acceptance in Tanzania. Vaccine side effects and fertility concerns should be addressed prior to a national vaccination program. Parents and pupils who initially decline vaccination should be

Water jacket for solid particle solar receiver

Science.gov (United States)

Wasyluk, David T.

2018-03-20

A solar receiver includes: water jacket panels each having a light-receiving side and a back side with a watertight sealed plenum defined in-between; light apertures passing through the watertight sealed plenums to receive light from the light-receiving sides of the water jacket panels; a heat transfer medium gap defined between the back sides of the water jacket panels and a cylindrical back plate; and light channeling tubes optically coupled with the light apertures and extending into the heat transfer medium gap. In some embodiments ends of the light apertures at the light receiving side of the water jacket panel are welded together to define at least a portion of the light-receiving side. A cylindrical solar receiver may be constructed using a plurality of such water jacket panels arranged with their light-receiving sides facing outward.

High Gain Advanced GPS Receiver

National Research Council Canada - National Science Library

Brown, Alison; Zhang, Gengsheng

2006-01-01

NAVSYS High Gain Advanced GPS Receiver (HAGR) uses a digital beam-steering antenna array to enable up to eight GPS satellites to be tracked, each with up to 10 dBi of additional antenna gain over a conventional receiver solution...

29 CFR 1917.155 - Air receivers.

Science.gov (United States)

2010-07-01

.... This section applies to compressed air receivers and equipment used for operations such as cleaning... transportation applications as railways, vehicles or cranes. (b) Gauges and valves. (1) Air receivers shall be... 29 Labor 7 2010-07-01 2010-07-01 false Air receivers. 1917.155 Section 1917.155 Labor Regulations...

Compressive Sensing for Spread Spectrum Receivers

DEFF Research Database (Denmark)

Fyhn, Karsten; Jensen, Tobias Lindstrøm; Larsen, Torben

2013-01-01

With the advent of ubiquitous computing there are two design parameters of wireless communication devices that become very important: power efficiency and production cost. Compressive sensing enables the receiver in such devices to sample below the Shannon-Nyquist sampling rate, which may lead...... the bit error rate performance is degraded by the subsampling in the CS-enabled receivers, this may be remedied by including quantization in the receiver model.We also study the computational complexity of the proposed receiver design under different sparsity and measurement ratios. Our work shows...

Southern African guidelines for the safe use of pre-exposure prophylaxis in men who have sex with men who are at risk for HIV infection

Directory of Open Access Journals (Sweden)

Southern African HIV Clinicians Society Consensus Committee

2012-06-01

Full Text Available Background. The use of oral antiretrovirals to prevent HIV infection among HIV-negative men who have sex with men (MSM has been shown to be safe and efficacious. A large, randomised, placebo-controlled trial showed a 44% reduction in the incidence of HIV infection among MSM receiving a daily oral fixed-dose combination of tenofovir disoproxil fumarate and emtricitabine (Truvada in combination with an HIV prevention package. Improved protection was seen with higher levels of adherence. Aim. The purpose of this guideline is to: (i explain what pre-exposure prophylaxis (PrEP is; (ii outline current indications for its use; (iii outline steps for appropriate client selection; and (iv provide guidance for monitoring and maintaining clients on PrEP. Method. PrEP is indicated for HIV-negative MSM who are assessed to be at high risk for HIV acquisition and who are willing and motivated to use PrEP as part of a package of HIV prevention services (including condoms, lubrication, sexually transmitted infection (STI management and risk reduction counselling. Recommendations. HIV testing, estimation of creatinine clearance and STI and hepatitis B screening are recommended as baseline investigations. Daily oral Truvada, along with adherence support, can then be prescribed for eligible MSM. PrEP should not be given to MSM with abnormal renal function, nor to clients who are unmotivated to use PrEP as part of an HIV prevention package; nor should it be commenced during an acute viral illness. Three-monthly follow-up visits to assess tolerance, renal function, adherence and ongoing eligibility is recommended. Six-monthly STI screens and annual creatinine levels to estimate creatinine clearance are recommended. Hepatitis B vaccination should be provided to susceptible clients. Gastro-intestinal symptoms and weight loss are common side-effects, mostly experienced for the first 4 - 8 weeks after initiating PrEP. There is a risk of the development of antiretroviral

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Science.gov (United States)

Günthard, Huldrych F.; Saag, Michael S.; Benson, Constance A.; del Rio, Carlos; Eron, Joseph J.; Gallant, Joel E.; Hoy, Jennifer F.; Mugavero, Michael J.; Sax, Paul E.; Thompson, Melanie A.; Gandhi, Rajesh T.; Landovitz, Raphael J.; Smith, Davey M.; Jacobsen, Donna M.; Volberding, Paul A.

2016-01-01

assessments are recommended before treatment, and monitoring during treatment is recommended to assess response, adverse effects, and adherence. Approaches are recommended to improve linkage to and retention in care are provided. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure. CONCLUSIONS AND RELEVANCE Antiretroviral agents remain the cornerstone of HIV treatment and prevention. All HIV-infected individuals with detectable plasma virus should receive treatment with recommended initial regimens consisting of an InSTI plus 2 NRTIs. Preexposure prophylaxis should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults. PMID:27404187

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society-USA Panel.

Science.gov (United States)

Günthard, Huldrych F; Saag, Michael S; Benson, Constance A; del Rio, Carlos; Eron, Joseph J; Gallant, Joel E; Hoy, Jennifer F; Mugavero, Michael J; Sax, Paul E; Thompson, Melanie A; Gandhi, Rajesh T; Landovitz, Raphael J; Smith, Davey M; Jacobsen, Donna M; Volberding, Paul A

2016-07-12

monitoring during treatment is recommended to assess response, adverse effects, and adherence. Approaches are recommended to improve linkage to and retention in care are provided. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure. Antiretroviral agents remain the cornerstone of HIV treatment and prevention. All HIV-infected individuals with detectable plasma virus should receive treatment with recommended initial regimens consisting of an InSTI plus 2 NRTIs. Preexposure prophylaxis should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults.

Optimal costs of HIV pre-exposure prophylaxis for men who have sex with men.

Directory of Open Access Journals (Sweden)

Jennie McKenney

Full Text Available Men who have sex with men (MSM are disproportionately affected by HIV due to their increased risk of infection. Oral pre-exposure prophylaxis (PrEP is a highly effictive HIV-prevention strategy for MSM. Despite evidence of its effectiveness, PrEP uptake in the United States has been slow, in part due to its cost. As jurisdictions and health organizations begin to think about PrEP scale-up, the high cost to society needs to be understood.We modified a previously-described decision-analysis model to estimate the cost per quality-adjusted life-year (QALY gained, over a 1-year duration of PrEP intervention and lifetime time horizon. Using updated parameter estimates, we calculated: 1 the cost per QALY gained, stratified over 4 strata of PrEP cost (a function of both drug cost and provider costs; and 2 PrEP drug cost per year required to fall at or under 4 cost per QALY gained thresholds.When PrEP drug costs were reduced by 60% (with no sexual disinhibition to 80% (assuming 25% sexual disinhibition, PrEP was cost-effective (at <$100,000 per QALY averted in all scenarios of base-case or better adherence, as long as the background HIV prevalence was greater than 10%. For PrEP to be cost saving at base-case adherence/efficacy levels and at a background prevalence of 20%, drug cost would need to be reduced to $8,021 per year with no disinhibition, and to $2,548 with disinhibition.Results from our analysis suggest that PrEP drug costs need to be reduced in order to be cost-effective across a range of background HIV prevalence. Moreover, our results provide guidance on the pricing of generic emtricitabine/tenofovir disoproxil fumarate, in order to provide those at high risk for HIV an affordable prevention option without financial burden on individuals or jurisdictions scaling-up coverage.

Adherence to Pre-Exposure Prophylaxis for HIV Prevention in a Clinical Setting.

Directory of Open Access Journals (Sweden)

Madeline C Montgomery

Full Text Available The HIV epidemic in the United States (US disproportionately affects gay, bisexual, and other men who have sex with men (MSM. Pre-exposure prophylaxis (PrEP using co-formulated tenofovir disoproxil fumarate (TDF and emtricitabine (FTC has demonstrated high efficacy in reducing HIV incidence among MSM. However, low adherence was reported in major efficacy trials and may present a substantial barrier to successful PrEP implementation. Rates of adherence to PrEP in "real-world" clinical settings in the US remain largely unknown.We reviewed demographic and clinical data for the first 50 patients to enroll in a clinical PrEP program in Providence, Rhode Island. We analyzed self-reported drug adherence as well as drug concentrations in dried blood spots (DBS from patients who attended either a three- or six-month follow-up appointment. We further assessed drug concentrations and the resistance profile of a single patient who seroconverted while taking PrEP.Of the first 50 patients to be prescribed PrEP, 62% attended a follow-up appointment at three months and 38% at six months. Of those who attended an appointment at either time point (70%, n = 35, 92% and 95% reported taking ±4 doses/week at three and six months, respectively. Drug concentrations were performed on a random sample of 20 of the 35 patients who attended a follow-up appointment. TDF levels consistent with ±4 doses/week were found in 90% of these patients. There was a significant correlation between self-reported adherence and drug concentrations (r = 0.49, p = 0.02. One patient who had been prescribed PrEP seroconverted at his three-month follow-up visit. The patient's drug concentrations were consistent with daily dosing. Population sequencing and ultrasensitive allele-specific PCR detected the M184V mutation, but no other TDF- or FTC-associated mutations, including those present as minor variants.In this clinical PrEP program, adherence was high, and self-reported drug adherence

Adherence to Pre-Exposure Prophylaxis for HIV Prevention in a Clinical Setting.

Science.gov (United States)

Montgomery, Madeline C; Oldenburg, Catherine E; Nunn, Amy S; Mena, Leandro; Anderson, Peter; Liegler, Teri; Mayer, Kenneth H; Patel, Rupa; Almonte, Alexi; Chan, Philip A

2016-01-01

The HIV epidemic in the United States (US) disproportionately affects gay, bisexual, and other men who have sex with men (MSM). Pre-exposure prophylaxis (PrEP) using co-formulated tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) has demonstrated high efficacy in reducing HIV incidence among MSM. However, low adherence was reported in major efficacy trials and may present a substantial barrier to successful PrEP implementation. Rates of adherence to PrEP in "real-world" clinical settings in the US remain largely unknown. We reviewed demographic and clinical data for the first 50 patients to enroll in a clinical PrEP program in Providence, Rhode Island. We analyzed self-reported drug adherence as well as drug concentrations in dried blood spots (DBS) from patients who attended either a three- or six-month follow-up appointment. We further assessed drug concentrations and the resistance profile of a single patient who seroconverted while taking PrEP. Of the first 50 patients to be prescribed PrEP, 62% attended a follow-up appointment at three months and 38% at six months. Of those who attended an appointment at either time point (70%, n = 35), 92% and 95% reported taking ±4 doses/week at three and six months, respectively. Drug concentrations were performed on a random sample of 20 of the 35 patients who attended a follow-up appointment. TDF levels consistent with ±4 doses/week were found in 90% of these patients. There was a significant correlation between self-reported adherence and drug concentrations (r = 0.49, p = 0.02). One patient who had been prescribed PrEP seroconverted at his three-month follow-up visit. The patient's drug concentrations were consistent with daily dosing. Population sequencing and ultrasensitive allele-specific PCR detected the M184V mutation, but no other TDF- or FTC-associated mutations, including those present as minor variants. In this clinical PrEP program, adherence was high, and self-reported drug adherence accurately

AtriplaR/anti-TB combination in TB/HIV patients. Drug in focus

Directory of Open Access Journals (Sweden)

Semvua Hadija H

2011-11-01

Full Text Available Abstract Background Co-administration of anti-tuberculosis and antiretroviral therapy is often inevitable in high-burden countries where tuberculosis is the most common opportunistic infection associated with HIV/AIDS. Concurrent use of rifampicin and several antiretroviral drugs is complicated by pharmacokinetic drug-drug interaction. Method Pubmed and Google search following the key words tuberculosis, HIV, emtricitabine, tenofovir efavirenz, interaction were used to find relevant information on each drug of the fixed dose combination AtriplaR Results Information on generic name, trade name, pharmacokinetic parameter, metabolism and the pharmacokinetic interaction with Anti-TB drugs of emtricitabine, tenofovir, and efavirenz was obtained. Conclusion Fixed dose combination of emtricitabine/tenofovir/efavirenz (ATRIPLAR which has been approved by Food and Drug Administration shows promising results as far as safety and efficacy is concerned in TB/HIV co-infection patients, hence can be considered effective and safe antiretroviral drug in TB/HIV management for adult and children above 3 years of age.

Reasons for receiving or not receiving HPV vaccination in primary schoolgirls in Tanzania: a case control study.

Directory of Open Access Journals (Sweden)

Deborah Watson-Jones

Full Text Available There are few data on factors influencing human papillomavirus (HPV vaccination uptake in sub-Saharan Africa. We examined the characteristics of receivers and non-receivers of HPV vaccination in Tanzania and identified reasons for not receiving the vaccine.We conducted a case control study of HPV vaccine receivers and non-receivers within a phase IV cluster-randomised trial of HPV vaccination in 134 primary schools in Tanzania. Girls who failed to receive vaccine (pupil cases and their parents/guardians (adult cases and girls who received dose 1 (pupil controls of the quadrivalent vaccine (Gardasil™ and their parents/guardians (adult controls were enrolled from 39 schools in a 1∶1 ratio and interviewed about cervical cancer, HPV vaccine knowledge and reasons why they might have received or not received the vaccine. Conditional logistic regression was used to determine factors independently associated with not receiving HPV vaccine.We interviewed 159 pupil/adult cases and 245 pupil/adult controls. Adult-factors independently associated with a daughter being a case were older age, owning fewer household items, not attending a school meeting about HPV vaccine, and not knowing anyone with cancer. Pupil-factors for being a case included having a non-positive opinion about the school de-worming programme, poor knowledge about the location of the cervix, and not knowing that a vaccine could prevent cervical cancer. Reasons for actively refusing vaccination included concerns about side effects and infertility. Most adult and pupil cases reported that they would accept the HPV vaccine if it were offered again (97% and 93% respectively.Sensitisation messages, especially targeted at older and poorer parents, knowledge retention and parent meetings are critical for vaccine acceptance in Tanzania. Vaccine side effects and fertility concerns should be addressed prior to a national vaccination program. Parents and pupils who initially decline vaccination

Heat receiving plates in thermonuclear device

International Nuclear Information System (INIS)

Kitamura, Kazunori.

1988-01-01

Purpose: To obtain a heat receiving plate structure capable of withstanding sputtering wear and retaining the thermal deformation and residual stress low upon junction and available at a reduced cost. Constitution: Junction structures between heat sinks and armours are the same as usual, whereas high melting armour (for example, made of tungsten) are used at the portion on a heat receiving plate where the thermal load and particle load are higher while materials having a heat expansion coefficient similar to that of the heat sink (stainless steel) are used at the portion where the thermal load and particle load are lower on a heat receiving plate depending on the thermal load and particle load distribution. This can reduce the thermal deformation for the entire divertor heat receiving plate to obtain a heat receiving plate of a good surface dimensional accuracy. (Takahashi, M.)

Design of double capacitances infrasonic receiver

International Nuclear Information System (INIS)

Wang Changhai; Han Kuixia; Wang Fei

2003-01-01

The article introduces the theory of infrasonic generation and reception of nuclear explosion. An idea of the design of double capacitances infrasonic receiver using CPLD technology is given in it. Compare with the single capacitance infrasonic receiver, sensitivity of the improved receiver can be improved scores of times, dynamic range can be improved largely, and the whole performance gets improvement a lots

Stability of heterodyne terahertz receivers

NARCIS (Netherlands)

Kooi, J.W.; Baselmans, J.J.A.; Baryshev, A.; Schieder, R.; Hajenius, M.; Gao, J.R.; Klapwijk, T.M.; Voronov, B.; Gol'tsman, G.

2006-01-01

In this paper we discuss the stability of heterodyne terahertz receivers based on small volume NbN phonon cooled hot electron bolometers (HEBs). The stability of these receivers can be broken down in two parts: the intrinsic stability of the HEB mixer and the stability of the local oscillator (LO)

High thermal load receiving heat plate

International Nuclear Information System (INIS)

Shibutani, Jun-ichi; Shibayama, Kazuhito; Yamamoto, Keiichi; Uchida, Takaho.

1993-01-01

The present invention concerns a high thermal load heat receiving plate such as a divertor plate of a thermonuclear device. The high thermal load heat receiving plate of the present invention has a cooling performance capable of suppressing the temperature of an armour tile to less than a threshold value of the material against high thermal loads applied from plasmas. Spiral polygonal pipes are inserted in cooling pipes at a portion receiving high thermal loads in the high temperature load heat receiving plate of the present invention. Both ends of the polygonal pipes are sealed by lids. An area of the flow channel in the cooling pipes is thus reduced. Heat conductivity on the cooling surface of the cooling pipes is increased in the high thermal load heat receiving plate having such a structure. Accordingly, temperature elevation of the armour tile can be suppressed. (I.S.)

Fundamentals of GPS Receivers A Hardware Approach

CERN Document Server

Doberstein, Dan

2012-01-01

While much of the current literature on GPS receivers is aimed at those intimately familiar with their workings, this volume summarizes the basic principles using as little mathematics as possible, and details the necessary specifications and circuits for constructing a GPS receiver that is accurate to within 300 meters. Dedicated sections deal with the features of the GPS signal and its data stream, the details of the receiver (using a hybrid design as exemplar), and more advanced receivers and topics including time and frequency measurements. Later segments discuss the Zarlink GPS receiver chip set, as well as providing a thorough examination of the TurboRogue receiver, one of the most accurate yet made. Guiding the reader through the concepts and circuitry, from the antenna to the solution of user position, the book’s deployment of a hybrid receiver as a basis for discussion allows for extrapolation of the core ideas to more complex, and more accurate designs. Digital methods are used, but any analogue c...

Single-Receiver GPS Phase Bias Resolution

Science.gov (United States)

Bertiger, William I.; Haines, Bruce J.; Weiss, Jan P.; Harvey, Nathaniel E.

2010-01-01

Existing software has been modified to yield the benefits of integer fixed double-differenced GPS-phased ambiguities when processing data from a single GPS receiver with no access to any other GPS receiver data. When the double-differenced combination of phase biases can be fixed reliably, a significant improvement in solution accuracy is obtained. This innovation uses a large global set of GPS receivers (40 to 80 receivers) to solve for the GPS satellite orbits and clocks (along with any other parameters). In this process, integer ambiguities are fixed and information on the ambiguity constraints is saved. For each GPS transmitter/receiver pair, the process saves the arc start and stop times, the wide-lane average value for the arc, the standard deviation of the wide lane, and the dual-frequency phase bias after bias fixing for the arc. The second step of the process uses the orbit and clock information, the bias information from the global solution, and only data from the single receiver to resolve double-differenced phase combinations. It is called "resolved" instead of "fixed" because constraints are introduced into the problem with a finite data weight to better account for possible errors. A receiver in orbit has much shorter continuous passes of data than a receiver fixed to the Earth. The method has parameters to account for this. In particular, differences in drifting wide-lane values must be handled differently. The first step of the process is automated, using two JPL software sets, Longarc and Gipsy-Oasis. The resulting orbit/clock and bias information files are posted on anonymous ftp for use by any licensed Gipsy-Oasis user. The second step is implemented in the Gipsy-Oasis executable, gd2p.pl, which automates the entire process, including fetching the information from anonymous ftp

Higher rates of metabolic syndrome among women taking zidovudine as compared to tenofovir in rural Africa: preliminary data from the CART-1 study.

Science.gov (United States)

Labhardt, Niklaus Daniel; Cheleboi, Molisana; Faturyiele, Olatunbosun; Motlatsi, Mokete M; Pfeiffer, Karolin; Lejone, Thabo Ismael; Cerutti, Bernard; Muser, Jürgen; Gupta, Ravi Shankar; Lynen, Lutgarde; Hatz, Christoph

2014-01-01

Due to its side effects stavudine (D4T) has been replaced by zidovudine (AZT) and tenofovir (TDF) in most low- and middle-income countries (LMICs). In 2014 about 38% of adult first-line regimens contain AZT and 62% TDF [1]. Whereas the unfavourable metabolic outcomes of D4T in comparison to TDF have been described extensively, studies from LMICs comparing metabolic profiles between patients on AZT and TDF are scarce. Given the high number of patients in LMICs still taking AZT, data on their metabolic profile are needed. We present rates of metabolic syndrome (MS) in adult patients taking either AZT- or TDF-containing first-line, non-nucleoside reverse transcriptase (NNRTI)-based regimens. Data derived from a cross-sectional multi-disease screening conducted in ten facilities in two rural districts of Lesotho, Southern Africa [2]. Patients were eligible if aged ≥25 years and on NNRTI-containing first-line ART ≥6 months. The MS definition for Africa of the International Diabetes Federation was applied [3]. Assessed potential predictors for MS were age, time on ART, virologic suppression, body-mass index (BMI), alcohol consumption, wealth quintile, NNRTI (nevirapine (NVP) or Efavirenz (EFV)), history of previous D4T exposure and ART-backbone (AZT or TDF). Statistical analyses - stratified for sex - comprised univariate logistic regression for each predictor variable with subsequent construction of a multivariate model including all predictors with an association to MS at a significance levelwomen. In women, aged ≥35 years, AZT-backbone, NVP-base, BMI ≥25kg/m2 and taking ART for ≥4.5 years were associated with MS in univariate analysis. In the multivariate model only AZT (adjusted odds-ratio: 2.2, 95% CI 1.4-3.6; p=0.001) and BMI ≥25kg/m2 (9.8; 2.8-34.1, pwomen who are on ART for ≥6 months predisposes to the development of metabolic syndrome. Given that, still 38% of first-line regimens in LMIC contain AZT, this finding needs to be verified in other

Alexandrite Lidar Receiver

National Research Council Canada - National Science Library

Wilkerson, Thomas

2000-01-01

...". The chosen vendor, Orca Photonics, In. (Redmond, WA), in close collaboration with USU personnel, built a portable, computerized lidar system that not only is suitable as a receiver for a near IR alexandrite laser, but also contains an independent Nd...

Effects of Oxytocin Administration on Receiving Help.

Science.gov (United States)

Human, Lauren J; Woolley, Joshua D; Mendes, Wendy Berry

2017-11-27

Receiving help can be a "mixed blessing." Despite the many psychosocial benefits it can carry, it sometimes has negative psychological consequences, such as loss in self-esteem or enhanced guilt. It is, therefore, important to understand the factors that modify responses to receiving help from others. We explored the role of the hormone oxytocin (OT) on affective and social responses to receiving help, given the putative role of OT in social bonding and attunement. To this end, we manipulated whether help was received from a same-sex interaction partner (confederate) versus a control condition, crossed with a double-blind administration of intranasal OT (vs. placebo), and examined subjective and observer-rated participant responses to help. We observed significant interactions between OT and the help manipulation. In the placebo condition, receiving help from the interaction partner compared with the control condition had negative consequences, such that participants reported greater negative affect and came to view themselves and their interaction partners more negatively after interacting together on several tasks. What is important, however, is that OT administration buffered against these negative subjective responses to receiving help. Further, outside observers rated participants who received OT administration as expressing greater happiness and gratitude in response to help, relative to those who received placebo. In sum, in the context of receiving help from a stranger, oxytocin administration fostered more positive affective and social responses. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Solar thermal central receivers

International Nuclear Information System (INIS)

Vant-Hull, L.L.

1993-01-01

Market issues, environmental impact, and technology issues related to the Solar Central Receiver concept are addressed. The rationale for selection of the preferred configuration and working fluid are presented as the result of a joint utility-industry analysis. A $30 million conversion of Solar One to an external molten salt receiver would provide the intermediate step to a commercial demonstration plant. The first plant in this series could produce electricity at 11.2 cents/kWhr and the seventh at 8.2 cents/kWhr, completely competitive with projected costs of new utility plants in 1992

Design and simulation analysis of non-receiver aware and receiver ...

African Journals Online (AJOL)

We present multicast extensions to our recently proposed Location Prediction Based Routing (LPBR) protocol, referred to as NR-MLPBR and R-MLPBR, to simultaneously reduce the number of multicast tree discoveries and number of links per tree and/or the hop count per source-receiver path in mobile ad hoc networks ...

Full-wave receiver architecture for the homodyne motion sensor

Energy Technology Data Exchange (ETDEWEB)

Haugen, Peter C.; Dallum, Gregory E.; Welsh, Patrick A.; Romero, Carlos E.

2015-09-29

A homodyne motion sensor or detector based on ultra-wideband radar utilizes the entire received waveform through implementation of a voltage boosting receiver. The receiver includes a receiver input and a receiver output. A first diode is connected to the receiver output. A first charge storage capacitor is connected from between the first diode and the receiver output to ground. A second charge storage capacitor is connected between the receiver input and the first diode. A second diode is connected from between the second charge storage capacitor and the first diode to ground. The dual diode receiver performs voltage boosting of a RF signal received at the receiver input, thereby enhancing receiver sensitivity.

Full-wave receiver architecture for the homodyne motion sensor

Science.gov (United States)

Haugen, Peter C; Dallum, Gregory E; Welsh, Patrick A; Romero, Carlos E

2013-11-19

A homodyne motion sensor or detector based on ultra-wideband radar utilizes the entire received waveform through implementation of a voltage boosting receiver. The receiver includes a receiver input and a receiver output. A first diode is connected to the receiver output. A first charge storage capacitor is connected from between the first diode and the receiver output to ground. A second charge storage capacitor is connected between the receiver input and the first diode. A second diode is connected from between the second charge storage capacitor and the first diode to ground. The dual diode receiver performs voltage boosting of a RF signal received at the receiver input, thereby enhancing receiver sensitivity.

Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy.

Directory of Open Access Journals (Sweden)

Oranat Chuchuen

Full Text Available Topical vaginal anti-HIV microbicides are an important focus in female-based strategies to prevent the sexual transmission of HIV. Understanding microbicide pharmacokinetics is essential to development, characterization and implementation of efficacious microbicide drug delivery formulations. Current methods to measure drug concentrations in tissue (e.g., LC-MS/MS, liquid chromatography coupled with tandem mass spectrometry are highly sensitive, but destructive and complex. This project explored the use of confocal Raman spectroscopy to detect microbicide drugs and to measure their local concentrations in fluids, drug delivery gels, and tissues. We evaluated three candidate microbicide drugs: tenofovir, Dapivirine and IQP-0528. Measurements were performed in freshly excised porcine buccal tissue specimens, gel vehicles and fluids using two Horiba Raman microscopes, one of which is confocal. Characteristic spectral peak calibrations for each drug were obtained using serial dilutions in the three matrices. These specific Raman bands demonstrated strong linear concentration dependences in the matrices and were characterized with respect to their unique vibrational signatures. At least one specific Raman feature was identified for each drug as a marker band for detection in tissue. Sensitivity of detection was evaluated in the three matrices. A specific peak was also identified for tenofovir diphosphate, the anti-HIV bioactive product of tenofovir after phosphorylation in host cells. Z-scans of drug concentrations vs. depth in excised tissue specimens, incubated under layers of tenofovir solution in a Transwell assay, showed decreasing concentration with depth from the surface into the tissue. Time-dependent concentration profiles were obtained from tissue samples incubated in the Transwell assay, for times ranging 30 minutes - 6 hours. Calibrations and measurements from tissue permeation studies for tenofovir showed good correlation with gold

Quantitative Analysis of Microbicide Concentrations in Fluids, Gels and Tissues Using Confocal Raman Spectroscopy

Science.gov (United States)

Chuchuen, Oranat; Henderson, Marcus H.; Sykes, Craig; Kim, Min Sung; Kashuba, Angela D. M.; Katz, David F.

2013-01-01

Topical vaginal anti-HIV microbicides are an important focus in female-based strategies to prevent the sexual transmission of HIV. Understanding microbicide pharmacokinetics is essential to development, characterization and implementation of efficacious microbicide drug delivery formulations. Current methods to measure drug concentrations in tissue (e.g., LC-MS/MS, liquid chromatography coupled with tandem mass spectrometry) are highly sensitive, but destructive and complex. This project explored the use of confocal Raman spectroscopy to detect microbicide drugs and to measure their local concentrations in fluids, drug delivery gels, and tissues. We evaluated three candidate microbicide drugs: tenofovir, Dapivirine and IQP-0528. Measurements were performed in freshly excised porcine buccal tissue specimens, gel vehicles and fluids using two Horiba Raman microscopes, one of which is confocal. Characteristic spectral peak calibrations for each drug were obtained using serial dilutions in the three matrices. These specific Raman bands demonstrated strong linear concentration dependences in the matrices and were characterized with respect to their unique vibrational signatures. At least one specific Raman feature was identified for each drug as a marker band for detection in tissue. Sensitivity of detection was evaluated in the three matrices. A specific peak was also identified for tenofovir diphosphate, the anti-HIV bioactive product of tenofovir after phosphorylation in host cells. Z-scans of drug concentrations vs. depth in excised tissue specimens, incubated under layers of tenofovir solution in a Transwell assay, showed decreasing concentration with depth from the surface into the tissue. Time-dependent concentration profiles were obtained from tissue samples incubated in the Transwell assay, for times ranging 30 minutes - 6 hours. Calibrations and measurements from tissue permeation studies for tenofovir showed good correlation with gold standard LC-MS/MS data

GIVING AND RECEIVING CONSTRUCTIVE FEEDBACK

Directory of Open Access Journals (Sweden)

Ірина Олійник

2015-05-01

Full Text Available The article scrutinizes the notion of feedback applicable in classrooms where team teaching is provided. The experience of giving and receiving feedback has been a good practice in cooperation between a U.S. Peace Corps volunteer and a Ukrainian counterpart. Giving and receiving feedback is an effective means of classroom observation that provides better insight into the process of teaching a foreign language. The article discusses the stages of feedback and explicates the notion of sharing experience between two teachers working simultaneously in the same classroom. The guidelines for giving and receiving feedback have been provided as well as the most commonly used vocabulary items have been listed. It has been proved that mutual feedback leads to improving teaching methods and using various teaching styles and techniques.

Decoding algorithm for vortex communications receiver

Science.gov (United States)

Kupferman, Judy; Arnon, Shlomi

2018-01-01

Vortex light beams can provide a tremendous alphabet for encoding information. We derive a symbol decoding algorithm for a direct detection matrix detector vortex beam receiver using Laguerre Gauss (LG) modes, and develop a mathematical model of symbol error rate (SER) for this receiver. We compare SER as a function of signal to noise ratio (SNR) for our algorithm and for the Pearson correlation algorithm. To our knowledge, this is the first comprehensive treatment of a decoding algorithm of a matrix detector for an LG receiver.

First-line HIV treatment: evaluation of backbone choice and its budget impact

Directory of Open Access Journals (Sweden)

Orietta Zaniolo

2013-06-01

Full Text Available OBJECTIVE: The gradual increase of persons living with HIV, mainly due to the reduced mortality achieved with effective antiretroviral therapies, calls for increased rationality and awareness in health resources consumption also during the early illness phases. Aim of this work is the estimation of the budget impact related to the variation in backbone prescribing trends in naïve patients.METHODS: Target population is the number of patients starting antiretroviral therapy each year, according to the Italian HIV surveillance registry, excluding patients receiving non-authorized or non-recommended regimens. We modeled 3-year mortality and durability rates on a dynamic cohort, basing on international literature. A prevalent patients analysis has also been conducted, for which the model is fed by a closed cohort consisting of all the patients without experience of virologic failure. The aim of this collateral analysis is to estimate the difference in current annual expenditures if the past prescription trends for patients starting therapy would have led to the evaluated hypothetical scenarios. Current Italian market shares of triple regimens containing first-choice or alternative backbones (tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine are compared to three hypothetical scenarios (base-case, minimum and maximum in which increasing shares of patients eligible to abacavir/lamivudine start first line treatment with this backbone. Annual cost for each regimen comprises drugs acquisition under hospital pricing rules, monitoring exams and preventive tests, valued basing on regional reimbursement tariffs.RESULTS: According to current prescribing trends, in the next three years about 13,000 patients starting HIV therapy will receive tenofovir/emtricitabine (83% of the target population, and minor portions other regimens (9% abacavir/lamivudine, 8% zidovudine/lamivudine. Patients that would be eligible to

An SDR based AIS receiver for satellites

DEFF Research Database (Denmark)

Larsen, Jesper Abildgaard; Mortensen, Hans Peter; Nielsen, Jens Frederik Dalsgaard

2011-01-01

For a few years now, there has been a high interest in monitoring the global ship traffic from space. A few satellite, capable of listening for ship borne AIS transponders have already been launched, and soon the AAUSAT3, carrying two different types of AIS receivers will also be launched. One...... of the AIS receivers onboard AAUSAT3 is an SDR based AIS receiver. This paper serves to describe the background of the AIS system, and how the SDR based receiver has been integrated into the AAUSAT3 satellite. Amongst some of the benefits of using an SDR based receiver is, that due to its versatility, new...... detection algorithms are easily deployed, and it is easily adapted the new proposed AIS transmission channels....

'Chaos' in superregenerative receivers

Energy Technology Data Exchange (ETDEWEB)

Commercon, Jean-Claude [INSA, Department d' Informatiques, Ba-hat t B. Pascal, 20 Avenue Albert Einsten, 69621 Villeurbaune (France)]. E-mail: jean-claude.commercon@insa-lyon.fr; Badard, Robert [INSA, Department d' Informatiques, Bat B. Pascal, 20 Avenue Albert Einsten, 69621 Villeurbaune (France)]. E-mail: robert.badard@insa-lyon.fr

2005-02-01

The superregenerative principle has been known since the early 1920s. The circuit is extremely simple and extremely sensitive. Today, superheterodyne receivers generally supplant superregenerative receivers in most applications because there are several undesirable characteristics: poor selectivity, reradiation, etc. Superregenerative receivers undergo a revival in recent papers for wireless systems, where low cost and very low power consumption are relevant: house/building meters (such as water, energy, gas counter), personal computer environment (keyboard, mouse), etc. Another drawback is the noise level which is higher than that of a well-designed superheterodyne receiver; without an antenna input signal, the output of the receiver hears in an earphone as a waterfall noise; this sound principally is the inherent input noise amplified and detected by the circuit; however, when the input noise is negligible with respect of an antenna input signal, we are faced to an other source of 'noise' self-generated by the superregenerative working. The main objective of this paper concerns this self-generated noise coming from an exponential growing followed by a re-injection process for which the final state is a function of the phase of the input signal.

Advanced Signal Processing for MIMO-OFDM Receivers

DEFF Research Database (Denmark)

Manchón, Carles Navarro

This thesis deals with a wide range of topics within the research area of advanced baseband receiver design for wireless communication systems. In particular, the work focuses on signal processing algorithms for receivers in multiple-input multiple-output (MIMO) orthogonal frequency-division mult......This thesis deals with a wide range of topics within the research area of advanced baseband receiver design for wireless communication systems. In particular, the work focuses on signal processing algorithms for receivers in multiple-input multiple-output (MIMO) orthogonal frequency...... the structure of the receiver with the hope that the resulting heuristic architecture will exhibit the desired behavior and performance. On the other hand, one can employ analytical frameworks to pose the problem as the optimization of a global objective function subject to certain constraints. This work...

PENENTUAN RECEIVED DATE DENGAN LOAD-ORIENTED MANUFACRURING CONTROL

Directory of Open Access Journals (Sweden)

Sri Hartini

2012-02-01

Full Text Available Salah satu kunci kompetitif sebuah perusahaan make to order adalah ketepatan dalam pemenuhan waktu penerimaan pesanan pada konsumen yang telah dijanjikan perusahaan ( received date. Penentuan received date yang selama ini dilakukan oleh JI  kurang tepat karena hanya memperkirakan waktu sekitar 10 – 12 minggu tanpa mempertimbangkan faktor produksi. Penelitian ini merancang received date dengan model load-oriented manufacturing control dimana penentuan received date didasarkan pada perhitungan manufacturing lead time yang mempertimbangkan waktu pengiriman order ke konsumen, kapasitas yang tersedia pada tiap stasiun kerja, waktu proses pada stasiun kerja dan aliran produksi di lantai produksi. Hasil validasi perhitungan  penentuan received date order sesuai  dengan sistem produksi PT JI dan lebih valid dibanding sistem awal. Kata kunci : make to order, received date, manufacturing leadtime, load-oriented manufacturing control   One of the competitive key of a make to order company is the accuracy in fulfilling orders which has been promised by the company towards the consumers (received date. Determining received date which has been applied by JI recently is not sufficient because it only predicts 10-12 weeks of time without considering production factors. This research designs received date with load-oriented manufacturing control model where determining received date is based on calculating manufacturing lead time that considers the time needed to deliver orders to the consumer, capacity available for each work station, work station process time, and production flow within the production floor.  Validation results from the calculations for determining received date order is adjusted to PT JI  production system and is more valid than the first system. Keywords : make to order, received date, manufacturing leadtime, load-oriented manufacturing control

Severe manifestation of psoriasis in a HIV infected patient: a case report

Directory of Open Access Journals (Sweden)

Alper Gunduz

2015-12-01

Full Text Available The human immunodeficiency virus (HIV epidemic in Turkey reveals a slow progression and at the end of November 2015, the total official number was reported to be 11,109 cases. Approximately 90% of HIV patients develop some type of skin disease. Especially patients with psoriasis and HIV infection often present with more severe and treatment-refractory cutaneous disease. Herein, we describe a case of a patient with previously known psoriasis worsened by HIV infection. A 37-year-old housewife was admitted to our clinic with previously known psoriasis worsened during the last two years with conversion to erythrodermic psoriasis which was not controlled even by PUVA, methotrexate and systemic cyclosporine. The patient had positive HIV antibody test. HIV RNA viral load was 120.000 copy/ml and CD4 count 88/ mm3 . She also had oral candidiasis and Pneumocystis jirovecii pneumonia. The patient received antiretroviral treatment including tenofovir/emtricitabine and lopinavir/ritonavir. Symptoms resolved gradually within one month with almost complete impovement of her erythrodermic psoriasis. . Four years later the patient was still on tenofovir/emtricitabine and lopinavir/ritonavir without concomitant spesific psoriasis treatment. Psoriasis manifestations can be severe in AIDS patients. Clinicians face diagnostic and therapeutic difficulties when psoriasis coexists with HIV infection. The HIV test should be considered in patients affected by severe erythrodermic psoriasis and resistant to conventional and biological treatments. [Dis Mol Med 2015; 3(4.000: 43-45

Adherence to antiretroviral prophylaxis for HIV prevention: a substudy cohort within a clinical trial of serodiscordant couples in East Africa.

Directory of Open Access Journals (Sweden)

Jessica E Haberer

Full Text Available Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation.Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda, we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to 80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort.The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use. Please see later in the article for the Editors' Summary.

Femtosecond Photon-Counting Receiver

Science.gov (United States)

Krainak, Michael A.; Rambo, Timothy M.; Yang, Guangning; Lu, Wei; Numata, Kenji

2016-01-01

An optical correlation receiver is described that provides ultra-precise distance and/or time/pulse-width measurements even for weak (single photons) and short (femtosecond) optical signals. A new type of optical correlation receiver uses a fourth-order (intensity) interferometer to provide micron distance measurements even for weak (single photons) and short (femtosecond) optical signals. The optical correlator uses a low-noise-integrating detector that can resolve photon number. The correlation (range as a function of path delay) is calculated from the variance of the photon number of the difference of the optical signals on the two detectors. Our preliminary proof-of principle data (using a short-pulse diode laser transmitter) demonstrates tens of microns precision.

Delphi Accounts Receivable Module -

Data.gov (United States)

Department of Transportation — Delphi accounts receivable module contains the following data elements, but are not limited to customer information, cash receipts, line of accounting details, bill...

Global Positioning System receiver evaluation results

Energy Technology Data Exchange (ETDEWEB)

Byrne, R.H.

1993-09-01

A Sandia project currently uses an outdated Magnavox 6400 Global Positioning System (GPS) receiver as the core of its navigation system. The goal of this study was to analyze the performance of the current GPS receiver compared to newer, less expensive models and to make recommendations on how to improve the performance of the overall navigation system. This paper discusses the test methodology used to experimentally analyze the performance of different GPS receivers, the test results, and recommendations on how an upgrade should proceed. Appendices contain detailed information regarding the raw data, test hardware, and test software.

Receiver function estimated by maximum entropy deconvolution

Institute of Scientific and Technical Information of China (English)

吴庆举; 田小波; 张乃铃; 李卫平; 曾融生

2003-01-01

Maximum entropy deconvolution is presented to estimate receiver function, with the maximum entropy as the rule to determine auto-correlation and cross-correlation functions. The Toeplitz equation and Levinson algorithm are used to calculate the iterative formula of error-predicting filter, and receiver function is then estimated. During extrapolation, reflective coefficient is always less than 1, which keeps maximum entropy deconvolution stable. The maximum entropy of the data outside window increases the resolution of receiver function. Both synthetic and real seismograms show that maximum entropy deconvolution is an effective method to measure receiver function in time-domain.

Stability of heterodyne terahertz receivers

OpenAIRE

Kooi, J. W.; Baselmans, J. J. A.; Baryshev, A.; Schieder, R.; Hajenius, M.; Gao, J. R.; Klapwijk, T. M.; Voronov, B.; Gol'tsman, G.

2006-01-01

In this paper we discuss the stability of heterodyne terahertz receivers based on small volume NbN phonon cooled hot electron bolometers (HEBs). The stability of these receivers can be broken down in two parts: the intrinsic stability of the HEB mixer and the stability of the local oscillator (LO) signal injection scheme. Measurements show that the HEB mixer stability is limited by gain fluctuations with a 1/f spectral distribution. In a 60 MHz noise bandwidth this results in an Allan varian...

Receiving more than data - a signal model, theory and implementation of a cognitive IEEE 802.15.4 receiver

Directory of Open Access Journals (Sweden)

Tim Esemann

2016-09-01

Full Text Available Standard medium access schemes sense the channel immediately prior transmission, but are blind during the transmission. Therefore, standard transceivers have limited cognitive capabilities which are important for operation in heterogeneous radio environments. Specifically, mobile interferers move gradually into the reception range before actually causing collisions. These gradual interferences cannot yet be detected, and upcoming collisions cannot be predicted. We present a theoretical analysis of the received and demodulated signal. This analysis and the derived signal model verifies that the received signal contains more than transmitted data exclusively. Enhanced signal processing extracts signal components of an interference at the receiver and enables advanced interference detection to provide information about approaching mobile interferers. Our theoretical analysis is evaluated by simulations and experiments with an IEEE 802.15.4 transmitter and an extended cognitive receiver.

Concentrated solar power generation using solar receivers

Science.gov (United States)

Anderson, Bruce N.; Treece, William Dean; Brown, Dan; Bennhold, Florian; Hilgert, Christoph

2017-08-08

Inventive concentrated solar power systems using solar receivers, and related devices and methods, are generally described. Low pressure solar receivers are provided that function to convert solar radiation energy to thermal energy of a working fluid, e.g., a working fluid of a power generation or thermal storage system. In some embodiments, low pressure solar receivers are provided herein that are useful in conjunction with gas turbine based power generation systems.

RF subsystem design for microwave communication receivers

Science.gov (United States)

Bickford, W. J.; Brodsky, W. G.

A system review of the RF subsystems of (IFF) transponders, tropscatter receivers and SATCOM receivers is presented. The quantity potential for S-band and X-band IFF transponders establishes a baseline requirement. From this, the feasibility of a common design for these and other receivers is evaluated. Goals are established for a GaAs MMIC (monolithic microwave integrated circuit) device and related local oscillator preselector and self-test components.

Long-Term Heating to Improve Receiver Performance

Energy Technology Data Exchange (ETDEWEB)

Glatzmaier, Greg C.; Cable, Robert; Newmarker, Marc

2017-06-27

The buildup of hydrogen in the heat transfer fluid (HTF) that circulates through components of parabolic trough power plants decreases receiver thermal efficiency, and ultimately, it decreases plant performance and electricity output. The generation and occurrence of hydrogen in the HTF provides the driving force for hydrogen to permeate from the HTF through the absorber tube wall and into the receiver annulus. Getters adsorb hydrogen from the annulus volume until they saturate and are no longer able to maintain low hydrogen pressure. The increase in hydrogen pressure within the annulus significantly degrades thermal performance of the receiver and decreases overall power-plant efficiency. NREL and Acciona Energy North America (Acciona) are developing a method to control the levels of dissolved hydrogen in the circulating HTF. The basic approach is to remove hydrogen from the expansion tanks of the HTF subsystem at a rate that maintains hydrogen in the circulating HTF to a target level. Full-plant steady-state models developed by the National Renewable Energy Laboratory (NREL) predict that if hydrogen is removed from the HTF within the expansion tanks, the HTF that circulates through the collector field remains essentially free of hydrogen until the HTF returns to the power block in the hot headers. One of the key findings of our modeling is the prediction that hydrogen will reverse-permeate out of the receiver annulus if dissolved hydrogen in the HTF is kept sufficiently low. To test this prediction, we performed extended heating of an in-service receiver that initially had high levels of hydrogen in its annulus. The heating was performed using NREL's receiver test stand. Results of our testing showed that receiver heat loss steadily decreased with daily heating, resulting in a corresponding improvement in receiver thermal efficiency.

Heat receivers for solar dynamic space power systems

Science.gov (United States)

Perez-Davis, Marla Esther

A review of state-of-the-art technology is presented and discussed for phase change materials. Some of the advanced solar dynamic designs developed as part of the Advanced Heat Receiver Conceptual Design Study performed for LeRC are discussed. The heat receivers are analyzed and several recommendations are proposed, including two new concepts. The first concept evaluated the effect of tube geometries inside the heat receiver. It was found that a triangular configuration would provide better heat transfer to the working fluid, although not necessarily with a reduction in receiver size. A sensible heat receiver considered in this study uses vapor grown graphite fiber-carbon (VGCF/C) composite as the thermal storage media and was designed for a 7 kW Brayton engine. The proposed heat receiver stores the required energy to power the system during eclipse in the VGCF/C composite. The heat receiver analysis was conducted through the Systems Improved Numerical Differencing Analyzer and Fluid Integrator (SINDA) software package. The proposed heat receiver compares well with other latent and advanced sensible heat receivers while avoiding the problems associated with latent heat storage salts and liquid metal heat pipes. The weight and size of the system can be optimized by changes in geometry and technology advances for this new material. In addition to the new concepts, the effect of atomic oxygen on several materials is reviewed. A test was conducted for atomic oxygen attack on boron nitride, which experienced a negligible mass loss when exposed to an atomic oxygen fluence of 5 x 10 exp 21 atoms/sq cm. This material could be used to substitute the graphite aperture plate of the heat receiver.

Efavirenz, Emtricitabine, and Tenofovir

Science.gov (United States)

... HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex ... of hormonal contraceptives (birth control pills, patches, rings, implants, or ... (''buffalo hump''), breasts, and around your stomach. You may notice a ...

List of documents received by the INDC secretariat

International Nuclear Information System (INIS)

1986-04-01

The Nuclear Data Section of the International Atomic Energy Agency receives documents originated by or for the International Nuclear Data Committee for distribution. This list includes all INDC documents received and distributed by the INDC secretariat during the period January 1984 to March 1986. In addition to the INDC documents received by the INDC Secretariat for distribution, this document also lists the titles of reports received as single copies for information. These documents cannot be obtained from the INDC Secretariat, but should be requested from the originating laboratory or organization. All of the single copy documents, which have been received between January 1984 and March 1986 are listed in Appendix A to this document

Efficient receiver tuning using differential evolution strategies

Science.gov (United States)

Wheeler, Caleb H.; Toland, Trevor G.

2016-08-01

Differential evolution (DE) is a powerful and computationally inexpensive optimization strategy that can be used to search an entire parameter space or to converge quickly on a solution. The Kilopixel Array Pathfinder Project (KAPPa) is a heterodyne receiver system delivering 5 GHz of instantaneous bandwidth in the tuning range of 645-695 GHz. The fully automated KAPPa receiver test system finds optimal receiver tuning using performance feedback and DE. We present an adaptation of DE for use in rapid receiver characterization. The KAPPa DE algorithm is written in Python 2.7 and is fully integrated with the KAPPa instrument control, data processing, and visualization code. KAPPa develops the technologies needed to realize heterodyne focal plane arrays containing 1000 pixels. Finding optimal receiver tuning by investigating large parameter spaces is one of many challenges facing the characterization phase of KAPPa. This is a difficult task via by-hand techniques. Characterizing or tuning in an automated fashion without need for human intervention is desirable for future large scale arrays. While many optimization strategies exist, DE is ideal for time and performance constraints because it can be set to converge to a solution rapidly with minimal computational overhead. We discuss how DE is utilized in the KAPPa system and discuss its performance and look toward the future of 1000 pixel array receivers and consider how the KAPPa DE system might be applied.

Precision Continuum Receivers for Astrophysical Applications

Science.gov (United States)

Wollack, Edward J.

2011-01-01

Cryogenically cooled HEMT (High Electron Mobility Transistor) amplifiers find widespread use in radioastronomy receivers. In recent years, these devices have also been commonly employed in broadband receivers for precision measurements of the Cosmic Microwave Background (CMB) radiation. In this setting, the combination of ultra-low-noise and low-spectral-resolution observations reinforce the importance achieving suitable control over the device environment to achieve fundamentally limited receiver performance. The influence of the intrinsic amplifier stability at low frequencies on data quality (e.g., achievable noise and residual temporal correlations), observational and calibration strategies, as well as architectural mitigation approaches in this setting will be discussed. The implications of device level 1/f fluctuations reported in the literature on system performance will be reviewed.

THE CORRELATED TRACK RECEIVER OF TONE TRACK CIRCUITS

Directory of Open Access Journals (Sweden)

K. V. Goncharov

2011-05-01

Full Text Available The work is devoted to further improvement of processing algorithm of checking signals of rail line. The simulation modeling of correlation track receiver of tone rail circuits has been executed; the benchmark analysis of correlation receiver and direct amplifier receiver has been executed.

Receiver subsystem analysis report (RADL Item 4-1). The 10-MWe solar thermal central-receiver pilot plant: Solar-facilities design integration

Science.gov (United States)

1982-04-01

The results of thermal hydraulic, design for the stress analyses which are required to demonstrate that the receiver design for the Barstow Solar Pilot Plant satisfies the general design and performance requirements during the plant's design life are presented. Recommendations are made for receiver operation. The analyses are limited to receiver subsystem major structural parts (primary tower, receiver unit core support structure), pressure parts (absorber panels, feedwater, condensate and steam piping/components, flash tank, and steam mainfold) and shielding.

Wake-up receiver based ultra-low-power WBAN

CERN Document Server

Lont, Maarten; Roermund, Arthur van

2014-01-01

This book presents the cross-layer design and optimization of wake-up receivers for wireless body area networks (WBAN), with an emphasis on low-power circuit design. This includes the analysis of medium access control (MAC) protocols, mixer-first receiver design, and implications of receiver impairments on wideband frequency-shift-keying (FSK) receivers. Readers will learn how the overall power consumption is reduced by exploiting the characteristics of body area networks. Theoretical models presented are validated with two different receiver implementations, in 90nm and 40nm CMOS technology.   • Provides an overview of wireless body area network design from the network layer to the circuit implementation, and an overview of the cross-layer design trade-offs; • Discusses design at both the network or MAC-layer and circuit-level, with an emphasis on circuit design; • Covers the design of low-power frequency shift keying (FSK) wake-up-receivers; • Validates theory presented with two different recei...

Communications/Electronics Receiver Performance Degradation Handbook (Second Edition)

Science.gov (United States)

1975-08-01

receiver to another in the Rf and IF filter characteristics modify the transfer of inter- forence power through the receiver to the IF output, and so the...modulation system the transmitted and received messages arce in general different bemaus* of small inte, forence or noise perturbations. The probability of

FFT analysis of sensible-heat solar-dynamic receivers

Science.gov (United States)

Lund, Kurt O.

The use of solar dynamic receivers with sensible energy storage in single-phase materials is considered. The feasibility of single-phase designs with weight and thermal performance comparable to existing two-phase designs is addressed. Linearized heat transfer equations are formulated for the receiver heat storage, representing the periodic input solar flux as the sum of steady and oscillating distributions. The steady component is solved analytically to produce the desired receiver steady outlet gas temperature, and the FFT algorithm is applied to the oscillating components to obtain the amplitudes and mode shapes of the oscillating solid and gas temperatures. The results indicate that sensible-heat receiver designs with performance comparable to state-of-the-art two-phase receivers are available.

Spread Spectrum Receiver Electromagnetic Interference (EMI) Test Guide

Science.gov (United States)

Wheeler, M. L.

1998-01-01

The objective of this test guide is to document appropriate unit level test methods and techniques for the performance of EMI testing of Direct Sequence (DS) spread spectrum receivers. Consideration of EMI test methods tailored for spread spectrum receivers utilizing frequency spreading, techniques other than direct sequence (such as frequency hopping, frequency chirping, and various hybrid methods) is beyond the scope of this test guide development program and is not addressed as part of this document EMI test requirements for NASA programs are primarily developed based on the requirements contained in MIL-STD-46 1 D (or earlier revisions of MIL-STD-46 1). The corresponding test method guidelines for the MIL-STD-461 D tests are provided in MIL-STD-462D. These test methods are well documented with the exception of the receiver antenna port susceptibility tests (intermodulation, cross modulation, and rejection of undesired signals) which must be tailored to the specific type of receiver that is being tested. Thus, test methods addressed in this guide consist only of antenna port tests designed to evaluate receiver susceptibility characteristics. MIL-STD-462D should be referred for guidance pertaining to test methods for EMI tests other than the antenna port tests. The scope of this test guide includes: (1) a discussion of generic DS receiver performance characteristics; (2) a summary of S-band TDRSS receiver operation; (3) a discussion of DS receiver EMI susceptibility mechanisms and characteristics; (4) a summary of military standard test guidelines; (5) recommended test approach and methods; and (6) general conclusions and recommendations for future studies in the area of spread spectrum receiver testing.

Flexible receiver adapter formal design review

International Nuclear Information System (INIS)

Krieg, S.A.

1995-01-01

This memo summarizes the results of the Formal (90%) Design Review process and meetings held to evaluate the design of the Flexible Receiver Adapters, support platforms, and associated equipment. The equipment is part of the Flexible Receiver System used to remove, transport, and store long length contaminated equipment and components from both the double and single-shell underground storage tanks at the 200 area tank farms

The Vaginal Microbiome and its Potential to Impact Efficacy of HIV Pre-exposure Prophylaxis for Women.

Science.gov (United States)

Velloza, Jennifer; Heffron, Renee

2017-10-01

This review describes existing evidence addressing the potential modulation of pre-exposure prophylaxis (PrEP) products, specifically 1% tenofovir (TFV) gel and oral tenofovir-based PrEP, by vaginal dysbiosis and discusses future considerations for delivering novel, long-acting PrEP products to women at high risk for vaginal dysbiosis and HIV. We describe results from analyses investigating the modification of PrEP efficacy by vaginal dysbiosis and studies of biological mechanisms that could render PrEP ineffective in the presence of specific microbiota. A secondary analysis from the CAPRISA-004 cohort demonstrated that there is no effect of the 1% TFV gel in the presence of non-Lactobacillus dominant microbiota. Another recent analysis comparing oral tenofovir-based PrEP efficacy among women with and without bacterial vaginosis in the Partners PrEP Study found that oral PrEP efficacy is not modified by bacterial vaginosis. Gardnerella vaginalis, commonly present in women with vaginal dysbiosis, can rapidly metabolize TFV particularly when it is locally applied and thereby prevent TFV integration into cells. Given that vaginal dysbiosis appears to modulate efficacy for 1% TFV gel but not for oral tenofovir-based PrEP, vaginal dysbiosis is potentially less consequential to HIV protection from TFV in the context of systemic drug delivery and high product adherence. Vaginal dysbiosis may undermine the efficacy of 1% TFV gel to protect women from HIV but not the efficacy of oral PrEP. Ongoing development of novel ring, injectable, and film-based PrEP products should investigate whether vaginal dysbiosis can reduce efficacy of these products, even in the presence of high adherence.

[Pulmonary hypertension in human immunodeficiency virus-infected patients: the role of antiretroviral therapy].

Science.gov (United States)

Olalla, Julián; Urdiales, Daniel; Pombo, Marta; del Arco, Alfonso; de la Torre, Javier; Prada, José Luis

2014-03-20

Pulmonary arterial hypertension (PAH) is a serious disorder, more prevalent in patients infected with human immunodeficiency virus (HIV). It is not entirely clear what role is played by highly active antiretroviral therapy (HAART) in PAH development or course. Our aim was to describe PAH prevalence in a series of HIV-infected patients and identify possible links with cumulative and current use of different antiretrovirals. Cross-sectional study of a cohort of HIV-infected patients attending a hospital in southern Spain. Demographic data, data on HIV infection status and on cumulative and recent antiretroviral treatment were recorded. Transthoracic echocardiography was performed in all study participants. PAH was defined as pulmonary artery systolic pressure of 36mmHg or more. A total of 400 patients participated in the study; 178 presented with tricuspid regurgitation and 22 of these presented with PAH (5.5%). No differences were encountered in age, sex, CD4 lymphocytes, proportion of naive patients or patients with AIDS. No differences were encountered in cumulative use of antiretrovirals. However, recent use of lamivudine was associated with a greater presence of PAH, whereas recent use of tenofovir and emtricitabine was associated with a lower presence of PAH. Logistic regression analysis was performed including the use of lamivudine, emtricitabine and tenofovir. Only recent use of tenofovir was associated with a lower presence of PAH (odds ratio 0.31; 95% confidence interval: 0.17-0.84). PAH prevalence in our study was similar to others series. Current use of tenofovir may be associated with lower PAH prevalence. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Analysis of signal acquisition in GPS receiver software

Directory of Open Access Journals (Sweden)

Vlada S. Sokolović

2011-01-01

Full Text Available This paper presents a critical analysis of the flow signal processing carried out in GPS receiver software, which served as a basis for a critical comparison of different signal processing architectures within the GPS receiver. It is possible to achieve Increased flexibility and reduction of GPS device commercial costs, including those of mobile devices, by using radio technology software (SDR, Software Defined Radio. The SDR application can be realized when certain hardware components in a GPS receiver are replaced. Signal processing in the SDR is implemented using a programmable DSP (Digital Signal Processing or FPGA (Field Programmable Gate Array circuit, which allows a simple change of digital signal processing algorithms and a simple change of the receiver parameters. The starting point of the research is the signal generated on the satellite the structure of which is shown in the paper. Based on the GPS signal structure, a receiver is realized with a task to extract an appropriate signal from the spectrum and detect it. Based on collected navigation data, the receiver calculates the position of the end user. The signal coming from the satellite may be at the carrier frequencies of L1 and L2. Since the SPS is used in the civil service, all the tests shown in the work were performed on the L1 signal. The signal coming to the receiver is generated in the spread spectrum technology and is situated below the level of noise. Such signals often interfere with signals from the environment which presents a difficulty for a receiver to perform proper detection and signal processing. Therefore, signal processing technology is continually being improved, aiming at more accurate and faster signal processing. All tests were carried out on a signal acquired from the satellite using the SE4110 input circuit used for filtering, amplification and signal selection. The samples of the received signal were forwarded to a computer for data post processing, i. e

Low Complexity Receiver Design for MIMO-Radar

KAUST Repository

Ahmed, Sajid

2012-09-08

In this work, an algorithm for the multiple-input multiple-output (MIMO) radar is proposed. It has low computational complexity compared to the available schemes, and relatively low side-lobe-levels in the receive beampattern compared to the phased-array and MIMO-radar. In the proposed algorithm, the received signal vector of MIMO-radar is divided into sub-vectors, and each sub-vector is multiplied with the corresponding weight vector. The number of sub-vectors and weight vectors are optimally found to maximise the received signal power from the target of interest direction. The proposed scheme can be effectively applied in passive radars to minimise the side-lobe levels and place deep nulls for interferers in the receive beampattern. Simulation results show that the proposed scheme has relatively lower side lobe levels and better detection capabilities compared to MIMO-radar and phased-array.

Low Complexity Receiver Design for MIMO-Radar

KAUST Repository

Ahmed, Sajid; Alouini, Mohamed-Slim

2012-01-01

In this work, an algorithm for the multiple-input multiple-output (MIMO) radar is proposed. It has low computational complexity compared to the available schemes, and relatively low side-lobe-levels in the receive beampattern compared to the phased-array and MIMO-radar. In the proposed algorithm, the received signal vector of MIMO-radar is divided into sub-vectors, and each sub-vector is multiplied with the corresponding weight vector. The number of sub-vectors and weight vectors are optimally found to maximise the received signal power from the target of interest direction. The proposed scheme can be effectively applied in passive radars to minimise the side-lobe levels and place deep nulls for interferers in the receive beampattern. Simulation results show that the proposed scheme has relatively lower side lobe levels and better detection capabilities compared to MIMO-radar and phased-array.

Scintillation-Hardened GPS Receiver

Science.gov (United States)

Stephens, Donald R.

2015-01-01

CommLargo, Inc., has developed a scintillation-hardened Global Positioning System (GPS) receiver that improves reliability for low-orbit missions and complies with NASA's Space Telecommunications Radio System (STRS) architecture standards. A software-defined radio (SDR) implementation allows a single hardware element to function as either a conventional radio or as a GPS receiver, providing backup and redundancy for platforms such as the International Space Station (ISS) and high-value remote sensing platforms. The innovation's flexible SDR implementation reduces cost, weight, and power requirements. Scintillation hardening improves mission reliability and variability. In Phase I, CommLargo refactored an open-source GPS software package with Kalman filter-based tracking loops to improve performance during scintillation and also demonstrated improved navigation during a geomagnetic storm. In Phase II, the company generated a new field-programmable gate array (FPGA)-based GPS waveform to demonstrate on NASA's Space Communication and Navigation (SCaN) test bed.

GPU Acceleration of DSP for Communication Receivers.

Science.gov (United States)

Gunther, Jake; Gunther, Hyrum; Moon, Todd

2017-09-01

Graphics processing unit (GPU) implementations of signal processing algorithms can outperform CPU-based implementations. This paper describes the GPU implementation of several algorithms encountered in a wide range of high-data rate communication receivers including filters, multirate filters, numerically controlled oscillators, and multi-stage digital down converters. These structures are tested by processing the 20 MHz wide FM radio band (88-108 MHz). Two receiver structures are explored: a single channel receiver and a filter bank channelizer. Both run in real time on NVIDIA GeForce GTX 1080 graphics card.

On the impact of receiver imperfections on the MMSE-IRC receiver performance in 5G networks

DEFF Research Database (Denmark)

Tavares, Fernando Menezes Leitão; Berardinelli, Gilberto; Mahmood, Nurul Huda

2014-01-01

The usage of Minimum Mean Square Error - Interference Rejection Combining (MMSE-IRC) receivers is expected to be a significant performance booster in the ultra-dense deployment of small cells envisioned by an upcoming 5th generation (5G) Radio Access Technology (RAT). However, hardware limitation...... simulation results confirm that a realistic MMSE-IRC receiver can achieve throughput gains close to ideal, provided a reasonably high resolution Analog-to-Digital Converter (ADC) as well as a supportive radio frame format design are used....

Shipping/Receiving and Quality Control

Data.gov (United States)

Federal Laboratory Consortium — Shipping receiving, quality control, large and precise inspection and CMM machines. Coordinate Measuring Machines, including "scanning" probes, optical comparators,...

Ways to rational management of accounts receivable at enterprises

Directory of Open Access Journals (Sweden)

Yevtushenko N. O.

2015-05-01

Full Text Available This article investigated the principal reasons of management problems an account receivable of enterprises. Credit politics of management is worked out by an account receivable of enterprises. Essence of the stages of construction of rational management an account receivable of enterprises is exposed. In the article are exposed the basic elements of control system for an account receivable such as mission, aims, strategy as politics of management. The basic stages of management politics are described for an account receivable of enterprises: analysis; organization of forming of principles of credit politics, terms of delivery of credit and procedure of collection of accounts receivable; planning of the use of modern forms of refunding, and similarly control.

37 CFR 1.412 - The United States Receiving Office.

Science.gov (United States)

2010-07-01

... Information § 1.412 The United States Receiving Office. (a) The United States Patent and Trademark Office is a Receiving Office only for applicants who are residents or nationals of the United States of America. (b) The... “United States Receiving Office” or by the abbreviation “RO/US.” (c) The major functions of the Receiving...

IMPROVEMENT WAYS OF ACCOUNTING AND INTERNAL AUDIT OF ENTERPRISE RECEIVABLES

Directory of Open Access Journals (Sweden)

V. D. Zelikman

2014-06-01

Full Text Available Purpose. Determination and substantiation of ways to improve accounting and internal audit of receivables at the enterprises. Methodology.The basic principles and ways for improvement of accounting and internal audit systems that should help Ukrainian enterprises to optimize receivables are considered. Findings. It is proved that the receivables optimization is possible on the basis of improving its accounting and internal audit. The basic ways for improvement of accounting and internal audit of receivable are determined. They are: improvement of normative coverage of receivables at the enterprises; providing further harmonization of financial and tax accounting in the part of formation of the doubtful debt receivables, accounting of bad and doubtful receivables and etc. The formation of department for internal audit to control the doubtful and bad debts; providing the timely control of the receivables and payables ratio; determination and support of the optimal value of the receivables at the enterprises. Originality. Improvement of accounting and internal audit of receivables at the enterprises by the way of development of internal audit system and optimization of the receivables size. Practical value. The proposed recommendations will improve the accounting and internal audit system of receivables at the enterprises of Ukraine.

Phase Noise Tolerant QPSK Receiver Using Phase Sensitive Wavelength Conversion

DEFF Research Database (Denmark)

Da Ros, Francesco; Xu, Jing; Lei, Lei

2013-01-01

A novel QPSK receiver based on a phase noise reduction pre-stage exploiting PSA in a HNLF and balanced detection is presented. Receiver sensitivity improvement over a conventional balanced receiver is demonstrated.......A novel QPSK receiver based on a phase noise reduction pre-stage exploiting PSA in a HNLF and balanced detection is presented. Receiver sensitivity improvement over a conventional balanced receiver is demonstrated....

Conceptual design of advanced central receiver power systems sodium-cooled receiver concept. Volume 2, Book 2. Appendices. Final report

Energy Technology Data Exchange (ETDEWEB)

1979-03-01

The appendices include: (A) design data sheets and P and I drawing for 100-MWe commercial plant design, for all-sodium storage concept; (B) design data sheets and P and I drawing for 100-MWe commercial plant design, for air-rock bed storage concept; (C) electric power generating water-steam system P and I drawing and equipment list, 100-MWe commercial plant design; (D) design data sheets and P and I drawing for 281-MWe commercial plant design; (E) steam generator system conceptual design; (F) heat losses from solar receiver surface; (G) heat transfer and pressure drop for rock bed thermal storage; (H) a comparison of alternative ways of recovering the hydraulic head from the advanced solar receiver tower; (I) central receiver tower study; (J) a comparison of mechanical and electromagnetic sodium pumps; (K) pipe routing study of sodium downcomer; and (L) sodium-cooled advanced central receiver system simulation model. (WHK)

Campus Projects Receiving "Earmarks."

Science.gov (United States)

Schonberger, Benjamin

1991-01-01

Specific campus projects that Congress has directed federal agencies to support this year at over 120 colleges and universities are listed. The agencies neither requested support nor sponsored merit-based competitions for the awards. In some cases, the institutions have a history of receiving special federal treatment. (MSE)

List of documents received by the INDC Secretariat

International Nuclear Information System (INIS)

1984-08-01

The Nuclear Data Section of the International Atomic Energy Agency receives documents originated by or for the International Nuclear Data Committee for distribution. The present list includes all INDC documents received and distributed by the INDC secretariat during the period January 1982 to June 1984, and supersedes last years' edition of this report, INDC(SEC)-85/UN. This list is produced directly from computer printout in two sorts: one ordered by accession number, and the other ordered by document number within each origin series (e.g. listing all INDC(SEC)-documents in one block). In addition to the INDC documents received by the INDC Secretariat for distribution, this document also lists the titles of reports received as single copies for information. All of the single copy documents which have been received between June 1983 and July 1984 are listed in Appendix A to this document

Anatomy of a digital coherent receiver

DEFF Research Database (Denmark)

Borkowski, Robert; Zibar, Darko; Tafur Monroy, Idelfonso

2014-01-01

, orthonormaliation, chromatic dispersion compensation/nonlinear compensation, resampling a nd timing recovery, polarization demultiplexing and equalization, frequency and phase recovery, digital demodulation. We also describe novel subsystems of a digital coherent receiver: modulation format recognition......Digital coherent receivers have gained significant attention in the last decade. The reason for this is that coherent detection, along with digital signal processing (DSP) allows for substantial increase of the channel capacity by employing advanced detection techniques. In this paper, we first...

List of documents received by the INDC Secretariat

International Nuclear Information System (INIS)

1987-09-01

The Nuclear Data Section of the International Atomic Energy Agency receives documents originated by or for the International Nuclear Data Committee for distribution. This list includes all INDC documents received and distributed by the INDC Secretariat during the period January 1984 to March 1986. This list is produced directly from computer printout in two sorts: one ordered by accession number, and the other ordered by document number within each origin series (e.g. listing all INDC(SEC)-documents in one block). In addition to the INDC documents received by the INDC Secretariat for distribution, this document also lists the titles of reports received as single copies for information

Design of simplified maximum-likelihood receivers for multiuser CPM systems.

Science.gov (United States)

Bing, Li; Bai, Baoming

2014-01-01

A class of simplified maximum-likelihood receivers designed for continuous phase modulation based multiuser systems is proposed. The presented receiver is built upon a front end employing mismatched filters and a maximum-likelihood detector defined in a low-dimensional signal space. The performance of the proposed receivers is analyzed and compared to some existing receivers. Some schemes are designed to implement the proposed receivers and to reveal the roles of different system parameters. Analysis and numerical results show that the proposed receivers can approach the optimum multiuser receivers with significantly (even exponentially in some cases) reduced complexity and marginal performance degradation.

Reduced quantitative ultrasound bone mineral density in HIV-infected patients on antiretroviral therapy in Senegal.

Directory of Open Access Journals (Sweden)

Amandine Cournil

Full Text Available BACKGROUND: Bone status in HIV-infected patients on antiretroviral treatment (ART is poorly documented in resource-limited settings. We compared bone mineral density between HIV-infected patients and control subjects from Dakar, Senegal. METHODS: A total of 207 (134 women and 73 men HIV-infected patients from an observational cohort in Dakar (ANRS 1215 and 207 age- and sex-matched controls from the general population were enrolled. Bone mineral density was assessed by quantitative ultrasound (QUS at the calcaneus, an alternative to the reference method (i.e. dual X-absorptiometry, often not available in resource-limited countries. RESULTS: Mean age was 47.0 (±8.5 years. Patients had received ART for a median duration of 8.8 years; 45% received a protease inhibitor and 27% tenofovir; 84% had undetectable viral load. Patients had lower body mass index (BMI than controls (23 versus 26 kg/m(2, P<0.001. In unadjusted analysis, QUS bone mineral density was lower in HIV-infected patients than in controls (difference: -0.36 standard deviation, 95% confidence interval (CI: -0.59;-0.12, P = 0.003. Adjusting for BMI, physical activity, smoking and calcium intake attenuated the difference (-0.27, CI: -0.53;-0.002, P = 0.05. Differences in BMI between patients and controls explained a third of the difference in QUS bone mineral density. Among patients, BMI was independently associated with QUS bone mineral density (P<0.001. An association between undetectable viral load and QUS bone density was also suggested (β = 0.48, CI: 0.02;0.93; P = 0.04. No association between protease inhibitor or tenofovir use and QUS bone mineral density was found. CONCLUSION: Senegalese HIV-infected patients had reduced QUS bone mineral density in comparison with control subjects, in part related to their lower BMI. Further investigation is needed to clarify the clinical significance of these observations.

Exploiting Redundancy in an OFDM SDR Receiver

Directory of Open Access Journals (Sweden)

Tomas Palenik

2009-01-01

Full Text Available Common OFDM system contains redundancy necessary to mitigate interblock interference and allows computationally effective single-tap frequency domain equalization in receiver. Assuming the system implements an outer error correcting code and channel state information is available in the receiver, we show that it is possible to understand the cyclic prefix insertion as a weak inner ECC encoding and exploit the introduced redundancy to slightly improve error performance of such a system. In this paper, an easy way to implement modification to an existing SDR OFDM receiver is presented. This modification enables the utilization of prefix redundancy, while preserving full compatibility with existing OFDM-based communication standards.

Improved noise-adding radiometer for microwave receivers

Science.gov (United States)

Batelaan, P. D.; Stelzried, C. T.; Goldstein, R. M.

1973-01-01

Use of input switch and noise reference standard is avoided by using noise-adding technique. Excess noise from solid state noise-diode is coupled into receiver through directional coupler and square-wave modulated at low rate. High sensitivity receivers for radioastronomy applications are utilized with greater confidence in stability of radiometer.

MR-based conductivity imaging using multiple receiver coils.

Science.gov (United States)

Lee, Joonsung; Shin, Jaewook; Kim, Dong-Hyun

2016-08-01

To propose a signal combination method for MR-based tissue conductivity mapping using a standard clinical scanner with multiple receiver coils. The theory of the proposed method is presented with two practical approaches, a coil-specific approach and a subject-specific approach. Conductivity maps were reconstructed using the transceive phase of the combined signal. The sensitivities of the coefficients used for signal combination were analyzed and the method was compared with other signal combination methods. For validation, multiple receiver brain coils and multiple receiver breast coils were used in phantom, in vivo brain, and in vivo breast studies. The variation among the conductivity estimates was conductivity estimates. MR-based tissue conductivity mapping is feasible when using a standard clinical MR scanner with multiple receiver coils. The proposed method reduces systematic errors in phase-based conductivity mapping that can occur due to the inhomogeneous magnitude of the combined receive profile. Magn Reson Med 76:530-539, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Ultrabroadband Phased-Array Receivers Based on Optical Techniques

Science.gov (United States)

2016-02-26

bandwidths, and with it receiver noise floors , are unavoidable. Figure 1. SNR of a thermally limited receiver based on Friis equation showing the...techniques for RF and photonic integration based on liquid crystal polymer substrates were pursued that would aid in the realization of potential imaging...These models assumed that sufficient LNA gain was used on the antenna to set the noise floor of the imaging receiver, which necessitated physical

Is There a Need for Viral Load Testing to Assess Treatment Failure in HIV-Infected Patients Who Are about to Change to Tenofovir-Based First-Line Antiretroviral Therapy? Programmatic Findings from Myanmar.

Science.gov (United States)

Thiha, Nay; Chinnakali, Palanivel; Harries, Anthony D; Shwe, Myint; Balathandan, Thanumalaya Perumal; Thein Than Tun, Sai; Das, Mrinalini; Tin, Htay Htay; Yi, Yi; Babin, François Xavier; Lwin, Thi Thi; Clevenbergh, Philippe Albert

2016-01-01

WHO recommends that stavudine is phased out of antiretroviral therapy (ART) programmes and replaced with tenofovir (TDF) for first-line treatment. In this context, the Integrated HIV Care Program, Myanmar, evaluated patients for ART failure using HIV RNA viral load (VL) before making the change. We aimed to determine prevalence and determinants of ART failure in those on first-line treatment. Patients retained on stavudine-based or zidovudine-based ART for >12 months with no clinical/immunological evidence of failure were offered VL testing from August 2012. Plasma samples were tested using real time PCR. Those with detectable VL>250 copies/ml on the first test were provided with adherence counseling and three months later a second test was performed with >1000 copies/ml indicating ART failure. We calculated the prevalence of ART failure and adjusted relative risks (aRR) to identify associated factors using log binomial regression. Of 4934 patients tested, 4324 (87%) had an undetectable VL at the first test while 610 patients had a VL>250 copies/ml. Of these, 502 had a second VL test, of whom 321 had undetectable VL and 181 had >1000 copies/ml signifying ART failure. There were 108 who failed to have the second test. Altogether, there were 94% with an undetectable VL, 4% with ART failure and 2% who did not follow the VL testing algorithm. Risk factors for ART failure were age 15-24 years (aRR 2.4, 95% CI: 1.5-3.8) compared to 25-44 years and previous ART in the private sector (aRR 1.6, 95% CI: 1.2-2.2) compared to the public sector. This strategy of evaluating patients on first-line ART before changing to TDF was feasible and identified a small proportion with ART failure, and could be considered by HIV/AIDS programs in Myanmar and other countries.

Design of Simplified Maximum-Likelihood Receivers for Multiuser CPM Systems

Directory of Open Access Journals (Sweden)

Li Bing

2014-01-01

Full Text Available A class of simplified maximum-likelihood receivers designed for continuous phase modulation based multiuser systems is proposed. The presented receiver is built upon a front end employing mismatched filters and a maximum-likelihood detector defined in a low-dimensional signal space. The performance of the proposed receivers is analyzed and compared to some existing receivers. Some schemes are designed to implement the proposed receivers and to reveal the roles of different system parameters. Analysis and numerical results show that the proposed receivers can approach the optimum multiuser receivers with significantly (even exponentially in some cases reduced complexity and marginal performance degradation.

Russian institute receives CMS Gold Award

CERN Multimedia

Patrice Loïez

2003-01-01

The Snezhinsk All-Russian Institute of Scientific Research for Technical Physics (VNIITF) of the Russian Federal Nuclear Centre (RFNC) is one of twelve CMS suppliers to receive awards for outstanding performance this year. The CMS Collaboration took the opportunity of the visit to CERN of the Director of VNIITF and his deputy to present the CMS Gold Award, which the institute has received for its exceptional performance in the assembly of steel plates for the CMS forward hadronic calorimeter. This calorimeter consists of two sets of 18 wedge-shaped modules arranged concentrically around the beam-pipe at each end of the CMS detector. Each module consists of steel absorber plates with quartz fibres inserted into them. The institute developed a special welding technique to assemble the absorber plates, enabling a high-quality detector to be produced at relatively low cost.RFNC-VNIITF Director Professor Georgy Rykovanov (right), is seen here receiving the Gold Award from Felicitas Pauss, Vice-Chairman of the CMS ...

Towards Self-Clocked Gated OCDMA Receiver

Science.gov (United States)

Idris, S.; Osadola, T.; Glesk, I.

2013-02-01

A novel incoherent OCDMA receiver with incorporated all-optical clock recovery for self-synchronization of a time gate for the multi access interferences (MAI) suppression and minimizing the effect of data time jitter in incoherent OCDMA system was successfully developed and demonstrated. The solution was implemented and tested in a multiuser environment in an out of the laboratory OCDMA testbed with two-dimensional wavelength-hopping time-spreading coding scheme and OC-48 (2.5 Gbp/s) data rate. The self-clocked all-optical time gate uses SOA-based fibre ring laser optical clock, recovered all-optically from the received OCDMA traffic to control its switching window for cleaning the autocorrelation peak from the surrounding MAI. A wider eye opening was achieved when the all-optically recovered clock from received data was used for synchronization if compared to a static approach with the RF clock being generated by a RF synthesizer. Clean eye diagram was also achieved when recovered clock is used to drive time gating.

Development, validation and clinical application of a method for the simultaneous quantification of lamivudine, emtricitabine and tenofovir in dried blood and dried breast milk spots using LC-MS/MS.

Science.gov (United States)

Waitt, Catriona; Diliiy Penchala, Sujan; Olagunju, Adeniyi; Amara, Alieu; Else, Laura; Lamorde, Mohammed; Khoo, Saye

2017-08-15

To present the validation and clinical application of a LC-MS/MS method for the quantification of lamivudine (3TC), emtricitabine (FTC) and tenofovir (TFV) in dried blood spots (DBS) and dried breast milk spots (DBMS). DBS and DBMS were prepared from 50 and 30μL of drug-spiked whole blood and human breast milk, respectively. Following extraction with acetonitrile and water, chromatographic separation utilised a Synergi polar column with a gradient mobile phase program consisting of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Detection and quantification was performed using a TSQ Quantum Ultra triple quadrupole mass spectrometer. The analytical method was used to evaluate NRTI drug levels in HIV-positive nursing mothers-infant pairs. The assay was validated over the concentration range of 16.6-5000ng/mL for 3TC, FTC and TFV in DBS and DBMS except for TFV in DBMS where linearity was established from 4.2-1250ng/mL. Intra and inter-day precision (%CV) ranged from 3.5-8.7 and accuracy was within 15% for all analytes in both matrices. The mean recovery in DBS was >61% and in DBMS >43% for all three analytes. Matrix effect was insignificant. Median AUC 0-8 values in maternal DBS and DBMS, respectively, were 4683 (4165-6057) and 6050 (5217-6417)ngh/mL for 3TC, 3312 (2259-4312) and 4853 (4124-6691)ngh/mL for FTC and 1559 (930-1915) and 56 (45-80)ngh/mL for TFV. 3TC and FTC were quantifiable (>16.6ng/mL) in DBS from 2/6 and 1/6 infants respectively whereas TFV was undetectable in all infants. DBS and DBMS sampling for bioanalysis of 3TC, FTC and TFV is straightforward, robust, accurate and precise, and ideal for use in low-resource settings. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

47 CFR 32.1170 - Receivables.

Science.gov (United States)

2010-10-01

... FOR TELECOMMUNICATIONS COMPANIES Instructions for Balance Sheet Accounts § 32.1170 Receivables. (a... of interest accrued to the date of the balance sheet on bonds, notes, and other commercial paper...

Wide-band coherent receiver development for enhanced surveillance

International Nuclear Information System (INIS)

Simpson, M.L.; Richards, R.K.; Hutchinson, D.P.

1998-03-01

Oak Ridge National Laboratory (ORNL) has been developing advanced coherent IR heterodyne receivers for plasma diagnostics in fusion reactors for over 20 years. Recent progress in wide band IR detectors and high speed electronics has significantly enhanced the measurement capabilities of coherent receivers. In addition, developments in new HgCdTe and quantum well IR photodetector (QWIP) focal plane arrays are providing the possibility of both active and passive coherent imaging. In this paper the authors discuss the implications of these new enabling technologies to the IR remote sensing community for enhanced surveillance. Coherent receivers, as opposed to direct or thermal detection, provide multiple dimensions of information about a scene or target in a single detector system. Combinations of range, velocity, temperature, and chemical species information are all available from a coherent heterodyne receiver. They present laboratory data showing measured noise equivalent power (NEP) of new QWIP detectors with heterodyne bandwidths greater than 7 GHz. For absorption measurements, a wide band coherent receiver provides the capability of looking between CO 2 lines at off-resonance peaks and thus the measurement of lines normally inaccessible with conventional heterodyne or direct detection systems. Also described are differential absorption lidar (DIAL) and Doppler laboratory measurements using an 8 x 8 HgCdTe focal plane array demonstrating the snapshot capability of coherent receiver detector arrays for enhanced chemical plume and moving hardbody capture. Finally they discuss a variety of coherent receiver configurations that can suppress (or enhance) sensitivity of present active remote sensing systems to speckle, glint, and other measurement anomalies

Antivirais incorporados no Brasil para hepatite B cronica: analise de custo-efetividade

Directory of Open Access Journals (Sweden)

Gustavo Laine Araujo de Oliveira

2013-08-01

Full Text Available OBJETIVO Avaliar o custo-efetividade de diferentes tratamentos medicamentosos para hepatite B crônica entre pacientes adultos. MÉTODOS Utilizando modelo de Markov, construiu-se coorte hipotética de 40 anos para pacientes HBeAg-positivo ou HBeAg-negativo. Foram comparados os usos de adefovir, entecavir, tenofovir e lamivudina (com terapia de resgate em caso de resistência viral para tratamento de pacientes adultos com hepatite B crônica, virgens de tratamento, com elevados níveis de alanina aminotransferase, sem evidência de cirrose e sem coinfecção por HIV. Valores para custo e efeito foram obtidos da literatura. A medida do efeito foi expressa em anos de vida ganhos (AVG. Taxa de desconto de 5% foi aplicada. Análise de sensibilidade univariada foi conduzida para avaliar incertezas do modelo. RESULTADOS O tratamento inicial com entecavir ou tenofovir apresentou melhores resultados clínicos. As menores razões custo-efetividade foram de entecavir para pacientes HBeAg-positivo (R$ 4.010,84/AVG e lamivudina para pacientes HBeAg-negativo (R$ 6.205,08/AVG. Para pacientes HBeAg-negativo, a razão custo-efetividade incremental de entecavir (R$ 14.101,05/AVG está abaixo do limiar recomendado pela Organização Mundial da Saúde. Análise de sensibilidade mostrou que variação nos custos dos medicamentos pode tornar tenofovir alternativa custo-efetiva tanto para pacientes HBeAg-positivo quanto para HBeAg-negativo. CONCLUSÕES Entecavir é alternativa recomendada para iniciar o tratamento de pacientes com hepatite B crônica no Brasil. Contudo, se houver redução no custo de tenofovir, esta pode se tornar alternativa mais custo-efetiva.

Patterns of HIV-1 drug resistance after first-line antiretroviral therapy (ART) failure in 6 sub-Saharan African countries: implications for second-line ART strategies.

Science.gov (United States)

Hamers, Raph L; Sigaloff, Kim C E; Wensing, Annemarie M; Wallis, Carole L; Kityo, Cissy; Siwale, Margaret; Mandaliya, Kishor; Ive, Prudence; Botes, Mariette E; Wellington, Maureen; Osibogun, Akin; Stevens, Wendy S; Rinke de Wit, Tobias F; Schuurman, Rob

2012-06-01

Human immunodeficiency virus type 1 (HIV-1) drug resistance may limit the benefits of antiretroviral therapy (ART). This cohort study examined patterns of drug-resistance mutations (DRMs) in individuals with virological failure on first-line ART at 13 clinical sites in 6 African countries and predicted their impact on second-line drug susceptibility. A total of 2588 antiretroviral-naive individuals initiated ART consisting of different nucleoside reverse transcriptase inhibitor (NRTI) backbones (zidovudine, stavudine, tenofovir, or abacavir, plus lamivudine or emtricitabine) with either efavirenz or nevirapine. Population sequencing after 12 months of ART was retrospectively performed if HIV RNA was >1000 copies/mL. The 2010 International Antiviral Society-USA list was used to score major DRMs. The Stanford algorithm was used to predict drug susceptibility. HIV-1 sequences were generated for 142 participants who virologically failed ART, of whom 70% carried ≥1 DRM and 49% had dual-class resistance, with an average of 2.4 DRMs per sequence (range, 1-8). The most common DRMs were M184V (53.5%), K103N (28.9%), Y181C (15.5%), and G190A (14.1%). Thymidine analogue mutations were present in 8.5%. K65R was frequently selected by stavudine (15.0%) or tenofovir (27.7%). Among participants with ≥1 DRM, HIV-1 susceptibility was reduced in 93% for efavirenz/nevirapine, in 81% for lamivudine/emtricitabine, in 59% for etravirine/rilpivirine, in 27% for tenofovir, in 18% for stavudine, and in 10% for zidovudine. Early failure detection limited the accumulation of resistance. After stavudine failure in African populations, zidovudine rather than tenofovir may be preferred in second-line ART. Strategies to prevent HIV-1 resistance are a global priority.

Digital Receiver Phase Meter

Science.gov (United States)

Marcin, Martin; Abramovici, Alexander

2008-01-01

The software of a commercially available digital radio receiver has been modified to make the receiver function as a two-channel low-noise phase meter. This phase meter is a prototype in the continuing development of a phase meter for a system in which radiofrequency (RF) signals in the two channels would be outputs of a spaceborne heterodyne laser interferometer for detecting gravitational waves. The frequencies of the signals could include a common Doppler-shift component of as much as 15 MHz. The phase meter is required to measure the relative phases of the signals in the two channels at a sampling rate of 10 Hz at a root power spectral density measurements in laser metrology of moving bodies. To illustrate part of the principle of operation of the phase meter, the figure includes a simplified block diagram of a basic singlechannel digital receiver. The input RF signal is first fed to the input terminal of an analog-to-digital converter (ADC). To prevent aliasing errors in the ADC, the sampling rate must be at least twice the input signal frequency. The sampling rate of the ADC is governed by a sampling clock, which also drives a digital local oscillator (DLO), which is a direct digital frequency synthesizer. The DLO produces samples of sine and cosine signals at a programmed tuning frequency. The sine and cosine samples are mixed with (that is, multiplied by) the samples from the ADC, then low-pass filtered to obtain in-phase (I) and quadrature (Q) signal components. A digital signal processor (DSP) computes the ratio between the Q and I components, computes the phase of the RF signal (relative to that of the DLO signal) as the arctangent of this ratio, and then averages successive such phase values over a time interval specified by the user.

Superior Coherent Receivers for AF Relaying with Distributed Alamouti Code

KAUST Repository

Khan, Fahd Ahmed

2012-01-01

Coherent receivers are derived for a pilot-symbol aided distributed Alamouti-coded system with imperfect channel state information. The derived coherent receivers do not perform channel estimation but rather use the received pilot signals for decoding. The derived receiver metrics use the statistics of the channel to give improved performance. The performance is further improved by using the decision history. Simulation results show that a performance gain of up to 1.8 dB can be achieved for the new receivers with decision history as compared with the conventional mismatched coherent receiver. © 2011 IEEE.

BPSK Receiver Based on Recursive Adaptive Filter with Remodulation

Directory of Open Access Journals (Sweden)

N. Milosevic

2011-12-01

Full Text Available This paper proposes a new binary phase shift keying (BPSK signal receiver intended for reception under conditions of significant carrier frequency offsets. The recursive adaptive filter with least mean squares (LMS adaptation is used. The proposed receiver has a constant, defining the balance between the recursive and the nonrecursive part of the filter, whose proper choice allows a simple construction of the receiver. The correct choice of this parameter could result in unitary length of the filter. The proposed receiver has performance very close to the performance of the BPSK receiver with perfect frequency synchronization, in a wide range of frequency offsets (plus/minus quarter of the signal bandwidth. The results obtained by the software simulation are confirmed by the experimental results measured on the receiver realized with the universal software radio peripheral (USRP, with the baseband signal processing at personal computer (PC.

Structural analysis of a reflux pool-boiler solar receiver

Energy Technology Data Exchange (ETDEWEB)

Hoffman, E.L.; Stone, C.M.

1991-06-01

Coupled thermal-structural finite element calculations of a reflux pool-boiler solar receiver were performed to characterize the operating stresses and to address issues affecting the service life of the receiver. Analyses performed using shell elements provided information for receiver material selection and design optimization. Calculations based on linear elastic fracture mechanics principles were performed using continuum elements to assess the vulnerability of a seam-weld to fatigue crack growth. All calculations were performed using ABAQUS, a general purpose finite element code, and elements specifically formulated for coupled thermal-structural analysis. Two materials were evaluated: 316L SS and Haynes 230 alloys. The receiver response was simulated for a combination of structural and thermal loads that represent the startup and operating conditions of the receiver. For both materials, maximum stresses in the receiver developed shortly after startup due to uneven temperature distribution across the receiver surface. The largest effective stress was near yield in the 316L SS receiver and below 39 percent of yield in the Haynes 230 receiver. The calculations demonstrated that stress reductions of over 25 percent could be obtained by reducing the aft dome thickness to one closer to the absorber. The fatigue calculations demonstrated that the stress distribution near the seam-weld notch depends primarily on the structural load created by internal pressurization of the receiver rather than the thermal, indicating that the thermal loads can be neglected when assessing the stress intensity near the seam-weld notch. The stress intensity factor, computed using the J-integral method and crack opening-displacement field equations, was significantly below the fatigue threshold for most steels. The calculations indicated that the weld notch was always loaded in compression, a condition which is not conducive to fatigue crack growth. 15 refs., 30 figs., 3 tabs.

Uptake of PrEP and condom and sexual risk behavior among MSM during the ANRS IPERGAY trial.

Science.gov (United States)

Sagaon-Teyssier, Luis; Suzan-Monti, Marie; Demoulin, Baptiste; Capitant, Catherine; Lorente, Nicolas; Préau, Marie; Mora, Marion; Rojas Castro, Daniela; Chidiac, Christian; Chas, Julie; Meyer, Laurence; Molina, Jean-Michel; Spire, Bruno

2016-01-01

The double-blind phase of the randomized ANRS IPERGAY trial, evaluating sexual activity-based oral HIV pre-exposure prophylaxis (PrEP), was conducted among high-risk men who have sex with men (MSM). Results showed an 86% (95% CI: 40-98) relative reduction in HIV incidence among participants with tenofovir disoproxil fumarate-emtricitabine vs. placebo. The present pooled analysis aimed to analyze (i) participants' adherence to the prescribed treatment and/or condom use during sexual intercourse and (ii) sexual behavior during the double-blind phase of the study. Four hundred MSM were enrolled in the trial. Every 2 months they completed online questionnaires collecting sexual behavior and PrEP adherence data regarding their most recent sexual intercourse. A total of 2232 questionnaires (M0-M24) were analyzed. Changes over time were evaluated using a mixed model accounting for multiple measures. Irrespective of sexual partner and practice type, on average, 42.6% (min: 32.1-max: 45.8%) reported PrEP use only during their most recent episode of sexual intercourse; 29% (22.9-35.6%) reported both PrEP and condom use; 11.7% (7.2-18.9%) reported condom-use only, and 16.7% (10.8-29.6%) reported no PrEP or condom use with no significant change during the study. Scheduled (i.e., correct) PrEP use was reported on average by 59.0% (47.2-68.5%) of those reporting PrEP use during their most recent sexual intercourse. Overall, 70.3% (65.3-79.4%) and 69.3% (58.3-75.4%) of participants reported, respectively, condomless anal and condomless receptive anal intercourse during their most recent sexual encounter without significant change during follow-up. Overall, on average 83.3% (min: 70.4-max: 89.2%) of participants protected themselves by PrEP intake or condom use or both during the trial, and no increase in at-risk sexual practices was observed. None of these indicators showed significant trend during the follow-up, although we found a tendency toward decrease (p = .19) of the

Adverse Drug Reactions Causing Admission to Medical Wards: A Cross-Sectional Survey at 4 Hospitals in South Africa.

Science.gov (United States)

Mouton, Johannes P; Njuguna, Christine; Kramer, Nicole; Stewart, Annemie; Mehta, Ushma; Blockman, Marc; Fortuin-De Smidt, Melony; De Waal, Reneé; Parrish, Andy G; Wilson, Douglas P K; Igumbor, Ehimario U; Aynalem, Getahun; Dheda, Mukesh; Maartens, Gary; Cohen, Karen

2016-05-01

Limited data exist on the burden of serious adverse drug reactions (ADRs) in sub-Saharan Africa, which has high HIV and tuberculosis prevalence. We determined the proportion of adult admissions attributable to ADRs at 4 hospitals in South Africa. We characterized drugs implicated in, risk factors for, and the preventability of ADR-related admissions.We prospectively followed patients admitted to 4 hospitals' medical wards over sequential 30-day periods in 2013 and identified suspected ADRs with the aid of a trigger tool. A multidisciplinary team performed causality, preventability, and severity assessment using published criteria. We categorized an admission as ADR-related if the ADR was the primary reason for admission.There were 1951 admissions involving 1904 patients: median age was 50 years (interquartile range 34-65), 1057 of 1904 (56%) were female, 559 of 1904 (29%) were HIV-infected, and 183 of 1904 (10%) were on antituberculosis therapy (ATT). There were 164 of 1951 (8.4%) ADR-related admissions. After adjustment for age and ATT, ADR-related admission was independently associated (P ≤ 0.02) with female sex (adjusted odds ratio [aOR] 1.51, 95% confidence interval [95% CI] 1.06-2.14), increasing drug count (aOR 1.14 per additional drug, 95% CI 1.09-1.20), increasing comorbidity score (aOR 1.23 per additional point, 95% CI 1.07-1.41), and use of antiretroviral therapy (ART) if HIV-infected (aOR 1.92 compared with HIV-negative/unknown, 95% CI 1.17-3.14). The most common ADRs were renal impairment, hypoglycemia, liver injury, and hemorrhage. Tenofovir disoproxil fumarate, insulin, rifampicin, and warfarin were most commonly implicated, respectively, in these 4 ADRs. ART, ATT, and/or co-trimoxazole were implicated in 56 of 164 (34%) ADR-related admissions. Seventy-three of 164 (45%) ADRs were assessed as preventable.In our survey, approximately 1 in 12 admissions was because of an ADR. The range of ADRs and implicated drugs reflect South Africa's high HIV

Changes in Bone Mineral Density, Body Composition, Vitamin D Status, and Mineral Metabolism in Urban HIV-Positive South African Women Over 12 Months.

Science.gov (United States)

Hamill, Matthew M; Pettifor, John M; Ward, Kate A; Norris, Shane A; Prentice, Ann

2017-08-01

Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are associated with bone loss and poor vitamin D status in white populations, though their relative roles are not known. No previous studies have examined longitudinal changes in areal bone mineral density (aBMD), measured by dual-energy X-ray absorptiometry (DXA), or in vitamin D status in HIV-positive African women. Of 247 premenopausal, urban, black African women from Soweto, South Africa, initially recruited, 187 underwent anthropometry, DXA scanning and blood and urine collections at both baseline and 12 months. Of these, 67 were HIV-negative throughout (Nref), 60 were HIV-positive with preserved CD4 counts at baseline (Ppres), and 60 were HIV-positive with low CD4 counts at baseline, eligible for ART by South African standards of care at the time (Plow). No participant had been exposed to ART at baseline. By 12 months, 51 Plow women had initiated ART, >85% of whom took combined tenofovir disoproxil fumarate (TDF), lamivudine, and efavirenz. By 12 months, Plow and Nref, but not Ppres, increased in body weight and fat mass (group-by-timepoint p ≤ 0.001, p = 0.002, respectively). Plow had significant decreases in aBMD of 2% to 3%, before and after size adjustment, at the femoral neck (p ≤ 0.002) and lumbar spine (p ≤ 0.001), despite significant weight gain. These decreases were associated with increased bone turnover but there were no significant differences or changes over time in vitamin D status, serum phosphate concentrations, or renal phosphate handling. Excluding data from nine Plow women unexposed to ART and 11 Ppres women who had initiated ART accentuated these findings, suggesting the bone loss in Plow was related to ART exposure. This is the first study describing DXA-defined bone loss in HIV-positive Sub-Saharan African women in association with ART. Further work is required to establish if bone loss continues with ongoing ART and, if so, whether this

Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naïve to Antiretroviral Therapy: A Pilot Randomized Trial.

Directory of Open Access Journals (Sweden)

Sergio Serrano-Villar

2016-01-01

Full Text Available Whether initiation of antiretroviral therapy (ART regimens aimed at achieving greater concentrations within gut associated lymphoid tissue (GALT impacts the level of mucosal immune reconstitution, inflammatory markers and the viral reservoir remains unknown. We included 12 HIV- controls and 32 ART-naïve HIV patients who were randomized to efavirenz, maraviroc or maraviroc+raltegravir, each with fixed-dose tenofovir disoproxil fumarate/emtricitabine. Rectal and duodenal biopsies were obtained at baseline and at 9 months of ART. We performed a comprehensive assay of T-cell subsets by flow cytometry, T-cell density in intestinal biopsies, plasma and tissue concentrations of antiretroviral drugs by high-performance liquid chromatography/mass spectroscopy, and plasma interleukin-6 (IL-6, lipoteichoic acid (LTA, soluble CD14 (sCD14 and zonulin-1 each measured by ELISA. Total cell-associated HIV DNA was measured in PBMC and rectal and duodenal mononuclear cells. Twenty-six HIV-infected patients completed the follow-up. In the duodenum, the quadruple regimen resulted in greater CD8+ T-cell density decline, greater normalization of mucosal CCR5+CD4+ T-cells and increase of the naïve/memory CD8+ T-cell ratio, and a greater decline of sCD14 levels and duodenal HIV DNA levels (P = 0.004 and P = 0.067, respectively, with no changes in HIV RNA in plasma or tissue. Maraviroc showed the highest drug distribution to the gut tissue, and duodenal concentrations correlated well with other T-cell markers in duodenum, i.e., the CD4/CD8 ratio, %CD4+ and %CD8+ HLA-DR+CD38+ T-cells. Maraviroc use elicited greater activation of the mucosal naïve CD8+ T-cell subset, ameliorated the distribution of the CD8+ T-cell maturational subsets and induced higher improvement of zonulin-1 levels. These data suggest that combined CCR5 and integrase inhibitor based combination therapy in ART treatment naïve patients might more effectively reconstitute duodenal immunity, decrease

Smooth time-dependent receiver operating characteristic curve estimators.

Science.gov (United States)

Martínez-Camblor, Pablo; Pardo-Fernández, Juan Carlos

2018-03-01

The receiver operating characteristic curve is a popular graphical method often used to study the diagnostic capacity of continuous (bio)markers. When the considered outcome is a time-dependent variable, two main extensions have been proposed: the cumulative/dynamic receiver operating characteristic curve and the incident/dynamic receiver operating characteristic curve. In both cases, the main problem for developing appropriate estimators is the estimation of the joint distribution of the variables time-to-event and marker. As usual, different approximations lead to different estimators. In this article, the authors explore the use of a bivariate kernel density estimator which accounts for censored observations in the sample and produces smooth estimators of the time-dependent receiver operating characteristic curves. The performance of the resulting cumulative/dynamic and incident/dynamic receiver operating characteristic curves is studied by means of Monte Carlo simulations. Additionally, the influence of the choice of the required smoothing parameters is explored. Finally, two real-applications are considered. An R package is also provided as a complement to this article.

Graphene integrated circuits: new prospects towards receiver realisation.

Science.gov (United States)

Saeed, Mohamed; Hamed, Ahmed; Wang, Zhenxing; Shaygan, Mehrdad; Neumaier, Daniel; Negra, Renato

2017-12-21

This work demonstrates a design approach which enables the fabrication of fully integrated radio frequency (RF) and millimetre-wave frequency direct-conversion graphene receivers by adapting the frontend architecture to exploit the state-of-the-art performance of the recently reported wafer-scale CVD metal-insulator-graphene (MIG) diodes. As a proof-of-concept, we built a fully integrated microwave receiver in the frequency range 2.1-2.7 GHz employing the strong nonlinearity and the high responsivity of MIG diodes to successfully receive and demodulate complex, digitally modulated communication signals at 2.45 GHz. In addition, the fabricated receiver uses zero-biased MIG diodes and consumes zero dc power. With the flexibility to be fabricated on different substrates, the prototype receiver frontend is fabricated on a low-cost, glass substrate utilising a custom-developed MMIC process backend which enables the high performance of passive components. The measured performance of the prototype makes it suitable for Internet-of-Things (IoT) and Radio Frequency Identification (RFID) systems for medical and communication applications.

Is phenytoin contraindicated in patients receiving cranial irradiation?

Energy Technology Data Exchange (ETDEWEB)

Borg, M.F. [Royal Adelaide Hospital, SA (Australia); Probert, J.C. [Auckland Hospital, Auckland (New Zealand). Dept. of Radiation Oncology; Zwi, L.J. [Auckland Univ. (New Zealand). Dept. of Medicine and Surgery

1995-02-01

Three recent publications have reported the development of erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and sodium phenytoin. Some authors have recommended that patients receiving whole brain radiation therapy and who have had seizures should not be prescribed phenytoin but an alternative anticonvulsant. This article reviews the current literature pertaining to the development of this potentially lethal complication in patients receiving whole brain radiation and phenytoin, with reference to the single recorded case of Stevens-Johnson syndrome in a patient receiving cranial irradiation and phenytoin in Auckland, New Zealand. While the clinical picture in the 16 patients reported in the literature and the current case report differed from the classical form of erythema multiforme, a similar pattern of presentation and outcome appeared in all patients reviewed, suggesting that the combination of phenytoin, cranial irradiation and the gradual reduction of concomitant steroids seem to lead to the development of erythema multiforme and/or Stevens-Johnson syndrome. The data presented, although sparse, suggest that phenytoin should not be prescribed in patients receiving cranial irradiation. 21 refs., 2 tabs., 3 figs.

Is phenytoin contraindicated in patients receiving cranial irradiation?

International Nuclear Information System (INIS)

Borg, M.F.; Probert, J.C.; Zwi, L.J.

1995-01-01

Three recent publications have reported the development of erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and sodium phenytoin. Some authors have recommended that patients receiving whole brain radiation therapy and who have had seizures should not be prescribed phenytoin but an alternative anticonvulsant. This article reviews the current literature pertaining to the development of this potentially lethal complication in patients receiving whole brain radiation and phenytoin, with reference to the single recorded case of Stevens-Johnson syndrome in a patient receiving cranial irradiation and phenytoin in Auckland, New Zealand. While the clinical picture in the 16 patients reported in the literature and the current case report differed from the classical form of erythema multiforme, a similar pattern of presentation and outcome appeared in all patients reviewed, suggesting that the combination of phenytoin, cranial irradiation and the gradual reduction of concomitant steroids seem to lead to the development of erythema multiforme and/or Stevens-Johnson syndrome. The data presented, although sparse, suggest that phenytoin should not be prescribed in patients receiving cranial irradiation. 21 refs., 2 tabs., 3 figs

Performance evaluation of GPS receiver under equatorial scintillation

Directory of Open Access Journals (Sweden)

Alison de Oliveira Moraes

2009-06-01

Full Text Available Equatorial scintillation is a phenomenon that occurs daily in the equatorial region after the sunset and affects radio signals that propagate through the ionosphere. Depending on the temporal and spatial situation, equatorial scintillation can represent a problem in the availability and precision of the Global Positioning System (GPS. This work is concerned with evaluating the impact of equatorial scintillation on the performance of GPS receivers. First, the morphology and statistical model of equatorial scintillation is briefly presented. A numerical model that generates synthetic scintillation data to simulate the effects of equatorial scintillation is presented. An overview of the main theoretical principles on GPS receivers is presented. The analytical models that describe the effects of scintillation at receiver level are presented and compared with numerical simulations using a radio software receiver and synthetic data. The results achieved by simulation agreed quite well with those predicted by the analytical models. The only exception is for links with extreme levels of scintillation and when weak signals are received.

Scalable graphene aptasensors for drug quantification

Science.gov (United States)

Vishnubhotla, Ramya; Ping, Jinglei; Gao, Zhaoli; Lee, Abigail; Saouaf, Olivia; Vrudhula, Amey; Johnson, A. T. Charlie

2017-11-01

Simpler and more rapid approaches for therapeutic drug-level monitoring are highly desirable to enable use at the point-of-care. We have developed an all-electronic approach for detection of the HIV drug tenofovir based on scalable fabrication of arrays of graphene field-effect transistors (GFETs) functionalized with a commercially available DNA aptamer. The shift in the Dirac voltage of the GFETs varied systematically with the concentration of tenofovir in deionized water, with a detection limit less than 1 ng/mL. Tests against a set of negative controls confirmed the specificity of the sensor response. This approach offers the potential for further development into a rapid and convenient point-of-care tool with clinically relevant performance.

Novel half-coherent receivers for amplify-and-forward relaying

KAUST Repository

Khan, Fahd Ahmed

2012-06-01

Consider a system in which the signal is transmitted from the source to the destination via an amplify-and-forward relay. For such a system, we derive in this paper, novel receivers that have complete knowledge of either the source-relay link or the relay-destination link. These receivers are termed as, \\'half-coherent receivers\\' as they have channel-state-information (CSI) of only one of two links. These receivers can be very useful in a system in which only the relay can afford high complexity by having a channel estimation module and the destination is unable to support channel estimation or a system in which only the destination can afford higher complexity and includes the channel estimation module. The analytical bit-error-rate (BER) performances of the proposed receivers are derived for Rician fading. Numerical results show considerable performance gains of the new receivers, especially at low signal-to-noise ratio. © 2012 IEEE.

Digital processing optical transmission and coherent receiving techniques

CERN Document Server

Binh, Le Nguyen

2013-01-01

With coherent mixing in the optical domain and processing in the digital domain, advanced receiving techniques employing ultra-high speed sampling rates have progressed tremendously over the last few years. These advances have brought coherent reception systems for lightwave-carried information to the next stage, resulting in ultra-high capacity global internetworking. Digital Processing: Optical Transmission and Coherent Receiving Techniques describes modern coherent receiving techniques for optical transmission and aspects of modern digital optical communications in the most basic lines. The

Intermediate Frequency Digital Receiver Based on Multi-FPGA System

Directory of Open Access Journals (Sweden)

Chengchang Zhang

2016-01-01

Full Text Available Aiming at high-cost, large-size, and inflexibility problems of traditional analog intermediate frequency receiver in the aerospace telemetry, tracking, and command (TTC system, we have proposed a new intermediate frequency (IF digital receiver based on Multi-FPGA system in this paper. Digital beam forming (DBF is realized by coordinated rotation digital computer (CORDIC algorithm. An experimental prototype has been developed on a compact Multi-FPGA system with three FPGAs to receive 16 channels of IF digital signals. Our experimental results show that our proposed scheme is able to provide a great convenience for the design of IF digital receiver, which offers a valuable reference for real-time, low power, high density, and small size receiver design.

5 CFR 551.425 - Time spent receiving medical attention.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Time spent receiving medical attention... Relation to Other Activities § 551.425 Time spent receiving medical attention. (a) Time spent waiting for and receiving medical attention for illness or injury shall be considered hours of work if: (1) The...

33 CFR 17.01-10 - Authority to receive gifts.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Authority to receive gifts. 17.01... GENERAL UNITED STATES COAST GUARD GENERAL GIFT FUND General Provisions § 17.01-10 Authority to receive gifts. (a) The Commandant, United States Coast Guard, may accept, receive, hold, or administer gifts...

TDRSS S-shuttle unique receiver equipment

Science.gov (United States)

Weinberg, A.; Schwartz, J. J.; Spearing, R.

1985-01-01

Beginning with STS-9, the Tracking and Date Relay Satellite system (TDRSS) will start providing S- and Ku-band communications and tracking support to the Space Shuttle and its payloads. The most significant element of this support takes place at the TDRSS White Sands Ground Terminal, which processes the Shuttle return link S- and Ku-band signals. While Ku-band hardware available to other TDRSS users is also applied to Ku-Shuttle, stringent S-Shuttle link margins have precluded the application of the standard TDRSS S-band processing equipment to S-Shuttle. It was therfore found necessary to develop a unique S-Shuttle Receiver that embodies state-of-the-art digital technology and processing techniques. This receiver, developed by Motorola, Inc., enhances link margins by 1.5 dB relative to the standard S-band equipment and its bit error rate performance is within a few tenths of a dB of theory. An overview description of the Space Shuttle Receiver Equipment (SSRE) is presented which includes the presentation of block diagrams and salient design features. Selected, measured performance results are also presented.

List of documents received by the INDC Secretariat

International Nuclear Information System (INIS)

1989-05-01

The Nuclear Data Section of the IAEA receives documents originated by or for the International Nuclear Data Committee for distribution. This list includes all INDC documents received and distributed by the INDC Secretariat during the period September 1987 to February 1989. The list is produced directly from computer printouts into two groups: one ordered by accession number, and the other ordered by document number within each series. The document lists also in an Appendix the titles of reports received as single copies for information

List of documents received by the INDC Secretariat

International Nuclear Information System (INIS)

1991-01-01

The Nuclear Data Section of the IAEA receives documents originated by or for the International Nuclear Data Committee (INDC) for distribution. This list includes all INDC documents received and distributed by the INDC Secretariat during the period March 1989 to June 1990. The list is produced directly from computer printout, into two groups: one ordered by accession number, and the other ordered by document number within each origin series. The document lists also in an appendix the titles of reports received as single copies for information

Frequency Estimator Performance for a Software-Based Beacon Receiver

Science.gov (United States)

Zemba, Michael J.; Morse, Jacquelynne Rose; Nessel, James A.; Miranda, Felix

2014-01-01

As propagation terminals have evolved, their design has trended more toward a software-based approach that facilitates convenient adjustment and customization of the receiver algorithms. One potential improvement is the implementation of a frequency estimation algorithm, through which the primary frequency component of the received signal can be estimated with a much greater resolution than with a simple peak search of the FFT spectrum. To select an estimator for usage in a QV-band beacon receiver, analysis of six frequency estimators was conducted to characterize their effectiveness as they relate to beacon receiver design.

Molecular Spectroscopy With a Compact 557-GHz Heterodyne Receiver

DEFF Research Database (Denmark)

Neumaier, Philipp F.-X.; Richter, Heiko; Stake, Jan

2014-01-01

We report on a heterodyne terahertz spectrometer based on a fully integrated 557-GHz receiver and a digital fast Fourier transform spectrometer. The receiver consists of a chain of multipliers and power amplifiers, followed by a heterostructure barrier varactor tripler that subharmonically pumps...... a membrane GaAs Schottky diode mixer. All sub-components are newly developed and optimized with regard to the overall receiver performance such as noise temperature, power consumption, weight and physical size. The receiver works at room temperature, has a double sideband noise temperature as low as 2000 K...

20 CFR 404.1042 - Wages when paid and received.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Wages when paid and received. 404.1042... DISABILITY INSURANCE (1950- ) Employment, Wages, Self-Employment, and Self-Employment Income Wages § 404.1042 Wages when paid and received. (a) In general. Wages are received by an employee at the time they are...

Performance and durability testing of parabolic trough receivers

Science.gov (United States)

Lei, Dongqiang; Fu, Xuqiang; Zhao, Dongming; Yuan, Guofeng; Wang, Zhifeng; Guo, Minghuan

2017-06-01

The paper describes the key performance and durability testing facilities of the parabolic trough receiver developed by Institute of Electrical Engineering, Chinese Academy of Sciences. The indoor heat loss test can be applied at 4-7 different temperature levels within 200-550 on receivers. The optical efficiency test bench consists of 12 metal halide lamps as the solar simulator and a 5 m length half-elliptical cylinder reflector with flat end reflectors. 3 ultra-precision temperature sensors are used in receiver each end to get the temperature difference. The residual gas analysis test bench is applied to analyze and predict the vacuum lifetime of the receiver. It can test the variations of composition and partial pressure of residual gases with temperature and time in the receiver annulus space by a high sensitivity quadrupole mass spectrometer gas analyzer. A coating accelerated ageing test bench, which is also used to test the thermal cycle, has been developed. This test bench uses the absorber tube of the recevier as the resistance heater to heat up the whole receiver. The coating lifetime can be predicted by the Arrhenius parameters. For the cycling test, the compressed air is used to directly cool the inner surface of the absorber tube. The thermal cycling test is performed with temperature cycles from 150 °C to 450 °C for 160 cycles. The maximum thermal cycling frequency is 8 cycles per day. The mechanical fatigue test bench is used to test the bellows and the glass-to-metal seals durability at the same time. Both bellows are expanded and compressed to 6.5 mm in turn with 10,000 cycles. A new rotating test bench was also developed to test the thermal efficiency of the receiver.

An Array of Optical Receivers for Deep-Space Communications

Science.gov (United States)

Vilnrotter, Chi-Wung; Srinivasan, Meera; Andrews, Kenneth

2007-01-01

An array of small optical receivers is proposed as an alternative to a single large optical receiver for high-data-rate communications in NASA s Deep Space Network (DSN). Because the telescope for a single receiver capable of satisfying DSN requirements must be greater than 10 m in diameter, the design, building, and testing of the telescope would be very difficult and expensive. The proposed array would utilize commercially available telescopes of 1-m or smaller diameter and, therefore, could be developed and verified with considerably less difficulty and expense. The essential difference between a single-aperture optical-communications receiver and an optical-array receiver is that a single-aperture receiver focuses all of the light energy it collects onto the surface of an optical detector, whereas an array receiver focuses portions of the total collected energy onto separate detectors, optically detects each fractional energy component, then combines the electrical signal from the array of detector outputs to form the observable, or "decision statistic," used to decode the transmitted data. A conceptual block diagram identifying the key components of the optical-array receiver suitable for deep-space telemetry reception is shown in the figure. The most conspicuous feature of the receiver is the large number of small- to medium-size telescopes, with individual apertures and number of telescopes selected to make up the desired total collecting area. This array of telescopes is envisioned to be fully computer- controlled via the user interface and prediction-driven to achieve rough pointing and tracking of the desired spacecraft. Fine-pointing and tracking functions then take over to keep each telescope pointed toward the source, despite imperfect pointing predictions, telescope-drive errors, and vibration caused by wind.

Investigation of the receivability of VLF standard time and frequency ...

African Journals Online (AJOL)

This study is on the receivability of some standard time and frequency signals in the VLF range in Zaria, Nigeria. Signal field strengths of various stations were estimated, and a suitable radio receiving system was set up to receive them. Using the assembled receiver, some of the transmissions, including the Omega W/L at ...

Solar central receiver reformer system for ammonia plants

Science.gov (United States)

1980-07-01

An overview of a study to retrofit the Valley Nitrogen Producers, Inc., El Centro, California 600 ST/SD Ammonia Plant with Solar Central Receiver Technology is presented. The retrofit system consists of a solar central receiver reformer (SCRR) operating in parallel with the existing fossil fired reformer. Steam and hydrocarbon react in the catalyst filled tubes of the inner cavity receiver to form a hydrogen rich mixture which is the syngas feed for the ammonia production. The SCRR system will displace natural gas presently used in the fossil reformer combustion chamber.

Solar advanced internal film receiver; Receptor avanzado de pelicular interna

Energy Technology Data Exchange (ETDEWEB)

Torre Cabezas, M. de la

1990-07-01

In a Solar Central Internal Film Receiver, the heat absorbing fluid (a molten nitrate salt) flows in a thin film down over the non illuminated side of an absorber panel. Since the molten salt working fluid is not contained in complicated tube manifolds, the receiver design is simples than a conventional tube type-receiver resulting in a lower cost and a more reliable receiver. The Internal Film Receiver can be considered as an alternative to the Direct Absorption Receiver, in the event that the current problems of the last one can not be solved. It also describes here the test facility which will be used for its solar test, and the test plans foreseen. (Author) 17 refs.

The Communication Between Designer and Design Receiver

DEFF Research Database (Denmark)

Dai, Zheng; Dai, Yan

2009-01-01

When people think about a product,the first impression always mainly influences the result.Product is the medium of communication between designer and designer receiver.Because both of them have varied different experience and background,the information would be biased during the transferring...... process.The common symbols which can be recognized by both of designer and receiver are the key tools for communication.In some case,the same symbol in one product would be leads to different receiver impression.Generally,impression includes 3 aspects:aesthetics,function, and emotion.Designer needs...... to create an attractive and accurate impression in product from these 3 aspects.For facing the dilemma of communication,some experimental approaches can help designer deal with unique and diversity situations.Solving the detail problem in each step could keep the original meaning of designer....

An Analog Correlator for Ultra-Wideband Receivers

Directory of Open Access Journals (Sweden)

Tu Chunjiang

2005-01-01

Full Text Available We present a new analog circuit exhibiting high bandwidth and low distortion, specially designed for signal correlation in an ultra-wideband receiver front end. The ultra-wideband short impulse signals are correlated with a local pulse template by the correlator. A comparator then samples the output for signal detection. A typical Gilbert mixer core is adopted for multiplication of broadband signals up to . As a result of synchronization of the received signal and the local template, the output voltage level after integration and sampling can reach up to , which is sufficient for detection by the comparator. The circuit dissipates about from double voltage supplies of and using SiGe BiCMOS technology. Simulation results are presented to show the feasibility of this circuit design for use in ultra-wideband receivers.

User's guide for MIRVAL: a computer code for comparing designs of heliostat-receiver optics for central receiver solar power plants

Energy Technology Data Exchange (ETDEWEB)

Leary, P L; Hankins, J D

1979-02-01

MIRVAL is a Monte Carlo program which simulates the heliostats and a portion of the receiver for solar energy central receiver power plants. Models for three receiver types and four kinds of heliostats are included in the code. The three receiver types modeled are an external cylinder, a cylindrical cavity with a downward-facing aperature, and a north-facing cavity. Three heliostats which track in elevation and azimuth are modeled, one of which is enclosed in a plastic dome. The fourth type consists of a rack of louvered reflective panels with the rack rotatable about a fixed horizontal axis. Phenomena whose effects are simulated are shadowing, blocking, mirror tracking, random errors in tracking and in the conformation of the reflective surface, optical figure of the reflective surface, insolation, angular distribution of incoming sun rays to account for limb darkening and scattering, attenuation of light between the mirrors and the receiver, reflectivity of the mirror surface, and mirror aiming strategy.

A Correlating Receiver for OFDM at Low SNR

NARCIS (Netherlands)

Kokkeler, Andre B.J.; Smit, Gerardus Johannes Maria

By extending OFDM symbols, acceptable BER performance can be achieved at low SNRs. Two alternative differential receiver architectures are presented, a receiver based on a FX correlator (Fourier transformation before correlation) and based on an XF correlator (correlation before Fourier

Joint Transmitter-Receiver Optimization in the Downlink CDMA Systems

Directory of Open Access Journals (Sweden)

Mohammad Saquib

2002-08-01

Full Text Available To maximize the downlink code-division multiple access (CDMA system capacity, we propose to minimize the total transmitted power of the system subject to users′ signal-to-interference ratio (SIR requirements via designing optimum transmitter sequences and utilizing linear optimum receivers (minimum mean square error (MMSE receiver. In our work on joint transmitter-receiver design for the downlink CDMA systems with multiple antennas and multipath channels, we develop several optimization algorithms by considering various system constraints and prove their convergence. We empirically observed that under the optimization algorithm with no constraint on the system, the optimum receiver structure matches the received transmitter sequences. A simulation study is performed to see how the different practical system constraints penalize the system with respect to the optimum algorithm with no constraint on the system.

Evaluation and Error Analysis for a Solar thermal Receiver

Energy Technology Data Exchange (ETDEWEB)

Pfander, M.

2001-07-01

In the following study a complete balance over the REFOS receiver module, mounted on the tower power plant CESA-1 at the Plataforma Solar de Almeria (PSA), is carried out. Additionally an error inspection of the various measurement techniques used in the REFOS project is made. Especially the flux measurement system Prohermes that is used to determine the total entry power of the receiver module and known as a major error source is analysed in detail. Simulations and experiments on the particular instruments are used to determine and quantify possible error sources. After discovering the origin of the errors they are reduced and included in the error calculation. the ultimate result is presented as an overall efficiency of the receiver module in dependence on the flux density at the receiver module's entry plane and the receiver operating temperature. (Author) 26 refs.

Evaluation and Error Analysis for a Solar Thermal Receiver

International Nuclear Information System (INIS)

Pfander, M.

2001-01-01

In the following study a complete balance over the REFOS receiver module, mounted on the tower power plant CESA-1 at the Plataforma Solar de Almeria (PSA), is carried out. Additionally an error inspection of the various measurement techniques used in the REFOS project is made. Especially the flux measurement system Pro hermes that is used to determine the total entry power of the receiver module and known as a major error source is analysed in detail. Simulations and experiments on the particular instruments are used to determine and quantify possible error sources. After discovering the origin of the errors they are reduced and included in the error calculation. The ultimate result is presented as an overall efficiency of the receiver module in dependence on the flux density at the receiver modules entry plane and the receiver operating temperature. (Author) 26 refs

United States Department of Energy solar receiver technology development

Science.gov (United States)

Klimas, P. C.; Diver, R. B.; Chavez, J. M.

The United States Department of Energy (DOE), through Sandia National Laboratories, has been conducting a Solar Thermal Receiver Technology Development Program, which maintains a balance between analytical modeling, bench and small scale testing, and experimentation conducted at scales representative of commercially-sized equipment. Central receiver activities emphasize molten salt-based systems on large scales and volumetric devices in the modeling and small scale testing. These receivers are expected to be utilized in solar power plants rated between 100 and 200 MW. Distributed receiver research focuses on liquid metal refluxing devices. These are intended to mate parabolic dish concentrators with Stirling cycle engines in the 5 to 25 kW(sub e) power range. The effort in the area of volumetric receivers is less intensive and highly cooperative in nature. A ceramic foam absorber of Sandia design was successfully tested on the 200 kW(sub t) test bed at Plataforma Solar during 1989. Material integrity during the approximately 90-test series was excellent. Significant progress has been made with parabolic dish concentrator-mounted receivers using liquid metals (sodium or a potassium/sodium mixture) as heat transport media. Sandia has successfully solar-tested a pool boiling reflux receiver sized to power a 25 kW Stirling engine. Boiling stability and transient operation were both excellent. This document describes these activities in detail and will outline plans for future development.

12 CFR 614.4700 - Financing foreign trade receivables.

Science.gov (United States)

2010-01-01

... OPERATIONS Banks for Cooperatives and Agricultural Credit Banks Financing International Trade § 614.4700 Financing foreign trade receivables. (a) Banks for cooperatives and agricultural credit banks, under policies adopted by their boards of directors, are authorized to finance foreign trade receivables on...

Contrasting two models of academic self-efficacy--domain-specific versus cross-domain--in children receiving and not receiving special instruction in mathematics.

Science.gov (United States)

Jungert, Tomas; Hesser, Hugo; Träff, Ulf

2014-10-01

In social cognitive theory, self-efficacy is domain-specific. An alternative model, the cross-domain influence model, would predict that self-efficacy beliefs in one domain might influence performance in other domains. Research has also found that children who receive special instruction are not good at estimating their performance. The aim was to test two models of how self-efficacy beliefs influence achievement, and to contrast children receiving special instruction in mathematics with normally-achieving children. The participants were 73 fifth-grade children who receive special instruction and 70 children who do not receive any special instruction. In year four and five, the children's skills in mathematics and reading were assessed by national curriculum tests, and in their fifth year, self-efficacy in mathematics and reading were measured. Structural equation modeling showed that in domains where children do not receive special instruction in mathematics, self-efficacy is a mediating variable between earlier and later achievement in the same domain. Achievement in mathematics was not mediated by self-efficacy in mathematics for children who receive special instruction. For normal achieving children, earlier achievement in the language domain had an influence on later self-efficacy in the mathematics domain, and self-efficacy beliefs in different domains were correlated. Self-efficacy is mostly domain specific, but may play a different role in academic performance depending on whether children receive special instruction. The results of the present study provided some support of the Cross-Domain Influence Model for normal achieving children. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

49 CFR 1110.5 - Consideration of comments received.

Science.gov (United States)

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Consideration of comments received. 1110.5 Section 1110.5 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION... PROCEEDINGS § 1110.5 Consideration of comments received. All timely comments will be considered before final...

Autonomous Operation of Super-Regenerative Receiver in BAN

NARCIS (Netherlands)

Kalyanasundaram, P.; Huang, L.; Dolmans, G.; Imamura, K.

2012-01-01

Super-regenerative receiver is one of the potential candidates to achieve ultra low power wireless communication in body area network (BAN). The main limitations of the super-regenerative receiver include the difficulty in choosing a good quench waveform to optimize its sensitivity and selectivity,

A Decentralized Receiver in Gaussian Interference

Directory of Open Access Journals (Sweden)

Christian D. Chapman

2018-04-01

Full Text Available Bounds are developed on the maximum communications rate between a transmitter and a fusion node aided by a cluster of distributed receivers with limited resources for cooperation, all in the presence of an additive Gaussian interferer. The receivers cannot communicate with one another and can only convey processed versions of their observations to the fusion center through a Local Array Network (LAN with limited total throughput. The effectiveness of each bound’s approach for mitigating a strong interferer is assessed over a wide range of channels. It is seen that, if resources are shared effectively, even a simple quantize-and-forward strategy can mitigate an interferer 20 dB stronger than the signal in a diverse range of spatially Ricean channels. Monte-Carlo experiments for the bounds reveal that, while achievable rates are stable when varying the receiver’s observed scattered-path to line-of-sight signal power, the receivers must adapt how they share resources in response to this change. The bounds analyzed are proven to be achievable and are seen to be tight with capacity when LAN resources are either ample or limited.

Actors with Multi-Headed Message Receive Patterns

DEFF Research Database (Denmark)

Sulzmann, Martin; Lam, Edmund Soon Lee; Van Weert, Peter

2008-01-01

style actors with receive clauses containing multi-headed message patterns. Patterns may be non-linear and constrained by guards. We provide a number of examples to show the usefulness of the extension. We also explore the design space for multi-headed message matching semantics, for example first-match......The actor model provides high-level concurrency abstractions to coordinate simultaneous computations by message passing. Languages implementing the actor model such as Erlang commonly only support single-headed pattern matching over received messages. We propose and design an extension of Erlang...... and rule priority-match semantics. The various semantics are inspired by the multi-set constraint matching semantics found in Constraint Handling Rules. This provides us with a formal model to study actors with multi-headed message receive patterns. The system can be implemented efficiently and we have...

Flexible Receiver Radiation Detection System (FRRDS) Users Manual

International Nuclear Information System (INIS)

Troyer, G.L.

1996-01-01

The Flexible Receiver Radiation Detection System (FRRDS) comprises a control computer, a remote data acquisition subsystem, and three hyperpure germanium gamma radiation detectors. The scope of this document is the description of various steps for the orderly start-up, use, and shutdown of the FRRDS. Only those items necessary for these oprations are included. This document is a companion to WHC-SD-W151-UM-002, 'Operating Instructions for the 42 Inch Flexible Receiver,' WHC-SD-W151-UM-003, 'Operating Instructions for the 4-6 Inch Flexible Receiver,' and the vendor supplied system users guide (Ref. 6)

RF-Frontend Design for Process-Variation-Tolerant Receivers

CERN Document Server

Sakian, Pooyan; van Roermund, Arthur

2012-01-01

This book discusses a number of challenges faced by designers of wireless receivers, given complications caused by the shrinking of electronic and mobile devices circuitry into ever-smaller sizes and the resulting complications on the manufacturability, production yield, and the end price of the products.  The authors describe the impact of process technology on the performance of the end product and equip RF designers with countermeasures to cope with such problems.  The mechanisms by which these problems arise are analyzed in detail and novel solutions are provided, including design guidelines for receivers with robustness to process variations and details of circuit blocks that obtain the required performance level. Describes RF receiver frontends and their building blocks from a system- and circuit-level perspective; Provides system-level analysis of a generic RF receiver frontend with robustness to process variations; Includes details of CMOS circuit design at 60GHz and reconfigurable circuits at 60GHz...

List of documents received by the INDC secretariat

International Nuclear Information System (INIS)

1983-05-01

The Nuclear Data Section of the International Atomic Energy Agency receives documents originated by or for the International Nuclear Data Committee for distribution. This list includes all INDC documents received and distributed by the INDC secretariat during the last ten years, and supersedes last year's edition of this report

Compact wideband CMOS receiver frontends for wireless communication

NARCIS (Netherlands)

Blaakmeer, S.C.

2010-01-01

Abstract Wireless communication is an integral part of our daily life, the mobile phone is an example of a very popular wireless communication device. A communication link consists of a transmitter, a receiver and the transmission medium, which air or vacuum for a wireless link. Part of the receiver

among People Receiving Antiretroviral Treatment in Western Uganda

African Journals Online (AJOL)

In this paper, we use survey (n=87) and interview (n=30) data to investigate orientations towards future childbearing among people receiving antiretroviral treatment and their family members in western Uganda. We investigate how reproductive options are perceived, by those receiving treatment and those closest to them, ...

Quad channel software defined receiver for passive radar application

Directory of Open Access Journals (Sweden)

Pető Tamás

2017-03-01

Full Text Available In recent times the growing utilization of the electromagnetic environment brings the passive radar researches more and more to the fore. For the utilization of the wide range of illuminators of opportunity the application of wideband radio receivers is required. At the same time the multichannel receiver structure has also critical importance in target direction finding and interference suppression. This paper presents the development of a multichannel software defined receiver specifically for passive radar applications. One of the relevant feature of the developed receiver platform is its up-to-date SoC (System on hip based structure, which greatly enhance the integration and signal processing capacity of the system, all while keeping the costs low. The software defined operation of the discussed receiver system is demonstrated with using DVB-T (Digital Video Broadcast – Terrestrial signal as illuminator of opportunity. During this demonstration the multichannel capabilities of the realized system are also tested with real data using direction finding and beamforming algorithms.

Uncertainty In Measuring Noise Parameters Of a Communication Receiver

International Nuclear Information System (INIS)

Korcz, Karol; Palczynska, Beata; Spiralski, Ludwik

2005-01-01

The paper presents the method of assessing uncertainty in measuring the usable sensitivity Es of communication receiver. The influence of partial uncertainties of measuring the noise factor F and the energy pass band of the receiver Δf on the combined standard uncertainty level is analyzed. The method to assess the uncertainty in measuring the noise factor on the basis of the systematic component of uncertainty, assuming that the main source of measurement uncertainty is the hardware of the measuring system, is proposed. The assessment of uncertainty in measuring the pass band of the receiver is determined with the assumption that input quantities of the measurement equation are not correlated. They are successive, discrete values of the spectral power density of the noise on the output of receiver. The results of the analyses of particular uncertainties components of measuring the sensitivity, which were carried out for a typical communication receiver, are presented

The ARSQ: the athletes' received support questionnaire.

Science.gov (United States)

Freeman, Paul; Coffee, Pete; Moll, Tjerk; Rees, Tim; Sammy, Nadine

2014-04-01

To address calls for context-specific measurement of social support, this article reports the development of the Athletes' Received Support Questionnaire (ARSQ) and demonstrates initial evidence for its validity. Across four studies there was support for a four-dimensional structure reflecting emotional, esteem, informational, and tangible received support. There was also support for unidimensional and higher-order models. Further, Study 3 provided some support for convergent validity, with significant correlations between the corresponding dimensions of the ARSQ and the Inventory of Socially Supportive Behaviors. Study 4 provided evidence for the nomological validity of the ARSQ. Emotional and esteem support significantly predicted self-confidence and positive affect, and tangible support significantly moderated the relationship between stress and negative affect. Collectively, these results provide initial evidence for the validity of the ARSQ, and offer researchers flexibility to adopt either a multidimensional or aggregated approach to measuring received support.

New type of nonglossy image-receiving sheet

Science.gov (United States)

Aono, Toshiaki; Shibata, Takeshi; Nakamura, Yoshisada

1990-07-01

We have developed a new type of non-glossy surface of an image receiving sheet for a photothermographic color hardcopy system. There is a basic conflict in realizing uniform dye transfer with use of a receiving sheet having a matted surface, because when the degree of roughness exceeds a certain extent, uneven dye transfer readily takes place. It: has been solved by use of "microscopic" phase separation of a certain water-soluble polymer blend which constitutes the surface layer of the image receiving sheet. One of the preferable polymer blends for our purpose proved to be a ternary system, consisting of sodium salt of polymethacrylic acid (PMAA-Na), ammonium salt of polyacrylic acid (PAA-NH4) and water. Phase separation, which proceeded during the evaporation of water from the coated mixture, turned out to be of a spinodal decomposition type and thus capable of stably providing a desirable non-glossy surface.

Watt-level wireless power transmission to multiple compact receivers

International Nuclear Information System (INIS)

Garraud, A; Munzer, D J; Althar, M; Garraud, N; Arnold, D P

2015-01-01

This paper reports an electrodynamic wireless power transmission (EWPT) system using a low-frequency (300 Hz) magnetic field to transmit watt-scale power levels to multiple compact receivers. As compared to inductively or resonantly coupled coils, EWPT facilitates transmission to multiple non-interacting receivers with little restriction on their orientation. A single 3.0 cm 3 receiver achieves 1.25 W power transmission with 8% efficiency at a distance of 1 cm (350 mW/cm 3 power density) from the transmitter. The same prototype achieves 9 mW at a distance of 9 cm. Moreover, we demonstrate simultaneous recharge of two wearable devices, using two receivers located in arbitrary positions and orientations. (paper)

List of documents received by the INDC Secretariat

International Nuclear Information System (INIS)

1979-05-01

The Nuclear Data Section of the International Atomic Energy Agency receives documents originated by or for the International Nuclear Data Committee for distribution. This list includes all INDC documents received and distributed between January 1968 and May 1979, and supersedes INDC(SEC)-66/UN. This list is produced directly from computer printout in two sorts: one ordered by accession number, and the other ordered by document number with-in each origin series (e.g. listing all INDC(SEC)-documents in one block). Reference to earlier INDSWG and ''interim'' INDC reports received between 1962 and 1967 are listed in report INDC/199 (dated November 1967)

SCaN Network Ground Station Receiver Performance for Future Service Support

Science.gov (United States)

Estabrook, Polly; Lee, Dennis; Cheng, Michael; Lau, Chi-Wung

2012-01-01

Objectives: Examine the impact of providing the newly standardized CCSDS Low Density Parity Check (LDPC) codes to the SCaN return data service on the SCaN SN and DSN ground stations receivers: SN Current Receiver: Integrated Receiver (IR). DSN Current Receiver: Downlink Telemetry and Tracking (DTT) Receiver. Early Commercial-Off-The-Shelf (COTS) prototype of the SN User Service Subsystem Component Replacement (USS CR) Narrow Band Receiver. Motivate discussion of general issues of ground station hardware design to enable simple and cheap modifications for support of future services.

Three scientists to receive presidential Enrico Fermi award

CERN Multimedia

2003-01-01

"Secretary of Energy Spencer Abraham today named John Bahcall, Raymond Davis, Jr. and Seymour Sack as winners of the Enrico Fermi Award. ... Drs. Bahcall and Davis will receive the award for their research in neutrino physics. Dr. Sack will receive the award for his contributions to national security" (1 page).

7 CFR 981.472 - Report of almonds received.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Report of almonds received. 981.472 Section 981.472... Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE ALMONDS GROWN IN CALIFORNIA Administrative Rules and Regulations § 981.472 Report of almonds received. (a) Each handler shall report to the...

Multi-parameter optimization design of parabolic trough solar receiver

International Nuclear Information System (INIS)

Guo, Jiangfeng; Huai, Xiulan

2016-01-01

Highlights: • The optimal condition can be obtained by multi-parameter optimization. • Exergy and thermal efficiencies are employed as objective function. • Exergy efficiency increases at the expense of heat losses. • The heat obtained by working fluid increases as thermal efficiency grows. - Abstract: The design parameters of parabolic trough solar receiver are interrelated and interact with one another, so the optimal performance of solar receiver cannot be obtained by the convectional single-parameter optimization. To overcome the shortcoming of single-parameter optimization, a multi-parameter optimization of parabolic trough solar receiver is employed based on genetic algorithm in the present work. When the thermal efficiency is taken as the objective function, the heat obtained by working fluid increases while the average temperature of working fluid and wall temperatures of solar receiver decrease. The average temperature of working fluid and the wall temperatures of solar receiver increase while the heat obtained by working fluid decreases generally by taking the exergy efficiency as an objective function. Assuming that the solar radiation intensity remains constant, the exergy obtained by working fluid increases by taking exergy efficiency as the objective function, which comes at the expense of heat losses of solar receiver.

Broadband direct RF digitization receivers

CERN Document Server

Jamin, Olivier

2014-01-01

This book discusses the trade-offs involved in designing direct RF digitization receivers for the radio frequency and digital signal processing domains.  A system-level framework is developed, quantifying the relevant impairments of the signal processing chain, through a comprehensive system-level analysis.  Special focus is given to noise analysis (thermal noise, quantization noise, saturation noise, signal-dependent noise), broadband non-linear distortion analysis, including the impact of the sampling strategy (low-pass, band-pass), analysis of time-interleaved ADC channel mismatches, sampling clock purity and digital channel selection. The system-level framework described is applied to the design of a cable multi-channel RF direct digitization receiver. An optimum RF signal conditioning, and some algorithms (automatic gain control loop, RF front-end amplitude equalization control loop) are used to relax the requirements of a 2.7GHz 11-bit ADC. A two-chip implementation is presented, using BiCMOS and 65nm...

Thermal State-of-Charge in Solar Heat Receivers

Science.gov (United States)

Hall, Carsie, A., III; Glakpe, Emmanuel K.; Cannon, Joseph N.; Kerslake, Thomas W.

1998-01-01

A theoretical framework is developed to determine the so-called thermal state-of-charge (SOC) in solar heat receivers employing encapsulated phase change materials (PCMS) that undergo cyclic melting and freezing. The present problem is relevant to space solar dynamic power systems that would typically operate in low-Earth-orbit (LEO). The solar heat receiver is integrated into a closed-cycle Brayton engine that produces electric power during sunlight and eclipse periods of the orbit cycle. The concepts of available power and virtual source temperature, both on a finite-time basis, are used as the basis for determining the SOC. Analytic expressions for the available power crossing the aperture plane of the receiver, available power stored in the receiver, and available power delivered to the working fluid are derived, all of which are related to the SOC through measurable parameters. Lower and upper bounds on the SOC are proposed in order to delineate absolute limiting cases for a range of input parameters (orbital, geometric, etc.). SOC characterization is also performed in the subcooled, two-phase, and superheat regimes. Finally, a previously-developed physical and numerical model of the solar heat receiver component of NASA Lewis Research Center's Ground Test Demonstration (GTD) system is used in order to predict the SOC as a function of measurable parameters.

Integrated synchronous receiver channel for optical instrumentation applications

Science.gov (United States)

Benten, Harold G. P. H.; Ruotsalainen, Tarmo; Maekynen, Anssi J.; Rahkonen, Timo E.; Kopola, Harri K.

1997-09-01

A two-channel synchronous receiver circuit for optical instrumentation applications has been designed and implemented. Each receiver channel comprises a.o. transimpedance preamplifier, voltage amplifiers, programmable feedback networks, and a synchronous detector. The function of the channel is to extract the slowly varying information carrying signal from a modulated carrier which is accompanied by relatively high levels of noise. As a whole, the channel can be characterized as a narrow band filter around the frequency of interest. Medical applications include arterial oxygen saturation (SaO2) measurement and dental pulp vitality measurement. In both cases, two optical signals with different frequencies are received by a single photodiode. The measured performance of the optical receiver shows its suitability for the above mentioned applications. Therefore the circuit will be used in a small sized, battery-operated sensor prototype to test the sensing method in a clinical environment. Other applications include the signal processing of optical position-sensitive detectors. A summary of measured receiver channel performance: input reduced noise current spectral density between 0.20 and 0.30 pA/(root)Hz at all relevant frequencies, total programmable channel transimpedance between 7 M(Omega) and 500 M(Omega) , lower -3 dB frequency of at least 50 Hz, upper -3 dB frequency of 40 kHz, maximum voltage swing at the demodulator output of 2.4 V.

Receiving Assistance and Local Food System Participation

Directory of Open Access Journals (Sweden)

Rebecca L. Som Castellano

2017-02-01

Full Text Available A body of literature has noted that local food systems (LFSs may not involve active participation by individuals with lower incomes. This is, in part, a function of racial and class hegemony, as well as physical and financial accessibility of LFSs. LFS institutions, such as farmers’ markets, have been working to facilitate receipt of food assistance programs, such as the Supplemental Nutrition Assistance Program (SNAP. Charitable assistance programs, such as food banks, have also been actively working to engage in LFSs, for example, by making local foods available. However, little research has explored the role that receiving public or charitable assistance can play in influencing LFS participation. In this article, I utilize quantitative and qualitative data collected from across the state of Ohio to examine the relationship between receiving assistance and LFS participation for women, who remain predominately responsible for food provisioning in the U.S., including among those who participate in LFSs. Quantitative results suggest that receiving assistance can increase participation in LFSs. Qualitative data provides more nuanced information about the importance of food assistance for women who want to participate in LFSs, and suggest that it is essential that food cooperatives and farmers’ markets are equipped to receive food assistance programs, such as SNAP, in order for women with lower incomes to participate in LFSs.

Noise and intercept point calculation for modern radio receiver planning

DEFF Research Database (Denmark)

Iversen, Christian Rye; Kolding, T. E.

2001-01-01

The paper presents analytical expressions for determining noise and intercept points for cascaded radio receiver stages. The theory allows for active receiver stages with frequency selectivity and flexible impedance levels. This makes the method highly usable for planning of modem receivers where...

Sideband ratio in double sideband receivers with a Michelson interferometer

NARCIS (Netherlands)

Romanini, M.; Baryshev, A. M.; Hesper, R.; Mena, F. P.; Wild, W.

2007-01-01

Terahertz heterodyne receivers typically use double sideband (DSB) mixers. The precise knowledge of the receiver sideband ratio (SBR) is a fundamental requirement for the calibration of the data taken with this type of receivers. At the moment the spectroscopic techniques developed for submillimeter

Initial results for compressive sensing in electronic support receiver systems

CSIR Research Space (South Africa)

Du Plessis, WP

2011-04-01

Full Text Available determined by the antenna and microwave system comprising the transmitter and receiver, while the instantaneous bandwidth is mainly determined by the Analog-to-Digital Converter (ADC) in the receiver. A radar can thus operate at any frequency within its... Electronic/Electromagnetic Support Measures (ESM) was used historically [1], [2]. Modern ES receiver systems are based on digital receivers allowing powerful signal processing techniques to be used [3], [4]. Recent developments in sampling technology...

DS-CDMA Receiver Based on a Five-Port Technology

Directory of Open Access Journals (Sweden)

Elvino S. Sousa

2005-07-01

Full Text Available High data rates, low-power consumption, and low complexity will be the most important parameters in the design of the next-generation mobile terminals. In this paper we are introducing a new paradigm in the design of direct sequence spread spectrum receiver by combining analog and digital signal processing. The main difference with respect to the conventional all-digital receiver design approach is that the proposed mixed analog/digital processing results in a symbol rate sampling rather than the high-rate subchip sampling. Analog signal despreading is the key part of the proposed receiver solution, which is based on a five-port device, a passive RF square-law-type device. It is used to perform two important tasks at the same time, namely, the direct conversion and analog despreading. To achieve lower complexity, the proposed receiver uses rectangular instead of pulse-matched despreading at the cost of only a small performance degradation. Also, we propose a new noncoherent pseudonoise (PN code tracking scheme based on error signal generated through the L1 norm. This results in comparable or even better PN code tracking performance than L2 norm circuitry, using less complex hardware. Further, we explore how this technology can be applied in the design of DS-CDMA RAKE receiver for mobile terminals. Depending on how the pilot signal is multiplexed, we propose two types of RAKE receivers. It is shown that under Rayleigh fading channel such receiver structures offer robustness and high performance, while maintaining the low complexity achievable through the five-port device.

Qualification test for the Flexible Receiver. Revision 1

International Nuclear Information System (INIS)

Keller, C.M.

1994-01-01

This document provides the test plan and procedures to certify and design verify the 42 in. and 4 in. -- 6 in. Flexible Receiver as a safety class 3 system. The Flexible Receiver will be used by projects W-151 and W-320 for removing equipment from tanks C-106 and Az-101

Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir

Science.gov (United States)

... so that the medication will have a greater effect. Although the combination of elvitegravir, cobicistat, emtricitabine and ... Gengraf, Neoral, Sandimmune), sirolimus (Rapamune), and tacrolimus (Prograf); oxcarbazepine (Oxtellar XR, Trileptal); perphenazine; quetiapine (Seroquel); phosphodiesterase (PDE5) ...

Billing and accounts receivable: fundamentals for improvement.

Science.gov (United States)

Bizon, M M

1993-07-01

If a healthcare facility's accounts receivable operation is experiencing problems, the patient accounts manager should survey all areas of his or her responsibility to determine the best method of resolving the difficulties. One effective technique to reduce billing problems is to take a proactive--not reactive--approach. If mistakes can be corrected before they get out of control, and if the patient accounts manager can ensure that claims will not be denied, a healthcare facility's accounts receivable should remain in good condition.

FFT Based VLSI Digital One Bit Electronic Warfare Receiver

National Research Council Canada - National Science Library

Chien-In, Henry

1998-01-01

... (1 GHz) digital receiver designed for electronic warfare applications. The receiver can process two simultaneous signals and has the potential for fabrication on a single multi-chip module (MCM...

75 FR 26843 - Petition for Exemption; Summary of Petition Received

Science.gov (United States)

2010-05-12

...] Petition for Exemption; Summary of Petition Received AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of petition for exemption received. SUMMARY: This notice contains a summary of a petition... the legal status of any petition or its final disposition. DATES: Comments on petitions received must...

Optimisation of optical receiver for 10 Gbit/s optical duobinary transmission system

DEFF Research Database (Denmark)

Zheng, Xueyan; Liu, Fenghai; Jeppesen, Palle

2001-01-01

Optimisation of a receiver for an optical duobinary signal is studied numerically. It is shown that a conventional receiver is not optimum neither when a DCF is used before the receiver nor without a DCF being used. The optimum receiver for an optical duobinary system is identified.......Optimisation of a receiver for an optical duobinary signal is studied numerically. It is shown that a conventional receiver is not optimum neither when a DCF is used before the receiver nor without a DCF being used. The optimum receiver for an optical duobinary system is identified....

Receiving right/wrong feedback: consequences for learning.

Science.gov (United States)

Fazio, Lisa K; Huelser, Barbie J; Johnson, Aaron; Marsh, Elizabeth J

2010-04-01

Prior work suggests that receiving feedback that one's response was correct or incorrect (right/wrong feedback) does not help learners, as compared to not receiving any feedback at all (Pashler, Cepeda, Wixted, & Rohrer, 2005). In three experiments we examined the generality of this conclusion. Right/wrong feedback did not aid error correction, regardless of whether participants learned facts embedded in prose (Experiment 1) or translations of foreign vocabulary (Experiment 2). While right/wrong feedback did not improve the overall retention of correct answers (Experiments 1 and 2), it facilitated retention of low-confidence correct answers (Experiment 3). Reviewing the original materials was very useful to learners, but this benefit was similar after receiving either right/wrong feedback or no feedback (Experiments 1 and 2). Overall, right/wrong feedback conveys some information to the learner, but is not nearly as useful as being told the correct answer or having the chance to review the to-be-learned materials.

Qualification test for the flexible receiver. Revision 2

Energy Technology Data Exchange (ETDEWEB)

Tedeschi, D.J.

1994-12-12

This document provides the test plan and procedures to certify and design verify the 42{double_prime} and 4{double_prime}-6{double_prime} Flexible Receiver as a safety class 3 system. The Flexible Receiver will be used by projects W-151 and W-320 for removing equipment from tanks C-106 and AZ-101.

Qualification test for the flexible receiver. Revision 2

International Nuclear Information System (INIS)

Tedeschi, D.J.

1994-01-01

This document provides the test plan and procedures to certify and design verify the 42 double-prime and 4 double-prime-6 double-prime Flexible Receiver as a safety class 3 system. The Flexible Receiver will be used by projects W-151 and W-320 for removing equipment from tanks C-106 and AZ-101

Solar central receiver reformer system for ammonia plants

Science.gov (United States)

1980-07-01

Details of the conceptual design, economic analysis, and development plan for a solar central receiver system for retrofitting the Valley Nitrogen Producers, Inc., El Centro, California 600 ST/SD Ammonia Plant are presented. The retrofit system consists of a solar central receiver reformer (SCRR) operating in parallel with the existing fossil fired reformer. Steam and hydrocarbon react in the catalyst filled tubes of the inner cavity receiver to form a hydrogen rich mixture which is the syngas feed for the ammonia production. The SCRR system displaces natural gas presently used in the fossil reformer combustion chamber. The solar reformer retrofit system characteristics and its interface with the existing plant are simple, incorporating state of the art components with proven technology. A northfield composed of one thousand forty second generation heliostats provides solar energy to the receiver which is positioned on top of a 90 meter high steel tower. The overall economics of this system can provide over 20% discount cash flow rate of return with proper investment and market conditions.

47 CFR 87.151 - Special requirements for differential GPS receivers.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Special requirements for differential GPS receivers. 87.151 Section 87.151 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... differential GPS receivers. (a) The receiver shall achieve a message failure rate less than or equal to one...

Communications Satellite Receiver Systems for Public Schools: A Technical Primer.

Science.gov (United States)

Texas Education Agency, Austin.

Designed to aid school districts contemplating use of some of the telecommunications services now available by satellite, this document contains information on home satellite receiving dishes (Television Receive-Only--TVROs), which can receive radio signals carrying television, sound, and data. This information includes: some factors involved in…

A low noise 665 GHz SIS quasi-particle waveguide receiver

Science.gov (United States)

Kooi, J. W.; Walker, C. K.; Leduc, H. G.; Hunter, T. R.; Benford, D. J.; Phillips, T. G.

1993-01-01

Recent results on a 565-690 GHz SIS heterodyne receiver employing a 0.36 micron(sup 2) Nb/AlOx/Nb SIS tunnel junction with high quality circular non-contacting back short and E-plane tuners in a full height wave guide mount are reported. No resonant tuning structures were incorporated in the junction design at this time, even though such structures are expected to help the performance of the receiver. The receiver operates to at least the gap frequency of Niobium, approximately 680 GHz. Typical receiver noise temperatures from 565-690 GHz range from 160K to 230K with a best value of 185K DSB at 648 GHz. With the mixer cooled from 4.3K to 2K the measured receiver noise temperatures decreased by approximately 15 percent, giving roughly 180K DSB from 660 to 680 GHz. The receiver has a full 1 GHz IF pass band and was successfully installed at the Caltech Submillimeter Observatory in Hawaii.

Testing the Grandchildren's Received Affection Scale using Affection Exchange Theory.

Science.gov (United States)

Mansson, Daniel H

2013-04-01

The purpose of this study was to test the Grandchildren's Received Affection Scale (GRAS) using Affection Exchange Theory (Floyd, 2006). In accordance with Affection Exchange Theory, it was hypothesized that grandchildren's scores on the Trait Affection Received Scale (i.e., the extent to which individuals by nature receive affection) would be related significantly and positively to their reports of received affection from their grandparents (i.e., their scores on the GRAS). Additionally, a research question was asked to explore if grandchildren's received affection from their grandparents is dependent on their grandparent's biological sex or lineage (i.e., maternal vs paternal). Thus, young adult grandchildren (N = 422) completed the GRAS and the Trait Affection Received Scale. The results of zero-order Pearson correlational analyses provided support for the hypothesis, whereas the results of MANOVAs tests only partially support extant grandparent-grandchild theory and research. These findings broaden the scope of Affection Exchange Theory and also bolster the GRAS's utility in future grandparent-grandchild affectionate communication research.

Analog fourier transform channelizer and OFDM receiver

OpenAIRE

2007-01-01

An OFDM receiver having an analog multiplier based I-Q channelizing filter, samples and holds consecutive analog I-Q samples of an I-Q baseband, the I-Q basebands having OFDM sub-channels. A lattice of analog I-Q multipliers and analog I-Q summers concurrently receives the held analog I-Q samples, performs analog I-Q multiplications and analog I-Q additions to concurrently generate a plurality of analog I-Q output signals, representing an N-point discrete Fourier transform of the held analog ...

Measuring Balance Across Multiple Radar Receiver Channels.

Energy Technology Data Exchange (ETDEWEB)

Doerry, Armin W.; Bickel, Douglas L.

2018-03-01

When radar receivers employ multiple channels, the general intent is for the receive channels to be as alike as possible, if not as ideal as possible. This is usually done via prudent hardware design, supplemented by system calibration. Towards this end, we require a quality metric for ascertaining the goodness of a radar channel, and the degree of match to sibling channels. We propose a relevant and useable metric to do just that. Acknowledgements This report was the result of an unfunded research and development activity.

Effectiveness of tipranavir versus darunavir as a salvage therapy in HIV-1 treatment-experienced patients.

Science.gov (United States)

Domínguez-Hermosillo, Juan Carlos; Mata-Marin, José Antonio; Herrera-González, Norma Estela; Chávez-García, Marcelino; Huerta-García, Gloria; Nuñez-Rodríguez, Nohemí; García-Gámez, José Gerardo; Jiménez-Romero, Anai; Gaytán-Martínez, Jesús Enrique

2016-09-30

Although both tipranavir (TPV) and darunavir (DRV) represent important options for the management of patients with multi-protease inhibitor (PI)-resistant human immunodeficiency virus (HIV), currently there are no studies comparing the effectiveness and safety of these two drugs in the Mexican population. The aim of this study was to compare the effectiveness of TPV versus DRV as a salvage therapy in HIV-1 treatment-experienced patients. This was a comparative, prospective, cohort study. Patients with HIV and triple-class drug resistance evaluated at the Hospital de Infectología "La Raza", National Medical Center, were included. All patients had the protease and retrotranscriptase genotype; resistance mutation interpretation was done using the Stanford database. A total of 35 HIV-1 triple-class drug-resistant patients were analyzed. All of them received tenofovir and raltegravir, 22 received darunavir/ritonavir (DRV/r), and 13 received tipranavir/ritonavir (TPV/r) therapies. The median baseline RNA HIV-1 viral load and CD4+ cell count were 4.34 log (interquartile range [IQR], 4.15-4.72) and 267 cells/mm3 (IQR, 177-320) for the DRV/r group, and 4.14 log (IQR, 3.51-4.85) and 445 cells/mm3 (IQR, 252-558) for the TPV/r group. At week 24 of treatment, 91% of patients receiving DRV/r and 100% of patients receiving TPV/r had an RNA HIV-1 viral load HIV-1 patients who were highly experienced in antiretroviral therapy.

High-k Scattering Receiver Mixer Performance for NSTX-U

Science.gov (United States)

Barchfeld, Robert; Riemenschneider, Paul; Domier, Calvin; Luhmann, Neville; Ren, Yang; Kaita, Robert

2016-10-01

The High-k Scattering system detects primarily electron-scale turbulence k θ spectra for studying electron thermal transport in NSTX-U. A 100 mW, 693 GHz probe beam passes through plasma, and scattered power is detected by a 4-pixel quasi optical, mixer array. Remotely controlled receiving optics allows the scattering volume to be located from core to edge with a k θ span of 7 to 40 cm-1. The receiver array features 4 RF diagonal input horns, where the electric field polarization is aligned along the diagonal of a square cross section horn, at 30 mm channel spacing. The local oscillator is provided by a 14.4 GHz source followed by a x48 multiplier chain, giving an intermediate frequency of 1 GHz. The receiver optics receive 4 discreet scattering angles simultaneously, and then focus the signals as 4 parallel signals to their respective horns. A combination of a steerable probe beam, and translating receiver, allows for upward or downward scattering which together can provide information about 2D turbulence wavenumber spectrum. IF signals are digitized and stored for later computer analysis. The performance of the receiver mixers is discussed, along with optical design features to enhance the tuning and performance of the mixers. Work supported in part by U.S. DOE Grant DE-FG02-99ER54518 and DE-AC02-09CH1146.

29 CFR 1910.169 - Air receivers.

Science.gov (United States)

2010-07-01

... and equipment used on transportation vehicles such as steam railroad cars, electric railway cars, and... therein are easily accessible. Under no circumstances shall an air receiver be buried underground or...

Usefulness of zebrafish larvae to evaluate drug-induced functional and morphological renal tubular alterations.

Science.gov (United States)

Gorgulho, Rita; Jacinto, Raquel; Lopes, Susana S; Pereira, Sofia A; Tranfield, Erin M; Martins, Gabriel G; Gualda, Emilio J; Derks, Rico J E; Correia, Ana C; Steenvoorden, Evelyne; Pintado, Petra; Mayboroda, Oleg A; Monteiro, Emilia C; Morello, Judit

2018-01-01

Prediction and management of drug-induced renal injury (DIRI) rely on the knowledge of the mechanisms of drug insult and on the availability of appropriate animal models to explore it. Zebrafish (Danio rerio) offers unique advantages for assessing DIRI because the larval pronephric kidney has a high homology with its human counterpart and it is fully mature at 3.5 days post-fertilization. Herein, we aimed to evaluate the usefulness of zebrafish larvae as a model of renal tubular toxicity through a comprehensive analysis of the renal alterations induced by the lethal concentrations for 10% of the larvae for gentamicin, paracetamol and tenofovir. We evaluated drug metabolic profile by mass spectrometry, renal function with the inulin clearance assay, the 3D morphology of the proximal convoluted tubule by two-photon microscopy and the ultrastructure of proximal convoluted tubule mitochondria by transmission electron microscopy. Paracetamol was metabolized by conjugation and oxidation with further detoxification with glutathione. Renal clearance was reduced with gentamicin and paracetamol. Proximal tubules were enlarged with paracetamol and tenofovir. All drugs induced mitochondrial alterations including dysmorphic shapes ("donuts", "pancakes" and "rods"), mitochondrial swelling, cristae disruption and/or loss of matrix granules. These results are in agreement with the tubular effects of gentamicin, paracetamol and tenofovir in man and demonstrate that zebrafish larvae might be a good model to assess functional and structural damage associated with DIRI.

29 CFR 1926.306 - Air receivers.

Science.gov (United States)

2010-07-01

... transportation vehicles such as steam railroad cars, electric railway cars, and automotive equipment. (2) New and... manholes therein are easily accessible. Under no circumstances shall an air receiver be buried underground...

Personal monitoring and assessment of doses received by radiation workers

International Nuclear Information System (INIS)

Swindon, T.N.; Morris, N.D.

1981-12-01

The Personal Radiation Monitoring Service operated by the Australian Radiation Laboratory is outlined and the types of monitors used for assessment of doses received by radiation workers are described. The distribution of doses received by radiation workers in different occupational categories is determined. From these distributions, the average doses received have been assessed and the maximum likely additional increase in cancer deaths in Australia as a result of occupational exposure estimated. This increase is shown to be very small. There is, however, a considerable spread of doses received by individuals within occupational groups

SEPIA - a new single pixel receiver at the APEX telescope

Science.gov (United States)

Belitsky, V.; Lapkin, I.; Fredrixon, M.; Meledin, D.; Sundin, E.; Billade, B.; Ferm, S.-E.; Pavolotsky, A.; Rashid, H.; Strandberg, M.; Desmaris, V.; Ermakov, A.; Krause, S.; Olberg, M.; Aghdam, P.; Shafiee, S.; Bergman, P.; Beck, E. De; Olofsson, H.; Conway, J.; Breuck, C. De; Immer, K.; Yagoubov, P.; Montenegro-Montes, F. M.; Torstensson, K.; Pérez-Beaupuits, J.-P.; Klein, T.; Boland, W.; Baryshev, A. M.; Hesper, R.; Barkhof, J.; Adema, J.; Bekema, M. E.; Koops, A.

2018-04-01

Context. We describe the new Swedish-ESO PI Instrument for APEX (SEPIA) receiver, which was designed and built by the Group for Advanced Receiver Development (GARD), at Onsala Space Observatory (OSO) in collaboration with ESO. It was installed and commissioned at the APEX telescope during 2015 with an ALMA Band 5 receiver channel and updated with a new frequency channel (ALMA Band 9) in February 2016. Aim. This manuscript aims to provide, for observers who use the SEPIA receiver, a reference in terms of the hardware description, optics and performance as well as the commissioning results. Methods: Out of three available receiver cartridge positions in SEPIA, the two current frequency channels, corresponding to ALMA Band 5, the RF band 158-211 GHz, and Band 9, the RF band 600-722 GHz, provide state-of-the-art dual polarization receivers. The Band 5 frequency channel uses 2SB SIS mixers with an average SSB noise temperature around 45 K with IF (intermediate frequency) band 4-8 GHz for each sideband providing total 4 × 4 GHz IF band. The Band 9 frequency channel uses DSB SIS mixers with a noise temperature of 75-125 K with IF band 4-12 GHz for each polarization. Results: Both current SEPIA receiver channels are available to all APEX observers.

10 CFR 20.1906 - Procedures for receiving and opening packages.

Science.gov (United States)

2010-01-01

... received at the licensee's facility if it is received during the licensee's normal working hours, or not later than 3 hours from the beginning of the next working day if it is received after working hours. (d... package for radiation levels unless the package contains quantities of radioactive material that are less...

Multistandard Receiver Design for Telemedicine Monitoring System

Directory of Open Access Journals (Sweden)

Hongmei Wang

2018-01-01

Full Text Available In short-distance wireless communications for telemedicine monitoring, different medical data measurement equipment has different wireless transmission modes. A multistandard receiver is designed that can adapt to different medical data measuring equipment. Using a second-order bandpass sampling for the design of antialiasing filters, two aliasing signals can be separated. Simultaneously, constraint conditions for sampling frequency are not as critical. The design is useful for a multistandard receiver in a telemedicine monitoring system and has the advantages such as saving spectrum resources and facilitating spectrum planning.

Reimbursement of VAT on written-off Receivables

DEFF Research Database (Denmark)

Florentsen, Bjarne; Møller, Michael; Nielsen, Niels Chr.

2003-01-01

In many OECD countries, a seller has a right to reimbursement of VAT (RVAT) she has paid on goods sold, but for which she has not yet received payment. Such reimbursement of VAT on receivables is economically inefficient. It leads to:@* Distortion of credit markets, by subsidizing direct credit...... at the cost of financial intermediaries.@* Price discrimination, by subsidizing buyers with low creditworthiness.@* A less efficient collection of bad debts, as trade with bad debts is made extremely expensive.The finance literature presents several `good' arguments in favor of trade credits, e.g. transaction...

Novinky v léčbě HIV infekce

Czech Academy of Sciences Publication Activity Database

Krečmerová, Marcela

2012-01-01

Roč. 8, č. 1 (2012), s. 18-21 ISSN 1801-2434 Institutional support: RVO:61388963 Keywords : HIV * AIDS * cART * HAART * tenofovir * reverse transcriptase * HIV protease * mikrobicides Subject RIV: CC - Organic Chemistry

Hearing Instrument using receivers with different performance characteristics

DEFF Research Database (Denmark)

2009-01-01

The invention regards a signal processing device in a hearing aid, wherein the signal processing device is electrically coupled to a connection socket operable to detachably connect a receiver to the socket and whereby the signal processing device further comprise a detector operable to detect...... a characteristics of the receiver which is connected to the signal processing device through the connection socket....

Proposal of a novel gravity-fed, particle-filled solar receiver

Science.gov (United States)

Johnson, Evan; Baker, Derek; Tari, Ilker

2017-06-01

Solar Thermal Electricity power plants utilizing solid particles as heat transfer and storage media have been proposed by several research groups, with studies citing benefits of increased thermal efficiency and lower cost. Several types of solid particle receivers have been proposed, with leading designs consisting of particles falling or suspended in air. A new solid particle receiver is proposed here, consisting of a receiver fully packed with particles flowing downward with gravity. Particle flow rate is regulated with an outlet valve. This Particle-Filled receiver concept is compared to other receiver designs, and initial cold and hot experiments are conducted. Mass flux values of up to 379 kg m-2 s-1 are demonstrated, and heat transfer coefficients between 136 and 251 W m-2 K-1 are found.

Design of a cavity heat pipe receiver experiment

Science.gov (United States)

Schneider, Michael G.; Brege, Mark H.; Greenlee, William J.

1992-01-01

A cavity heat pipe experiment has been designed to test the critical issues involved with incorporating thermal energy storage canisters into a heat pipe. The experiment is a replication of the operation of a heat receiver for a Brayton solar dynamic power cycle. The heat receiver is composed of a cylindrical receptor surface and an annular heat pipe with thermal energy storage canisters and gaseous working fluid heat exchanger tubes surrounding it. Hardware for the cavity heat pipe experiment will consist of a sector of the heat pipe, complete with gas tube and thermal energy storage canisters. Thermal cycling tests will be performed on the heat pipe sector to simulate the normal energy charge/discharge cycle of the receiver in a spacecraft application.

Social effects of migration in receiving countries.

Science.gov (United States)

Ohndorf, W

1989-06-01

This paper examines the impact of post-1945 migration into Western, Middle, and Northern Europe from Southern Europe, Turkey, and Northern Africa, and migration to the traditional immigration countries by Asian and Latin American immigrants, on the social structures of receiving countries. Between 1955 and 1974, 1) traditional migration to the US and Australia became less important for European countries while traditional receiving countries accepted many immigrants from developing countries; and 2) rapid economic revival in Western and Northern Europe caused a considerable labor shortage which was filled by migrant workers especially from Southern Europe, Turkey, and Northern Africa, who stayed only until they reached their economic goals. Since 1974, job vacancies have declined and unemployment has soared. This employment crisis caused some migrants 1) to return to their countries of origin, 2) to bring the rest of their families to the receiving country, or 3) to lengthen their stay considerably. The number of refugees has also significantly increased since the mid-970s, as has the number of illegal migrants. After the mid-1970s, Europe began to experience integration problems. The different aspects of the impact of migration on social structures include 1) improvement of the housing situation for foreigners, 2) teaching migrants the language of the receiving country, 3) solving the unemployment problem of unskilled migrants, 4) improvement of educational and vocational qualifications of 2nd generation migrants, 5) development of programs to help unemployed wives of migrants to learn the language and meet indigenous women, 6) encouraging migrants to maintain their cultural identity and assisting them with reintegration if they return to their original country, 7) coping with the problems of refugees, and 8) solving the problems of illegal migration. Almost all receiving countries now severely restrict further immigration. [Those policies should result in

Low proportion of high school senior athletes receiving recommended immunizations.

Science.gov (United States)

Karpinos, Ashley Rowatt; Rizzone, Katherine H; Cribbs, Sarah P; Roumie, Christianne L

2014-05-01

The preparticipation physical evaluation (PPE) often serves as the only preventive health care visit for athletes, but immunization status is not uniformly addressed in such visits. Thus, athletes may not be receiving recommended immunizations. Our aim was to determine the proportion of high school senior athletes who received all recommended immunizations. Our hypothesis was that females would be less likely than males to receive all recommended immunizations given suboptimal human papillomavirus (HPV) vaccine uptake. We conducted a cross-sectional survey evaluation of the immunization status of high school senior athletes in Davidson County, TN. The primary composite outcome was receipt of recommended immunizations for tetanus, meningococcal, and seasonal influenza. For females, the primary outcome also included completion of the HPV series. A total of 162 participants, 104 males and 58 females, were included. More males than females received all recommended immunizations (15.4% vs 3.5%; P = 0.02). When HPV immunization was excluded from the composite outcome, there was no difference in the proportion of males and females who received all recommended immunizations (15.4% vs 15.5%; P = 0.98). The odds of receiving all recommended immunizations was 0.14 (95% CI, 0.03-0.72) for females compared with males when adjusted for covariates. Athletes seen at retail-based clinics for their PPE were less likely to receive all recommended immunizations compared with athletes seen in primary care (OR, 0.13; 95% CI, 0.02-0.69). Only 1 in 6 high school senior athletes received the recommended tetanus, meningococcal, and influenza immunizations. A lower proportion of females, only 1 in 28, received all recommended immunizations due to the HPV series. Policy changes requiring a review of immunizations at the PPE would benefit many high school athletes.

Is There a Need for Viral Load Testing to Assess Treatment Failure in HIV-Infected Patients Who Are about to Change to Tenofovir-Based First-Line Antiretroviral Therapy? Programmatic Findings from Myanmar.

Directory of Open Access Journals (Sweden)

Nay Thiha

Full Text Available WHO recommends that stavudine is phased out of antiretroviral therapy (ART programmes and replaced with tenofovir (TDF for first-line treatment. In this context, the Integrated HIV Care Program, Myanmar, evaluated patients for ART failure using HIV RNA viral load (VL before making the change. We aimed to determine prevalence and determinants of ART failure in those on first-line treatment.Patients retained on stavudine-based or zidovudine-based ART for >12 months with no clinical/immunological evidence of failure were offered VL testing from August 2012. Plasma samples were tested using real time PCR. Those with detectable VL>250 copies/ml on the first test were provided with adherence counseling and three months later a second test was performed with >1000 copies/ml indicating ART failure. We calculated the prevalence of ART failure and adjusted relative risks (aRR to identify associated factors using log binomial regression.Of 4934 patients tested, 4324 (87% had an undetectable VL at the first test while 610 patients had a VL>250 copies/ml. Of these, 502 had a second VL test, of whom 321 had undetectable VL and 181 had >1000 copies/ml signifying ART failure. There were 108 who failed to have the second test. Altogether, there were 94% with an undetectable VL, 4% with ART failure and 2% who did not follow the VL testing algorithm. Risk factors for ART failure were age 15-24 years (aRR 2.4, 95% CI: 1.5-3.8 compared to 25-44 years and previous ART in the private sector (aRR 1.6, 95% CI: 1.2-2.2 compared to the public sector.This strategy of evaluating patients on first-line ART before changing to TDF was feasible and identified a small proportion with ART failure, and could be considered by HIV/AIDS programs in Myanmar and other countries.

High Flux Microchannel Receiver Development with Adap-tive Flow Control

Energy Technology Data Exchange (ETDEWEB)

Drost, Kevin [Oregon State Univ., Corvallis, OR (United States)

2015-08-15

This project is focused on the demonstration of a microchannel-based solar receiver (MSR). The MSR concept consists of using a modular arrangement of arrayed microchannels to heat a working fluid in a concentrating solar receiver, allowing a much higher solar flux on the receiver and consequently a significant reduction in thermal losses, size, and cost.

Review and future perspective of central receiver design and performance

Science.gov (United States)

Zhu, Guangdong; Libby, Cara

2017-06-01

Concentrating solar power (CSP) technology provides a commercial solar option to the utility-scale electricity market. CSP is unique in its ability to include low-cost thermal storage; thus, it can generate electricity when the sun is not available and dispatch electricity to meet varying load requirements. Within the suite of CSP technologies, the central receiver design represents the state-of-the-art technology, promising low cost, high performance, and dispatchable energy production. Current total capacity of central receiver plants worldwide is about 1.0 gigawatt (electric) with operating plants in Spain and the United States, as well as projects under construction in Asia, the Middle East, and North Africa. Central receiver technology has been under development since the 1950s, and a variety of central receiver designs have been explored. A distinguishing feature is the heat transfer medium. Central receiver designs exist that use dense fluids, gases, and solid particles in this role. Water/steam and molten salt receivers have been adopted in current commercial plants and are often coupled with a steam-Rankine power cycle with an operating temperature of less than 600°C. Many new central receiver concepts, such as the volumetric air, supercritical carbon dioxide (sCO2), solid particle, and liquid-metal receiver designs, are under active research and development (R&D). New designs target operating temperatures generally higher than 700°C-800°C—and even above 1000°C—so that higher-performance power cycles such as the sCO2-Brayton cycle or air-Brayton/steam-Rankine combined cycle can be used to promote greater overall system efficiency. Central receiver thermal storage provides dispatchability unavailable from variable-output renewables such as solar photovoltaic and wind power. Case study analysis of the California grid shows that there is a limit on the amount of non-dispatchable renewable generation that the grid can accommodate, beyond which

Review and Future Perspective of Central Receiver Design and Performance

Energy Technology Data Exchange (ETDEWEB)

Zhu, Guangdong; Libby, Cara

2017-06-27

Concentrating solar power (CSP) technology provides a commercial solar option to the utility-scale electricity market. CSP is unique in its ability to include low-cost thermal storage; thus, it can generate electricity when the sun is not available and dispatch electricity to meet varying load requirements. Within the suite of CSP technologies, the central receiver design represents the state-of-the-art technology, promising low cost, high performance, and dispatchable energy production. Current total capacity of central receiver plants worldwide is about 1.0 gigawatt (electric) with operating plants in Spain and the United States, as well as projects under construction in Asia, the Middle East, and North Africa. Central receiver technology has been under development since the 1950s, and a variety of central receiver designs have been explored. A distinguishing feature is the heat transfer medium. Central receiver designs exist that use dense fluids, gases, and solid particles in this role. Water/steam and molten salt receivers have been adopted in current commercial plants and are often coupled with a steam-Rankine power cycle with an operating temperature of less than 600 degrees C. Many new central receiver concepts, such as the volumetric air, supercritical carbon dioxide (sCO2), solid particle, and liquid-metal receiver designs, are under active research and development (R&D). New designs target operating temperatures generally higher than 700 degrees C-800 degrees C -- and even above 1000 degrees C -- so that higher-performance power cycles such as the sCO2-Brayton cycle or air-Brayton/steam-Rankine combined cycle can be used to promote greater overall system efficiency. Central receiver thermal storage provides dispatchability unavailable from variable-output renewables such as solar photovoltaic and wind power. Case study analysis of the California grid shows that there is a limit on the amount of non-dispatchable renewable generation that the grid can

Simultaneous determination of antiretroviral drugs in human hair with liquid chromatography-electrospray ionization-tandem mass spectrometry.

Science.gov (United States)

Wu, Yan; Yang, Jin; Duan, Cailing; Chu, Liuxi; Chen, Shenghuo; Qiao, Shan; Li, Xiaoming; Deng, Huihua

2018-04-15

The determination of the concentrations of antiretroviral drugs in hair is believed to be an important means for the assessment of the long-term adherence to highly active antiretroviral therapy. At present, the combination of tenofovir, lamivudine and nevirapine is widely used in China. However, there was no research reporting simultaneous determination of the three drugs in hair. The present study aimed to develop a sensitive method for simultaneous determination of the three drugs in 2-mg and 10-mg natural hair (Method 1 and Method 2). Hair samples were incubated in methanol at 37 °C for 16 h after being rinsed with methanol twice. The analysis was performed on high performance liquid chromatography tandem mass spectrometry with electronic spray ionization in positive mode and multiple reactions monitoring. Method 1 and Method 2 showed the limits of detection at 160 and 30 pg/mg for tenofovir, at 5 and 6 pg/mg for lamivudine and at 15 and 3 pg/mg for nevirapine. The two methods showed good linearity with the square of correlation coefficient >0.99 at the ranges of 416-5000 and 77-5000 pg/mg for tenofovir, 12-5000 and 15-5000 pg/mg for lamivudine and 39-50,000 and 6-50,000 pg/mg for nevirapine. They gave intra-day and inter-day coefficient of variation <15% and the recoveries ranging from 80.6 to 122.3% and from 83.1 to 114.4%. Method 2 showed LOD and LOQ better than Method 1 for tenofovir and nevirapine and matched Method 1 for lamivudine, but there was high consistency between them in the determination of the three drugs in hair. The population analysis with Method 2 revealed that the concentrations in hair were decreased with the distance of hair segment away from the scalp for the three antiretroviral drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

Clinical use of vaginal or rectally applied microbicides in patients suffering from HIV/AIDS.

Science.gov (United States)

Gupta, Satish Kumar; Nutan

2013-10-22

Microbicides, primarily used as topical pre-exposure prophylaxis, have been proposed to prevent sexual transmission of HIV. This review covers the trends and challenges in the development of safe and effective microbicides to prevent sexual transmission of HIV Initial phases of microbicide development used such surfactants as nonoxynol-9 (N-9), C13G, and sodium lauryl sulfate, aiming to inactivate the virus. Clinical trials of microbicides based on N-9 and C31G failed to inhibit sexual transmission of HIV. On the contrary, N-9 enhanced susceptibility to sexual transmission of HIV-1. Subsequently, microbicides based on polyanions and a variety of other compounds that inhibit the binding, fusion, or entry of virus to the host cells were evaluated for their efficacy in different clinical setups. Most of these trials failed to show either safety or efficacy for prevention of HIV transmission. The next phase of microbicide development involved antiretroviral drugs. Microbicide in the form of 1% tenofovir vaginal gel when tested in a Phase IIb trial (CAPRISA 004) in a coitally dependent manner revealed that tenofovir gel users were 39% less likely to become HIV-infected compared to placebo control. However, in another trial (VOICE MTN 003), tenofovir gel used once daily in a coitally independent mode failed to show any efficacy to prevent HIV infection. Tenofovir gel is currently in a Phase III safety and efficacy trial in South Africa (FACTS 001) employing a coitally dependent dosing regimen. Further, long-acting microbicide-delivery systems (vaginal ring) for slow release of such antiretroviral drugs as dapivirine are also undergoing clinical trials. Discovering new markers as correlates of protective efficacy, novel long-acting delivery systems with improved adherence in the use of microbicides, discovering new compounds effective against a broad spectrum of HIV strains, developing multipurpose technologies incorporating additional features of efficacy against other

Expression of Genes for Drug Transporters in the Human Female Genital Tract and Modulatory Effect of Antiretroviral Drugs.

Directory of Open Access Journals (Sweden)

Karolin Hijazi

Full Text Available Anti-retroviral (ARV -based microbicides are one of the strategies pursued to prevent HIV-1 transmission. Delivery of ARV drugs to subepithelial CD4+ T cells at concentrations for protection is likely determined by drug transporters expressed in the cervicovaginal epithelium. To define the role of drug transporters in mucosal disposition of topically applied ARV-based microbicides, these must be tested in epithelial cell line-based biopharmaceutical assays factoring the effect of relevant drug transporters. We have characterised gene expression of influx and efflux drug transporters in a panel of cervicovaginal cell lines and compared this to expression in cervicovaginal tissue. We also investigated the effect of dapivirine, darunavir and tenofovir, currently at advanced stages of microbicides development, on expression of drug transporters in cell lines. Expression of efflux ABC transporters in cervical tissue was best represented in HeLa, Ect1/E6E7 and End1/E6E7 cell lines. Expression of influx OCT and ENT transporters in ectocervix matched expression in Hela while expression of influx SLCO transporters in vagina was best reflected in VK2/E6E7 cell line. Stimulation with darunavir and dapivirine upregulated MRP transporters, including MRP5 involved in transport of tenofovir. Dapivirine also significantly downregulated tenofovir substrate MRP4 in cervical cell lines. Treatment with darunavir and dapivirine showed no significant effect on expression of BCRP, MRP2 and P-glycoprotein implicated in efflux of different ARV drugs. Darunavir strongly induced expression in most cell lines of CNT3 involved in cell uptake of nucleotide/nucleoside analogue reverse transcriptase inhibitors and SLCO drug transporters involved in cell uptake of protease inhibitors. This study provides insight into the suitability of cervicovaginal cell lines for assessment of ARV drugs in transport kinetics studies. The modulatory effect of darunavir and dapivirine on

Expression of Genes for Drug Transporters in the Human Female Genital Tract and Modulatory Effect of Antiretroviral Drugs.

Science.gov (United States)

Hijazi, Karolin; Cuppone, Anna M; Smith, Kieron; Stincarelli, Maria A; Ekeruche-Makinde, Julia; De Falco, Giulia; Hold, Georgina L; Shattock, Robin; Kelly, Charles G; Pozzi, Gianni; Iannelli, Francesco

2015-01-01

Anti-retroviral (ARV) -based microbicides are one of the strategies pursued to prevent HIV-1 transmission. Delivery of ARV drugs to subepithelial CD4+ T cells at concentrations for protection is likely determined by drug transporters expressed in the cervicovaginal epithelium. To define the role of drug transporters in mucosal disposition of topically applied ARV-based microbicides, these must be tested in epithelial cell line-based biopharmaceutical assays factoring the effect of relevant drug transporters. We have characterised gene expression of influx and efflux drug transporters in a panel of cervicovaginal cell lines and compared this to expression in cervicovaginal tissue. We also investigated the effect of dapivirine, darunavir and tenofovir, currently at advanced stages of microbicides development, on expression of drug transporters in cell lines. Expression of efflux ABC transporters in cervical tissue was best represented in HeLa, Ect1/E6E7 and End1/E6E7 cell lines. Expression of influx OCT and ENT transporters in ectocervix matched expression in Hela while expression of influx SLCO transporters in vagina was best reflected in VK2/E6E7 cell line. Stimulation with darunavir and dapivirine upregulated MRP transporters, including MRP5 involved in transport of tenofovir. Dapivirine also significantly downregulated tenofovir substrate MRP4 in cervical cell lines. Treatment with darunavir and dapivirine showed no significant effect on expression of BCRP, MRP2 and P-glycoprotein implicated in efflux of different ARV drugs. Darunavir strongly induced expression in most cell lines of CNT3 involved in cell uptake of nucleotide/nucleoside analogue reverse transcriptase inhibitors and SLCO drug transporters involved in cell uptake of protease inhibitors. This study provides insight into the suitability of cervicovaginal cell lines for assessment of ARV drugs in transport kinetics studies. The modulatory effect of darunavir and dapivirine on expression of drug

Characteristics of HIV-1 serodiscordant couples enrolled in a clinical trial of antiretroviral pre-exposure prophylaxis for HIV-1 prevention.

Directory of Open Access Journals (Sweden)

Andrew Mujugira

Full Text Available Stable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort.HIV-1 serodiscordant couples, in which the HIV-1 infected partner did not meet national guidelines for initiation of antiretroviral therapy, were enrolled at 9 research sites in Kenya and Uganda. The HIV-1 susceptible partner was randomized to daily oral tenofovir, emtricitabine-tenofovir, or matching placebo with monthly follow-up for 24-36 months.From July 2008 to November 2010, 7920 HIV-1 serodiscordant couples were screened and 4758 enrolled. For 62% (2966/4758 of enrolled couples, the HIV-1 susceptible partner was male. Median age was 33 years for HIV-1 susceptible and HIV-1 infected partners [IQR (28-40 and (26-39 respectively]. Most couples (98% were married, with a median duration of partnership of 7.0 years (IQR 3.0-14.0 and recent knowledge of their serodiscordant status [median 0.4 years (IQR 0.1-2.0]. During the month prior to enrollment, couples reported a median of 4 sex acts (IQR 2-8; 27% reported unprotected sex and 14% of male and 1% of female HIV-1 susceptible partners reported sex with outside partners. Among HIV-1 infected partners, the median plasma HIV-1 level was 3.94 log(10 copies/mL (IQR 3.31-4.53 and median CD4 count was 496 cells/µL (IQR 375-662; the majority (64% had WHO stage 1 HIV-1 disease.Couples at high risk of HIV-1 transmission were rapidly recruited into the Partners PrEP Study, the largest efficacy trial of oral PrEP. (ClinicalTrials.gov NCT00557245.

MULTI-GNSS RECEIVER FOR AEROSPACE NAVIGATION AND POSITIONING APPLICATIONS

Directory of Open Access Journals (Sweden)

T. R. Peres

2014-03-01

Full Text Available The upcoming Galileo system opens a wide range of new opportunities in the Global Navigation Satellite System (GNSS market. However, the characteristics of the future GNSS signals require the development of new GNSS receivers. In the frame of the REAGE project, DEIMOS and ISEL have developed a GNSS receiver targeted for aerospace applications, supporting current and future GPS L1 and Galileo E1 signals, based on commercial (or, in the furthest extent, industrial grade components. Although the REAGE project aimed at space applications, the REAGE receiver is also applicable to many terrestrial applications (ground or airborne, such as Georeferencing and Unmanned Aerial Vehicle (UAV navigation. This paper presents the architecture and features of the REAGE receiver, as well as some results of the validation campaign with GPS L1 and Galileo E1 signals.

Financial reserve. Hospitals leery of credit lines, factoring receivables.

Science.gov (United States)

Edwards, D E; Hamilton, W C; Hauser, R

1991-10-01

Opening lines of credit and factoring (selling) accounts receivable are two ways to generate operating cash that non-healthcare industries have long used successfully. A recent survey of hospital officials across the nation, however, showed these techniques are used infrequently in health care. Among the 281 hospitals responding: Only 45 percent use lines of credit; Less than 5 percent pursue accounts receivable factoring; and Only 12 percent plan to begin factoring receivables in the future. As hospitals look for ways to offset depleted cash reserves, these percentages may increase.

Submillimeter heterodyne receiver for the CSO telescope

International Nuclear Information System (INIS)

Gulkis, S.

1988-01-01

This task is to build a cryogenically cooled 620 to 700 GHz astronomical receiver that will be used as a facility instrument at the CalTech Submillimeter Observatory (CSO) on Mauna Kea, Hawaii. The receiver will have applications as a very high resolution spectrometer to investigate spectral lines in planetary and satellite atmospheres, and comets. The receiver will also be used to make continuum measurements of planets, satellites, and asteroids. During FY88, a scale model (200 GHz) SIS mixer radiometer was built and intrgrated into a cryostat designed for use on the CSO telescope. This system will serve as a model to guide the work on the higher frequency mixer. A solid state local oscillator source that covers two bands in the 600 to 700 GHz has been developed under contract JPL and will be delivered before the end of the year. Work has continued on the SIS materials needed for the 620 to 700 GHz mixer. Test hardware has been developed which allow the 1 to 5 curves for SIS material to be easily measured

Novel coherent receivers for AF distributed STBC using disintegrated channel estimation

KAUST Repository

Khan, Fahd Ahmed; Chen, Yunfei; Alouini, Mohamed-Slim

2011-01-01

For a single relay network, disintegrated channel estimation (DCE), where the source-relay channel is estimated at the relay and the relay-destination channel is estimated at the destination, gives better performance than the cascaded channel estimation. We derive novel receivers for the relay network with disintegrated channel estimation. The derived receivers do not require channel estimation at the destination, as they use the received pilot signals and the source-relay channel estimate for decoding directly. We also consider the effect of quantized source-relay channel estimate on the performance of the designed receivers. Simulation results show that a performance gain of up to 2.2 dB can be achieved by the new receivers, compared with the conventional mismatched coherent receiver with DCE. © 2011 IEEE.

Novel coherent receivers for AF distributed STBC using disintegrated channel estimation

KAUST Repository

Khan, Fahd Ahmed

2011-05-01

For a single relay network, disintegrated channel estimation (DCE), where the source-relay channel is estimated at the relay and the relay-destination channel is estimated at the destination, gives better performance than the cascaded channel estimation. We derive novel receivers for the relay network with disintegrated channel estimation. The derived receivers do not require channel estimation at the destination, as they use the received pilot signals and the source-relay channel estimate for decoding directly. We also consider the effect of quantized source-relay channel estimate on the performance of the designed receivers. Simulation results show that a performance gain of up to 2.2 dB can be achieved by the new receivers, compared with the conventional mismatched coherent receiver with DCE. © 2011 IEEE.

Acyclic nucleoside phosphonates: A key class of antiviral drugs

Czech Academy of Sciences Publication Activity Database

De Clercq, E.; Holý, Antonín

2005-01-01

Roč. 4, č. 13 (2005), 928-940 ISSN 1474-1776 Institutional research plan: CEZ:AV0Z4055905 Keywords : tenofovir * adefovir * cidofovir Subject RIV: CC - Organic Chemistry Impact factor: 18.775, year: 2005

Brief Report: Medication Sharing Is Rare Among African HIV-1 Serodiscordant Couples Enrolled in an Efficacy Trial of Oral Pre-exposure Prophylaxis (PrEP) for HIV-1 Prevention.

Science.gov (United States)

Thomson, Kerry A; Haberer, Jessica E; Marzinke, Mark A; Mujugira, Andrew; Hendrix, Craig W; Celum, Connie; Ndase, Patrick; Ronald, Allan; Bangsberg, David R; Baeten, Jared M

2017-06-01

Sharing of pre-exposure prophylaxis (PrEP) medications is a concern for PrEP implementation. For HIV-1 serodiscordant couples, sharing may undermine the HIV-1 prevention benefit and also cause antiretroviral resistance if taken by HIV-1 infected partners. Within a PrEP efficacy trial among HIV-1 serodiscordant couples, we assessed the occurrence of PrEP sharing by self-report and plasma tenofovir concentrations in HIV-1 infected partners. PrEP sharing was self-reported at <0.01% of visits, and 0%-1.6% of randomly selected and 0% of purposively selected specimens from HIV-1 infected participants had detectable tenofovir concentrations (median: 66.5 ng/mL, range: 1.3-292 ng/mL). PrEP sharing within HIV-1 serodiscordant couples was extremely rare.

Flight Performance Evaluation of Three GPS Receivers for Sounding Rocket Tracking

Science.gov (United States)

Bull, Barton; Diehl, James; Montenbruck, Oliver; Markgraf, Markus; Bauer, Frank (Technical Monitor)

2002-01-01

In preparation for the European Space Agency Maxus-4 mission, a sounding rocket test flight was carried out at Esrange, near Kiruna, Sweden on February 19, 2001 to validate existing ground facilities and range safety installations. Due to the absence of a dedicated scientific payload, the flight offered the opportunity to test multiple GPS receivers and assess their performance for the tracking of sounding rockets. The receivers included an Ashtech G12 HDMA receiver, a BAE (Canadian Marconi) Allstar receiver and a Mitel Orion receiver. All of them provide C/A code tracking on the L1 frequency to determine the user position and make use of Doppler measurements to derive the instantaneous velocity. Among the receivers, the G12 has been optimized for use under highly dynamic conditions and has earlier been flown successfully on NASA sounding rockets. The Allstar is representative of common single frequency receivers for terrestrial applications and received no particular modification, except for the disabling of the common altitude and velocity constraints that would otherwise inhibit its use for space application. The Orion receiver, finally, employs the same Mitel chipset as the Allstar, but has received various firmware modifications by DLR to safeguard it against signal losses and improve its tracking performance. While the two NASA receivers were driven by a common wrap-around antenna, the DLR experiment made use of a switchable antenna system comprising a helical antenna in the tip of the rocket and two blade antennas attached to the body of the vehicle. During the boost a peak acceleration of roughly l7g's was achieved which resulted in a velocity of about 1100 m/s at the end of the burn. At apogee, the rocket reached an altitude of over 80 km. A detailed analysis of the attained flight data is given together with a evaluation of different receiver designs and antenna concepts.

Distributed Iterative Processing for Interference Channels with Receiver Cooperation

DEFF Research Database (Denmark)

Badiu, Mihai Alin; Manchón, Carles Navarro; Bota, Vasile

2012-01-01

We propose a method for the design and evaluation of distributed iterative algorithms for receiver cooperation in interference-limited wireless systems. Our approach views the processing within and collaboration between receivers as the solution to an inference problem in the probabilistic model...

Improved timing recovery in wireless mobile receivers

CSIR Research Space (South Africa)

Olwal, TO

2007-06-01

Full Text Available are transmitted to the receiver. In the proposed method, the receiver exploits the soft decisions computed at each turbo decoding iteration to provide reliable estimates of a soft timing signal, which in turn, improves the decoding time. The derived method... as ( ) ( )( )1 2 1 2, ,..., , ,...,Q Qk k k k k k k k ka a x x x P a x x xη∗ ∗∈Β= ∑ (29) where ( )1 2, ,..., Qk k kx x x are the Q coded bits in a multilevel symbol modulation scheme [32]. According to [29], the soft information demapper computes posteriori...

Monolithic optoelectronic integrated broadband optical receiver with graphene photodetectors

Directory of Open Access Journals (Sweden)

Cheng Chuantong

2017-07-01

Full Text Available Optical receivers with potentially high operation bandwidth and low cost have received considerable interest due to rapidly growing data traffic and potential Tb/s optical interconnect requirements. Experimental realization of 65 GHz optical signal detection and 262 GHz intrinsic operation speed reveals the significance role of graphene photodetectors (PDs in optical interconnect domains. In this work, a novel complementary metal oxide semiconductor post-backend process has been developed for integrating graphene PDs onto silicon integrated circuit chips. A prototype monolithic optoelectronic integrated optical receiver has been successfully demonstrated for the first time. Moreover, this is a firstly reported broadband optical receiver benefiting from natural broadband light absorption features of graphene material. This work is a perfect exhibition of the concept of monolithic optoelectronic integration and will pave way to monolithically integrated graphene optoelectronic devices with silicon ICs for three-dimensional optoelectronic integrated circuit chips.

Monolithic optoelectronic integrated broadband optical receiver with graphene photodetectors

Science.gov (United States)

Cheng, Chuantong; Huang, Beiju; Mao, Xurui; Zhang, Zanyun; Zhang, Zan; Geng, Zhaoxin; Xue, Ping; Chen, Hongda

2017-07-01

Optical receivers with potentially high operation bandwidth and low cost have received considerable interest due to rapidly growing data traffic and potential Tb/s optical interconnect requirements. Experimental realization of 65 GHz optical signal detection and 262 GHz intrinsic operation speed reveals the significance role of graphene photodetectors (PDs) in optical interconnect domains. In this work, a novel complementary metal oxide semiconductor post-backend process has been developed for integrating graphene PDs onto silicon integrated circuit chips. A prototype monolithic optoelectronic integrated optical receiver has been successfully demonstrated for the first time. Moreover, this is a firstly reported broadband optical receiver benefiting from natural broadband light absorption features of graphene material. This work is a perfect exhibition of the concept of monolithic optoelectronic integration and will pave way to monolithically integrated graphene optoelectronic devices with silicon ICs for three-dimensional optoelectronic integrated circuit chips.

Design of a 1 Tb/s superchannel coherent receiver

NARCIS (Netherlands)

Millar, D.S.; Maher, R.; Lavery, D.; Koike-Akino, T.; Pajovic, M.; Alvarado, A.; Paskov, M.; Kojima, K.; Parsons, K.; Thomsen, B.C.; Savory, S.J.; Bayvel, P.

2016-01-01

We describe the design of a trained and pilot-aided digital coherent receiver, capable of detecting a 1 Tb/s superchannel with a single optical front-end. Algorithms for receiver training are described, which calculate the equalizer coefficients, subchannel SNRs, and centroids of the transmitted

Enzymuria in neonates receiving continuous intravenous infusion of gentamicin

DEFF Research Database (Denmark)

Colding, H; Brygge, K; Brendstrup, L

1992-01-01

with non-treatment periods in the same newborn infant (33 infants). The same tendency applied to AAP. Newborn infants receiving continuous intravenous infusion of gentamicin were not found to be at greater risk of nephrotoxicity than those receiving intermittent gentamicin treatment, using NAG and AAP...

The Issues of the Management of Receivables: Lithuanian Case

Directory of Open Access Journals (Sweden)

Remeikiene Rita

2016-06-01

Full Text Available Constant changes in business environment determine the significance of receivables to business. The analysis of the current situation in Lithuania has revealed that a substantial part of business enterprises are facing the problem of overdue receivables. This issue emerged as extremely topical after the beginning of the economic crisis in 2008. A number of scientific studies confirmed that the level of receivables has a significant impact not only on smooth business operation but also on operational results and serves as the cause of numerous economic and social problems, faced by both business enterprises and the state. Rising level of receivables determines slower recovery of total economics because it has a negative impact on the sustainability of the public sector of the country. In addition, the scientists highlight economic problems such as production capacity losses, general decrease in competitiveness and failure to satisfy the debt claims. The social problems include the increase in unemployment rate, fall of living standards, dissatisfaction with poor economics of the country and uncertainty about the future. The aim of this article is to analyse the impact of receivables on business in Lithuania. The methods of the research include scientific literature analysis and statistical data analysis.

Hypersensitivity reactions in patients receiving hemodialysis.

Science.gov (United States)

Butani, Lavjay; Calogiuri, Gianfranco

2017-06-01

To describe hypersensitivity reactions in patients receiving maintenance hemodialysis. PubMed search of articles published during the past 30 years with an emphasis on publications in the past decade. Case reports and review articles describing hypersensitivity reactions in the context of hemodialysis. Pharmacologic agents are the most common identifiable cause of hypersensitivity reactions in patients receiving hemodialysis. These include iron, erythropoietin, and heparin, which can cause anaphylactic or pseudoallergic reactions, and topical antibiotics and anesthetics, which lead to delayed-type hypersensitivity reactions. Many hypersensitivity reactions are triggered by complement activation and increased bradykinin resulting from contact system activation, especially in the context of angiotensin-converting enzyme inhibitor use. Several alternative pharmacologic preparations and dialyzer membranes are available, such that once an etiology for the reaction is established, recurrences can be prevented without affecting the quality of care provided to patients. Although hypersensitivity reactions are uncommon in patients receiving hemodialysis, they can be life-threatening. Moreover, considering the large prevalence of the end-stage renal disease population, the implications of such reactions are enormous. Most reactions are pseudoallergic and not mediated by immunoglobulin E. The multiplicity of potential exposures and the complexity of the environment to which patients on dialysis are exposed make it challenging to identify the precise cause of these reactions. Great diligence is needed to investigate hypersensitivity reactions to avoid recurrence in this high-risk population. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Design of coherent receiver optical front end for unamplified applications.

Science.gov (United States)

Zhang, Bo; Malouin, Christian; Schmidt, Theodore J

2012-01-30

Advanced modulation schemes together with coherent detection and digital signal processing has enabled the next generation high-bandwidth optical communication systems. One of the key advantages of coherent detection is its superior receiver sensitivity compared to direct detection receivers due to the gain provided by the local oscillator (LO). In unamplified applications, such as metro and edge networks, the ultimate receiver sensitivity is dictated by the amount of shot noise, thermal noise, and the residual beating of the local oscillator with relative intensity noise (LO-RIN). We show that the best sensitivity is achieved when the thermal noise is balanced with the residual LO-RIN beat noise, which results in an optimum LO power. The impact of thermal noise from the transimpedance amplifier (TIA), the RIN from the LO, and the common mode rejection ratio (CMRR) from a balanced photodiode are individually analyzed via analytical models and compared to numerical simulations. The analytical model results match well with those of the numerical simulations, providing a simplified method to quantify the impact of receiver design tradeoffs. For a practical 100 Gb/s integrated coherent receiver with 7% FEC overhead, we show that an optimum receiver sensitivity of -33 dBm can be achieved at GFEC cliff of 8.55E-5 if the LO power is optimized at 11 dBm. We also discuss a potential method to monitor the imperfections of a balanced and integrated coherent receiver.

Receive antenna selection for underlay cognitive radio with instantaneous interference constraint

KAUST Repository

Hanif, Muhammad Fainan

2015-06-01

Receive antenna selection is a low complexity scheme to reap diversity benefits.We analyze the performance of a receive antenna selection scheme in spectrum sharing systems where the antenna that results in highest signal-to-interference plus noise ratio at the secondary receiver is selected to improve the performance of secondary transmission. Exact and asymptotic behaviours of the received SINR are derived for both general and interference limited scenarios over general fading environment. These results are then applied to the outage and average bit error rate analysis when the secondary transmitter changes the transmit power in finite discrete levels to satisfy the instantaneous interference constraint at the primary receiver.

Assessment of hospital-based adult triage at emergency receiving ...

African Journals Online (AJOL)

The study was conducted in 6 of the 7 hospitals in the region. ... gency department, the rest receive emergency patients/perform triage from .... gional Referral Hospital (government facility) with emer- ... sionals who were involved in daily initial management of ..... for receiving emergency cases can be complex especially.

Gluconeogenesis continues in premature infants receiving total parenteral nutrition

Science.gov (United States)

To determine the contribution of total gluconeogenesis, to glucose production in preterm infants receiving total parenteral nutrition (TPN) providing glucose exceeding normal infant glucose turnover rate, eight infants (0.955 +/- 0.066 kg, 26.5 - 0.5 wks, 4-1 d) were studied while receiving routine ...