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Sample records for drug tenofovir pmpa

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

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

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    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.

  11. 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

  12. 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

  13. Discovery of Orally Available Prodrugs of the Glutamate Carboxypeptidase II (GCPII) Inhibitor 2-Phosphonomethylpentanedioic Acid (2-PMPA)

    Czech Academy of Sciences Publication Activity Database

    Majer, Pavel; Jančařík, Andrej; Krečmerová, Marcela; Tichý, Tomáš; Tenora, Lukáš; Wozniak, K.; Wu, Y.; Pommier, E.; Ferraris, D.; Rais, R.; Slusher, B. S.

    2016-01-01

    Roč. 59, č. 6 (2016), s. 2810-2819 ISSN 0022-2623 Institutional support: RVO:61388963 Keywords : glutamate carboxypeptidase II * glutamate * 2-PMPA * prodrug Subject RIV: CC - Organic Chemistry Impact factor: 6.259, year: 2016

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

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    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

  15. 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.

  16. 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.

  17. Emtricitabine/tenofovir disoproxil fumarate.

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    2004-01-01

    Gilead Sciences is developing a fixed-dose co-formulation of two of its reverse transcriptase inhibitors, emtricitabine [Emtriva] and tenofovir disoproxil fumarate [Viread], for once-daily dosing in combination with other antiretrovirals for the treatment of HIV infection. Each co-formulated tablet will contain 300 mg of tenofovir disoproxil fumarate and 200 mg of emtricitabine. Emtricitabine [Emtriva] is a nucleoside reverse transcriptase inhibitor (NRTI) with demonstrated potent activity against HIV and hepatitis B virus (HBV). It was first approved in the US by the FDA in July 2003 and is indicated for adults aged > or =18 years. Safety and effectiveness in paediatric patients have not been established. In antiretroviral-treatment-experienced patients, the use of emtricitabine may be considered for adults with HIV strains that are expected to be susceptible to the drug as assessed by genotypic or phenotypic testing. The recommended dose of emtricitabine is one 200 mg capsule daily, with or without food. In the European Union, emtricitabine is indicated in combination with other antiretroviral agents for the treatment of HIV in adults and children, where it is also licensed as an oral 10 mg/mL solution. The oral solution is for use in infants older than 4 months, children and patients unable to swallow hard capsules, and patients with renal impairment who require dose reduction. Tenofovir disoproxil fumarate [Viread] is a nucleotide reverse transcriptase inhibitor that is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced patients. The drug was first approved in the US in October 2001, followed by further approvals in the European Union, Australia, Iceland, Brazil, Canada and Switzerland. The drug has been launched in all these countries. In February 2003, the EMEA's advisory committee adopted a positive opinion to extend the indication of tenofovir disoproxil fumarate in all 15 member states to

  18. 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.

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

    Science.gov (United States)

    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

  20. Acute Liver Toxicity due to Efavirenz/Emtricitabine/Tenofovir

    Directory of Open Access Journals (Sweden)

    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.

  1. 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...

  2. 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.

  3. Retrovirus XMRV Is Inhibited by Host Proteins and Anti-HIV Drugs AZT, Tenofovir, and Raltegravir | Center for Cancer Research

    Science.gov (United States)

    A newly discovered retrovirus, XMRV, isolated from prostate cancer tissues for the first time in 2006, has recently been reported in patients with this cancer, as well as in patients with chronic fatigue syndrome (CFS). However, five subsequent studies could not validate these reports. Since XMRV was isolated from the T and B cells of CFS patients, Vinay Pathak and his colleagues in the HIV Drug Resistance Program sought to determine how XMRV was countering intracellular defense mechanisms that inhibit retroviral replication in human cells.

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

    Science.gov (United States)

    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.

  5. Tenofovir alafenamide versus tenofovir disoproxil fumarate: is there a true difference in efficacy and safety?

    Science.gov (United States)

    Hill, Andrew; Hughes, Sophie L; Gotham, Dzintars; Pozniak, Anton L

    2018-04-01

    Higher plasma tenofovir concentrations are associated with higher risks of renal and bone adverse events. The pharmacokinetic boosters ritonavir (RTV) and cobicistat (COBI) significantly increase plasma area under the curve (AUC) concentrations of tenofovir disoproxil fumarate (TDF), by 25-37%. When combined with RTV or COBI, the dose of tenofovir alafenamide (TAF) is lowered from 25 mg to 10 mg daily, but the TDF dose is maintained at 300 mg daily. To assess the differences in safety and efficacy between tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) in regimens with and without the pharmacokinetic boosters RTV and COBI. A PubMed/Embase search inclusive of dates up to 17 July 2017 identified 11 randomised head-to-head trials (8111 patients) of TDF versus TAF. The Mantel-Haenszel method was used to calculate pooled risk differences and 95% confidence intervals using random-effects models. A pre-defined sub-group analysis compared TAF with TDF, either when boosted with RTV or COBI, or when unboosted. Nine clinical trials compared TAF and TDF for treatment of HIV-1 and two were for hepatitis B treatment. The eleven clinical trials documented 4574 patients with boosting RTV or COBI in both arms, covering 7198 patient-years of follow-up. Some 3537 patients received unboosted regimens, totalling 3595 patient-years of follow-up. Boosted TDF-treated patients showed borderline lower HIV RNA suppression TAF and unboosted TDF. TDF boosted with RTV or COBI was associated with higher risks of bone and renal adverse events, and lower HIV RNA suppression rates, compared with TAF. By contrast, when ritonavir and cobicistat were not used, there were no efficacy differences between TAF and TDF, and marginal differences in safety. The health economic value of TAF versus low-cost generic TDF may be limited when these drugs are used without cobicistat or ritonavir.

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

    Science.gov (United States)

    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.

  7. 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.

  8. 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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

  12. Mucosal effects of tenofovir 1% gel.

    Science.gov (United States)

    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.

  13. Effect of Cobicistat on Tenofovir Disoproxil Fumarate (TDF): What Is True for TAF May Also Be True for TDF.

    Science.gov (United States)

    Cattaneo, Dario; Minisci, Davide; Baldelli, Sara; Mazzali, Cristina; Giacomelli, Andrea; Milazzo, Laura; Meraviglia, Paola; Resnati, Chiara; Rizzardini, Giuliano; Clementi, Emilio; Galli, Massimo; Gervasoni, Cristina

    2018-01-01

    The dose of tenofovir alafenamide is reduced from 25 to 10 mg daily when given with boosting agents. However, such dose reduction has never been adopted for tenofovir disoproxil fumarate (TDF). In this study, we aim to quantify the effect of cobicistat (COBI) both on tenofovir concentrations and TDF durability in real life setting. HIV-positive patients receiving TDF-containing antiretroviral therapies with at least 1 assessment of tenofovir plasma trough concentrations were included in the study. Univariate and multivariate regression analyses were performed considering tenofovir concentration as the dependent variable and clinical characteristics as independent covariates. Subsequently, survival and Cox analyses were performed considering as the primary outcome TDF discontinuation for any reasons. Patients were given TDF with protease inhibitors/ritonavir (n = 212), non-nucleoside reverse transcriptase inhibitors (n = 176), integrase inhibitors (dolutegravir or raltegravir, n = 46), or with elvitegravir/COBI (ELV/COBI) (n = 76). By multivariate analysis, concomitant antiretroviral therapies resulted significantly associated with tenofovir levels, with the highest drug concentrations measured in patients given ELV/COBI. By survival analysis, we found that patients given TDF with ELV/COBI had the lowest rate of drug durability. Overall, these patients had a 2.3-fold increased risk to experience TDF discontinuation. Coadministration with COBI resulted in significantly higher tenofovir concentrations and higher TDF discontinuation compared with other antiretroviral regimens. Accordingly, the possibility that the lack of proper dose adjustment for TDF when given with COBI might have biased the safety comparisons with tenofovir alafenamide during registrative trials cannot be ruled out.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  18. Analysis of Polymorphic Membrane Protein Expression in Cultured Cells Identifies PmpA and PmpH of Chlamydia psittaci as Candidate Factors in Pathogenesis and Immunity to Infection.

    Science.gov (United States)

    Van Lent, Sarah; De Vos, Winnok H; Huot Creasy, Heather; Marques, Patricia X; Ravel, Jacques; Vanrompay, Daisy; Bavoil, Patrik; Hsia, Ru-Ching

    2016-01-01

    The polymorphic membrane protein (Pmp) paralogous families of Chlamydia trachomatis, Chlamydia pneumoniae and Chlamydia abortus are putative targets for Chlamydia vaccine development. To determine whether this is also the case for Pmp family members of C. psittaci, we analyzed transcription levels, protein production and localization of several Pmps of C. psittaci. Pmp expression profiles were characterized using quantitative real-time PCR (RT-qPCR), immunofluorescence (IF) and immuno-electron microscopy (IEM) under normal and stress conditions. We found that PmpA was highly produced in all inclusions as early as 12 hpi in all biological replicates. In addition, PmpA and PmpH appeared to be unusually accessible to antibody as determined by both immunofluorescence and immuno-electron microscopy. Our results suggest an important role for these Pmps in the pathogenesis of C. psittaci, and make them promising candidates in vaccine development.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

  1. Tenofovir and its potential in the treatment of hepatitis B virus

    Directory of Open Access Journals (Sweden)

    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

  2. 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 ...

  3. Topical Delivery of Tenofovir Disoproxil Fumarate and Emtricitabine from Pod-Intravaginal Rings Protects Macaques from Multiple SHIV Exposures

    OpenAIRE

    Srinivasan, Priya; Moss, John A.; Gunawardana, Manjula; Churchman, Scott A.; Yang, Flora; Dinh, Chuong T.; Mitchell, James M.; Zhang, Jining; Fanter, Rob; Miller, Christine S.; Butkyavichene, Irina; McNicholl, Janet M.; Smith, Thomas J.; Baum, Marc M.; Smith, James M.

    2016-01-01

    Topical preexposure prophylaxis (PrEP) against HIV has been marginally successful in recent clinical trials with low adherence rates being a primary factor for failure. Controlled, sustained release of antiretroviral (ARV) drugs may help overcome these low adherence rates if the product is protective for extended periods of time. The oral combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is currently the only FDA-approved ARV drug for HIV PrEP. A novel pod-intravagina...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  7. 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.

  8. Tenofovir-induced Fanconi syndrome and osteomalacia in two HIV-infected patients: Role of intracellular tenofovir diphosphate levels and review of the literature

    NARCIS (Netherlands)

    Haverkort, M.E.; van der Spek, B.W.; Lips, P.T.A.M.; Slieker, W.A.; ter Heine, R.; Huitema, A.D.; Bronsveld, W.

    2011-01-01

    We present 2 human immunodeficiency virus-infected patients with tenofovir disoproxil fumarate-induced Fanconi syndrome, leading to osteomalacia. Intracellular tenofovir diphosphate levels were measured in 1 patient and were found to be very high, with plasma tenofovir levels just slightly elevated.

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

    Science.gov (United States)

    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.

  10. Tenofovir alafenamide (TAF) as the successor of tenofovir disoproxil fumarate (TDF).

    Science.gov (United States)

    De Clercq, Erik

    2016-11-01

    Tenofovir alafenamide (TAF) can be considered a new prodrug of tenofovir (TFV), as successor of tenofovir disoproxil fumarate (TDF). It is in vivo as potent against human immunodeficiency virus (HIV) at a 30-fold lower dose (10mg) than TDF (300mg). TAF has been approved in November 2015 (in the US and EU), as a single-tablet regimen (STR) containing 150mg elvitegravir (E), 150mg cobicistat (C), 200mg emtricitabine [(-)FTC] (F) and 10mg TAF, marketed as Genvoya®, on 01 March 2016 in the US as an STR containing 25mg rilpivirine (R), 200mg F and 25mg TAF, marketed as Odefsey®, and on 4 April 2016 in the US, as an STR containing 200mg F and 25mg TAF, marketed as Descovy®, for the treatment of HIV infections. STR combinations containing TAF and emtricitabine could be paired with a range of third agents, for example, darunavir and cobicistat. TAF has a much lower risk of kidney toxicity or bone density changes than TDF, and also offers long-term potential in the pre-exposure prophylaxis (PrEP) of HIV infections. TAF is specifically accumulated in lymphatic tissue, and in the liver, and hence also holds great potential for the treatment of hepatitis B virus (HBV) infections. Akin to TDF, TAF is converted intracellularly to TFV. Its active diphosphate metabolite (TFVpp) is targeted at the RNA-dependent DNA polymerase (reverse transcriptase) of either HIV or HBV. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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

  12. 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.

  13. Chiral analysis of anti-acquired immunodeficiency syndrome drug, 9-(R)-[2-(phosphonomethoxy)propyl]adenine (tenofovir), and related antiviral acyclic nucleoside phosphonates by CE using beta-CD as chiral selector

    Czech Academy of Sciences Publication Activity Database

    Šolínová, Veronika; Kašička, Václav; Sázelová, Petra; Holý, Antonín

    2009-01-01

    Roč. 30, č. 12 (2009), s. 2245-2254 ISSN 0173-0835 R&D Projects: GA ČR(CZ) GA203/06/1044; GA ČR(CZ) GA203/08/1428; GA AV ČR 1QS400550501; GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : antiviral drugs * capillary electrophoresis * enantioseparation Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.077, year: 2009

  14. The Epi-TAF for Tenofovir Disoproxil Fumarate?

    Science.gov (United States)

    Walensky, Rochelle P; Horn, Tim H; Paltiel, A David

    2016-04-01

    Approximately 84% of human immunodeficiency virus (HIV)-infected US residents on antiretroviral therapy currently receive some form of tenofovir disoproxil fumarate (TDF) as part of their HIV treatment regimen. The TDF analogue tenofovir alafenamide (TAF) has demonstrated equal efficacy but with decreased renal injury and bone mineral density loss compared with TDF. We examine how much more society ought to be willing to pay for TAF over TDF, in exchange for its improved toxicity profile. Using cost-effectiveness methods, we find that current conditions warrant an annual premium of up to $1000 over the average wholesale price (AWP) of TDF. Once generic coformulations of tenofovir/lamivudine become accessible, however, the appropriate premium for TAF will likely merit a downward adjustment, using generic TDF-based costs as the benchmark. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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 ...

  17. 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.

  18. 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

  19. 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.

    Science.gov (United States)

    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.

  20. Occurrence of adverse drug reactions in patients taking tenofovir ...

    African Journals Online (AJOL)

    Setting: Harare central hospital opportunistic infections clinic. Methods: A cross sectional survey of 100 conveniently sampled HIV-positive adult patients was carried out. Study variables were socio-demographic factors, renal and Central Nervous System (CNS) adverse effects, treatment history and self-reported adherence.

  1. 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

  2. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection.

    Science.gov (United States)

    Agarwal, Kosh; Brunetto, Maurizia; Seto, Wai Kay; Lim, Young-Suk; Fung, Scott; Marcellin, Patrick; Ahn, Sang Hoon; Izumi, Namiki; Chuang, Wan-Long; Bae, Ho; Sharma, Manoj; Janssen, Harry L A; Pan, Calvin Q; Çelen, Mustafa Kemal; Furusyo, Norihiro; Shalimar, Dr; Yoon, Ki Tae; Trinh, Huy; Flaherty, John F; Gaggar, Anuj; Lau, Audrey H; Cathcart, Andrea L; Lin, Lanjia; Bhardwaj, Neeru; Suri, Vithika; Mani Subramanian, G; Gane, Edward J; Buti, Maria; Chan, Henry L Y

    2018-04-01

    Tenofovir alafenamide (TAF) is a new prodrug of tenofovir developed to treat patients with chronic hepatitis B virus (HBV) infection at a lower dose than tenofovir disoproxil fumarate (TDF) through more efficient delivery of tenofovir to hepatocytes. In 48-week results from two ongoing, double-blind, randomized phase III trials, TAF was non-inferior to TDF in efficacy with improved renal and bone safety. We report 96-week outcomes for both trials. In two international trials, patients with chronic HBV infection were randomized 2:1 to receive 25 mg TAF or 300 mg TDF in a double-blinded fashion. One study enrolled HBeAg-positive patients and the other HBeAg-negative patients. We assessed efficacy in each study, and safety in the pooled population. At week 96, the differences in the rates of viral suppression were similar in HBeAg-positive patients receiving TAF and TDF (73% vs. 75%, respectively, adjusted difference -2.2% (95% CI -8.3 to 3.9%; p = 0.47), and in HBeAg-negative patients receiving TAF and TDF (90% vs. 91%, respectively, adjusted difference -0.6% (95% CI -7.0 to 5.8%; p = 0.84). In both studies the proportions of patients with alanine aminotransferase above the upper limit of normal at baseline, who had normal alanine aminotransferase at week 96 of treatment, were significantly higher in patients receiving TAF than in those receiving TDF. In the pooled safety population, patients receiving TAF had significantly smaller decreases in bone mineral density than those receiving TDF in the hip (mean % change -0.33% vs. -2.51%; p TAF remained as effective as TDF, with continued improved renal and bone safety, two years after the initiation of treatment. Clinicaltrials.gov number: NCT01940471 and NCT01940341. At week 96 of two ongoing studies comparing the efficacy and safety of tenofovir alafenamide (TAF) to tenofovir disoproxil fumarate (TDF) for the treatment of chronic hepatitis B patients, TAF continues to be as effective as TDF with continued

  3. Hypophosphatemic osteomalacia induced by tenofovir in HIV-infected patients.

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. Improved Bone Safety of Tenofovir Alafenamide Compared to Tenofovir Disoproxil Fumarate Over 2 Years in Patients With Chronic HBV Infection.

    Science.gov (United States)

    Seto, Wai-Kay; Asahina, Yasuhiro; Brown, Todd T; Peng, Cheng-Yuan; Stanciu, Carol; Abdurakhmanov, Dzhamal; Tabak, Fehmi; Nguyen, Tuan T; Chuang, Wan-Long; Inokuma, Tetsuro; Ikeda, Fusao; Santantonio, Teresa Antonia; Habersetzer, François; Ramji, Alnoor; Lau, Audrey H; Suri, Vithika; Flaherty, John F; Wang, Hongyuan; Gaggar, Anuj; Subramanian, G Mani; Mukewar, Shrikant; Brunetto, Maurizia R; Fung, Scott; Chan, Henry Lik-Yuen

    2018-06-19

    Long-term use of tenofovir disoproxil fumarate (TDF) reduces bone mineral density (BMD). Tenofovir alafenamide (TAF), a new prodrug of tenofovir, has shown non-inferior efficacy to TDF in patients with chronic hepatitis B virus (HBV) infection, with improved bone effects at 48 weeks. We performed a randomized trial to evaluate the bone safety of TAF compared with TDF over 2 years, assessing baseline risk factors for bone loss, were evaluated after 2 years of treatment. In a double-blind study, hepatitis B e antigen (HBeAg)-positive patients (n=873) and HBeAg-negative patients (n=425) were randomly assigned (2:1) to groups given TAF (25 mg, n=866) or TDF (300 mg, n=432) once daily. We assessed bone safety, including hip and spine BMD, using dual-energy X-ray absorptiometry and measured changes in serum markers of bone turnover over 96 weeks. At baseline, treatment groups were well matched. At week 96, patients receiving TAF had significantly smaller decreases in hip BMD (mean reduction of 0.33%) than patients receiving TDF (mean reduction of 2.51%) (PTAF vs reduction of 2.57% in patients receiving TDF) (PTAF and TDF groups increased at week 96 compared to week 48 (PTAF group had minimal changes in markers of bone turnover by 12 weeks of treatment, but the TDF group had significant changes, compared to baseline. Risk factors for bone loss had fewer effects in patients receiving TAF than TDF at week 96. In double-blind randomized trials, we found that after 2 years of treatment, patients receiving TAF had continued improvements in bone safety compared with patients receiving TDF. Clinicaltrial.gov no: NCT01940471 and NCT01940341. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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...

  16. Whole body bone scintigraphy in tenofovir-related osteomalacia: a case report

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    Di Biagio Antonio

    2009-07-01

    Full Text Available Abstract Introduction Tenofovir disoproxil fumarate (Viread® is the only nucleotide reverse transcriptase inhibitor currently approved for the treatment of HIV. It is frequently prescribed not only for its efficacy but also for its decreased side effect profile compared with other nucleotide analogs. In addition, it is now increasingly recognized as a cause of acquired Fanconi's syndrome in individuals with HIV. Case presentation We describe a 48-year-old woman infected with HIV, with chronic renal insufficiency, who developed Fanconi's syndrome after inclusion of tenofovir disoproxil fumarate in her antiretroviral therapy. A whole body bone scintigraphy was performed, revealing an abnormal distribution of radiotracer uptake, with characteristic changes compatible with osteomalacia. All symptoms disappeared after tenofovir discontinuation and mineral supplementation. No other explanation for the sudden and complete resolution of the bone disease was found. Conclusion The case highlights the role of whole body bone scintigraphy in the diagnosis of tenofovir-related osteomalacia.

  17. 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...

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Tenofovir Disoproxil Fumarate Fails to Prevent HIV Acquisition or the Establishment of a Viral Reservoir: Two Case Reports.

    Science.gov (United States)

    Fox, Julie; Brady, Michael; Alexander, Hannah; Davies, Olubanke; Robinson, Nicola; Pace, Mathew; Else, Laura; Cason, John; Khoo, Saye; Back, David; Fidler, Sarah; Frater, John

    2016-03-01

    The use of antiretrovirals as pre-exposure prophylaxis (PrEP) is highly efficacious in HIV prevention. The World Health Organization recently recommended Truvada(®) (Gilead Sciences, Inc.) or tenofovir disoproxil fumarate (TDF) for high-risk individuals, with limited data for single-agent TDF PrEP in men who have sex with men (MSM). We report two cases of TDF PrEP failure in MSM who had received long-term TDF for hepatitis B infection and had therapeutic levels of drug immediately after HIV acquisition. Rapid antiretroviral intensification at diagnosis of acute HIV infection failed to limit immune dysfunction or prevent the establishment of a viral reservoir.

  2. 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...

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

    DEFF Research Database (Denmark)

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  7. 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.

  8. 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  13. Single-dose and steady-state pharmacokinetics of tenofovir disoproxil fumarate in human immunodeficiency virus-infected children.

    Science.gov (United States)

    Hazra, Rohan; Balis, Frank M; Tullio, Antonella N; DeCarlo, Ellen; Worrell, Carol J; Steinberg, Seth M; Flaherty, John F; Yale, Kitty; Poblenz, Marianne; Kearney, Brian P; Zhong, Lijie; Coakley, Dion F; Blanche, Stephane; Bresson, Jean Louis; Zuckerman, Judith A; Zeichner, Steven L

    2004-01-01

    Tenofovir disoproxil fumarate (DF) is a potent nucleotide analog reverse transcriptase inhibitor approved for the treatment of human immunodeficiency virus (HIV)-infected adults. The single-dose and steady-state pharmacokinetics of tenofovir were evaluated following administration of tenofovir DF in treatment-experienced HIV-infected children requiring a change in antiretroviral therapy. Using increments of tenofovir DF 75-mg tablets, the target dose was 175 mg/m(2); the median administered dose was 208 mg/m(2). Single-dose pharmacokinetics were evaluated in 18 subjects, and the geometric mean area under the concentration-time curve from 0 h to infinity (AUC(0- infinity )) was 2,150 ng. h/ml and the geometric mean maximum concentration (C(max)) was 266 ng/ml. Subsequently, other antiretrovirals were added to each patient's regimen based upon treatment history and baseline viral resistance results. Steady-state pharmacokinetics were evaluated in 16 subjects at week 4. The steady-state, geometric mean AUC for the 24-h dosing interval was 2,920 ng. h/ml and was significantly higher than the AUC(0- infinity ) after the first dose (P = 0.0004). The geometric mean C(max) at steady state was 302 ng/ml. Tenofovir DF was generally very well tolerated. Steady-state tenofovir exposures in children receiving tenofovir DF-containing combination antiretroviral therapy approached values seen in HIV-infected adults (AUC, approximately 3,000 ng. h/ml; C(max), approximately 300 ng/ml) treated with tenofovir DF at 300 mg.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  16. 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.

  17. Cost effectiveness of tenofovir disoproxil fumarate for the treatment of chronic hepatitis B from a Canadian public payer perspective.

    Science.gov (United States)

    Dakin, Helen; Sherman, Morris; Fung, Scott; Fidler, Carrie; Bentley, Anthony

    2011-12-01

    Previous research has demonstrated that tenofovir disoproxil fumarate (DF) is the most cost-effective nucleos(t)ide treatment for chronic hepatitis B (CHB) in the UK, Spain, Italy and France. However, to our knowledge, no published studies have yet evaluated the cost effectiveness of any treatments for CHB in a Canadian setting, where relative prices and management of CHB differ from those in Europe. Our objective was to determine the cost effectiveness of tenofovir DF compared with other nucleos(t)ide therapies licensed for CHB in Canada from the perspective of publicly funded healthcare payers. A Markov model was used to calculate the costs and benefits of nucleos(t)ide therapy in three groups of patients with hepatitis B e antigen (HBeAg)-positive and -negative CHB: nucleos(t)ide-naive patients without cirrhosis; nucleos(t)ide-naive patients with compensated cirrhosis; and lamivudine-resistant patients. Disease progression was modelled as annual transitions between 18 disease states. Transition probabilities, quality of life and costs were based on published studies. Health benefits were measured in QALYs. The reference year for costs was 2007 and costs and outcomes were discounted at 5% per annum. First-line tenofovir DF was the most effective nucleos(t)ide strategy for managing CHB, generating 6.85-9.39 QALYs per patient. First-line tenofovir DF was also the most cost-effective strategy in all patient subgroups investigated, costing between $Can43,758 and $Can48,015 per QALY gained compared with lamivudine then tenofovir. First-line tenofovir DF strongly dominated first-line entecavir. Giving tenofovir DF monotherapy immediately after lamivudine resistance developed was less costly and more effective than any other active treatment strategy investigated for lamivudine-resistant CHB, including second-line use of adefovir or adefovir + lamivudine. Probabilistic sensitivity analysis demonstrated 50% confidence that first-line tenofovir DF is the most cost

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

    Science.gov (United States)

    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.

  19. Superior Efficacy and Improved Renal and Bone Safety After Switching from a Tenofovir Disoproxil Fumarate- to a Tenofovir Alafenamide-Based Regimen Through 96 Weeks of Treatment.

    Science.gov (United States)

    DeJesus, Edwin; Haas, Bernard; Segal-Maurer, Sorana; Ramgopal, Moti N; Mills, Anthony; Margot, Nicolas; Liu, Ya-Pei; Makadzange, Tariro; McCallister, Scott

    2018-04-01

    We previously demonstrated superior efficacy and safety advantages in HIV-infected, virologically suppressed adults switched to a regimen containing tenofovir alafenamide (TAF) as compared with those remaining on a tenofovir disoproxil fumarate (TDF) regimen through week 48. We now report long-term data through week 96. In this randomized, active-controlled, multicenter, open-label, noninferiority trial (ClinicalTrials.gov No. NCT01815736), we randomized virologically suppressed (HIV-1 RNA TAF group or to continue one of four TDF-containing regimens (TDF group) for 96 weeks. We evaluated efficacy (HIV-1 RNA TAF n = 959, TDF n = 477). At week 96, TAF was superior to TDF in virologic efficacy, with 93% on TAF and 89% on TDF having HIV-1 RNA TAF versus TDF continued through week 96 (p TAF group versus TDF through week 96 (p TAF group as compared with one case in the TDF group. Switching to EVG/COBI/FTC/TAF (E/C/F/TAF) was associated with statistically significant efficacy and safety advantages over remaining on a standard-of-care TDF-based regimen.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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%.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.......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....

  6. 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.

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

    NARCIS (Netherlands)

    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

  8. 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.

  9. Urine assay for tenofovir to monitor adherence in real time to tenofovir disoproxil fumarate/emtricitabine as pre-exposure prophylaxis.

    Science.gov (United States)

    Koenig, H C; Mounzer, K; Daughtridge, G W; Sloan, C E; Lalley-Chareczko, L; Moorthy, G S; Conyngham, S C; Zuppa, A F; Montaner, L J; Tebas, P

    2017-07-01

    Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is approved for pre-exposure prophylaxis (PrEP) against HIV infection. Adherence is critical for the success of PrEP, but current adherence measurements are inadequate for real-time adherence monitoring. We developed and validated a urine assay to measure tenofovir (TFV) to objectively monitor adherence to PrEP. We developed a urine assay using high-performance liquid chromatography coupled to tandem mass spectrometry with high sensitivity/specificity for TFV that allowed us to determine TFV concentrations in log 10 categories between 0 and 10 000 ng/mL. We validated the assay in three cohorts: (1) HIV-positive subjects with undetectable viral loads on a TDF/FTC-based regimen, (2) healthy HIV-negative subjects who received a single dose of TDF/FTC, and (3) HIV-negative subjects receiving daily TDF/FTC as PrEP for 24 weeks. The urine assay detected TFV with greater sensitivity than plasma-based measures and with a window of measurements within 7 days of the last TDF/FTC dose. Based on the urine log-linear clearance after the last dose and its concordance with all detectable plasma levels, a urine TFV concentration > 1000 ng/mL was identified as highly predictive of the presence of TFV in plasma at > 10 ng/mL. The urine assay was able to distinguish high and low adherence patterns within the last 48 h (> 1000 ng/mL versus 10-1000 ng/mL), as well as nonadherence (< 10 ng/mL) extended over at least 1 week prior to measurement. We provide proof of concept that a semiquantitative urine assay measuring levels of TFV could be further developed into a point-of-care test and be a useful tool to monitor adherence to PrEP. © 2017 British HIV Association.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  16. 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

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

    OpenAIRE

    Glidden, David; Grant, Robert; Mulligan, Kathleen; Solomon, MM; Lama, JR; Glidden, DV; McMahan, V; Liu, AY; Vicente, J; Veloso, VG; Mayer, KH; Chariyalertsak, S

    2014-01-01

    Objective: 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. Design and methods: The Iniciativa Profilaxis Pre-Exposición (iP

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

    Science.gov (United States)

    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

  19. 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.

    Science.gov (United States)

    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

    antiretrovirals, and 169 (15%) had previous virological failure on a non-darunavir regimen. The study regimen was non-inferior to the control for virological rebound cumulative through week 48 (19 [2·5%] of 763 patients in the study group vs eight (2·1%) of 378 patients in the control group; difference 0·4%, 95% CI -1·5 to 2·2; p<0·0001). No resistance to any study drug was observed. Numbers of discontinuations related to adverse events (11 [1%] of 763 patients in the study group vs four [1%] of 378 patients in the control group) and grade 3-4 adverse events (52 [7%] patients vs 31 [8%] patients) were similar between the two groups. There was a small non-clinically relevant but statistically significant (0·2 [SD 1·1] vs 0·1 [1·1], p=0.010) difference between the two groups in change from baseline in total cholesterol to HDL-cholesterol ratio. Only one serious adverse event (pancreatitis in the study group) was deemed as possibly related to the study regimen. Our findings show the safety and efficacy of single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide as a potential switch option for the treatment of HIV-1 infection in adults with viral suppression. Janssen. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. 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....

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  3. Brief Report: Randomized, Double-Blind Comparison of Tenofovir Alafenamide (TAF) vs Tenofovir Disoproxil Fumarate (TDF), Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine (E/C/F) for Initial HIV-1 Treatment: Week 144 Results.

    Science.gov (United States)

    Arribas, José R; Thompson, Melanie; Sax, Paul E; Haas, Bernhard; McDonald, Cheryl; Wohl, David A; DeJesus, Edwin; Clarke, Amanda E; Guo, Susan; Wang, Hui; Callebaut, Christian; Plummer, Andrew; Cheng, Andrew; Das, Moupali; McCallister, Scott

    2017-06-01

    In 2 double-blind phase 3 trials, 1733 antiretroviral-naive adults were randomized to tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF), each coformulated with elvitegravir/cobicistat/emtricitabine (E/C/F). At 144 weeks, TAF was superior to TDF in virologic efficacy, with 84.2% vs 80.0% having HIV-1 RNA TAF had less impact than TDF on bone mineral density and renal biomarkers. No participants on TAF had renal-related discontinuations vs 12 on TDF (P TAF vs 4 for TDF. There were greater increases in lipids with TAF vs TDF, with no difference in the total cholesterol to high-density lipoprotein ratio. For initial HIV therapy, E/C/F/TAF is superior to E/C/F/TDF in efficacy and bone and renal safety.

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

    Science.gov (United States)

    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.

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

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    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.

  6. Preexposure prophylaxis will have a limited impact on HIV-1 drug resistance in sub-Saharan Africa: a comparison of mathematical models

    NARCIS (Netherlands)

    van de Vijver, David A. M. C.; Nichols, Brooke E.; Abbas, Ume L.; Boucher, Charles A. B.; Cambiano, Valentina; Eaton, Jeffrey W.; Glaubius, Robert; Lythgoe, Katrina; Mellors, John; Phillips, Andrew; Sigaloff, Kim C.; Hallett, Timothy B.

    2013-01-01

    Preexposure prophylaxis (PrEP) with tenofovir and emtricitabine can prevent new HIV-1 infections, but there is a concern that use of PrEP could increase HIV drug resistance resulting in loss of treatment options. We compared standardized outcomes from three independent mathematical models simulating

  7. Cost Effectiveness of ‘On Demand’ Hiv Pre-Exposure Prophylaxis for Non-Injection Drug-Using Men Who Have Sex with Men in Canada

    Directory of Open Access Journals (Sweden)

    Estelle Ouellet

    2015-01-01

    Full Text Available BACKGROUND: Recent trials report the efficacy of continuous tenofovir-based pre-exposure prophylaxis (PrEP for prevention of HIV infection. The cost effectiveness of ‘on demand’ PrEP for non-injection drug-using men who have sex with men at high risk of HIV acquisition has not been evaluated.

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

    Science.gov (United States)

    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.

  9. 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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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

  18. 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

  19. Efficacy and tolerance of a combination of tenofovir disoproxil fumarate plus emtricitabine in patients with chronic hepatitis B : A European multicenter study

    NARCIS (Netherlands)

    Si-Ahmed, Si-Nafa; Pradat, Pierre; Zoutendijk, Roeland; Buti, Maria; Mallet, Vincent; Cruiziat, Claire; Deterding, Katja; Dumortier, Jerome; Bailly, Francois; Esteban, Rafael; Wedemeyer, Heiner; Janssen, Harry L.; Zoulim, Fabien

    2011-01-01

    Background and aims: The combination of tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) is used extensively to treat HIV infection and also has potent activity against hepatitis B virus (HBV) infection. The aim of this study was to assess the efficacy and tolerance of TDF + FTC in

  20. Vitamin D3 supplementation increases spine bone mineral density in adolescents and young adults with HIV infection being treated with tenofovir disoproxil fumarate: a randomized, placebo controlled trial

    Science.gov (United States)

    Background: Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized vitamin D3 (VITD3) would increase BMD in adolescents/young adults receiving TDF. Methods: Randomized double-blind placebo-controlled trial of directly observed VITD3 50,000 IU vs. placebo every 4 ...

  1. 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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

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    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

  5. 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.

  6. 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.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  9. 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.

  10. Pre-exposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine and Kidney Tubular Dysfunction in HIV-Uninfected Individuals.

    Science.gov (United States)

    Jotwani, Vasantha; Scherzer, Rebecca; Glidden, David V; Mehrotra, Megha; Defechereux, Patricia; Liu, Albert; Gandhi, Monica; Bennett, Michael; Coca, Steven G; Parikh, Chirag R; Grant, Robert M; Shlipak, Michael G

    2018-06-01

    Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is becoming increasingly adopted for HIV prevention. Tenofovir can cause proximal tubular damage and chronic kidney disease in HIV-infected persons, but little is known regarding its nephrotoxic potential among HIV-uninfected persons. In this study, we evaluated the effects of PrEP on urine levels of the following: α1-microglobulin (α1m), a marker of impaired tubular reabsorption; albuminuria, a measure of glomerular injury; and total proteinuria. The Iniciativa Profilaxis Pre-Exposicion (iPrEx) study randomized HIV-seronegative men and transgender women who have sex with men to oral TDF/FTC or placebo. The iPrEx open-label extension (iPrEx-OLE) study enrolled former PrEP trial participants to receive open-label TDF/FTC. A cross-sectional analysis compared urine biomarker levels by study arm in iPrEx (N = 100 treatment arm, N = 100 placebo arm). Then, urine biomarker levels were compared before and after PrEP initiation in 109 participants of iPrEx-OLE. In iPrEx, there were no significant differences in urine α1m, albuminuria, or proteinuria by treatment arm. In iPrEx-OLE, after 24 weeks on PrEP, urine α1m and proteinuria increased by 21% [95% confidence interval (CI): 10 to 33] and 18% (95% CI: 8 to 28), respectively. The prevalence of detectable α1m increased from 44% to 65% (P < 0.001) and estimated glomerular filtration rate declined by 4 mL/min/1.73 m (P < 0.001). There was no significant change in albuminuria (6%; 95% CI: -7% to 20%). PrEP with TDF/FTC was associated with a statistically significant rise in urine α1m and proteinuria after 6 months, suggesting that PrEP may result in subclinical tubule dysfunction.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  13. 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.

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

    Science.gov (United States)

    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.

  15. 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.

  16. Increased Dapivirine tissue accumulation through vaginal film codelivery of dapivirine and Tenofovir.

    Science.gov (United States)

    Akil, Ayman; Devlin, Brid; Cost, Marilyn; Rohan, Lisa Cencia

    2014-05-05

    The HIV-1 replication inhibitor dapivirine (DPV) is one of the most promising drug candidates being used in topical microbicide products for prevention of HIV-1 sexual transmission. To be able to block HIV-1 replication, DPV must have access to the viral reverse transcriptase enzyme. The window for DPV to access the enzyme happens during the HIV-1 cellular infection cycle. Thus, in order for DPV to exert its anti-HIV activity, it must be present in the mucosal tissue or cells where HIV-1 infection occurs. A dosage form containing DPV must be able to deliver the drug to the tissue site of action. Polymeric films are solid dosage forms that dissolve and release their payload upon contact with fluids. Films have been used as vaginal delivery systems of topical microbicide drug candidates including DPV. For use in topical microbicide products containing DPV, polymeric films must prove their ability to deliver DPV to the target tissue site of action. Ex vivo exposure studies of human ectocervical tissue to DPV film revealed that DPV was released from the film and did diffuse into the tissue in a concentration dependent manner indicating a process of passive diffusion. Analysis of drug distribution in the tissue revealed that DPV accumulated mostly at the basal layer of the epithelium infiltrating the upper part of the stroma. Furthermore, as a combination microbicide product, codelivery of DPV and TFV from a polymeric film resulted in a significant increase in DPV tissue concentration [14.21 (single entity film) and 31.03 μg/g (combination film)], whereas no impact on TFV tissue concentration was found. In vitro release experiments showed that this observation was due to a more rapid DPV release from the combination film as compared to the single entity film. In conclusion, the findings of this study confirm the ability of polymeric films to deliver DPV and TFV to human ectocervical tissue and show that codelivery of the two agents has a significant impact on DPV

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

    Science.gov (United States)

    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

  18. 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.

  19. 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

    Science.gov (United States)

    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...

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

    Directory of Open Access Journals (Sweden)

    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

  1. Drug Facts

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    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...

  2. Discovery of drugs that possess activity against feline leukemia virus.

    Science.gov (United States)

    Greggs, Willie M; Clouser, Christine L; Patterson, Steven E; Mansky, Louis M

    2012-04-01

    Feline leukemia virus (FeLV) is a gammaretrovirus that is a significant cause of neoplastic-related disorders affecting cats worldwide. Treatment options for FeLV are limited, associated with serious side effects, and can be cost-prohibitive. The development of drugs used to treat a related retrovirus, human immunodeficiency virus type 1 (HIV-1), has been rapid, leading to the approval of five drug classes. Although structural differences affect the susceptibility of gammaretroviruses to anti-HIV drugs, the similarities in mechanism of replication suggest that some anti-HIV-1 drugs may also inhibit FeLV. This study demonstrates the anti-FeLV activity of four drugs approved by the US FDA (Food and Drug Administration) at non-toxic concentrations. Of these, tenofovir and raltegravir are anti-HIV-1 drugs, while decitabine and gemcitabine are approved to treat myelodysplastic syndromes and pancreatic cancer, respectively, but also have anti-HIV-1 activity in cell culture. Our results indicate that these drugs may be useful for FeLV treatment and should be investigated for mechanism of action and suitability for veterinary use.

  3. 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.

  4. 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.

  5. 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.

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  8. Drug Facts

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    Full Text Available ... Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use and Other People Drug Use and Families Drug Use and Kids Drug Use and Unborn ...

  9. Drug Facts

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    Full Text Available ... Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, ... Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug Use and Kids ...

  10. Drug Facts

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    Full Text Available ... People Drug Use and Families Drug Use and Kids Drug Use and Unborn Children Drug Use and ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used ...

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

    Science.gov (United States)

    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.

  12. Efavirenz, Emtricitabine, and Tenofovir

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    ... 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 ...

  13. 77 FR 15110 - Antiviral Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    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...

  14. 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.

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

    Science.gov (United States)

    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.

  16. Drug Facts

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    Full Text Available ... Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used Drugs in the Past Drug Use ... Videos Information About Drugs Alcohol ...

  17. Drug Allergy

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    ... Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days or ... you take the drug. Drugs commonly linked to allergies Although any drug can cause an allergic reaction, ...

  18. New and investigational antiretroviral drugs for HIV infection: mechanisms of action and early research findings.

    Science.gov (United States)

    Saag, Michael S

    2012-12-01

    Numerous investigational antiretroviral agents are in clinical development. Among them are festinavir (BMS986001), a thymidine analogue similar to stavudine with reduced potential for toxicity; GS-7340, a prodrug of tenofovir that achieves greater intracellular concentrations; MK-1439, a nonnucleoside analogue reverse transcriptase inhibitor (NNRTI) that retains activity against common NNRTI-associated resistance mutations; and albuvirtide, a long-acting parenteral fusion inhibitor. Investigational integrase strand transfer inhibitors (InSTIs) include elvitegravir, recently approved by the US Food and Drug Administration (FDA) as part of a once-daily, single-tablet formulation with cobicistat/tenofovir/emtricitabine; dolutegravir, which maintains some activity against raltegravir- and elvitegravir-resistant mutants; and S/GSK1265744, which also maintains some activity against resistance mutations in the integrase gene and is being developed as a long-lasting parenteral agent. Novel 2-(quinolin-3-yl)acetic acid derivatives (LEDGINs), agents that were originally thought to inhibit the interaction of integrase with its cofactor lens epithelium-derived growth factor p75 (LEDGF/p75), be active against InSTI-resistant mutants and to have additive activity when combined with InSTIs. This article summarizes a presentation by Michael S. Saag, MD, at the IAS-USA live Improving the Management of HCV Disease continuing medical education program held in New York in October 2012.

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

    Science.gov (United States)

    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.

  20. Drug Safety

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    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  1. Drug Abuse

    Science.gov (United States)

    ... Cocaine Heroin Inhalants Marijuana Prescription drugs, including opioids Drug abuse also plays a role in many major social problems, such as drugged driving, violence, stress, and child abuse. Drug abuse can lead to ...

  2. Drug Facts

    Medline Plus

    Full Text Available ... Use and Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  3. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Kids Drug Use and Unborn Children Drug Use and Your Health Other Effects on ... Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids ...

  4. Club Drugs

    Science.gov (United States)

    ... uses. Other uses of these drugs are abuse. Club drugs are also sometimes used as "date rape" drugs, to make someone unable to say no to or fight back against sexual assault. Abusing these drugs can ...

  5. Phenotype, Genotype, and Drug Resistance in Subtype C HIV-1 Infection.

    Science.gov (United States)

    Derache, Anne; Wallis, Carole L; Vardhanabhuti, Saran; Bartlett, John; Kumarasamy, Nagalingeswaran; Katzenstein, David

    2016-01-15

    Virologic failure in subtype C is characterized by high resistance to first-line antiretroviral (ARV) drugs, including efavirenz, nevirapine, and lamivudine, with nucleoside resistance including type 2 thymidine analog mutations, K65R, a T69del, and M184V. However, genotypic algorithms predicting resistance are mainly based on subtype B viruses and may under- or overestimate drug resistance in non-B subtypes. To explore potential treatment strategies after first-line failure, we compared genotypic and phenotypic susceptibility of subtype C human immunodeficiency virus 1 (HIV-1) following first-line ARV failure. AIDS Clinical Trials Group 5230 evaluated patients failing an initial nonnucleoside reverse-transcriptase inhibitor (NNRTI) regimen in Africa and Asia, comparing the genotypic drug resistance and phenotypic profile from the PhenoSense (Monogram). Site-directed mutagenesis studies of K65R and T69del assessed the phenotypic impact of these mutations. Genotypic algorithms overestimated resistance to etravirine and rilpivirine, misclassifying 28% and 32%, respectively. Despite K65R with the T69del in 9 samples, tenofovir retained activity in >60%. Reversion of the K65R increased susceptibility to tenofovir and other nucleosides, while reversion of the T69del showed increased resistance to zidovudine, with little impact on other NRTI. Although genotype and phenotype were largely concordant for first-line drugs, estimates of genotypic resistance to etravirine and rilpivirine may misclassify subtype C isolates compared to phenotype. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  11. Pharmacokinetics of antiretroviral drugs in anatomical sanctuary sites: the male and female genital tract.

    Science.gov (United States)

    Else, Laura J; Taylor, Stephen; Back, David J; Khoo, Saye H

    2011-01-01

    HIV resides within anatomical 'sanctuary sites', where local drug exposure and viral dynamics may differ significantly from the systemic compartment. Suboptimal antiretroviral concentrations in the genital tract may result in compartmentalized viral replication, selection of resistant mutations and possible re-entry of wild-type/resistant virus into the systemic circulation. Therefore, achieving adequate antiretroviral exposure in the genital tract has implications for the prevention of sexual and vertical transmission of HIV. Penetration of antiretrovirals in the genital tract is expressed by accumulation ratios derived from the measurement of drug concentrations in time-matched seminal plasma/cervicovaginal fluid and plasma samples. Penetration varies by gender and may be drug (as opposed to class) specific with high interindividual variability. Concentrations in seminal plasma are highest for nucleoside analogues and lowest for protease inhibitors and efavirenz. Seminal accumulation of newer agents, raltegravir and maraviroc, is moderate (rank order of accumulation is nucleoside/nucleotide reverse transcriptase inhibitors [lamivudine/zidovudine/tenofovir/didanosine > stavudine/abacavir] > raltegravir > indinavir/maraviroc/nevirapine > efavirenz/protease inhibitors [amprenavir/atazanavir/darunavir > lopinavir/ritonavir > saquinavir] > enfuvirtide). In the female genital tract, the nucleoside analogues exhibit high accumulation ratios, whereas protease inhibitors have limited penetration; however, substantial variability exists between individuals and study centres. Second generation non-nucleoside reverse transcriptase inhibitor etravirine, and maraviroc and raltegravir, demonstrate effective accumulation in cervicovaginal secretions (rank order of accumulation is nucleoside/nucleotide reverse transcriptase inhibitor [zidovudine/lamivudine/didanosine > emtricitabine/tenofovir] > indinavir > maraviroc/raltegravir/darunavir/etravirine > nevirapine

  12. Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1

    DEFF Research Database (Denmark)

    Raffi, François; Babiker, Abdel G; Richert, Laura

    2014-01-01

    BACKGROUND: Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen. METHODS: Between August, 2010......-inferior to standard treatment and represents a treatment option for patients with CD4 cell counts higher than 200 cells per μL. FUNDING: European Union Sixth Framework Programme, Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck Laboratories....

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

    Science.gov (United States)

    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.

  14. Drug allergies

    Science.gov (United States)

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The first time ...

  15. Study Drugs

    Science.gov (United States)

    ... to quit, they may have withdrawal symptoms like depression, thoughts of suicide, intense drug cravings, sleep problems, and fatigue. The health risks aren't the only downside to study drugs. Students caught with illegal prescription drugs may get suspended ...

  16. Drug Facts

    Medline Plus

    Full Text Available ... symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to ...

  17. Drug Facts

    Medline Plus

    Full Text Available ... Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen ... to prescription drugs. The addiction slowly took over his life. I need different people around me. To ...

  18. Drug Reactions

    Science.gov (United States)

    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as ginkgo and blood thinners ...

  19. Drug Facts

    Science.gov (United States)

    ... Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol ...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  3. 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.

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

    Science.gov (United States)

    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.

  5. 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.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  7. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? Does Drug Treatment Work? What Are the Treatment Options? What Is Recovery? ...

  8. Drug Facts

    Medline Plus

    Full Text Available ... 4357) at any time to find drug treatment centers near you. I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from drugs. But she's afraid ...

  9. Patterns of adverse drug reaction signals in NAFDAC Pharmacovigilance activities from September to November, 2014.

    Science.gov (United States)

    Awodele, Olufunsho; Ibrahim, Ali; Orhii, Paul

    2016-03-16

    Adverse drug reaction signals are reported information on possible causal relationships between an adverse event and a drug. The National Pharmacovigilance Centre (NPC) in Nigeria has over 3,000 reported adverse drug reaction cases which have been adequately entered into the ADR data bank. Data mining of ADR reports from September to November, 2014 were carried out in this present study with the intention to describe the pattern of ADRs and generate possible signals. A total of about 100 reported cases with arrays of adverse drug reactions were reported between September and November, 2014 and the data were analyzed using SPSS version 17. Efavirenz/Tenofovir/Lamivudine combination was the highest reported drugs (24.2%) while efavirenz alone was reported in 8 times (8.8%) and HIV (63.3%) was the highest reported indication of drug use. Efavirenz caused central nervous system adverse reactions as revealed in the ADRs analyses. Zidovudine/Lamivudine/Nevirapine combination in concomitant use with Cotrimoxazole were reported 8 times with generalized maculopapular rashes on the trunk with some area of hyper pigmentation with intense itching documented twice and big/swollen rashes all over the faces. Zidovudine was also reported four times to cause severe anaemia. More surveillance is advocated so as to ascertain the consistency of the observed ADRs and thereafter establish appropriate signals.

  10. Substance use - prescription drugs

    Science.gov (United States)

    Substance use disorder - prescription drugs; Substance abuse - prescription drugs; Drug abuse - prescription drugs; Drug use - prescription drugs; Narcotics - substance use; Opioid - substance use; Sedative - substance ...

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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.

  14. 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.

    Science.gov (United States)

    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.

  15. 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

  16. 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.

  17. 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.

  18. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can ...

  19. Prescription Drugs

    Science.gov (United States)

    ... different competition is going on: the National Football League (NFL) vs. drug use. Read More » 92 Comments ... Future survey highlights drug use trends among the Nation’s youth for marijuana, alcohol, cigarettes, e-cigarettes (e- ...

  20. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth ... 662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter ...

  1. Drug Facts

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    Full Text Available ... form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts ... addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain ...

  2. Drug Facts

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    Full Text Available ... Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of ... Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1- ...

  3. Drug Control

    Science.gov (United States)

    Leviton, Harvey S.

    1975-01-01

    This article attempts to assemble pertinent information about the drug problem, particularily marihuana. It also focuses on the need for an educational program for drug control with the public schools as the main arena. (Author/HMV)

  4. Drug Facts

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    Full Text Available ... Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs ... Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call ...

  5. Drug Facts

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    Full Text Available ... Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone ... use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted ...

  6. Drug Facts

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    Full Text Available ... Numbers and Websites Search Share Listen English Español Information about this page Click on the button that ... about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana ...

  7. Drug Facts

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    Full Text Available ... Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) ... treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice ( ...

  8. Drug Facts

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    Full Text Available ... call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I ... The National Institute on Drug Abuse (NIDA) is part of the National Institutes of Health (NIH) , the ...

  9. Orphan drugs

    OpenAIRE

    Goločorbin-Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojša; Mikov, Momir

    2013-01-01

    Introduction. Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in ”adopting” them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of ...

  10. Drug Testing

    Science.gov (United States)

    ... testing, substance abuse testing, toxicology screen, tox screen, sports doping tests What is it used for? Drug screening is used to find out whether or not a person has taken a certain drug or drugs. It ... Sports organizations. Professional and collegiate athletes usually need to ...

  11. Drug Facts

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    Full Text Available ... to main content Easy-to-Read Drug Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts ... Past Drug Use Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page ...

  12. Drug Facts

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    Full Text Available ... can call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from ...

  13. Drug Facts

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    Full Text Available ... the computer will read the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos ... I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from ...

  14. Drug Facts

    Medline Plus

    Full Text Available ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs ... adicción. English Español About the National Institute on Drug Abuse (NIDA) | About This Website Tools and Resources | Contact ...

  15. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? Does Drug Treatment Work? What Are the Treatment Options? What Is Recovery? ...

  16. Drug Facts

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    Full Text Available ... Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol ...

  17. 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

  18. WAr on DrugS

    African Journals Online (AJOL)

    2009-04-12

    Apr 12, 2009 ... ABStrAct. Since drugs became both a public and social issue in Nigeria, fear about both the real and .... drugs as being morally reprehensible, and ..... tice system (see for instance, Shaw, 1995; ..... A cut throat business:.

  19. Drug transporter gene expression in human colorectal tissue and cell lines: modulation with antiretrovirals for microbicide optimization.

    Science.gov (United States)

    Mukhopadhya, Indrani; Murray, Graeme I; Berry, Susan; Thomson, John; Frank, Bruce; Gwozdz, Garry; Ekeruche-Makinde, Julia; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

    2016-02-01

    The objectives of this study were to comprehensively assess mRNA expression of 84 drug transporters in human colorectal biopsies and six representative cell lines, and to investigate the alteration of drug transporter gene expression after exposure to three candidate microbicidal antiretroviral (ARV) drugs (tenofovir, darunavir and dapivirine) in the colorectal epithelium. The outcome of the objectives informs development of optimal ARV-based microbicidal formulations for prevention of HIV-1 infection. Drug transporter mRNA expression was quantified from colorectal biopsies and cell lines by quantitative real-time PCR. Relative mRNA expression was quantified in Caco-2 cells and colorectal explants after induction with ARVs. Data were analysed using Pearson's product moment correlation (r), hierarchical clustering and principal component analysis (PCA). Expression of 58 of the 84 transporters was documented in colorectal biopsies, with genes for CNT2, P-glycoprotein (P-gp) and MRP3 showing the highest expression. No difference was noted between individual subjects when analysed by age, gender or anatomical site (rectum or recto-sigmoid) (r = 0.95-0.99). High expression of P-gp and CNT2 proteins was confirmed by immunohistochemical staining. Similarity between colorectal tissue and cell-line drug transporter gene expression was variable (r = 0.64-0.84). PCA showed distinct clustering of human colorectal biopsy samples, with the Caco-2 cells defined as the best surrogate system. Induction of Caco-2 cell lines with ARV drugs suggests that darunavir-based microbicides incorporating tenofovir may result in drug-drug interactions likely to affect distribution of individual drugs to sub-epithelial target cells. These findings will help optimize complex formulations of rectal microbicides to realize their full potential as an effective approach for pre-exposure prophylaxis against HIV-1 infection. © The Author 2015. Published by Oxford University Press on behalf of the

  20. Combined Analysis of the Prevalence of drug Resistant Hepatitis B Virus in antiviral therapy Experienced patients in Europe (CAPRE)

    DEFF Research Database (Denmark)

    Hermans, L E; Svicher, V; Pas, S D

    2016-01-01

    BACKGROUND: European guidelines recommend treatment of chronic hepatitis B virus infection (CHB) with the nucleos(t)ide analogs (NAs) entecavir or tenofovir. However, many European CHB patients have been exposed to other NAs, which are associated with therapy failure and resistance. The CAPRE study...... was performed to gain insight in prevalence and characteristics of NA resistance in Europe. METHODS: A survey was performed on genotypic resistance testing results acquired during routine monitoring of CHB patients with detectable serum hepatitis B virus DNA in European tertiary referral centers. RESULTS: Data...... from 1568 patients were included. The majority (73.8%) were exposed to lamivudine monotherapy. Drug-resistant strains were detected in 52.7%. The most frequently encountered primary mutation was M204V/I (48.7%), followed by A181T/V (3.8%) and N236T (2.6%). In patients exposed to entecavir (n = 102...

  1. COPD - control drugs

    Science.gov (United States)

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...

  2. A significant reduction in the frequency of HIV-1 drug resistance in Québec from 2001 to 2011 is associated with a decrease in the monitored viral load.

    Directory of Open Access Journals (Sweden)

    Hugues Charest

    Full Text Available BACKGROUND: HIV drug resistance represents a major threat for effective treatment. We assessed the trends in the frequency of drug resistance mutations and the monitored viral load (VL in treatment-naïve (TN and treatment-experienced (TE individuals infected with HIV-1 in Québec, Canada, between 2001 and 2011. METHODS AND FINDINGS: Resistance data were obtained from 4,105 and 5,086 genotypic tests performed on TN and TE patients, respectively. Concomitantly, 274,161 VL tests were carried out in the Province. Changes over time in drug resistance frequency and in different categories of VL were assessed using univariate logistic regression. Multiple logistic regression was used to evaluate associations between the rates of certain mutations and antiretroviral prescriptions. From 2001 to 2011, the proportion of undetectable VL test results continually increased, from 42.1% to 75.9%, while a significant decrease in the frequency of resistance mutations associated with protease inhibitors [PI (from 54% to 16%], nucleoside [NRTI (from 78% to 37% and non-nucleoside reverse transcriptase inhibitors [NNRTI (from 44% to 31%] was observed in TE patients. In TN individuals, the overall frequency of transmitted drug resistance was 13.1%. A multiple logistic regression analysis indicated that the introduction of co-formulated emtricitabine/tenofovir or emtricitabine/tenofovir/efavirenz was positively associated with the decrease of the frequency of the M184I/V mutations observed overtime (p = 0.0004. CONCLUSIONS: We observed a significant decrease in the frequency of drug resistance mutations in TE patients, concomitant with a decrease in the proportion of patients with detectable viremia. These findings may be related to both the increased potencies and adherence to therapy associated with newer antiretroviral regimens. Nevertheless, our data demonstrate that broad use of antiretrovirals does not increase the level of circulating drug resistant

  3. [Orphan drugs].

    Science.gov (United States)

    Golocorbin Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojsa; Mikov, Momir

    2013-01-01

    Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in "adopting" them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of drugs meant to treat diseases whose pathogenesis has not yet been clarified in majority of cases. The aim of this paper is to present previous and present status of orphan drugs in Serbia and other countries. THE BEGINNING OF ORPHAN DRUGS DEVELOPMENT: This problem was first recognized by Congress of the United States of America in January 1983, and when the "Orphan Drug Act" was passed, it was a turning point in the development of orphan drugs. This law provides pharmaceutical companies with a series of reliefs, both financial ones that allow them to regain funds invested into the research and development and regulatory ones. Seven years of marketing exclusivity, as a type of patent monopoly, is the most important relief that enables companies to make large profits. There are no sufficient funds and institutions to give financial support to the patients. It is therefore necessary to make health professionals much more aware of rare diseases in order to avoid time loss in making the right diagnosis and thus to gain more time to treat rare diseases. The importance of discovery, development and production of orphan drugs lies in the number of patients whose life quality can be improved significantly by administration of these drugs as well as in the number of potential survivals resulting from the treatment with these drugs.

  4. AIDSinfo Drug Database

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content Drugs Home Drugs Find information on FDA-approved HIV/ ... infection drugs and investigational HIV/AIDS drugs. Search Drugs Search drug Search Icon What's this? Close Popup ...

  5. 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) ...

  6. Drug Facts

    Medline Plus

    Full Text Available ... Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What ... Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800- ...

  7. Drug Facts

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    Full Text Available ... Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? ... Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662- ...

  8. Antineoplastic Drugs

    Science.gov (United States)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  9. Drugged Driving

    Science.gov (United States)

    ... Survey Results Synthetic Cannabinoids (K2/Spice) Unpredictable Danger Drug and Alcohol Use in College-Age Adults in 2016 Monitoring the Future 2016 Survey Results Drug and Alcohol Use in College-Age Adults in 2015 View All NIDA Home ...

  10. Evolution of antiretroviral drug costs in Brazil in the context of free and universal access to AIDS treatment.

    Science.gov (United States)

    Nunn, Amy S; Fonseca, Elize M; Bastos, Francisco I; Gruskin, Sofia; Salomon, Joshua A

    2007-11-13

    Little is known about the long-term drug costs associated with treating AIDS in developing countries. Brazil's AIDS treatment program has been cited widely as the developing world's largest and most successful AIDS treatment program. The program guarantees free access to highly active antiretroviral therapy (HAART) for all people living with HIV/AIDS in need of treatment. Brazil produces non-patented generic antiretroviral drugs (ARVs), procures many patented ARVs with negotiated price reductions, and recently issued a compulsory license to import one patented ARV. In this study, we investigate the drivers of recent ARV cost trends in Brazil through analysis of drug-specific prices and expenditures between 2001 and 2005. We compared Brazil's ARV prices to those in other low- and middle-income countries. We analyzed trends in drug expenditures for HAART in Brazil from 2001 to 2005 on the basis of cost data disaggregated by each ARV purchased by the Brazilian program. We decomposed the overall changes in expenditures to compare the relative impacts of changes in drug prices and drug purchase quantities. We also estimated the excess costs attributable to the difference between prices for generics in Brazil and the lowest global prices for these drugs. Finally, we estimated the savings attributable to Brazil's reduced prices for patented drugs. Negotiated drug prices in Brazil are lowest for patented ARVs for which generic competition is emerging. In recent years, the prices for efavirenz and lopinavir-ritonavir (lopinavir/r) have been lower in Brazil than in other middle-income countries. In contrast, the price of tenofovir is US$200 higher per patient per year than that reported in other middle-income countries. Despite precipitous price declines for four patented ARVs, total Brazilian drug expenditures doubled, to reach US$414 million in 2005. We find that the major driver of cost increases was increased purchase quantities of six specific drugs: patented lopinavir

  11. Evolution of antiretroviral drug costs in Brazil in the context of free and universal access to AIDS treatment.

    Directory of Open Access Journals (Sweden)

    Amy S Nunn

    2007-11-01

    Full Text Available Little is known about the long-term drug costs associated with treating AIDS in developing countries. Brazil's AIDS treatment program has been cited widely as the developing world's largest and most successful AIDS treatment program. The program guarantees free access to highly active antiretroviral therapy (HAART for all people living with HIV/AIDS in need of treatment. Brazil produces non-patented generic antiretroviral drugs (ARVs, procures many patented ARVs with negotiated price reductions, and recently issued a compulsory license to import one patented ARV. In this study, we investigate the drivers of recent ARV cost trends in Brazil through analysis of drug-specific prices and expenditures between 2001 and 2005.We compared Brazil's ARV prices to those in other low- and middle-income countries. We analyzed trends in drug expenditures for HAART in Brazil from 2001 to 2005 on the basis of cost data disaggregated by each ARV purchased by the Brazilian program. We decomposed the overall changes in expenditures to compare the relative impacts of changes in drug prices and drug purchase quantities. We also estimated the excess costs attributable to the difference between prices for generics in Brazil and the lowest global prices for these drugs. Finally, we estimated the savings attributable to Brazil's reduced prices for patented drugs. Negotiated drug prices in Brazil are lowest for patented ARVs for which generic competition is emerging. In recent years, the prices for efavirenz and lopinavir-ritonavir (lopinavir/r have been lower in Brazil than in other middle-income countries. In contrast, the price of tenofovir is US$200 higher per patient per year than that reported in other middle-income countries. Despite precipitous price declines for four patented ARVs, total Brazilian drug expenditures doubled, to reach US$414 million in 2005. We find that the major driver of cost increases was increased purchase quantities of six specific drugs

  12. Cost-Effectiveness and Cost Thresholds of Generic and Brand Drugs in a National Chronic Hepatitis B Treatment Program in China.

    Directory of Open Access Journals (Sweden)

    Mehlika Toy

    Full Text Available Chronic liver disease and liver cancer associated with chronic hepatitis B (CHB are leading causes of death among adults in China. Although newborn hepatitis B immunization has successfully reduced the prevalence of CHB in children, about 100 million Chinese adults remain chronically infected. If left unmanaged, 15-25% will die from liver cancer or liver cirrhosis. Antiviral treatment is not necessary for all patients with CHB, but when it is indicated, good response to treatment would prevent disease progression and reduce disease mortality and morbidity, and costly complications. The aim of this study is to analyze the cost-effectiveness of generic and brand antiviral drugs for CHB treatment in China, and assessing various thresholds at which a highly potent, low resistance antiviral drug would be cost-saving and/or cost-effective to introduce in a national treatment program. We developed a Markov simulation model of disease progression using effectiveness and cost data from the medical literature. We measured life-time costs, quality adjusted life years (QALYs, incremental cost-effectiveness ratios (ICERs, and clinical outcomes. The no treatment strategy incurred the highest health care costs ($12,932-$25,293 per patient, and the worst health outcomes, compared to the antiviral treatment strategies. Monotherapy with either entecavir or tenofovir yielded the most QALYs (14.10-19.02 for both HBeAg-positive and negative patients, with or without cirrhosis. Threshold analysis showed entercavir or tenofovir treatment would be cost saving if the drug price is $32-75 (195-460 RMB per month, highly cost-effective at $62-110 (379-670 RMB per month and cost-effective at $63-120 (384-734 RMB per month. This study can support policy decisions regarding the implementation of a national health program for chronic hepatitis B treatment in China at the population level.

  13. Drug repurposing based on drug-drug interaction.

    Science.gov (United States)

    Zhou, Bin; Wang, Rong; Wu, Ping; Kong, De-Xin

    2015-02-01

    Given the high risk and lengthy procedure of traditional drug development, drug repurposing is gaining more and more attention. Although many types of drug information have been used to repurpose drugs, drug-drug interaction data, which imply possible physiological effects or targets of drugs, remain unexploited. In this work, similarity of drug interaction was employed to infer similarity of the physiological effects or targets for the drugs. We collected 10,835 drug-drug interactions concerning 1074 drugs, and for 700 of them, drug similarity scores based on drug interaction profiles were computed and rendered using a drug association network with 589 nodes (drugs) and 2375 edges (drug similarity scores). The 589 drugs were clustered into 98 groups with Markov Clustering Algorithm, most of which were significantly correlated with certain drug functions. This indicates that the network can be used to infer the physiological effects of drugs. Furthermore, we evaluated the ability of this drug association network to predict drug targets. The results show that the method is effective for 317 of 561 drugs that have known targets. Comparison of this method with the structure-based approach shows that they are complementary. In summary, this study demonstrates the feasibility of drug repurposing based on drug-drug interaction data. © 2014 John Wiley & Sons A/S.

  14. [Club drugs].

    Science.gov (United States)

    Guerreiro, Diogo Frasquilho; Carmo, Ana Lisa; da Silva, Joaquim Alves; Navarro, Rita; Góis, Carlos

    2011-01-01

    Club drugs are the following substances: Methylenedioxymethamphetamine (MDMA); Methamphetamine; Lysergic Acid Diethylamide (LSD); Ketamine; Gamma-hydroxybutyrate (GHB) and Flunitrazepam. These substances are mainly used by adolescents and young adults, mostly in recreational settings like dance clubs and rave parties. These drugs have diverse psychotropic effects, are associated with several degrees of toxicity, dependence and long term adverse effects. Some have been used for several decades, while others are relatively recent substances of abuse. They have distinct pharmacodynamic and pharmacokinetic properties, are not easy to detect and, many times, the use of club drugs is under diagnosed. Although the use of these drugs is increasingly common, few health professionals feel comfortable with the diagnosis and treatment. The authors performed a systematic literature review, with the goal of synthesising the existing knowledge about club drugs, namely epidemiology, mechanism of action, detection, adverse reactions and treatment. The purpose of this article is creating in Portuguese language a knowledge data base on club drugs, that health professionals of various specialties can use as a reference when dealing with individual with this kind of drug abuse.

  15. In vitro resistance profile of the candidate HIV-1 microbicide drug dapivirine.

    Science.gov (United States)

    Schader, Susan M; Oliveira, Maureen; Ibanescu, Ruxandra-Ilinca; Moisi, Daniela; Colby-Germinario, Susan P; Wainberg, Mark A

    2012-02-01

    Antiretroviral-based microbicides may offer a means to reduce the sexual transmission of HIV-1. Suboptimal use of a microbicide may, however, lead to the development of drug resistance in users that are already, or become, infected with HIV-1. In such cases, the efficacy of treatments may be compromised since the same (or similar) antiretrovirals used in treatments are being developed as microbicides. To help predict which drug resistance mutations may develop in the context of suboptimal use, HIV-1 primary isolates of different subtypes and different baseline resistance profiles were used to infect primary cells in vitro in the presence of increasing suboptimal concentrations of the two candidate microbicide antiretrovirals dapivirine (DAP) and tenofovir (TFV) alone or in combination. Infections were ongoing for 25 weeks, after which reverse transcriptase genotypes were determined and scrutinized for the presence of any clinically recognized reverse transcriptase drug resistance mutations. Results indicated that suboptimal concentrations of DAP alone facilitated the emergence of common nonnucleoside reverse transcriptase inhibitor resistance mutations, while suboptimal concentrations of DAP plus TFV gave rise to fewer mutations. Suboptimal concentrations of TFV alone did not frequently result in the development of resistance mutations. Sensitivity evaluations for stavudine (d4T), nevirapine (NVP), and lamivudine (3TC) revealed that the selection of resistance as a consequence of suboptimal concentrations of DAP may compromise the potential for NVP to be used in treatment, a finding of potential relevance in developing countries.

  16. Drug Facts

    Medline Plus

    Full Text Available ... MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco ... Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You ...

  17. Drug Facts

    Medline Plus

    Full Text Available ... Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA ( ... Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/ ...

  18. Drug Facts

    Medline Plus

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth ( ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  19. Drug Facts

    Medline Plus

    Full Text Available ... Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain ... About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other ...

  20. Drug Metabolism

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 3. Drug Metabolism: A Fascinating Link Between Chemistry and Biology. Nikhil Taxak Prasad V Bharatam. General Article Volume 19 Issue 3 March 2014 pp 259-282 ...

  1. Drugged Driving

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  2. Club Drugs

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  3. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    behind metabolic reactions, importance, and consequences with several ... required for drug action. ... lism, which is catalyzed by enzymes present in the above-men- ... catalyze the transfer of one atom of oxygen to a substrate produc-.

  4. Drug Facts

    Medline Plus

    Full Text Available ... Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and ... Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can ...

  5. Drug Facts

    Medline Plus

    Full Text Available ... 800-662-HELP (4357) at any time to find drug treatment centers near you. I want my ... is making positive changes in her life. She finds support from family and friends who don't ...

  6. Drug Facts

    Medline Plus

    Full Text Available ... That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, ... Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) ...

  7. Drug Facts

    Medline Plus

    Full Text Available ... Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? ... of Health (NIH) , the principal biomedical and behavioral research agency of the United States Government. NIH is ...

  8. Drug Reactions

    Science.gov (United States)

    ... Kids and Teens Pregnancy and Childbirth Women Men Seniors Your Health Resources Healthcare Management End-of-Life Issues Insurance & Bills Self Care Working With Your Doctor Drugs, Procedures & Devices Over-the- ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... prescription drugs. The addiction slowly took over his life. I need different people around me. To stop ... marijuana, "Cristina" is making positive changes in her life. She finds support from family and friends who ...

  10. Drug Resistance

    Science.gov (United States)

    ... Drug-resistance testing is also recommended for all pregnant women with HIV before starting HIV medicines and also in some pregnant women already taking HIV medicines. Pregnant women will work with their health ...

  11. Drug Facts

    Medline Plus

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  12. Drug Addiction

    Science.gov (United States)

    ... as hearing colors Impulsive behavior Rapid shifts in emotions Permanent mental changes in perception Rapid heart rate ... Drug use can negatively affect academic performance and motivation to excel in school. Legal issues. Legal problems ...

  13. Drug Facts

    Medline Plus

    Full Text Available ... That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ... Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) ...

  14. 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.

    Science.gov (United States)

    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

    Osteopenia, osteoporosis, and low bone mineral density are frequent in patients with HIV. We assessed the 96 week loss of bone mineral density associated with a nucleoside or nucleotide reverse transcriptase inhibitor (NtRTI)-sparing regimen. Antiretroviral-naive adults with HIV were enrolled in 78 clinical sites in 15 European countries into a randomised (1:1), open-label, non-inferiority trial (NEAT001/ANRS143) assessing the efficacy and safety of darunavir (800 mg once per day) and ritonavir (100 mg once per day) plus either raltegravir (400 mg twice per day; NtRTI-sparing regimen) or tenofovir (245 mg once per day) and emtricitabine (200 mg once per day; standard regimen). For this bone-health substudy, 20 of the original sites in six countries participated, and any patient enrolled at one of these sites who met the following criteria was eligible: plasma viral loads greater than 1000 HIV RNA copies per mL and CD4 cell counts of fewer than 500 cells per μL, except in those with symptomatic HIV infection. Exclusion criteria included treatment for malignant disease, testing positive for hepatitis B virus surface antigen, pregnancy, creatinine clearance less than 60 mL per min, treatment for osteoporosis, systemic steroids, or oestrogen-replacement therapy. The two primary endpoints were the mean percentage changes in lumbar spine and total hip bone mineral density at week 48, assessed by dual energy x-ray absorptiometry (DXA) scans. We did the analysis with an intention-to-treat-exposed approach with antiretroviral modifications ignored. The parent trial is registered with ClinicalTrials.gov, number NCT01066962, and is closed to new participants. Between Aug 2, 2010, and April 18, 2011, we recruited 146 patients to the substudy, 70 assigned to the NtRTI-sparing regimen and 76 to the standard regimen. DXA data were available for 129, 121 and 107 patients at baseline, 48 and 96 weeks respectively. At week 48, the mean percentage loss in bone mineral density in the

  15. Legal Drugs Are Good Drugs and Illegal Drugs Are Bad Drugs

    OpenAIRE

    Indrati, Dina; Prasetyo, Herry

    2011-01-01

    ABSTRACT : Labelling drugs are important issue nowadays in a modern society. Although it is generally believed that legal drugs are good drugs and illegal drugs are bad drugs, it is evident that some people do not aware about the side effects of drugs used. Therefore, a key contention of this philosophical essay is that explores harms minimisation policy, discuss whether legal drugs are good drugs and illegal drugs are bad drugs and explores relation of drugs misuse in a psychiatric nursing s...

  16. Drugs@FDA: FDA Approved Drug Products

    Science.gov (United States)

    ... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing ... Download Drugs@FDA Express for free Search by Drug Name, Active Ingredient, or Application Number Enter at ...

  17. 3D printed, controlled release, tritherapeutic tablet matrix for advanced anti-HIV-1 drug delivery.

    Science.gov (United States)

    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.

  18. Study Drugs

    OpenAIRE

    Lam, Stephanie Phuong; Roosta, Natalie; Nielsen, Mikkel Fuhr; Meyer, Maria Holmgaard; Friis, Katrine Birk

    2016-01-01

    In recent years, students around the world, started to use preparations as Ritalin and Modafinil,also known as study drugs, to improve their cognitive abilities1. It is a common use among thestudents in United States of America, but it is a new tendency in Denmark. Our main focus is tolocate whether study drugs needs to be legalized in Denmark or not. To investigate this ourstarting point is to understand central ethical arguments in the debate. We have chosen twoarguments from Nick Bostrom a...

  19. Drug Facts

    Medline Plus

    Full Text Available ... Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the button ... sobre el abuso de drogas, y adicción. English Español About the National Institute on Drug Abuse (NIDA) | ...

  20. Drugs reviews

    African Journals Online (AJOL)

    Angel_D

    tests (LFTs) to monitor hepatotoxicity (liver [hepatic] damage) is uncommon in many resource-poor ... cholesterol ester storage disease. ... The problem with many patients is that they are taking several drugs often ... Urine, saliva and other body fluids may be coloured orange-red: this can be very alarming to patients.

  1. Drug resistance

    NARCIS (Netherlands)

    Gorter, J.A.; Potschka, H.; Noebels, J.L.; Avoli, M.; Rogawski, M.A.; Olsen, R.W.; Delgado-Escueta, A.V.

    2012-01-01

    Drug resistance remains to be one of the major challenges in epilepsy therapy. Identification of factors that contribute to therapeutic failure is crucial for future development of novel therapeutic strategies for difficult-to-treat epilepsies. Several clinical studies have shown that high seizure

  2. Capping Drugs

    Indian Academy of Sciences (India)

    preventing disease in human beings or in animals. In the process ... of requirement. In the process, they may cause toxic side effects. .... the liver to release the physiologically active drug. Similarly ... patients addicted to alcohol. However, it is a ...

  3. Drug Facts

    Medline Plus

    Full Text Available ... Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the ... información sobre el abuso de drogas, y adicción. English Español About the National Institute on Drug Abuse ( ...

  4. Drug abuse first aid

    Science.gov (United States)

    ... use of these drugs is a form of drug abuse. Medicines that are for treating a health problem ... about local resources. Alternative Names Overdose from drugs; Drug abuse first aid References Myck MB. Hallucinogens and drugs ...

  5. 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

    Directory of Open Access Journals (Sweden)

    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.

  6. Drug Safety: Managing Multiple Drugs

    Science.gov (United States)

    ... This series is produced by Consumers Union and Consumer Reports Best Buy Drugs , a public information project sup- ported by grants from the Engelberg Foundation and the National Library of Medicine of ... Consumer and Prescriber Education Grant Program which is funded ...

  7. Legal Drugs Are Good Drugs And Illegal Drugs Are Bad Drugs

    Directory of Open Access Journals (Sweden)

    Dina Indrati

    2011-07-01

    Full Text Available ABSTRACT : Labelling drugs are important issue nowadays in a modern society. Although it is generally believed that legal drugs are good drugs and illegal drugs are bad drugs, it is evident that some people do not aware about the side effects of drugs used. Therefore, a key contention of this philosophical essay is that explores harms minimisation policy, discuss whether legal drugs are good drugs and illegal drugs are bad drugs and explores relation of drugs misuse in a psychiatric nursing setting and dual diagnosis.Key words: Legal, good drugs, illegal, bad drugs.

  8. P39: Effectiveness of tenofovir/3(F)TC plus NNRTI compared to zidovudine/3TC plus NNRTI first-line regimens in Argentina

    OpenAIRE

    Fábio, Caldas de Mesquita; Pati, Pascom Ana Roberta; Clarissa, Habckost Dutra de Barros; Juliana, Machado Givisiez; Taques, dos Santos Christ Maria; Larissa, de Faro Valverde; Marcelo, Araújo de Freitas; Nestor, Sosa; Peter, Reiss; William, Pape Jean; Omar, Sued; Andrew, Revell; Dechao, Wang; Peter, Reiss; Ard, van Sighem

    2014-01-01

    Introduction: Latin America contains the third highest estimated number of people living with HIV-1 in the world [1]. Illicit drug users (DUs) are vulnerable to HIV and other blood-borne pathogens as a result of sharing contaminated syringes and other equipment [1]. Epidemiological aspects of HIV-1 infection in the Brazilian Amazon are poorly known, especially in risk groups. This study determined the prevalence and factors associated with infection by HIV-1 among DUs in the Marajó Archipelag...

  9. Drugs Approved for Neuroblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  10. Drugs Approved for Leukemia

    Science.gov (United States)

    This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  11. Drugs Approved for Retinoblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  12. National Drug Code Directory

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Drug Listing Act of 1972 requires registered drug establishments to provide the Food and Drug Administration (FDA) with a current list of all drugs manufactured,...

  13. Other Drugs of Abuse

    Science.gov (United States)

    ... People Abuse » Other Drugs of Abuse Other Drugs of Abuse Listen There are many other drugs of abuse, ... and Rehab Resources About the National Institute on Drug Abuse (NIDA) | About This Website Tools and Resources | Contact ...

  14. Urine drug screen

    Science.gov (United States)

    Drug screen - urine ... detect the presence of illegal and some prescription drugs in your urine. Their presence may indicate that you recently used these drugs. Some drugs may remain in your system for ...

  15. Understanding drugs and behaviour

    National Research Council Canada - National Science Library

    Parrott, Andrew

    2004-01-01

    ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix xi Part I Drugs and Their Actions . . . . . . . . . . . . . . . . . . . . . . 1 Psychoactive drugs: introduction and overview . . . . . . . . 2 The brain...

  16. 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.

  17. 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.

    Science.gov (United States)

    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.

  18. Prescription Drug Abuse

    Science.gov (United States)

    ... drug abuse. And it's illegal, just like taking street drugs. Why Do People Abuse Prescription Drugs? Some people abuse prescription drugs ... common risk of prescription drug abuse is addiction . People who abuse ... as if they were taking street drugs. That's one reason most doctors won't ...

  19. Drug abuse

    International Nuclear Information System (INIS)

    Simon, T.R.; Seastrunk, J.W.; Malone, G.; Knesevich, M.A.; Hickey, D.C.

    1991-01-01

    This paper reports that this study used SPECT to examine patients who have abused drugs to determine whether SPECT could identify abnormalities and whether these findings have clinical importance. Fifteen patients with a history of substance abuse (eight with cocaine, six with amphetamine, and one with organic solvent) underwent SPECT performed with a triple-headed camera and Tc-99m HMPAO both early for blood flow and later for functional information. These images were then processed into a 3D videotaped display used in group therapy. All 15 patients had multiple areas of decreased tracer uptake peppered throughout the cortex but mainly affecting the parietal lobes, expect for the organic solvent abuser who had a large parietal defect. The videotapes were subjectively described by a therapist as an exceptional tool that countered patient denial of physical damage from substance abuse. Statistical studies of recidivism between groups is under way

  20. Personality, Drug Preference, Drug Use, and Drug Availability

    Science.gov (United States)

    Feldman, Marc; Boyer, Bret; Kumar, V. K.; Prout, Maurice

    2011-01-01

    This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals (n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967)…

  1. Issues in resistance, adherence, and comparative efficacy of the single-tablet regimen combination of tenofovir, emtricitabine, and efavirenz in the management of HIV-1 infection

    Directory of Open Access Journals (Sweden)

    Rebick G

    2012-09-01

    Full Text Available Gabriel Rebick, Sharon L WalmsleyDivision of Infectious Diseases, Department of Medicine, University Health Network, University of Toronto, Toronto, ON, CanadaAbstract: Atripla is the first once-daily, single-tablet, triple-combination antiretroviral therapy. It is recommended for the initial treatment of the naïve patient with human immunodeficiency virus-1 (HIV-1 infection in all current guidelines, based on its proven efficacy in numerous head-to-head randomized clinical trials. Not only has it proven efficacy, but the fixed-dose combination, Atripla, has resulted in an improvement in adherence, quality of life, and satisfaction among naïve as well as virally suppressed patients switching from another regimen. Despite the advantages, tolerability issues can arise that are related primarily to the efavirenz component, which is known to cause central nervous side effects such as dizziness, abnormal dreams, and anxiety. Although generally self-limited, these side-effects can lead to treatment discontinuation in the short- or long-term. Based on the observation of neural tube defects in macaque models, and isolated case reports in human fetuses with first trimester exposure, it is rated as Food and Drug Administration pregnancy category D, and considered as contraindicated in the first trimester of pregnancy where alternatives are available. Given the low genetic barrier of each of the individual components, resistance remains an important issue for patients with poor adherence, but is balanced in part by the long half-life of the drugs. Transmitted resistance is described in up to 16% of newly infected patients in population surveys, and is particularly prevalent in men who have sex with men. Minority variants that may impart resistant to efavirenz are not detected with currently used HIV-1 genotype assays, but nonetheless may also be implicated in patients who fail initial treatment. Several single-tablet regimens are recently licensed or in

  2. Drugs Approved for Rhabdomyosarcoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for rhabdomyosarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries. There may be drugs used in rhabdomyosarcoma that are not listed here.

  3. Information for Consumers (Drugs)

    Science.gov (United States)

    ... approved drugs Drugs@FDA Information on FDA-approved brand name and generic drugs including labeling and regulatory history Drugs with Approved Risk Evaluation and Mitigation Strategies (REMS) REMS is a risk management plan required by FDA for certain prescription drugs, ...

  4. Drugs and lactation

    International Nuclear Information System (INIS)

    Kelssering, G.; Aguiar, L.F.; Ribeiro, R.M.; Souza, A.Z. de

    1988-01-01

    Different kinds of drugs who can be transferred through the mother's milk to the lactant and its effects are showed in this work. A list of them as below: cardiotonics, diuretics, anti-hypertensives, beta-blockings, anti-arrythmics, drugs with gastrintestinal tract action, hormones, antibiotics and chemotherapeutics, citostatic drugs, central nervous system action drugs and anticoagulants drugs. (L.M.J.) [pt

  5. Drug Retention Times

    Energy Technology Data Exchange (ETDEWEB)

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user.

  6. Drug Reactions - Multiple Languages

    Science.gov (United States)

    ... PDF Drug Interactions - HIV medicines, part 6 - English MP3 Drug Interactions - HIV medicines, part 6 - 简体中文 (Chinese, Simplified (Mandarin dialect)) MP3 Drug Interactions - HIV medicines, part 6 - English MP4 ...

  7. Teenagers and drugs

    Science.gov (United States)

    Teenagers and drugs; Symptoms of drug use in teenagers; Drug abuse - teenagers; Substance abuse - teenagers ... for a specialist who has experience working with teenagers. Do not hesitate, get help right away. The ...

  8. Drug Interaction API

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Interaction API is a web service for accessing drug-drug interactions. No license is needed to use the Interaction API. Currently, the API uses DrugBank for its...

  9. 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).

    Science.gov (United States)

    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.

  10. 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.

  11. Effects of Drugs

    Science.gov (United States)

    ... Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search ... who aren't yet born. Drug use can hurt the body and the brain, sometimes forever. Drug use can also lead to addiction, a long-lasting brain disease in which people ...

  12. Drugs and Young People

    Science.gov (United States)

    Drug abuse is a serious public health problem. It affects almost every community and family in some way. Drug abuse in children and teenagers may pose a ... of young people may be more susceptible to drug abuse and addiction than adult brains. Abused drugs ...

  13. DRUG POLICY AND DRUG ADDICTION IN TURKEY

    OpenAIRE

    İLHAN, Mustafa Necmi

    2018-01-01

    The NationalStrategy Document on Drugs and Emergency Action Plan started with thecontributions of all the relevant institutions within the year of 2014 wasprepared and after that in accordance with the Prime Ministry Notice entitledFight Against Drugs published within this scope, the committees for FightAgainst Drugs were established (under the presidency of Deputy Prime Ministerand with the help of Ministry of Health, Ministry of Justice, Ministry of Laborand Social Security, Ministry of Fam...

  14. Drug interactions with oral sulphonylurea hypoglycaemic drugs.

    Science.gov (United States)

    Hansen, J M; Christensen, L K

    1977-01-01

    The effect of the oral sulphonylurea hypoglycaemic drugs may be influenced by a large number of other drugs. Some of these combinations (e.g. phenylbutazone, sulphaphenazole) may result in cases of severe hypoglycaemic collapse. Tolbutamide and chlorpropamide should never be given to a patient without a prior careful check of which medicaments are already being given. Similarly, no drug should be given to a diabetic treated with tolbutamide and chlorpropamide without consideration of the possibility of interaction phenomena.

  15. International Drug Control Policy

    Science.gov (United States)

    2009-08-24

    Common illegal drugs include cannabis, cocaine, opiates, and synthetic drugs. International trade in these drugs represents a lucrative and what...into effect, decriminalizing “personal use” amounts of marijuana , heroin, cocaine, methamphetamine, and other internationally sanctioned drugs.15 While...President Calls for Legalizing Marijuana ,”CNN.com, May 13, 2009. 15 “Mexico Legalizes Drug Possession,” Associated Press, August 21, 2009. 16 In support

  16. Drug Products in the Medicaid Drug Rebate Program

    Data.gov (United States)

    U.S. Department of Health & Human Services — Active drugs that have been reported by participating drug manufacturers under the Medicaid Drug Rebate Program. All drugs are identified by National Drug Code...

  17. Drug-Target Kinetics in Drug Discovery.

    Science.gov (United States)

    Tonge, Peter J

    2018-01-17

    The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.

  18. [Designer drugs in Jutland].

    Science.gov (United States)

    Simonsen, K W; Kaa, E

    2001-04-16

    The aim of this investigation was to examine illegal tablets and capsules seized in Jutland, the western part of Denmark, during the period 1995-1999. The drugs are described according to technical appearance (colour, logo, score, diameter) and content of synthetic drugs. All illegal tablets and capsules received during the period 1995-1999 (109 cases containing 192 different samples) were examined. MDMA was the most common drug and was seen during the entire period. Amphetamine was the second most common drug and has been frequently detected during the the last two years. Drugs like MDE, MBDB, BDB, and 2-CB were rarely seen and they disappeared quickly from the illegal market. MDA appeared on the market at the end of 1999. Only 53% of the tablets contained MDMA as the sole drug. Eighty-one percent of the tablets/capsules contained only one synthetic drug, whereas 13% contained a mixture of two or more synthetic drugs. Six per cent of the samples did not contain a euphoric drug/designer drug. The content of MDMA, MDE, and amphetamine in the tablets varied greatly. MDMA is apparently the drug preferred by the users, but still only half of the tablets contained MDMA as the only drug. The rest of the tablets contained either another synthetic drug or a mixture of drugs. In conclusion, the increasing supply of various drugs with different and unpredictable effects and of miscellaneous quality brings about the risk of serious and complicated intoxications.

  19. Medicaid Drug Rebate Program Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — Product Data for Drugs in the Medicaid Drug Rebate Program. The rebate drug product data file contains the active drugs that have been reported by participating drug...

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Cigs Other Drugs Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse ...

  1. Food-drug interactions

    DEFF Research Database (Denmark)

    Schmidt, Lars E; Dalhoff, Kim

    2002-01-01

    Interactions between food and drugs may inadvertently reduce or increase the drug effect. The majority of clinically relevant food-drug interactions are caused by food-induced changes in the bioavailability of the drug. Since the bioavailability and clinical effect of most drugs are correlated......, the bioavailability is an important pharmacokinetic effect parameter. However, in order to evaluate the clinical relevance of a food-drug interaction, the impact of food intake on the clinical effect of the drug has to be quantified as well. As a result of quality review in healthcare systems, healthcare providers...... are increasingly required to develop methods for identifying and preventing adverse food-drug interactions. In this review of original literature, we have tried to provide both pharmacokinetic and clinical effect parameters of clinically relevant food-drug interactions. The most important interactions are those...

  2. Discovery and Development of the Anti-Human Immunodeficiency Virus Drug, Emtricitabine (Emtriva, FTC).

    Science.gov (United States)

    Liotta, Dennis C; Painter, George R

    2016-01-01

    efficacy of the drug. In August 1998, FTC was granted "Fast Track" status, based primarily on its potential for once daily dosing. While the outcomes of two subsequent phase III trials were positive, a third phase III clinical trial involving combinations of 3TC or FTC with stavudine and neviripine had to be terminated due to serious liver-related adverse events. Although analysis of the data suggested that the liver toxicity was due to neviripine, the FDA decided that the study could not be used for drug registration. Ultimately, in January 2003, Gilead Sciences acquired Triangle Pharmaceuticals and completed the development of FTC (emtricitabine), which was approved for once a day, oral administration in July 2003. A year later, Truvada, a once a day, oral, fixed dose combination of emtricitabine and tenofovir disoproxyl fumarate received FDA approval and quickly became the accepted first line therapy when used with a third antiretroviral agent. In July 2006, the FDA approved Atripla, a once a day, oral, fixed dose combination of emtricitabine, tenofovir disoproxyl fumarate, and efavirenz, which represented the culmination of two decades of research that had transformed AIDS from a death sentence to a manageable chronic disease.

  3. Drugs and drug policy in the Netherlands

    NARCIS (Netherlands)

    Leuw, Ed.

    1991-01-01

    The Dutch parliament enacted the revised Opium Act in 1976. This penal law is part of the Dutch drug policy framework that includes tolerance for nonconforming lifestyles, risk reduction in regard to the harmful health and social consequences of drug taking, and penal measures directed against

  4. Food-Drug Interactions

    Directory of Open Access Journals (Sweden)

    Arshad Yar Khan

    2011-03-01

    Full Text Available The effect of drug on a person may be different than expected because that drug interacts with another drug the person is taking (drug-drug interaction, food, beverages, dietary supplements the person is consuming (drug-nutrient/food interaction or another disease the person has (drug-disease interaction. A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances. Regarding food-drug interactions physicians and pharmacists recognize that some foods and drugs, when taken simultaneously, can alter the body's ability to utilize a particular food or drug, or cause serious side effects. Clinically significant drug interactions, which pose potential harm to the patient, may result from changes in pharmaceutical, pharmacokinetic, or pharmacodynamic properties. Some may be taken advantage of, to the benefit of patients, but more commonly drug interactions result in adverse drug events. Therefore it is advisable for patients to follow the physician and doctors instructions to obtain maximum benefits with least fooddrug interactions. The literature survey was conducted by extracting data from different review and original articles on general or specific drug interactions with food. This review gives information about various interactions between different foods and drugs and will help physicians and pharmacists prescribe drugs cautiously with only suitable food supplement to get maximum benefit for the patient.

  5. Cost-effectiveness analysis of dolutegravir plus backbone compared with raltegravir plus backbone, darunavir+ritonavir plus backbone and efavirenz/tenofovir/emtricitabine in treatment naïve and experienced HIV-positive patients

    Directory of Open Access Journals (Sweden)

    Restelli U

    2017-06-01

    Full Text Available Umberto Restelli,1,2 Giuliano Rizzardini,3,4 Andrea Antinori,5 Adriano Lazzarin,6 Marzia Bonfanti,1 Paolo Bonfanti,7 Davide Croce1,2 1Centre for Research on Health Economics, Social and Health Care Management, LIUC – Università Cattaneo, Castellanza, Varese, Italy; 2School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 3First and Second Divisions of Infectious Diseases, “Luigi Sacco” Hospital, Milan, Italy; 4School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 5National Institute for Infectious Diseases “L Spallanzani”, Rome, 6Department of Infectious Diseases, San Raffaele Scientific Institute, 7Department of Infectious and Tropical Diseases, A Manzoni Hospital, Lecco, Italy Background: In January 2014, the European Medicines Agency issued a marketing authorization for dolutegravir (DTG, a second-generation integrase strand transfer inhibitor for HIV treatment. The study aimed at determining the incremental cost-effectiveness ratio (ICER of the use of DTG+backbone compared with raltegravir (RAL+backbone, darunavir (DRV+ritonavir(r+backbone and efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC in HIV-positive treatment-naïve patients and compared with RAL+backbone in treatment-experienced patients, from the Italian National Health Service’s point of view.Materials and methods: A published Monte Carlo Individual Simulation Model (ARAMIS-DTG model was used to perform the analysis. Patients pass through mutually exclusive health states (defined in terms of diagnosis of HIV with or without opportunistic infections [OIs] and cardiovascular disease [CVD] and successive lines of therapy. The model considers costs (2014 and quality of life per monthly cycle in a lifetime horizon. Costs and quality-adjusted life years (QALYs are dependent on OI, CVD, AIDS events, adverse events and antiretroviral therapies.Results: In

  6. Characterization of HIV-1 antiretroviral drug resistance after second-line treatment failure in Mali, a limited-resources setting

    Science.gov (United States)

    Maiga, Almoustapha Issiaka; Fofana, Djeneba Bocar; Cisse, Mamadou; Diallo, Fodié; Maiga, Moussa Youssoufa; Traore, Hamar Alassane; Maiga, Issouf Alassane; Sylla, Aliou; Fofana, Dionke; Taiwo, Babafemi; Murphy, Robert; Katlama, Christine; Tounkara, Anatole; Calvez, Vincent; Marcelin, Anne-Geneviève

    2012-01-01

    Objectives We describe the outcomes of second-line drug resistance profiles and predict the efficacy of drugs for third-line therapy in patients monitored without the benefit of plasma HIV-1 RNA viral load (VL) or resistance testing. Methods We recruited 106 HIV-1-infected patients after second-line treatment failure in Mali. VL was determined by the Abbott RealTime system and the resistance by the ViroSeq HIV-1 genotyping system. The resistance testing was interpreted using the latest version of the Stanford algorithm. Results Among the 106 patients, 93 had isolates successfully sequenced. The median age, VL and CD4 cells were respectively 35 years, 72 000 copies/mL and 146 cells/mm3. Patients were exposed to a median of 4 years of treatment and to six antiretrovirals. We found 20% of wild-type viruses. Resistance to etravirine was noted in 38%, to lopinavir in 25% and to darunavir in 12%. The duration of prior nucleos(t)ide reverse transcriptase inhibitor exposure was associated with resistance to abacavir (P < 0.0001) and tenofovir (P = 0.0001), and duration of prior protease inhibitor treatment with resistance to lopinavir (P < 0.0001) and darunavir (P = 0.06). Conclusion Long duration of therapy prior to failure was associated with high levels of resistance and is directly related to limited access to VL monitoring and delayed switches to second-line treatment, precluding efficacy of drugs for third-line therapy. This study underlines the need for governments and public health organizations to recommend the use of VL monitoring and also the availability of darunavir and raltegravir for third-line therapies in the context of limited-resource settings. PMID:22888273

  7. IMPROVING ACCESS TO DRUGS

    Directory of Open Access Journals (Sweden)

    Max Joseph Herman

    2012-11-01

    Full Text Available Although essentially not all therapies need drug intervention, drugs is still an important components in health sector, either in preventive, curative, rehabilitative or promotion efforts. Hence the access to drugs is a main problem, either in international or national scale even to the smallest unit. The problem on access to drugs is very complicated and cannot be separated especially from pharmacy management problems; moreover in general from the overall lack of policy development and effective of health policy, and also the implementation process. With the policy development and effective health policy, rational drug uses, sufficient health service budget so a country can overcome the health problems. Besides infrastructures, regulations, distribution and cultural influences; the main obstacles for drug access is drugs affordability if the price of drugs is an important part and determined by many factors, especially the drug status whether is still patent orgenerics that significantly decrease cost of health cares and enhance the drugs affordability. The determination of essential drug prices in developing countries should based on equity principal so that poor people pay cheaper and could afford the essential drugs. WHO predicts two third of world population can not afford the essential drugs in which in developing countries, some are because of in efficient budget allocation in consequence of drug distribution management, including incorrect selection and allocation and also irrational uses. In part these could be overcome by enhancing performances on the allocation pharmacy needs, including the management of information system, inventory management, stock management and the distribution. Key words: access, drugs, essential drugs, generic drugs

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Drug-induced thrombocytopenia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B

    1997-01-01

    induced by non-cytotoxic drugs is characterised by heterogeneous clinical picture and recovery is generally rapid. Although corticosteroids seem inefficient, we still recommend that severe symptomatic cases of drug-induced thrombocytopenia are treated as idiopathic thrombocytopenic purpura due...

  10. Drugs@FDA Database

    Data.gov (United States)

    U.S. Department of Health & Human Services — Information about FDA-approved brand name and generic prescription and over-the-counter human drugs and biological therapeutic products. Drugs@FDA includes most of...

  11. Inflammatory Drug (NSAID)

    African Journals Online (AJOL)

    Inflammatory Drug (NSAID)-Induced Seizures in a Patient with HIV Infection ... interaction not supported by existing literature, and it is possible that the background HIV infection may have a role to .... Foods and Drug Administration and Control.

  12. CMS Drug Spending

    Data.gov (United States)

    U.S. Department of Health & Human Services — CMS has released several information products that provide spending information for prescription drugs in the Medicare and Medicaid programs. The CMS Drug Spending...

  13. Drug Enforcement Administration

    Science.gov (United States)

    ... de informacin confidencial --> DEA NEWS The Drug Enforcement Administration and Discovery Education name grand winner of Operation ... JUN 15 (Washington) The United States Drug Enforcement Administration, DEA Educational Foundation and Discovery Education awarded Porter ...

  14. Antimicrobial (Drug) Resistance

    Science.gov (United States)

    ... with facebook share with twitter share with linkedin Antimicrobial (Drug) Resistance Go to Information for Researchers ► Credit: ... and infectious diseases. Why Is the Study of Antimicrobial (Drug) Resistance a Priority for NIAID? Over time, ...

  15. Drugs to be Discontinued

    Data.gov (United States)

    U.S. Department of Health & Human Services — Companies are required under Section 506C of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (as amended by the Food and Drug Administration Safety and...

  16. Prescription Drug Profiles PUF

    Data.gov (United States)

    U.S. Department of Health & Human Services — This release contains the Prescription Drug Profiles Public Use Files (PUFs) drawn from Medicare prescription drug claims for the year of the date on which the...

  17. Prescription Drug Abuse

    Science.gov (United States)

    ... what the doctor prescribed, it is called prescription drug abuse. It could be Taking a medicine that ... purpose, such as getting high Abusing some prescription drugs can lead to addiction. These include opioids, sedatives, ...

  18. National Drug IQ Challenge

    Science.gov (United States)

    ... National Drug IQ Challenge 2017 Reto nacional del coeficiente intelectual (CI) sobre las drogas y el alcohol 2016 National Drug IQ Challenge 2016 Reto nacional del coeficiente intelectual (CI) sobre las drogas y el alcohol 2015 ...

  19. Medication/Drug Allergy

    Science.gov (United States)

    ... Training Home Conditions Medication/Drug Allergy Medication/Drug Allergy Make an Appointment Find a Doctor Ask a ... risk for adverse reactions to medications. Facts about Allergies The tendency to develop allergies may be inherited. ...

  20. Drugs in sport

    OpenAIRE

    Robinson, D

    2007-01-01

    This new edition includes fresh information regarding drugs use and abuse in sport and the updated worldwide anti-doping laws, and changes to the prohibited and therapeutic use exemption lists. The objectives of the book are to review/discuss the latest information on drugs in sport by considering i) actions of drugs and hormones, ii) medication and nutritional supplements in sport, iii) the latest doping control regulations of the WADA, iv) the use of banned therapeutic drugs in sport, v) an...

  1. Sociology of Drug Consumption

    OpenAIRE

    2004-01-01

    In this article which is a review of sociological ideas and studies of drug abusers in social situation, drug addiction steps (particularly alcohol, heroin and cocaine consumption) are revised and some explanations are made. Also, the role of some sociological ideas in drug addiction is considered in which Anomie Theory reads: "because of such duality, the individuals who are not satisfied with their role are in hurt." According to this theory, drug users choose seclusion and neglecting usual...

  2. Drug development in neuropsychopharmacology.

    Science.gov (United States)

    Fritze, Jürgen

    2008-03-01

    Personalized medicine is still in its infancy concerning drug development in neuropsychopharmacology. Adequate biomarkers with clinical relevance to drug response and/or tolerability and safety largely remain to be identified. Possibly, this kind of personalized medicine will first gain clinical relevance in the dementias. The clinical relevance of the genotyping of drug-metabolizing enzymes as suggested by drug licensing authorities for the pharmacokinetic evaluation of medicinal products needs to be proven in sound clinical trials.

  3. Drug interactions with radiopharmaceuticals

    International Nuclear Information System (INIS)

    Hesslewood, S.; Leung, E.

    1994-01-01

    Considerable information on documented drug and radiopharmaceutical interactions has been assembled in a tabular form, classified by the type of nuclear medicine study. The aim is to provide a rapid reference for nuclear medicine staff to look for such interactions. The initiation of drug chart monitoring or drug history taking of nuclear medicine patients and the reporting of such events are encouraged. (orig.)

  4. Drugs of Abuse.

    Science.gov (United States)

    Joseph, Donald E., Ed.

    This Drug Enforcement Administration publication delivers clear, scientific information about drugs in a factual, straightforward way, combined with precise photographs shot to scale. The publication is intended to serve as an A to Z guide for drug history, effects, and identification information. Chapters are included on the Controlled Substances…

  5. Drug Enforcement Administration.

    Science.gov (United States)

    Department of Justice, Washington, DC.

    This fact sheet contains information relating to drug abuse and abusers; drug traffic legislation; law enforcement; and descriptions of commonly used narcotics, stimulants, depressants, and hallucinogens. Also included is a short but explicit listing of audiovisual aids, an annotated bibliography, and drug identification pictures. The booklet…

  6. Collegiate Drug Management Guide.

    Science.gov (United States)

    Janosik, Steven M.; Anderson, David S.

    A checklist to help colleges and universities reevaluate their policies and procedures regarding drug use among college students is presented. It is designed to supplement the "Collegiate Alcohol Risk Assessment Guide." In this guide drugs other than alcohol are of concern, although alcohol is viewed by many as the "drug of choice" among college…

  7. Writing Drug Cultures

    DEFF Research Database (Denmark)

    Nissen, Morten

    2012-01-01

    The paper juxtaposes the cultural mediation of experience through drugs with that performed with text. As a sample of the currently radically changing relations between professional and lay knowledge in the field of drug interventions, the website of a Copenhagen institution for young drug users ...

  8. Dynamics of Drug Use

    Science.gov (United States)

    Rollins, Joan H.; Holden, Raymond H.

    1977-01-01

    This paper analyzes data from interviews with 167 drug users in the community, including age, sex, birth order, education, family constellation, and circumstances of first drug use. The majority of subjects had tried to stop using drugs, but most had been unsuccessful at the time of the interview. (Author)

  9. Drugs in breast milk.

    Science.gov (United States)

    Hervada, A R; Feit, E; Sagraves, R

    1978-09-01

    The amount of drug excreted into breast milk is dependent upon the lipid solubility of the medication, the mechanism of transport, the degree of ionization, and change in plasma pH. The higher the lipid solubility, the greater the concentration in human milk. The majority of drugs are transported into mammary blood capillaries by passive diffusion. The rest are transported by reverse pinocytosis. Once the drug has entered the epithelial cells of breast tissue, the drug molecules are excreted into the human milk by active transport, passive diffusion, or apocrine secretion. The amount of free (active) drug available for transport depends on the degree of protein binding the plasma pH. Another factor affecting excretion of drugs is the time when breast feeding occurs. In the 1st few days of life, when colostrum is present, water-soluble drugs pass through the breast more easily than afterwards when milk is produced. Then lipid-soluble drugs cross in higher concentrations. The effect on nursing infants is dependent on the amount excreted into the milk, the total amount absorbed by the infant, and the toxicity of the drug. The use of the following drugs in breast feeding mothers is reviewed: anticoagulants, antihypertensives and diuretics, antimicrobials, drugs affecting the central nervous system (alcohol, chloral hydrate, meprobamate, lithium, and aspirin), marijuana, other drugs (antihistamines, atropine, ergot alkaloids, laxatives, nicotine, iodides, propylthiouracil, theophylline), hormones (insulin, thyroxine, and oral contraceptives), and radiopharmaceuticals.

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/ ...

  11. Drug metabolism and ageing.

    Science.gov (United States)

    Wynne, Hilary

    2005-06-01

    Older people are major consumers of drugs and because of this, as well as co-morbidity and age-related changes in pharmacokinetics and pharmacodynamics, are at risk of associated adverse drug reactions. While age does not alter drug absorption in a clinically significant way, and age-related changes in volume of drug distribution and protein binding are not of concern in chronic therapy, reduction in hepatic drug clearance is clinically important. Liver blood flow falls by about 35% between young adulthood and old age, and liver size by about 24-35% over the same period. First-pass metabolism of oral drugs avidly cleared by the liver and clearance of capacity-limited hepatically metabolized drugs fall in parallel with the fall in liver size, and clearance of drugs with a high hepatic extraction ratio falls in parallel with the fall in hepatic blood flow. In normal ageing, in general, activity of the cytochrome P450 enzymes is preserved, although a decline in frail older people has been noted, as well as in association with liver disease, cancer, trauma, sepsis, critical illness and renal failure. As the contribution of age, co-morbidity and concurrent drug therapy to altered drug clearance is impossible to predict in an individual older patient, it is wise to start any drug at a low dose and increase this slowly, monitoring carefully for beneficial and adverse effects.

  12. Abuse of prescription drugs.

    Science.gov (United States)

    Wilford, B B

    1990-01-01

    An estimated 3% of the United States population deliberately misuse or abuse psychoactive medications, with severe consequences. According to the National Institute on Drug Abuse, more than half of patients who sought treatment or died of drug-related medical problems in 1989 were abusing prescription drugs. Physicians who contribute to this problem have been described by the American Medical Association as dishonest--willfully misprescribing for purposes of abuse, usually for profit; disabled by personal problems with drugs or alcohol; dated in their knowledge of current pharmacology or therapeutics; or deceived by various patient-initiated fraudulent approaches. Even physicians who do not meet any of these descriptions must guard against contributing to prescription drug abuse through injudicious prescribing, inadequate safeguarding of prescription forms or drug supplies, or acquiescing to the demands or ruses used to obtain drugs for other than medical purposes. PMID:2349801

  13. Drug Retention Times

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user. Based on anecdotal evidence, most people “party” during extended time away from the work environment. Therefore, the following scenarios were envisioned: (1) a person uses an illicit drug at a party on Saturday night (infrequent user); (2) a person uses a drug one time on Friday night and once again on Saturday night (infrequent user); and (3) a person uses a drug on Friday night, uses a drug twice on Saturday night, and once again on Sunday (frequent user).

  14. Rings in drugs.

    Science.gov (United States)

    Taylor, Richard D; MacCoss, Malcolm; Lawson, Alastair D G

    2014-07-24

    We have analyzed the rings, ring systems, and frameworks in drugs listed in the FDA Orange Book to understand the frequency, timelines, molecular property space, and the application of these rings in different therapeutic areas and target classes. This analysis shows that there are only 351 ring systems and 1197 frameworks in drugs that came onto the market before 2013. Furthermore, on average six new ring systems enter drug space each year and approximately 28% of new drugs contain a new ring system. Moreover, it is very unusual for a drug to contain more than one new ring system and the majority of the most frequently used ring systems (83%) were first used in drugs developed prior to 1983. These observations give insight into the chemical novelty of drugs and potentially efficient ways to assess compound libraries and develop compounds from hit identification to lead optimization and beyond.

  15. [Drugs in pregnancy].

    Science.gov (United States)

    Danchev, N; Astrug, A; Tsankova, V; Nikolova, I

    2006-01-01

    The use of drugs in pregnancy is being discussed. The influence of different factors, both physiological and drug related (physicochemical characteristics, dose, duration of pharmacotherapy) on the processes of absorption, distribution, protein binding, metabolism and excretion are reviewed. The up-to-date classification of the drugs in relation to their effects on the fetus is presented. Special emphasize is given to drugs (antibiotics, cardio-vascular, psychotropic etc.) used for the treatment of acute and chronic conditions in the course of pregnancy. Drugs used for symptoms like pain, high temperature and constipation are also reviewed. Recommendations for the use of safer drugs in pregnancy are given. Drugs with proven teratogenic effects are presented.

  16. Derrida and drugs

    OpenAIRE

    Gough, Tim

    2008-01-01

    Derrida, in the interview Rhetoric of Drugs (1993), following on from the explication of the notion of pharmakon (both poison and beneficial drug, at the same time), outlines a possible �theory� of drugs and addiction. It has several key features:\\ud � there are no drugs in nature: the definition of �drug� is an institutionalised one\\ud � the concept of drugs is non-scientific, non-positive\\ud � drugs are a parasitism �at once accidental and essential�; and are thus a topic ...

  17. The US Food and Drug Administration's tentative approval process and the global fight against HIV.

    Science.gov (United States)

    Chahal, Harinder Singh; Murray, Jeffrey S; Shimer, Martin; Capella, Peter; Presto, Ryan; Valdez, Mary Lou; Lurie, Peter G

    2017-12-01

    In 2004, the US government began to utilize the Food and Drug Administration's (USFDA) tentative approval process (tFDA) as a basis to determine which HIV drugs are appropriate to be purchased and used in resource-constrained settings. This process permits products that are not approved for marketing in the US, including medicines with active patents or marketing restrictions in the US, to be purchased and distributed in resource-constrained settings. Although the tFDA was originally intended to support the United States' President's Emergency Plan for AIDS Relief (PEPFAR), the USFDA list has become a cornerstone of international HIV programmes that support procurement of ARVs, such as the World Health Organization and the Global Fund to Fight AIDS, Tuberculosis, and Malaria. Our objective in this article is to help the global HIV policy makers and implementers of HIV programmes better understand the benefits and limitations of the tFDA by providing an in-depth review of the relevant legal and regulatory processes. USFDA's dedicated tFDA process for ARVs used by the PEPFAR programme has a wide impact globally; however, the implementation and the regulatory processes governing the programme have not been thoroughly described in the medical literature. This paper seeks to help stakeholders better understand the legal and regulatory aspects associated with review of ARVs under the tFDA by describing the following: (1) the tFDA and its importance to global ARV procurement; (2) the regulatory pathways for applications under tFDA for the PEPFAR programme, including modifications to applications, review timelines and costs; (3) the role of US patents, US marketing exclusivity rights, and the Medicines Patents Pool in tFDA; and (4) an overview of how applications for PEPFAR programme are processed through the USFDA. We also provide a case study of a new ARV, tenofovir alafenamide fumarate (TAF), not yet reviewed by USFDA for PEPFAR use. In this paper, we describe the

  18. Generic Drugs: Questions and Answers

    Science.gov (United States)

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Drugs Home Drugs Resources for You Information for Consumers (Drugs) Questions & Answers Generic Drugs: Questions & Answers Share Tweet Linkedin Pin it More ...

  19. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse Hepatitis (Viral) ...

  20. Drugs Approved for Esophageal Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for esophageal cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  1. Drugs Approved for Liver Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for liver cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  2. Drugs Approved for Kaposi Sarcoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Kaposi sarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  3. Drugs Approved for Vaginal Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) to prevent vaginal cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  4. Drugs Approved for Skin Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for skin cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  5. Drugs Approved for Vulvar Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for vulvar cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  6. Drugs Approved for Wilms Tumor

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Wilms tumor and other childhood kidney cancers. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  7. Drugs Approved for Bone Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bone cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  8. Drugs Approved for Malignant Mesothelioma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for malignant mesothelioma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  9. Drugs Approved for Penile Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for penile cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  10. Drugs Approved for Endometrial Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for endometrial cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors ... GA: CDC, DHHS. Retrieved November 2017. How are Drug Misuse and HIV Related? Drug misuse and addiction ...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens ... Substance Use and SUDs in LGBT Populations Treatment Trends & Statistics Women and Drugs Publications Search Publications Orderable ...

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and ... Link campaign. This campaign shows teens and young adults that non-injection drug use and alcohol use ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing ... please visit: http://www.cdc.gov/hiv/risk/age/youth/index.html​ . Resources Publications Drug Facts: Drug ...

  15. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugged Driving Drug Testing Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse Hepatitis ( ... Party" "Text Message" NIDA Home Site Map Accessibility Privacy FOIA(NIH) Working at NIDA FAQs Contact Subscribe ...

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with drug misuse are among the main ... lead people to engage in impulsive and unsafe behaviors. Injection drug use. People typically associate drug misuse ...

  17. Drugs Approved for Breast Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Breast Cancer This page lists cancer drugs approved by the ... are not listed here. Drugs Approved to Prevent Breast Cancer Evista (Raloxifene Hydrochloride) Raloxifene Hydrochloride Tamoxifen Citrate Drugs ...

  18. TRANSDERMAL DRUG DELIVERY SYSTEM: REVIEW

    OpenAIRE

    Vishvakarama Prabhakar; Agarwal Shivendra; Sharma Ritika; Saurabh Sharma

    2012-01-01

    Various new technologies have been developed for the transdermal delivery of some important drugs. Today about 74% of drugs are taken orally and are found not to be as effective as desired. To improve such characters transdermal drug delivery system was emerged. Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery and differs from traditional topical drug delivery. Transdermal drug delivery systems (TDDS) are dosage forms involve...

  19. Supersaturating drug delivery systems

    DEFF Research Database (Denmark)

    Laitinen, Riikka; Löbmann, Korbinian; Grohganz, Holger

    2017-01-01

    of the bioavailability of poorly water-soluble drugs by increasing the driving force for drug absorption. However, ASDs often require a high weight percentage of carrier (usually a hydrophilic polymer) to ensure molecular mixing of the drug in the carrier and stabilization of the supersaturated state, often leading......Amorphous solid dispersions (ASDs) are probably the most common and important supersaturating drug delivery systems for the formulation of poorly water-soluble compounds. These delivery systems are able to achieve and maintain a sustained drug supersaturation which enables improvement...... strategy for poorly-soluble drugs. While the current research on co-amorphous formulations is focused on preparation and characterization of these systems, more detailed research on their supersaturation and precipitation behavior and the effect of co-formers on nucleation and crystal growth inhibition...

  20. Recreational drugs of abuse.

    Science.gov (United States)

    Albertson, Timothy E

    2014-02-01

    The use of recreational drugs of abuse continues to expand without limitations to national boundaries, social status, race, or education. Beyond the prevalence of illicit drug use and dependence, their contribution to the global burden of disease and death are large and troubling. All medical providers should be aware of the evolving drugs of abuse and their medical and social consequences. In addition to heroin and stimulants such as cocaine and methamphetamine, new designer stimulants called "bath salts" and cannabinoids called "spice," along with the abuse of prescription drugs and volatile substances, are now widely recognized problems in many societies. The wide variety and continuingly expanding clinical manifestations of toxicity of recreational drugs of abuse is not widely appreciated by clinicians. This edition attempts to summarize six major classes of drugs of abuse and their clinical effects with special emphasis on their immunological and respiratory effects.

  1. Therapeutic drug monitoring of atypical antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Grundmann Milan

    2014-12-01

    Full Text Available Schizophrenia is a severe psychiatric disorder often associated with cognitive impairment and affective, mainly depressive, symptoms. Antipsychotic medication is the primary intervention for stabilization of acute psychotic episodes and prevention of recurrences and relapses in patients with schizophrenia. Typical antipsychotics, the older class of antipsychotic agents, are currently used much less frequently than newer atypical antipsychotics. Therapeutic drug monitoring (TDM of antipsychotic drugs is the specific method of clinical pharmacology, which involves measurement of drug serum concentrations followed by interpretation and good cooperation with the clinician. TDM is a powerful tool that allows tailor-made treatment for the specific needs of individual patients. It can help in monitoring adherence, dose adjustment, minimizing the risk of toxicity and in cost-effectiveness in the treatment of psychiatric disorders. The review provides complex knowledge indispensable to clinical pharmacologists, pharmacists and clinicians for interpretation of TDM results.

  2. Discontinued drugs in 2012: cardiovascular drugs.

    Science.gov (United States)

    Zhao, Hong-Ping; Jiang, Hong-Min; Xiang, Bing-Ren

    2013-11-01

    The continued high rate of cardiovascular morbidity and mortality has attracted wide concern and great attention of pharmaceutical industry. In order to reduce the attrition of cardiovascular drug R&D, it might be helpful recapitulating previous failures and identifying the potential factors to success. This perspective mainly analyses the 30 cardiovascular drugs dropped from clinical development in 2012. Reasons causing the termination of the cardiovascular drugs in the past 5 years are also tabulated and analysed. The analysis shows that the attrition is highest in Phase II trials and financial and strategic factors and lack of clinical efficacy are the principal reasons for these disappointments. To solve the four problems (The 'better than the Beatles' problem, the 'cautious regulator' problem, the 'throw money at it' tendency and the 'basic researchbrute force' bias) is recommended as the main measure to increase the number and quality of approvable products.

  3. Abuse of prescription drugs.

    OpenAIRE

    Wilford, B B

    1990-01-01

    An estimated 3% of the United States population deliberately misuse or abuse psychoactive medications, with severe consequences. According to the National Institute on Drug Abuse, more than half of patients who sought treatment or died of drug-related medical problems in 1989 were abusing prescription drugs. Physicians who contribute to this problem have been described by the American Medical Association as dishonest--willfully misprescribing for purposes of abuse, usually for profit; disable...

  4. Radiopharmaceutical drug review process

    International Nuclear Information System (INIS)

    Frankel, R.

    1985-01-01

    To ensure proper radioactive drug use (such as quality, diagnostic improvement, and minimal radioactive exposure), the Food and Drug Administration evaluates new drugs with respect to safety, effectiveness, and accuracy and adequacy of the labeling. The IND or NDA process is used for this purpose. A brief description of the process, including the Chemical Classification System and the therapeutic potential classification, is presented as it applies to radiopharmaceuticals. Also, the status of the IND or NDA review of radiopharmaceuticals is given

  5. Drug procurement and management.

    Science.gov (United States)

    Salhotra, V S

    2003-03-01

    A strong drug procurement and management system under the RNTCP is critical to programme success. Significant improvements in manufacturing, inspection, supply, storage and quality control practices and procedures have been achieved due to an intensive RNTCP network. Drugs used in RNTCP are rifampicin, isoniazid, ethambutol, pyrazinamide and streptomycin. Patients of TB are categorised into I, II and III and each category has a different standarised treatment. Procurement, distribution system and quality assurance of drugs are narrated in brief in this article.

  6. Grapefruit and drug interactions.

    Science.gov (United States)

    2012-12-01

    Since the late 1980s, grapefruit juice has been known to affect the metabolism of certain drugs. Several serious adverse effects involving drug interactions with grapefruit juice have been published in detail. The components of grapefruit juice vary considerably depending on the variety, maturity and origin of the fruit, local climatic conditions, and the manufacturing process. No single component accounts for all observed interactions. Other grapefruit products are also occasionally implicated, including preserves, lyophylised grapefruit juice, powdered whole grapefruit, grapefruit seed extract, and zest. Clinical reports of drug interactions with grapefruit juice are supported by pharmacokinetic studies, each usually involving about 10 healthy volunteers, in which the probable clinical consequences were extrapolated from the observed plasma concentrations. Grapefruit juice inhibits CYP3A4, the cytochrome P450 isoenzyme most often involved in drug metabolism. This increases plasma concentrations of the drugs concerned, creating a risk of overdose and dose-dependent adverse effects. Grapefruit juice also inhibits several other cytochrome P450 isoenzymes, but they are less frequently implicated in interactions with clinical consequences. Drugs interacting with grapefruit and inducing serious clinical consequences (confirmed or very probable) include: immunosuppressants, some statins, benzodiazepines, most calcium channel blockers, indinavir and carbamazepine. There are large inter-individual differences in enzyme efficiency. Along with the variable composition of grapefruit juice, this makes it difficult to predict the magnitude and clinical consequences of drug interactions with grapefruit juice in a given patient. There is increasing evidence that transporter proteins such as organic anion transporters and P-glycoprotein are involved in interactions between drugs and grapefruit juice. In practice, numerous drugs interact with grapefruit juice. Although only a few

  7. Drug Trafficking in Haiti

    National Research Council Canada - National Science Library

    Burns, DeEtta

    2002-01-01

    .... The thesis argues that Haiti's geographic location, political culture, illegal immigrants, entrepreneurial class and weak institutions have made it a major transshipment point for drugs to the United...

  8. Drugs in East Germany.

    Science.gov (United States)

    Dressler, J; Müller, E

    1997-09-01

    Germany was divided into two parts after World War II. The closed border and a nonconvertible currency in the Eastern part were the factors that did not allow a drug market to develop. Alcohol and medicaments were used as substitute drugs. Since Germany was reunified 5 years ago, there are now the same conditions prevailing for the procurement and sale of drugs in East Germany as there are in the Western German states. This report describes the current state of drug traffic, especially in Saxony, under the new social conditions.

  9. Population and Drugs

    OpenAIRE

    Feberová, Beata

    2008-01-01

    PEOPLE AND DRUGS II. Author: Križanová L. Tutor: Práznovcová L. Dept. of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Czech Republic Background: It is necessary to rationalize the system of funding of health service. One of the ways how to achieve this aim is monitoring of drug prescription and patient's financial participation on the therapy. Aim of study: Observation and analysis of drug prescription aimed at the prescription of the drug...

  10. Drug induced lung disease

    International Nuclear Information System (INIS)

    Schaefer-Prokop, Cornelia; Eisenhuber, Edith

    2010-01-01

    There is an ever increasing number of drugs that can cause lung disease. Imaging plays an important role in the diagnosis, since the clinical symptoms are mostly nonspecific. Various HRCT patterns can be correlated - though with overlaps - to lung changes caused by certain groups of drugs. Alternative diagnosis such as infection, edema or underlying lung disease has to be excluded by clinical-radiological means. Herefore is profound knowledge of the correlations of drug effects and imaging findings essential. History of drug exposure, suitable radiological findings and response to treatment (corticosteroids and stop of medication) mostly provide the base for the diagnosis. (orig.)

  11. Microwave Assisted Drug Delivery

    DEFF Research Database (Denmark)

    Jónasson, Sævar Þór; Zhurbenko, Vitaliy; Johansen, Tom Keinicke

    2014-01-01

    In this work, the microwave radiation is adopted for remote activation of pharmaceutical drug capsules inside the human body in order to release drugs at a pre-determined time and location. An array of controllable transmitting sources is used to produce a constructive interference at a certain...... focus point inside the body, where the drugs are then released from the specially designed capsules. An experimental setup for microwave activation has been developed and tested on a body phantom that emulates the human torso. A design of sensitive receiving structures for integration with a drug...

  12. Projecting future drug expenditures--2009.

    Science.gov (United States)

    Hoffman, James M; Shah, Nilay D; Vermeulen, Lee C; Doloresco, Fred; Martin, Patrick K; Blake, Sharon; Matusiak, Linda; Hunkler, Robert J; Schumock, Glen T

    2009-02-01

    Drug expenditure trends in 2007 and 2008, projected drug expenditures for 2009, and factors likely to influence drug expenditures are discussed. Various factors are likely to influence drug expenditures in 2009, including drugs in development, the diffusion of new drugs, drug safety concerns, generic drugs, Medicare Part D, and changes in the drug supply chain. The increasing availability of important generic drugs and drug safety concerns continue to moderate growth in drug expenditures. The drug supply chain remains dynamic and may influence drug expenditures, particularly in specialized therapeutic areas. Initial data suggest that the Medicare Part D benefit has influenced drug expenditures, but the ultimate impact of the benefit on drug expenditures remains unclear. From 2006 to 2007, total U.S. drug expenditures increased by 4.0%, with total spending rising from $276 billion to $287 billion. Drug expenditures in clinics continue to grow more rapidly than in other settings, with a 9.9% increase from 2006 to 2007. Hospital drug expenditures increased at a moderate rate of only 1.6% from 2006 to 2007; through the first nine months of 2008, hospital drug expenditures increased by only 2.8% compared with the same period in 2007. In 2009, we project a 0-2% increase in drug expenditures in outpatient settings, a 1-3% increase in expenditures for clinic-administered drugs, and a 1-3% increase in hospital drug expenditures.

  13. DRUGS IN SPORT

    Directory of Open Access Journals (Sweden)

    David R. Mottram

    2005-12-01

    Full Text Available This new edition includes fresh information regarding drugs use and abuse in sport and the updated worldwide anti-doping laws, and changes to the prohibited and therapeutic use exemption lists. The objectives of the book are to review/discuss the latest information on drugs in sport by considering i actions of drugs and hormones, ii medication and nutritional supplements in sport, iii the latest doping control regulations of the WADA, iv the use of banned therapeutic drugs in sport, v an assessment of the prevalence of drug taking in sport. FEATURES A common, uniform strategy and evidence-based approach to organizing and interpreting the literature is used in all chapters. This textbook is composed of twelve parts with sub-sections in all of them. The topics of the parts are: i An introduction to drugs and their use in sport, ii Drug use and abuse in sport, iii Central nervous system stimulants, iv WADA regulations in relation to drugs used in the treatment of respiratory tract disorders, v Androgenic anabolic steroids, vi Peptide and glycoprotein hormones and sport, vii Blood boosting and sport, viii Drug treatment of inflammation in sports injuries, ix Alcohol, anti-anxiety drugs and sport, x Creatine, xi Doping control and sport, xii Prevalence of drug misuse in sport. Each specific chapter has been systematically developed from the data available in prospective, retrospective, case-control, and cross-sectional studies. The tables and figures are numerous, helpful and very useful. AUDIENCE The book provides a very useful resource for students on sports related courses, coaches and trainers, researchers, nutritionists, exercise physiologists, pharmacologists, healthcare professionals in the fields of sports medicine and those involved in the management and administration side of sport. The readers are going to discover that this is an excellent reference book. Extensively revised new edition of this book is also a first-rate resource for

  14. Emergent HIV-1 Drug Resistance Mutations Were Not Present at Low-Frequency at Baseline in Non-Nucleoside Reverse Transcriptase Inhibitor-Treated Subjects in the STaR Study.

    Science.gov (United States)

    Porter, Danielle P; Daeumer, Martin; Thielen, Alexander; Chang, Silvia; Martin, Ross; Cohen, Cal; Miller, Michael D; White, Kirsten L

    2015-12-07

    At Week 96 of the Single-Tablet Regimen (STaR) study, more treatment-naïve subjects that received rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF) developed resistance mutations compared to those treated with efavirenz (EFV)/FTC/TDF by population sequencing. Furthermore, more RPV/FTC/TDF-treated subjects with baseline HIV-1 RNA >100,000 copies/mL developed resistance compared to subjects with baseline HIV-1 RNA ≤100,000 copies/mL. Here, deep sequencing was utilized to assess the presence of pre-existing low-frequency variants in subjects with and without resistance development in the STaR study. Deep sequencing (Illumina MiSeq) was performed on baseline and virologic failure samples for all subjects analyzed for resistance by population sequencing during the clinical study (n = 33), as well as baseline samples from control subjects with virologic response (n = 118). Primary NRTI or NNRTI drug resistance mutations present at low frequency (≥2% to 20%) were detected in 6.6% of baseline samples by deep sequencing, all of which occurred in control subjects. Deep sequencing results were generally consistent with population sequencing but detected additional primary NNRTI and NRTI resistance mutations at virologic failure in seven samples. HIV-1 drug resistance mutations emerging while on RPV/FTC/TDF or EFV/FTC/TDF treatment were not present at low frequency at baseline in the STaR study.

  15. Emergent HIV-1 Drug Resistance Mutations Were Not Present at Low-Frequency at Baseline in Non-Nucleoside Reverse Transcriptase Inhibitor-Treated Subjects in the STaR Study

    Directory of Open Access Journals (Sweden)

    Danielle P. Porter

    2015-12-01

    Full Text Available At Week 96 of the Single-Tablet Regimen (STaR study, more treatment-naïve subjects that received rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF developed resistance mutations compared to those treated with efavirenz (EFV/FTC/TDF by population sequencing. Furthermore, more RPV/FTC/TDF-treated subjects with baseline HIV-1 RNA >100,000 copies/mL developed resistance compared to subjects with baseline HIV-1 RNA ≤100,000 copies/mL. Here, deep sequencing was utilized to assess the presence of pre-existing low-frequency variants in subjects with and without resistance development in the STaR study. Deep sequencing (Illumina MiSeq was performed on baseline and virologic failure samples for all subjects analyzed for resistance by population sequencing during the clinical study (n = 33, as well as baseline samples from control subjects with virologic response (n = 118. Primary NRTI or NNRTI drug resistance mutations present at low frequency (≥2% to 20% were detected in 6.6% of baseline samples by deep sequencing, all of which occurred in control subjects. Deep sequencing results were generally consistent with population sequencing but detected additional primary NNRTI and NRTI resistance mutations at virologic failure in seven samples. HIV-1 drug resistance mutations emerging while on RPV/FTC/TDF or EFV/FTC/TDF treatment were not present at low frequency at baseline in the STaR study.

  16. 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

    IMPORTANCE New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. OBJECTIVE To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. EVIDENCE REVIEW A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. FINDINGS Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory

  17. Drugs and Alcohol

    Science.gov (United States)

    Scott, Victor F.

    1978-01-01

    Millions of people in this country take medications, and millions drink alcohol. Both are drugs and have effects on the organs and systems with which they or their metabolites come in contact. This short article discusses some of the combined effects of prescribed drugs and alcohol on some systems, with special emphasis on the liver. PMID:712865

  18. [Drugs and light].

    Science.gov (United States)

    Tønnesen, H H

    1997-06-30

    The number of drugs that are found to be photochemically unstable or able to induce phototoxic side-effects is steadily increasing. It can be difficult, however, to obtain relevant information on the photoreactivity of drugs or drug products from the commonly used handbooks. This is because of lack of standard methods of evaluation or a requirement for official specifications for a given product. The author points to the main problems connected with interactions between drugs and light in vitro and in vivo. The most obvious result of exposure to light is reduced potency of the drug because of photodecomposition. Adverse effects due to the formation of photodegradation products during storage and use have also been reported. The drug substance can further cause light-induced side-effects after administration to the patient, e.g. phototoxicity and photoallergy. More data on photoreactivity are needed in order to minimize the side-effects of frequently used drugs. The article includes a list of potential photosensitizing drug substances on the Norwegian market.

  19. Alternative drugs of abuse.

    Science.gov (United States)

    Sutter, M E; Chenoweth, J; Albertson, T E

    2014-02-01

    The incidence of drug abuse with alternative agents is increasing. The term "alternative drugs of abuse" is a catch-all term for abused chemicals that do not fit into one of the classic categories of drugs of abuse. The most common age group abusing these agents range from 17 to 25 years old and are often associated with group settings. Due to their diverse pharmacological nature, legislative efforts to classify these chemicals as a schedule I drug have lagged behind the development of new alternative agents. The potential reason for abuse of these agents is their hallucinogenic, dissociative, stimulant, anti-muscarinic, or sedative properties. Some of these drugs are easily obtainable such as Datura stramonium (Jimson Weed) or Lophophora williamsii (Peyote) because they are natural plants indigenous to certain regions. The diverse pharmacology and clinical effects of these agents are so broad that they do not produce a universal constellation of signs and symptoms. Detailed physical exams are essential for identifying clues leading one to suspect an alternative drug of abuse. Testing for the presence of these agents is often limited, and even when available, the results do not return in a timely fashion. Intoxications from these agents pose unique challenges for health care providers. Physician knowledge of the physiological effects of these alternative agents and the local patterns of drug of abuse are important for the accurate diagnosis and optimal care of poisoned patients. This review summarizes the current knowledge of alternative drugs of abuse and highlights their clinical presentations.

  20. Drug induced aseptic meningitis

    African Journals Online (AJOL)

    PROF. EZECHUKWU

    2013-09-29

    Sep 29, 2013 ... Abstract. Drug-induced aseptic meningitis (DIAM) is a rare but important and often challenging diagnosis for the physician. Intake of antimicrobials, steroids, anal- gesics amongst others has been implicated. Signs and symptoms generally develop within 24-48 hours of drug ingestion. The pa- tient often ...

  1. Student Drug Use.

    Science.gov (United States)

    Nowlis, Helen H.

    This paper discusses the nature and extent of student drug use, its meaning and significance, society's response to it, and some of the problems resulting from efforts to control it. Drugs are any substance which by its chemical nature affects the structure or function of the living organism. Abuse refers to any use of a non-medically approved…

  2. Drug delivery and formulations.

    Science.gov (United States)

    Breitkreutz, Jörg; Boos, Joachim

    2011-01-01

    Paediatric drug delivery is a major challenge in drug development. Because of the heterogeneous nature of the patient group, ranging from newborns to adolescents, there is a need to use appropriate excipients, drug dosage forms and delivery devices for different age groups. So far, there is a lack of suitable and safe drug formulations for children, especially for the very young and seriously ill patients. The new EU legislation will enforce paediatric clinical trials and drug development. Current advances in paediatric drug delivery include interesting new concepts such as fast-dissolving drug formulations, including orodispersible tablets and oral thin strips (buccal wafers), and multiparticulate dosage forms based on mini-tabletting or pelletization technologies. Parenteral administration is likely to remain the first choice for children in the neonatal period and for emergency cases. Alternative routes of administration include transdermal, pulmonary and nasal drug delivery systems. A few products are already available on the market, but others still need further investigations and clinical proof of concept.

  3. Vaginal drug distribution modeling.

    Science.gov (United States)

    Katz, David F; Yuan, Andrew; Gao, Yajing

    2015-09-15

    This review presents and applies fundamental mass transport theory describing the diffusion and convection driven mass transport of drugs to the vaginal environment. It considers sources of variability in the predictions of the models. It illustrates use of model predictions of microbicide drug concentration distribution (pharmacokinetics) to gain insights about drug effectiveness in preventing HIV infection (pharmacodynamics). The modeling compares vaginal drug distributions after different gel dosage regimens, and it evaluates consequences of changes in gel viscosity due to aging. It compares vaginal mucosal concentration distributions of drugs delivered by gels vs. intravaginal rings. Finally, the modeling approach is used to compare vaginal drug distributions across species with differing vaginal dimensions. Deterministic models of drug mass transport into and throughout the vaginal environment can provide critical insights about the mechanisms and determinants of such transport. This knowledge, and the methodology that obtains it, can be applied and translated to multiple applications, involving the scientific underpinnings of vaginal drug distribution and the performance evaluation and design of products, and their dosage regimens, that achieve it. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Drugs in sport.

    Science.gov (United States)

    McGrath, J C; Cowan, D A

    2008-06-01

    This themed issue of the British Journal of Pharmacology has been compiled and edited by Ian McGrath, Regius Professor of Physiology at University of Glasgow and David Cowan, Director of the Drug Control Centre at King's College London. It contains 11 articles covering the mechanisms of action of the major groups of drugs used illicitly in sport. The articles, written by experts in how drugs work, set out where drugs can or cannot affect sporting performance, how this relates to their legitimate medicinal use, their other detrimental effects and how they can be detected. Publication coincides with Olympic year, when sport is highlighted in the public mind and much speculation is made concerning the use of drugs. The articles provide a framework of expert, accurate knowledge to inform and facilitate these debates and to help to overcome the ill-informed and dangerous anecdotal information by which sports men and women are persuaded to misuse drugs in the mistaken belief that this will improve their performance without present or future ill effects. A unique article is included by the Spedding brothers, Mike with a long career in drug discovery and Charlie, the 1984 Los Angeles Olympic Marathon Bronze Medallist and still the English National Marathon record holder. From their unique experience, they describe the insidious and unfair way that drug-assisted performance undermines the ethos of sport and endangers the vital place of sport in maintaining the health of the population.

  5. Dendrimers for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Abhay Singh Chauhan

    2018-04-01

    Full Text Available Dendrimers have come a long way in the last 25 years since their inception. Originally created as a wonder molecule of chemistry, dendrimer is now in the fourth class of polymers. Dr. Donald Tomalia first published his seminal work on Poly(amidoamine (PAMAM dendrimers in 1985. Application of dendrimers as a drug delivery system started in late 1990s. Dendrimers for drug delivery are employed using two approaches: (i formulation and (ii nanoconstruct. In the formulation approach, drugs are physically entrapped in a dendrimer using non-covalent interactions, whereas drugs are covalently coupled on dendrimers in the nanoconstruct approach. We have demonstrated the utility of PAMAM dendrimers for enhancing solubility, stability and oral bioavailability of various drugs. Drug entrapment and drug release from dendrimers can be controlled by modifying dendrimer surfaces and generations. PAMAM dendrimers are also shown to increase transdermal permeation and specific drug targeting. Dendrimer platforms can be engineered to attach targeting ligands and imaging molecules to create a nanodevice. Dendrimer nanotechnology, due to its multifunctional ability, has the potential to create next generation nanodevices.

  6. Academic Drug Discovery Centres

    DEFF Research Database (Denmark)

    Kirkegaard, Henriette Schultz; Valentin, Finn

    2014-01-01

    Academic drug discovery centres (ADDCs) are seen as one of the solutions to fill the innovation gap in early drug discovery, which has proven challenging for previous organisational models. Prior studies of ADDCs have identified the need to analyse them from the angle of their economic...

  7. Current obesity drug treatment

    Directory of Open Access Journals (Sweden)

    Marcio C. Mancini

    2006-03-01

    Full Text Available Pharmacological treatment of obesity is an area of sudden changes,development of new drugs and treatment propositions. This articlepresents information on physiological agents that are currentlybeing used as well as drugs that were widely used but are nomore available.

  8. Drugs, Alcohol & Pregnancy.

    Science.gov (United States)

    Dye, Christina

    Expectant parents are introduced to the effects of a variety of drugs on the unborn baby. Material is divided into seven sections. Section 1 deals with the most frequently used recreational drugs, including alcohol, marijuana, narcotics, depressants, stimulants, inhalants, and hallucinogens. Sections 2 and 3 focus on the effects of prescription…

  9. Drug Impact Index.

    Science.gov (United States)

    Western Center for Drug-Free Schools and Communities.

    The Drug Impact Index provides a set of indicators designed to determine the extent of the local drug problem in a community. Each indicator includes a technical note on the data sources, a graph showing comparative statistics on that indicator for the Portland area and for the State of Oregon, and brief remarks on the implications of the data.…

  10. [Drug-Drug Interactions with Consideration of Pharmacogenetics].

    Science.gov (United States)

    Ozawa, Shogo

    2018-01-01

     Elderly patients often suffer from a variety of diseases and therefore may be prescribed several kinds of drugs. Interactions between these drugs may cause problems in some patients. Guidelines for drug interactions were released on July 8, 2014 "Drug Interaction Guideline for Drug Development and Labeling Recommendations (Final Draft)". These guidelines include the theoretical basis for evaluating the mechanisms of drug interaction, the possible extent of drug interactions, and take into consideration special populations (e.g., infants, children, elderly patients, patients with hepatic or renal dysfunction, and subjects with minor deficient alleles for drug metabolizing enzymes and drug transporters). In this symposium article, I discuss this last special population: altered drug metabolism and drug interactions in subjects with minor alleles of genes encoding deficient drug metabolizing enzymes. I further discuss a drug label for eliglustat (Cerdelga) with instructions for patients with ultra-rapid, extensive, intermediate, and poor metabolizer phenotypes that arise from different CYP2D6 gene alleles.

  11. Parents who use drugs

    DEFF Research Database (Denmark)

    Rhodes, Tim; Bernays, Sarah; Houmøller, Kathrin

    2010-01-01

    Parents who use drugs parent in a context of heightened concern regarding the damaging effects of parental drug use on child welfare and family life. Yet there is little research exploring how parents who use drugs account for such damage and its limitation. We draw here upon analyses of audio......-recorded depth qualitative interviews, conducted in south-east England between 2008 and 2009, with 29 parents who use drugs. Our approach to thematic analysis treated accounts as co-produced and socially situated. An over-arching theme of accounts was 'damage limitation'. Most damage limitation work centred...... on efforts to create a sense of normalcy of family life, involving keeping drug use secret from children, and investing heavily in strategies to maintain ambiguity regarding children's awareness. Our analysis highlights that damage limitation strategies double-up in accounts as resources of child protection...

  12. Metabonomics and drug development.

    Science.gov (United States)

    Ramana, Pranov; Adams, Erwin; Augustijns, Patrick; Van Schepdael, Ann

    2015-01-01

    Metabolites as an end product of metabolism possess a wealth of information about altered metabolic control and homeostasis that is dependent on numerous variables including age, sex, and environment. Studying significant changes in the metabolite patterns has been recognized as a tool to understand crucial aspects in drug development like drug efficacy and toxicity. The inclusion of metabonomics into the OMICS study platform brings us closer to define the phenotype and allows us to look at alternatives to improve the diagnosis of diseases. Advancements in the analytical strategies and statistical tools used to study metabonomics allow us to prevent drug failures at early stages of drug development and reduce financial losses during expensive phase II and III clinical trials. This chapter introduces metabonomics along with the instruments used in the study; in addition relevant examples of the usage of metabonomics in the drug development process are discussed along with an emphasis on future directions and the challenges it faces.

  13. Drug metabolism in birds

    Science.gov (United States)

    Pan, Huo Ping; Fouts, James R.

    1979-01-01

    Papers published over 100 years since the beginning of the scientific study of drug metabolism in birds were reviewed. Birds were found to be able to accomplish more than 20 general biotransformation reactions in both functionalization and conjugation. Chickens were the primary subject of study but over 30 species of birds were used. Large species differences in drug metabolism exist between birds and mammals as well as between various birds, these differences were mostly quantitative. Qualitative differences were rare. On the whole, drug metabolism studies in birds have been neglected as compared with similar studies on insects and mammals. The uniqueness of birds and the advantages of using birds in drug metabolism studies are discussed. Possible future studies of drug metabolism in birds are recommended.

  14. Drug therapy of leprosy

    Directory of Open Access Journals (Sweden)

    A. A. Kubanov

    2016-01-01

    Full Text Available Leprosy (Hansen’s disease is a chronic granulomatous bacterial infection mainly affecting the skin and peripheral nervous system yet also involving other organs and systems as a result of a pathological process. The causative agent of leprosy - Mycobacterium leprae - is an obligate intracellular microorganism. Despite the removal of a threat of a leprosy epidemic, European countries still record outbreaks of the disease mainly among migrants coming from endemic areas. A golden standard of the treatment of leprosy is a WHO-recommended combined drug therapy comprising drugs such as dapsone, clofazimine and rifampicin. The article provides current data on the mechanisms of action, efficacy and safety of these drugs and their combined scheme of treatment obtained as a result of clinical trials. Moreover, it also reviews new regimens of the drug therapy of leprosy including those with the use of drugs from the group of fluoroquinols as well as immunotherapy of the disease.

  15. Drug Pricing Reforms

    DEFF Research Database (Denmark)

    Kaiser, Ulrich; Mendez, Susan J.; Rønde, Thomas

    2015-01-01

    Reference price systems for prescription drugs have found widespread use as cost containment tools. Under such regulatory regimes, patients co-pay a fraction of the difference between pharmacy retail price of the drug and a reference price. Reference prices are either externally (based on drug...... prices in other countries) or internally (based on domestic drug prices) determined. In a recent study, we analysed the effects of a change from external to internal reference pricing in Denmark in 2005, finding that the reform led to substantial reductions in prices, producer revenues, and expenditures...... for patients and the health insurance system. We also estimated an increase in consumer welfare but the size effect depends on whether or not perceived quality differences between branded and other drugs are taken into account....

  16. [Drug induced diarrhea].

    Science.gov (United States)

    Morard, Isabelle; Hadengue, Antoine

    2008-09-03

    Diarrhea is a frequent adverse event involving the most frequently antibiotics, laxatives and NSAI. Drug induced diarrhea may be acute or chronic. It may be due to expected, dose dependant properties of the drug, to immuno-allergic or bio-genomic mechanisms. Several pathophysiological mechanisms have been described resulting in osmotic, secretory or inflammatory diarrhea, shortened transit time, or malabsorption. Histopathological lesions sometimes associated with drug induced diarrhea are usually non specific and include ulcerations, inflammatory or ischemic lesions, fibrous diaphragms, microscopic colitis and apoptosis. The diagnosis of drug induced diarrhea, sometimes difficult to assess, relies on the absence of other obvious causes and on the rapid disappearance of the symptoms after withdrawal of the suspected drug.

  17. Adoption of new HIV treatment guidelines and drug substitutions within first-line as a measure of quality of care in rural Lesotho: health centers and hospitals compared.

    Science.gov (United States)

    Labhardt, Niklaus D; Sello, Motlalepula; Lejone, Thabo; Ehmer, Jochen; Mokhantso, Mohlaba; Lynen, Lutgarde; Pfeiffer, Karolin

    2012-10-01

    In 2007, Lesotho launched new national antiretroviral treatment (ART) guidelines, prioritising tenofovir and zidovudine over stavudine as a backbone together with lamivudine. We compared the rate of adoption of these new guidelines and substitution of first-line drugs by health centers (HC) and hospitals in two catchment areas in rural Lesotho. Retrospective cohort analysis. Patients aged ≥16 years were stratified into a HC- and a hospital-group. Type of backbone at ART-initiation (i), substitutions within first line (ii) and type of backbone among patients retained by December 2010 (iii). A multiple logistic regression model including HC vs. hospital, patient characteristics (sex, age, WHO-stage, baseline CD4-count, concurrent pregnancy, concurrent tuberculosis treatment) and year of ART-start, was used. Of 3936 adult patients initiated on ART between 2007 and 2010, 1971 started at hospitals and 1965 at HCs. Hospitals were more likely to follow the new guidelines as measured by prescription of backbones without stavudine (Odds-ratio 1.55; 95%CI: 1.32-1.81) and had a higher rate of drug substitutions while on first-line ART (2.39; 1.83-3.13). By December 2010, patients followed at health centres were more likely to still receive stavudine (2.28; 1.83-2.84). Health centers took longer to adopt the new guidelines and substituted drugs less frequently. Decentralised ART-programmes need close support, supervision and mentoring to absorb new guidelines and to adhere to them. © 2012 Blackwell Publishing Ltd.

  18. 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

  19. How Much Do We Know about Drug Resistance Due to PrEP Use? Analysis of Experts' Opinion and Its Influence on the Projected Public Health Impact.

    Directory of Open Access Journals (Sweden)

    Dobromir T Dimitrov

    Full Text Available Randomized controlled trials reported that pre-exposure prophylaxis (PrEP with tenofovir and emtricitabine rarely selects for drug resistance. However, drug resistance due to PrEP is not completely understood. In daily practice, PrEP will not be used under the well-controlled conditions available in the trials, suggesting that widespread use of PrEP can result in increased drug resistance.We surveyed expert virologists with questions about biological assumptions regarding drug resistance due to PrEP use. The influence of these assumptions on the prevalence of drug resistance and the fraction of HIV transmitted resistance was studied with a mathematical model. For comparability, 50% PrEP-coverage of and 90% per-act efficacy of PrEP in preventing HIV acquisition are assumed in all simulations.Virologists disagreed on the following: the time until resistance emergence (range: 20-180 days in infected PrEP users with breakthrough HIV infections; the efficacy of PrEP against drug-resistant HIV (25%-90%; and the likelihood of resistance acquisition upon transmission (10%-75%. These differences translate into projections of 0.6%- 1% and 3.5%-6% infected individuals with detectable resistance 10 years after introducing PrEP, assuming 100% and 50% adherence, respectively. The rate of resistance emergence following breakthrough HIV infection and the rate of resistance reversion after PrEP use is discontinued, were the factors identified as most influential on the expected resistance associated with PrEP. Importantly, 17-23% infected individuals could virologically fail treatment as a result of past PrEP use or transmitted resistance to PrEP with moderate adherence.There is no broad consensus on quantification of key biological processes that underpin the emergence of PrEP-associated drug resistance. Despite this, the contribution of PrEP use to the prevalence of the detectable drug resistance is expected to be small. However, individuals who become

  20. Drugs Approved for Cervical Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for cervical cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  1. Drugs Approved for Multiple Myeloma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for multiple myeloma and other plasma cell neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  2. Drugs Approved for Testicular Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for testicular cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  3. Drugs Approved for Hodgkin Lymphoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Hodgkin lymphoma. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  4. Drugs Approved for Myeloproliferative Neoplasms

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for myeloproliferative neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  5. Herb-drug interactions.

    Science.gov (United States)

    Fugh-Berman, A

    2000-01-08

    Concurrent use of herbs may mimic, magnify, or oppose the effect of drugs. Plausible cases of herb-drug interactions include: bleeding when warfarin is combined with ginkgo (Ginkgo biloba), garlic (Allium sativum), dong quai (Angelica sinensis), or danshen (Salvia miltiorrhiza); mild serotonin syndrome in patients who mix St John's wort (Hypericum perforatum) with serotonin-reuptake inhibitors; decreased bioavailability of digoxin, theophylline, cyclosporin, and phenprocoumon when these drugs are combined with St John's wort; induction of mania in depressed patients who mix antidepressants and Panax ginseng; exacerbation of extrapyramidal effects with neuroleptic drugs and betel nut (Areca catechu); increased risk of hypertension when tricyclic antidepressants are combined with yohimbine (Pausinystalia yohimbe); potentiation of oral and topical corticosteroids by liquorice (Glycyrrhiza glabra); decreased blood concentrations of prednisolone when taken with the Chinese herbal product xaio chai hu tang (sho-salko-to); and decreased concentrations of phenytoin when combined with the Ayurvedic syrup shankhapushpi. Anthranoid-containing plants (including senna [Cassia senna] and cascara [Rhamnus purshiana]) and soluble fibres (including guar gum and psyllium) can decrease the absorption of drugs. Many reports of herb-drug interactions are sketchy and lack laboratory analysis of suspect preparations. Health-care practitioners should caution patients against mixing herbs and pharmaceutical drugs.

  6. Drug abuse in athletes

    Directory of Open Access Journals (Sweden)

    Reardon CL

    2014-08-01

    Full Text Available Claudia L Reardon, Shane Creado Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA Abstract: Drug abuse occurs in all sports and at most levels of competition. Athletic life may lead to drug abuse for a number of reasons, including for performance enhancement, to self-treat otherwise untreated mental illness, and to deal with stressors, such as pressure to perform, injuries, physical pain, and retirement from sport. This review examines the history of doping in athletes, the effects of different classes of substances used for doping, side effects of doping, the role of anti-doping organizations, and treatment of affected athletes. Doping goes back to ancient times, prior to the development of organized sports. Performance-enhancing drugs have continued to evolve, with “advances” in doping strategies driven by improved drug testing detection methods and advances in scientific research that can lead to the discovery and use of substances that may later be banned. Many sports organizations have come to ban the use of performance-enhancing drugs and have very strict consequences for people caught using them. There is variable evidence for the performance-enhancing effects and side effects of the various substances that are used for doping. Drug abuse in athletes should be addressed with preventive measures, education, motivational interviewing, and, when indicated, pharmacologic interventions. Keywords: doping, athletes, steroids, drug abuse, mental illness

  7. Anticancer drugs during pregnancy.

    Science.gov (United States)

    Miyamoto, Shingo; Yamada, Manabu; Kasai, Yasuyo; Miyauchi, Akito; Andoh, Kazumichi

    2016-09-01

    Although cancer diagnoses during pregnancy are rare, they have been increasing with the rise in maternal age and are now a topic of international concern. In some cases, the administration of chemotherapy is unavoidable, though there is a relative paucity of evidence regarding the administration of anticancer drugs during pregnancy. As more cases have gradually accumulated and further research has been conducted, we are beginning to elucidate the appropriate timing for the administration of chemotherapy, the regimens that can be administered with relative safety, various drug options and the effects of these drugs on both the mother and fetus. However, new challenges have arisen, such as the effects of novel anticancer drugs and the desire to bear children during chemotherapy. In this review, we outline the effects of administering cytotoxic anticancer drugs and molecular targeted drugs to pregnant women on both the mother and fetus, as well as the issues regarding patients who desire to bear children while being treated with anticancer drugs. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial

    NARCIS (Netherlands)

    Raffi, François; Babiker, Abdel G.; Richert, Laura; Molina, Jean-Michel; George, Elizabeth C.; Antinori, Andrea; Arribas, Jose R.; Grarup, Jesper; Hudson, Fleur; Schwimmer, Christine; Saillard, Juliette; Wallet, Cédrick; Jansson, Per O.; Allavena, Clotilde; van Leeuwen, Remko; Delfraissy, Jean-François; Vella, Stefano; Chêne, Geneviève; Pozniak, Anton; Dedes, Nikos; Autran, Brigitte; Bucciardini, Raffaella; Horban, Andrzej; Arribas, José; Boffito, Marta; Pillay, Deenan; Franquet, Xavier; Schwarze, Siegfried; Fischer, Aurélie; Diallo, Alpha; Moecklinghoff, Christiane; Stellbrink, Hans-Jürgen; Gatell, José; Sandström, Eric; Flepp, Markus; Ewings, Fiona; 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; Soussi, Malika; Taieb, Audrey; 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; 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; Palmisano, 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, André; 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; Raffi, Francois; Ragnaud, Jean Marie; Weiss, Laurence; Yazdanpanah, Yazdan; 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; Galli, Massimo; Lazzarin, Adriano; Mazzotta, Francesco; Vullo, Vincenzo; Prins, Jan; Richter, Clemens; Verhagen, Dominique; Eeden, Van; Doroana, Manuela; Antunes, Francisco; Maltez, Fernando; Sarmento-Castro, Rui; Gonzalez Garcia, Juan; López Aldeguer, José; Clotet, Bonaventura; Domingo, Pere; Gatell, Jose M.; Knobel, Hernando; Marquez, Manuel; Pilar Miralles, Martin; 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; Boucher, Charles; Calvez, Vincent; Collins, Simon; Dunn, David; Fox, Zoe; Perno, Carlo Federico; Ammassari, Adriana; Stoehr, Wolgang; Schmidt, Reinhold Ernst; Odermarsky, Michal; Smith, Colette; Thiébaut, Rodolphe; Arribas, Jose; de La Serna, Jose Ignacio Bernardino; Castagna, Antonella; Furrer, Hans-Jackob; Mocroft, Amanda; Reiss, Peter; Fragola, Vincenzo; Lauriola, Marco; Murri, Rita; Nieuwkerk, Pythia; Spire, Bruno; Volny-Anne, Alain; West, Brian; Amieva, Hélène; Llibre Codina, Josep Maria

    2014-01-01

    Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen. Between August, 2010, and September, 2011, we

  9. Selection of an entecavir-resistant mutant despite prolonged hepatitis B virus DNA suppression, in a chronic hepatitis B patient with preexistent lamivudine resistance : successful rescue therapy with tenofovir

    NARCIS (Netherlands)

    Leemans, Wilhelmus F; Niesters, Hubert G; van der Eijk, Annemiek A; Janssen, Harry L; Schalm, Solko W; de Man, Robert A

    BACKGROUND AND OBJECTIVE: Entecavir has potent activity against hepatitis B virus. Drug resistance has not been reported in nucleoside-naïve patients and is low in lamivudine-refractory patients. METHODS AND RESULTS: A 43-year-old man was treated with lamivudine for hepatitis B e antigen-positive

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Notes Podcasts E-Newsletters Public Education Projects National Drug & Alcohol Facts Week NIDA TV PEERx Drugs & Health Blog ... Award for Addiction Science USA Science & Engineering Festival Drug & Alcohol Chat Day HBO Addiction Project Learn the Link ...

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... www.cdc.gov/actagainstaids/basics/whatishiv.html ). Atlanta, GA: CDC, DHHS. Retrieved November 2017. How are Drug ... lead people to engage in impulsive and unsafe behaviors. Injection drug use. People typically associate drug misuse ...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... or reduce their drug use and related risk behaviors, including drug injection and unsafe sexual practices. Drug use disorder treatment programs also serve an important role in providing ...

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... risk for getting HIV. Drug and alcohol intoxication affect judgment and can lead to unsafe sexual practices, ... effects of drugs. Drug misuse and addiction can affect a person's overall health, thereby altering susceptibility to ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... is partly due to the addictive and intoxicating effects of many drugs, which can alter judgment and ... HIV or transmitting it to someone else. Biological effects of drugs. Drug misuse and addiction can affect ...

  15. State Drug Utilization Data 2003

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Twitter YouTube Flickr RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts ... to HIV and progression of AIDS. Drugs of abuse and HIV both affect the brain. Research has ...

  17. State Drug Utilization Data 2011

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  18. State Drug Utilization Data 2009

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  19. Drugs Approved for Pancreatic Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for pancreatic cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  20. State Drug Utilization Data 2016

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  1. Drugs Approved for Lung Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for lung cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  2. Drugs Approved for Bladder Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bladder cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana ... person at risk for getting HIV. Drug and alcohol intoxication affect judgment and can lead to unsafe ...

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available Skip to main content En español Researchers Medical & Health Professionals Patients & Families Parents & Educators Children & Teens Search ... Drug Testing Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse Hepatitis (Viral) HIV/ ...

  5. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... or reduce their drug use and related risk behaviors, including drug injection and unsafe sexual practices. Drug use disorder treatment programs also serve an important role in ...

  6. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl ... groups of young people, guiding the use of technology, the discussion between friends, and the importance of ...

  7. State Drug Utilization Data 2017

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  8. State Drug Utilization Data 1996

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  9. Drugs Approved for Thyroid Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Thyroid Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Thyroid Cancer Cabozantinib-S-Malate Caprelsa (Vandetanib) Cometriq (Cabozantinib-S-Malate) Doxorubicin ...

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse Hepatitis (Viral) HIV/AIDS Mental ... is partly due to the addictive and intoxicating effects of many drugs, which can alter judgment and ...

  11. State Drug Utilization Data 2008

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  12. State Drug Utilization Data 1992

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  13. State Drug Utilization Data 1995

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  14. State Drug Utilization Data 1998

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  15. State Drug Utilization Data 2014

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  16. State Drug Utilization Data 2005

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  17. State Drug Utilization Data 2002

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  18. State Drug Utilization Data 2004

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  19. State Drug Utilization Data 1993

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  20. State Drug Utilization Data 2006

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  1. State Drug Utilization Data 2012

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  2. State Drug Utilization Data 1999

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  3. State Drug Utilization Data 2015

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  4. State Drug Utilization Data 1997

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  5. State Drug Utilization Data 1991

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  6. State Drug Utilization Data 2001

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  7. State Drug Utilization Data 2007

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  8. State Drug Utilization Data 2013

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  9. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the ... AIDS, as well as HIV/AIDS research and policies. AIDS.gov New Media Tools : These new media ...

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl ... AIDS (acquired immune deficiency syndrome). AIDS is a disease of the immune system for which there is ...

  11. Drug: D05157 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05157 Drug Nicotine polacrilex (USAN); Nicorette (TN) ... Other ... DG01718 ... Drugs... for addictive disorder ... DG01715 ... Drugs for nicotine dependence Cyp substrate ... DG01638 ... CYP2A6 substrate Cy

  12. Drug: D00123 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00123 Drug Cyanamide (JP17); Cyanamide (TN) ... CH2N2 D00123.gif ... Other ... DG01718 ... Drugs... for addictive disorder ... DG01716 ... Drugs for alcohol dependence Same as: C01566 Therapeutic category: 3

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... Campaign! NIDA acknowledges the following television networks, organizations, educational institutions, magazines, newspapers, companies, events, and radio stations ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... parents and teachers). It provides them with useful information on the science behind drug use. NIDA’s Easy-to-Read Drug Facts Web site describes the dangers of drug misuse and ...

  15. Drug: D00330 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00330 Drug Flurbiprofen (JP17/USP/INN); Ansaid (TN) ... C15H13FO2 D00330.gif ... Anti...-inflammatory ... DG01908 ... Antiinflammatory drug, propionic acid derivatives ... DG01504 ... Nonsteroidal antiinflammatory drug (NSAI

  16. State Drug Utilization Data 1994

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  17. Neurocircuitry of drug reward

    Science.gov (United States)

    Ikemoto, Satoshi; Bonci, Antonello

    2013-01-01

    In recent years, neuroscientists have produced profound conceptual and mechanistic advances on the neurocircuitry of reward and substance use disorders. Here, we will provide a brief review of intracranial drug self-administration and optogenetic self-stimulation studies that identified brain regions and neurotransmitter systems involved in drug- and reward-related behaviors. Also discussed is a theoretical framework that helps to understand the functional properties of the circuitry involved in these behaviors. The circuitry appears to be homeostatically regulated and mediate anticipatory processes that regulate behavioral interaction with the environment in response to salient stimuli. That is, abused drugs or, at least, some may act on basic motivation and mood processes, regulating behavior-environment interaction. Optogenetics and related technologies have begun to uncover detailed circuit mechanisms linking key brain regions in which abused drugs act for rewarding effects. PMID:23664810

  18. Drug Dosing Toolkit

    Science.gov (United States)

    ... Drugs and Alcohol Exercise Mental Health Sex and Sexuality Smoking FAQs Tips and Tools Community For Health ... Homeless Veterans Returning Service Members Rural Veterans Seniors & Aging Veterans Volunteers Women Veterans Careers, Job Help & Training ...

  19. Antimicrobial (Drug) Resistance Prevention

    Science.gov (United States)

    ... June 6, 2018 HIV Vaccine Elicits Antibodies in Animals that Neutralize Dozens of HIV Strains , June 4, 2018 ... Antimicrobial (Drug) Resistance > Understanding share with facebook share with twitter share ...

  20. MSIS Drug Utilization Datamart

    Data.gov (United States)

    U.S. Department of Health & Human Services — This page provides background needed to take advantage of the capabilities of the MSIS Drug Utilization Datamart. This mart allows the user to develop high-level...

  1. Street Drugs and Pregnancy

    Science.gov (United States)

    ... help you quit. Or contact: National Council on Alcoholism and Drug Dependence (800) 622-2255 Substance Abuse Treatment Facility Locator (800) 662-4357 Last reviewed: November, 2016 Pregnancy Is it safe? Other Pregnancy topics ') document.write(' ...

  2. DrugFacts: Heroin

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  3. Drug Facts: Anabolic Steroids

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  4. Cholesterol - drug treatment

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000314.htm Cholesterol - drug treatment To use the sharing features on ... treatment; Hardening of the arteries - statin Statins for Cholesterol Statins reduce your risk of heart disease, stroke, ...

  5. Bibliography [On Drugs].

    Science.gov (United States)

    National Association of Student Personnel Administrators, Detroit, MI.

    A bibliography of materials on drugs is presented. The book and paper back entries are annotated. Selected technical references are listed under these major findings: (1) dependency, (2) barbiturates, (3) amphetamines, and (4) general pharmacology. (PS)

  6. Mucoadhesive drug delivery systems

    Directory of Open Access Journals (Sweden)

    Rahamatullah Shaikh

    2011-01-01

    Full Text Available Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal.

  7. Drug-induced pancreatitis.

    Science.gov (United States)

    Nitsche, Claudia; Maertin, Sandrina; Scheiber, Jonas; Ritter, Christoph A; Lerch, Markus M; Mayerle, Julia

    2012-04-01

    Drugs are thought to be a rare cause for acute pancreatitis; however 525 different drugs are listed in the World Health Organization (WHO) database suspected to cause acute pancreatitis as a side effect. Many of them are widely used to treat highly prevalent diseases. The true incidence is not entirely clear since only few systematic population based studies exist. The majority of the available data are derived from case reports or case control studies. Furthermore, the causality for many of these drugs remains elusive and for only 31 of these 525 dugs a definite causality was established. Definite proof for causality is defined by the WHO classification if symptoms reoccur upon rechallenge.In the actual algorithm the diagnosis is confirmed if no other cause of acute pancreatitis can be detected, and the patient is taking one of the suspected drugs.

  8. Drug therapy smartens up

    Science.gov (United States)

    Martin, Christian

    2015-11-01

    The submission of the first 'smart pill' for market approval, combined with progress in the European nanomedicine landscape, illustrates the positive outlook for drug therapy and health monitoring, explains Christian Martin.

  9. Drug Development Process

    Science.gov (United States)

    ... Preclinical Research Preclinical Research Drugs undergo laboratory and animal testing to answer basic questions about safety. More Information ... Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products

  10. Neuropathy secondary to drugs

    Science.gov (United States)

    ... Paclitaxel Suramin Vincristine Drugs used to fight infections: Chloroquine Dapsone Isoniazid (INH), used against tuberculosis Metronidazole (Flagyl) ... to treat gout) Disulfiram (used to treat alcohol use) Arsenic Gold Symptoms Symptoms may include any of ...

  11. The drug swindlers.

    Science.gov (United States)

    Silverman, M; Lydecker, M; Lee, P R

    1990-01-01

    In a number of important developing nations--among them Indonesia, India, and Brazil--clinical pharmacologists and other drug experts are revealing mounting concern over the marketing of fraudulent drug products. These are shaped, colored, flavored, marked, and packaged to mimic the real product. They may contain the actual antibiotic or other drug indicated on the label, but so "cut" that the product provides only a small fraction of the labeled amount, or they may contain only useless flour or starch. At best, they are worthless. At the worst, they can kill. In most instances, it is believed that these "drugs" are produced and marketed by local or domestic fly-by-night groups and not by multinational pharmaceutical firms. Blame for these practices is placed on inadequate or unenforced laws, only trivial punishments, bribery and corruption, and the fact that generally "nobody inspects the inspectors."

  12. Vitiligo, drug induced (image)

    Science.gov (United States)

    ... this person's face have resulted from drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally ... is the case with this individual. The typical vitiligo lesion is flat and depigmented, but maintains the ...

  13. Drugs and driving

    NARCIS (Netherlands)

    Walsh, J. Michael; De Gier, Johan J.; Christopherson, Asbjørg S.; Verstraete, Alain G.

    The authors present a global overview on the issue of drugs and driving covering four major areas: (1) Epidemiology and Prevalence-which reviews epidemiological research, summarizes available information, discusses the methodological shortcomings of extant studies, and makes recommendations for

  14. Medicaid Drug Claims Statistics

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Medicaid Drug Claims Statistics CD is a useful tool that conveniently breaks up Medicaid claim counts and separates them by quarter and includes an annual count.

  15. Transdermal drug delivery

    OpenAIRE

    Prausnitz, Mark R.; Langer, Robert

    2008-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability ...

  16. Immunosuppressive drugs and fertility

    OpenAIRE

    Leroy, Clara; Rigot, Jean-Marc; Leroy, Maryse; Decanter, Christine; Le Mapihan, Kristell; Parent, Anne-Sophie; Le Guillou, Anne-Claire; Yakoub-Agha, Ibrahim; Dharancy, Sébastien; Noel, Christian; Vantyghem, Marie-Christine

    2015-01-01

    Immunosuppressive drugs are used in the treatment of inflammatory and autoimmune diseases, as well as in transplantation. Frequently prescribed in young people, these treatments may have deleterious effects on fertility, pregnancy outcomes and the unborn child. This review aims to summarize the main gonadal side effects of immunosuppressants, to detail the effects on fertility and pregnancy of each class of drug, and to provide recommendations on the management of patients who are seen prior ...

  17. Microfabrication for Drug Delivery

    Science.gov (United States)

    Koch, Brendan; Rubino, Ilaria; Quan, Fu-Shi; Yoo, Bongyoung; Choi, Hyo-Jick

    2016-01-01

    This review is devoted to discussing the application of microfabrication technologies to target challenges encountered in life processes by the development of drug delivery systems. Recently, microfabrication has been largely applied to solve health and pharmaceutical science issues. In particular, fabrication methods along with compatible materials have been successfully designed to produce multifunctional, highly effective drug delivery systems. Microfabrication offers unique tools that can tackle problems in this field, such as ease of mass production with high quality control and low cost, complexity of architecture design and a broad range of materials. Presented is an overview of silicon- and polymer-based fabrication methods that are key in the production of microfabricated drug delivery systems. Moreover, the efforts focused on studying the biocompatibility of materials used in microfabrication are analyzed. Finally, this review discusses representative ways microfabrication has been employed to develop systems delivering drugs through the transdermal and oral route, and to improve drug eluting implants. Additionally, microfabricated vaccine delivery systems are presented due to the great impact they can have in obtaining a cold chain-free vaccine, with long-term stability. Microfabrication will continue to offer new, alternative solutions for the development of smart, advanced drug delivery systems. PMID:28773770

  18. Emerging drugs of abuse.

    Science.gov (United States)

    Nelson, Michael E; Bryant, Sean M; Aks, Steven E

    2014-02-01

    Many new emerging drugs of abuse are marketed as legal highs despite being labeled "not for human consumption" to avoid regulation. The availability of these substances over the Internet and in "head shops" has lead to a multitude of emergency department visits with severe complications including deaths worldwide. Despite recent media attention, many of the newer drugs of abuse are still largely unknown by health care providers. Slight alterations of the basic chemical structure of substances create an entirely new drug no longer regulated by current laws and an ever-changing landscape of clinical effects. The purity of each substance with exact pharmacokinetic and toxicity profiles is largely unknown. Many of these substances can be grouped by the class of drug and includes synthetic cannabinoids, synthetic cathinones, phenethylamines, as well as piperazine derivatives. Resultant effects generally include psychoactive and sympathomimetic-like symptoms. Additionally, prescription medications, performance enhancing medications, and herbal supplements are also becoming more commonly abused. Most new drugs of abuse have no specific antidote and management largely involves symptom based goal directed supportive care with benzodiazepines as a useful adjunct. This paper will focus on the history, epidemiology, clinical effects, laboratory analysis, and management strategy for many of these emerging drugs of abuse. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. [Drugs and occupational accident].

    Science.gov (United States)

    Bratzke, H; Albers, C

    1996-02-01

    In a case of a fatal occupational accident (construction worker, fall from roof, urine test positive for cocaine and THC, e.g. cannabis) the question arised to what extent those drug-related occupational accidents occur. In the literature only few cases, mainly dealing with cannabis influence, have been reported, however, a higher number is suspected. Cocaine and other stimulating drugs (amphetamine) are more often used to increase physical fitness. By direct or indirect interference with vigilance these compounds may provoke accidents. Due to the lack of a legal basis proving of the influence of drugs at the working place is still very limited, although highly sensitive chemical-toxicological assay procedures are available to detect even the chronic abuse (in hair). In the general conditions of accident insurances a compensation is excluded when alcohol is involved, but drugs are not mentioned. It is indeed difficult to establish a concentration limit for drugs like that existing for alcohol (1.1%). In each case the assay of the drug involved and exact knowledge of its specific effects is in an essential prerequisite to prove the causal relationship.

  20. New drugs of abuse.

    Science.gov (United States)

    Rech, Megan A; Donahey, Elisabeth; Cappiello Dziedzic, Jacqueline M; Oh, Laura; Greenhalgh, Elizabeth

    2015-02-01

    Drug abuse is a common problem and growing concern in the United States, and over the past decade, novel or atypical drugs have emerged and have become increasingly popular. Recognition and treatment of new drugs of abuse pose many challenges for health care providers due to lack of quantitative reporting and routine surveillance, and the difficulty of detection in routine blood and urine analyses. Furthermore, street manufacturers are able to rapidly adapt and develop new synthetic isolates of older drugs as soon as law enforcement agencies render them illegal. In this article, we describe the clinical and adverse effects and purported pharmacology of several new classes of drugs of abuse including synthetic cannabinoids, synthetic cathinones, salvia, desomorphine, and kratom. Because many of these substances can have severe or life-threatening adverse effects, knowledge of general toxicology is key in recognizing acute intoxication and overdose; however, typical toxidromes (e.g., cholinergic, sympathomimetic, opioid, etc.) are not precipitated by many of these agents. Medical management of patients who abuse or overdose on these drugs largely consists of supportive care, although naloxone may be used as an antidote for desomorphine overdose. Symptoms of aggression and psychosis may be treated with sedation (benzodiazepines, propofol) and antipsychotics (haloperidol or atypical agents such as quetiapine or ziprasidone). Other facets of management to consider include treatment for withdrawal or addiction, nutrition support, and potential for transmission of infectious diseases. © 2014 Pharmacotherapy Publications, Inc.