1 In Vitro Phenotypic Susceptibility of Human Immunodeficiency Virus Type 2 Clinical Isolates to Protease Inhibitors. Delphine Desbois, Bénédicte Roquebert, Gilles Peytavin, Florence Damond, Gilles Collin, Antoine Bénard, Pauline Campa, Sophie Matheron, Geneviève Chêne, Françoise Brun-Vézinet, et al. To cite this version: Delphine Desbois, Bénédicte Roquebert, Gilles Peytavin, Florence Damond, Gilles Collin, et al.. In Vitro Phenotypic Susceptibility of Human Immunodeficiency Virus Type 2 Clinical Isolates to Protease Inhibitors.. Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2008, 52 (4), pp < /AAC >. <inserm > HAL Id: inserm Submitted on 12 Mar 2008
2 HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
3 AAC Accepts, published online ahead of print on 28 January 2008 Antimicrob. Agents Chemother. doi: /aac Copyright 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved. HAL author manuscript 1 Antimicrobial Agents and Chemotherapy 2008;:epub 2008;52(4): ahead of print In vitro Phenotypic Susceptibility of HIV-2 Clinical Isolates to Protease Inhibitors Running title: Phenotypic susceptibility of HIV-2 to protease inhibitors Delphine Desbois 1, Bénédicte Roquebert 1, Gilles Peytavin 2, Florence Damond 1, Gilles Collin 1, Antoine Bénard 5, Pauline Campa 4, Sophie Matheron 3, Geneviève Chêne 5, Françoise Brun-Vézinet 1 and Diane Descamps 1 * for the French ANRS HIV-2 Cohort (ANRS CO 05 VIH-2). 1-Laboratoire de Virologie, Service de Microbiologie, Hôpital Bichat-Claude Bernard, Paris, France 2-Laboratoire de Toxicologie, Service de Pharmacie, Hôpital Bichat-Claude Bernard, Paris, France 15 3-Service de Maladies Infectieuses et Tropicales, Hôpital Bichat-Claude Bernard, Paris, 16 France 17 4-Service de Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Paris, France 18 5-ISPED Université Victor Segalen Bordeaux 2 INSERM U593, Bordeaux, France *Corresponding author:
4 21 Dr Diane Descamps 22 Laboratoire de Virologie Hôpital Bichat Claude Bernard 46 rue Henri Huchard Paris, France Tel: ; Fax: ;
5 30 31 Abstract We determine phenotypic susceptibility of HIV-2 isolates to amprenavir, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, saquinavir and tipranavir. Saquinavir, lopinavir and darunavir are potent on wild-type HIV-2 isolates and should be preferred as first-line options for HIV-2- infected patients. Other protease inhibitors are less active on HIV-2 than on HIV-1. Key words: HIV-2, phenotypic susceptibility, protease inhibitors, phenotypic resistance, resistance mutations
6 40 41 Few data are available on HIV-2 susceptibility to antiretroviral agents. In France, as recommended by the national expert group on the treatment of HIV infection, HIV-2-infected patients receive highly active antiretroviral therapy (HAART) regimens as HIV-1-infected individuals except non nucleoside reverse transcriptase inhibitors or fusion inhibitors classes (17) (12). However, a recent study showed that CD4 cell recovery was poor in antiretroviral- naive HIV-2 infected patients starting treatment with HAART (8). Thus it appears crucial to determine HIV-2 susceptibility to the current PIs available, in order to define the optimal regimen to be recommended. We selected nine PI-naive HIV-2-infected patients from the French HIV-2 ANRS cohort. Six of these patients subsequently received HAART regimens including a PI (indinavir, nelfinavir, saquinavir and/or ritonavir) for a median of 13 months (range 2-36), and had plasma viruses harboring mutations in the protease gene. PBMC co-culture isolates were available for these patients before (T0, n=6) and during (T1 (n=6), T2 (n=2)) PI exposure. Protease gene sequences of plasma and PBMC isolates were determined as previously described (3). Amino acid changes were compared with those associated with drug resistance in HIV-1 (International AIDS Society-USA (IAS-USA). We determine the in vitro phenotypic susceptibility of clinical HIV-2 isolates and HIV-2 ROD and HIV-1 BRU reference strains to amprenavir, atazanavir, darunavir, 58 indinavir, lopinavir, nelfinavir, saquinavir and tipranavir using the ANRS PBMC assay (4). 59 Phenotypic inhibitory quotients (PIQs) were calculated for each clinical HIV-2 isolate, as the 60 ratio between the trough plasma PI concentration and the IC50. The PIQs were not adjusted for 61 protein binding. The Table shows the phenotypic results and protease gene sequences of the 62 HIV-2 clinical isolates, and the HIV-2 and HIV-1 reference isolates. 63 The protease sequences of wild-type HIV-2 strains, when compared to HIV-1 clade B consensus 64 sequence, contained several amino acids associated with HIV-1 PI resistance, such as 10I/V 65 16E, 20V, 32I, 33V, 35G, 36I, 43T, 46I, 47V, 58E, 62V, 69K, 71V, 73A, 82I and 93L. Other
7 66 differences were observed at positions involved in but not associated with HIV-1 resistance, 67 such as 13A, 34A, 60K, 63E, 76M, 77T, 85F and 89I. Relative to HIV-1 reference strain, the 68 median IC50 values of the HIV-2 wild-type isolates were 31-fold higher for amprenavir, 8-fold higher for atazanavir, 7-fold higher for tipranavir, and 3-fold higher for indinavir and nelfinavir. Darunavir, lopinavir and saquinavir IC50 and IC90 values were similar for HIV-1 and the wild- type HIV-2 isolates (table). Viruses isolated from the six PI experienced patients at T1 and T2 harboured the I82F, I84V and L90M substitutions, alone or in combination with minor HIV-1 PI mutations such as V10I, V33I, I54M, I64V, V71I and I89V. Compared to the corresponding wild-type isolates, the eight mutants showed 4 to >10-fold increases in the IC50 and/or IC90 values of all tested PIs, at both T1 and T2. The PIQs values of amprenavir, atazanavir, indinavir, nelfinavir and tipranavir were respectively 33-fold, 8-fold, 3-fold, 3-fold and 7-fold lower for HIV-2 wild-type strains than for HIV-1. Darunavir, lopinavir and saquinavir PIQ values were similar. PIs are designed to fit the active site of the HIV-1 protease and are sensitive to structural changes in the viral protein. It has been reported that the therapeutic outcome of HIV-2-infected patients might be influenced by the choice of PIs (1) (15). For amprenavir our data are in keeping with those reported elsewhere, showing significantly lesser activity against HIV-2 wildtype strains than against HIV-1 (9) (14) (16). These phenotypic results could be explained by the natural presence in HIV-2 protease of amino acids associated with resistance to HIV-1, 85 which might influence the binding affinity of the PIs for HIV-2 protease (2) (3) (9) (10) (11). In 86 our study, all the HIV-2 wild-type strains protease sequences naturally presented the amino 87 acids 32I and 47V associated with resistance in HIV-1 infection to amprenavir according to IAS 88 USA list and to different genotypic resistance interpretation algorithms 89 (www.hivfrenchresistance.org,www.hivdb.stanford.edu,www.kuleuven.be/rega/cev/links/rega_a 90 lgorithm). We found that clinical HIV-2 isolates and HIV-1 reference strains had similar 91 phenotypic susceptibility to saquinavir, lopinavir and darunavir. As amprenavir and darunavir 92 are structurally close, we expected darunavir to be relatively ineffective in HIV-2.
8 93 Crystallographic studies with HIV-1 showed that darunavir interacts directly with the main 94 chains of aspartic acid residues (Asp-29 and Asp-30), whereas other PIs interact with side 95 chains in the S2 subsite of the HIV-1 enzyme (6) (7). Moreover, it has been reported in HIV that the binding affinity of darunavir for wild-type protease was > 100-fold higher than other PIs due to a slower dissociation rate of this molecule from the protease active site (5). In the same way, crystallography structure studies of the HIV-2 protease and binding affinity experiments might help us to understand the difference observed in the natural susceptibility of HIV-2 strains for these two drugs as well as phenotypic resistance in HIV-2 mutated strains. The IC50 and IC90 values of atazanavir, indinavir, nelfinavir and tipranavir for the HIV-2 isolates were higher than those observed for HIV-1 raising the hypothesis of a lower activity of these PIs against HIV-2. However these values were lower than their respective trough plasma concentrations. This might be explained by the fact that HIV-2 wild-type isolates harbored several amino acids associated with PI resistance in HIV-1. PI treatment-associated amino acid changes in the HIV-2 protease gene occurred at positions known to confer PI resistance in HIV-1 and were not associated with the use of a particular PI without any order of accumulation. They altered the phenotypic susceptibility of the isolates to all the PIs tested here. These results are in keeping with data published elsewhere (2) (3) (9) (11) (13) (15). Mutagenesis experiments coupled with phenotypic susceptibility testing might help to determine the impact of each substitutions in PI resistance. Saquinavir, lopinavir and 112 darunavir appear to be the best choices for first-line therapy of HIV-2 infection, while 113 amprenavir should not be used. Atazanavir and tipranavir might be used with care (17). Our 114 results suggest that treatment guidelines for HIV-1-infected patients should not be directly 115 extrapolated to HIV-2-infected patients. Virological efficacy data in vivo might help us to 116 evaluate the place of PIs in HIV-2 antiretroviral strategy.
9 117 Acknowledgements 118 This work was supported by Agence nationale de Recherche sur le SIDA et les Hépatites 119 virales (ANRS). 120 We thank Laetitia Stephant for her technical skills This work was presented at the 14th Conference on Retroviruses and Opportunistic Infection, February 25-28, 2007, Los Angeles, CA, USA. Drugs and sources Amprenavir was provided by GlaxoSmithKline (Marly-le-Roi, France), atazanavir by Bristol-Myers Squibb (Rueil-Malmaison, France), darunavir by Tibotec (Mechelen, Belgium), indinavir by Merck Sharp & Dohme-Chibret (West Point, PA, USA), lopinavir by Abbott (Rungis, France), nelfinavir and saquinavir by Roche (Neuilly sur Seine, France) and tipranavir by Boehringer-Ingelheim (Ridgefield, CT, USA). 130
10 131 References Adje-Toure, C. A., R. Cheingsong, J. G. Garcia-Lerma, S. Eholie, M. Borget, J. Bouchez, R. A. Otten, C. Maurice, M. Sassan-Morokro, R. E. Ekpini, M. Nolan, T. Chorba, W. Heneine, and J. N. Nkengasong Antiretroviral therapy in HIV-2- infected patients: Changes in plasma viral load, CD4+ cells counts and drug resistance profiles of patients treated in Abidjan, Cote d'ivoire. AIDS 17:S49-S Colson, P., M. Henry, M. Tivoli, H. Gallais, J. A. Gastaut, J. Moreau, and C. Tamalet Presented at the XII International HIV drug resistance workshop: Basic principles and Clinical Implications, Los Cabos, Mexico. 3. Damond, F., F. Brun-Vezinet, S. Matheron, G. Peytavin, P. Campa, S. Pueyo, F. Mammano, S. Lastere, I. Farfara, F. Simon, G. Chene, and D. Descamps Polymorphism of the human immunodeficiency virus type 2 (HIV-2) protease gene and selection of drug resistance mutations in HIV-2-infected patients treated with protease inhibitors. J Clin Microbiol 43: Damond, F., G. Collin, S. Matheron, G. Peytavin, P. Campa, S. Delarue, A. Taieb, A. Benard, G. Chene, F. Brun-Vezinet, and D. Descamps Letter. In vitro phenotypic susceptibility to nucleoside reverse transcriptase inhibitors of HIV-2 isolates with the Q151M mutation in the reverse transcriptase gene. Antivir Ther 10: De Wit, M., I. Keuleers, E. Gustin, I. Dierynck, S. Hallenberger, and K. Hertogs Presented at the XIV Conference on Retroviruses and Opportunistic Infections., Los 151 Angeles,CA, US, February 25-28, Koh, Y., H. Nakata, K. Maeda, H. Ogata, G. Bilcer, T. Devasamudram, J. F. Kincaid, P. 153 Boross, Y. F. Wang, Y. Tie, P. Volarath, L. Gaddis, R. W. Harrison, I. T. Weber, A. K. 154 Ghosh, and H. Mitsuya Novel bis-tetrahydrofuranylurethane-containing nonpeptidic 155 protease inhibitor (PI) UIC (TMC114) with potent activity against multi-pi-resistant 156 human immunodeficiency virus in vitro. Antimicrob Agents Chemother 47:
11 Kovalevsky, A. Y., F. Liu, S. Leshchenko, A. K. Ghosh, J. M. Louis, R. W. Harrison, and 158 I. T. Weber Ultra-high resolution crystal structure of HIV-1 protease mutant reveals 159 two binding sites for clinical inhibitor TMC114. J Mol Biol 363: Matheron, S., F. Damond, A. Benard, A. Taieb, P. Campa, G. Peytavin, S. Pueyo, F. Brun-Vezinet, and G. Chene CD4 cell recovery in treated HIV-2-infected adults is lower than expected: results from the French ANRS CO5 HIV-2 cohort. Aids 20: Ntemgwa, M., B. G. Brenner, M. Oliveira, D. Moisi, and M. A. Wainberg Natural polymorphisms in the human immunodeficiency virus type 2 protease can accelerate time to development of resistance to protease inhibitors. Antimicrob Agents Chemother 51: Parreira, R., F. Monteiro, E. Padua, J. Piedade, T. Venenno, M. T. Paixao, and A. Esteves Natural polymorphisms of HIV type 2 pol sequences from drug-naive individuals. AIDS Res Hum Retroviruses 22: Pieniazek, D., M. Rayfield, D. J. Hu, J. N. Nkengasong, V. Soriano, W. Heneine, C. Zeh, S. M. Agwale, C. Wambebe, L. Odama, and S. Z. Wiktor HIV-2 protease sequences of subtypes A and B harbor multiple mutations associated with protease inhibitor resistance in HIV-1. Aids 18: Ren, J., L. E. Bird, P. P. Chamberlain, G. B. Stewart-Jones, D. I. Stuart, and D. K. Stammers Structure of HIV-2 reverse transcriptase at 2.35-A resolution and the mechanism of resistance to non-nucleoside inhibitors. Proc Natl Acad Sci U S A 99: Rodes, B., A. Holguin, V. Soriano, M. Dourana, K. Mansinho, F. Antunes, and J. 177 Gonzalez-Lahoz Emergence of drug resistance mutations in Human 178 Immunodeficiency virus type 2-infected subjects undergoing antiretroviral therapy. Journal of 179 Clinical Microbiology 38: Rodes, B., J. Sheldon, C. Toro, V. Jimenez, M. A. Alvarez, and V. Soriano Susceptibility to protease inhibitors in HIV-2 primary isolates from patients failing 182 antiretroviral therapy. J Antimicrob Chemother 57:
12 van der Ende, M. E., K. Brinkman, M. Keuters, J. M. Prins, S. A. Danner, A. D. M. E. 184 Osterhaus, and M. Schutten Antiretroviral therapy in HIV2 infected patients in the 185 Netherlands: Results in 17 patients. AIDS 14:S Withrouw, M., C. Pannecouque, W. M. Switzer, T. M. Folks, E. De Clercq, and W. Heneine Susceptibility of HIV-2, SIV and SHIV to various anti-hiv-1 compounds: implications for treatment and postexposure prophylaxis. Antivir Ther 9: Yeni, P Rapport 2006 Prise en charge médicale des personnes infectées par le VIH, vol. Flammarion.
13 Legend of the table Table Title : Phenotypic susceptibilities to PIs and protease mutations compared to HIV-2 subtypes A and B consensus sequences of the 9 wild-type isolates
14 ISOLATES IC50 IC90 IC50 IC90 IC50 IC90 IC50 IC90 IC50 IC90 IC50 IC90 IC50 IC90 IC50 IC90 BRU (HIV-1 reference isolate) HIV-2 Isolates ROD (HIV-2 reference isolate) Patient 1 (subtype H) T0: 10I-40P-41Y-60H-63N-70T-73G-89L-92E T1: 10I-34E*-40P-41Y-60H-63N-70T-73G-82F*-89L-92E Fold increase in IC50 between T1/T Patient 2 (subtype A) T0: 14H-17D-43T-68N/D <0.01 < <0.006 < T1: 5L/F*-14Y/H*-17G/D*-43T-54I/M*-62V/A*-70R/K*-71I* >12.5 > Fold increase in IC50 between T1/T / / / / Patient 3 (subtype A) T0: 14H-60K/N-65E T1: 54M*-65E-71I*-74N*-90M* >12.5 > Fold increase in IC50 between T1/T / / 15 5 Patient 4 (subtype A) T0: 10I-17D-40D-43I-46V-66V/A-70R/K T1: 10I-17D-40D-43I-45K/R*-46V-54M*-64I/V*-69K/R*-71V/I*-90M* Fold increase in IC50 between T1/T Patient 5 (subtype A) T0: 14H-40D-70K-72R/K-91T/S T1: 10I*-40D-43I*-70K-82F*-84V*-85L*-89V*-90M*-91T/L*-98N/K* >17.6 > T2: 10V/I*-40D-43I*-56V*-70K-82F*-84V*-89V*-90M* Fold increase in IC50 between T1/T / / Fold increase in IC50 between T2/T Patient 6 (subtype B) T0: 14Y-61N-99L T1: 14Y-19P*-33I*-61N-71I*-75M*-84V*-90M* T2: 14Y-19P*-61N-64V*-71I*-90M*-95I* >17.6 > Fold increase in IC50 between T1/T Fold increase in IC50 between T2/T / / Patient 7 (subtype B) T0: 12T-14Y-19P-40N-41D-61N-62I-96S-99L Phenotypic susceptibilities to PIs and protease mutations compared to HIV-2 subtypes A and B consensus sequences before (T0) and after (T1. T2) PIs initiating treatment of the 9 HIV-2 isolates. Amprenavir Atazanavir Darunavir Indinavir Lopinavir Nelfinavir Saquinavir Tipranavir Patient 8 (subtype B) T0: 12Q-14R-17G/D-19P-61N-62I-92A Patient 9 (subtype A) T0: 41D Median IC 50 and IC 90 value at T0 (+/- SD) 0.60 (+/- 0.20) 3.30 (+/- 1.50) 0.06 (+/- 0.05) 0.30 (+/- 0.08) (+/- 0.04) 0.03 (+/- 0.16) 0.02 (+/- 0.10) 0.40 (+/- 0.80) 0.03 (+/- 0.01) 0.14 (+/- 0.10) 0.06 (+/- 0.08) 0.40 (+/- 0.60) (+/- 4.60) 0.05 (+/- 27.0) 0.30 (+/- 0.05) 2.50 (+/- 1.10) *Substitutions selected between T0 and T1/T2. IC50 and IC90 values are measured in µm
Mobility management and vertical handover decision making in heterogeneous wireless networks Mariem Zekri To cite this version: Mariem Zekri. Mobility management and vertical handover decision making in
ibalance-abf: a Smartphone-Based Audio-Biofeedback Balance System Céline Franco, Anthony Fleury, Pierre-Yves Guméry, Bruno Diot, Jacques Demongeot, Nicolas Vuillerme To cite this version: Céline Franco,
La mort du narrateur et l interprétation du roman. L exemple de Pedro Páramo de Juan Rulfo Sylvie Patron To cite this version: Sylvie Patron. La mort du narrateur et l interprétation du roman. L exemple
Virginia Woolf, Comment devrait-on lire un livre? ou le théoricien du commun François-Ronan Dubois To cite this version: François-Ronan Dubois. Virginia Woolf, Comment devrait-on lire un livre? ou le théoricien
Analyse échographique de la cicatrisation tendineuse après réparation arthroscopique de la coiffe des rotateurs Martin Schramm To cite this version: Martin Schramm. Analyse échographique de la cicatrisation
A usage coverage based approach for assessing product family design Jiliang Wang To cite this version: Jiliang Wang. A usage coverage based approach for assessing product family design. Other. Ecole Centrale
AAC Accepts, published online ahead of print on 0 November 006 Antimicrob. Agents Chemother. doi:10.118/aac.00870-06 Copyright 006, American Society for Microbiology and/or the Listed Authors/Institutions.
AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 22, Number 11, 2006, pp. 1178 1182 Mary Ann Liebert, Inc. Sequence Note Natural Polymorphisms of HIV Type 2 pol Sequences from Drug-Naive Individuals RICARDO
A graph based framework for the definition of tools dealing with sparse and irregular distributed data-structures Serge Chaumette, Jean-Michel Lepine, Franck Rubi To cite this version: Serge Chaumette,
Overview of model-building strategies in population PK/PD analyses: 2002-2004 literature survey. Céline Dartois, Karl Brendel, Emmanuelle Comets, Céline Laffont, Christian Laveille, Brigitte Tranchand,
HIV Drug resistanceimplications for therapy Deenan Pillay Africa Centre for Health and Population Studies, UKZN University College London Potential implications of HAART without virological monitoring:
Auto-Scaling, Load Balancing and Monitoring in Commercial and Open-Source Clouds Eddy Caron, Luis Rodero-Merino, Frédéric Desprez, Adrian Muresan To cite this version: Eddy Caron, Luis Rodero-Merino, Frédéric
Les identités féminines dans le conte traditionnel occidental et ses réécritures : une perception actualisée des élèves Sarah Brasseur To cite this version: Sarah Brasseur. Les identités féminines dans
HIV Drug Resistance in the Asia- Pacific David A Cooper National Centre in HIV Epidemiology and Clinical Research The University of New South Wales Sydney, Australia HIVDR in Asia Pacific Transmitted resistance
Perspective Incomplete Viral Suppression Under Potent Antiretroviral Therapy: Determinants of Treatment Outcome At the International AIDS Society USA course in Los Angeles in March 22, Steven G. Deeks,
Use of tabletop exercise in industrial training disaster. Alexis Descatha, Thomas Loeb, François Dolveck, Nathalie-Sybille Goddet, Valerie Poirier, Michel Baer To cite this version: Alexis Descatha, Thomas
1 Appendix B: DESCRIPTION OF HIV PROGRESSION SIMULATION * Our simulation separately tracks the number of accumulated genetic mutations that may confer resistance to each of the three main drug categories
A 12-22 Month Follow-Up of HIV Patients Whose Therapy Was Optimized by Using HIV Genotyping Cynthia J. Carlyn, MD * Aldona L. Baltch, MD * Marty H. St. Clair, BS Mary J. George, PhD * Raymond P. Smith,
Faut-il des cyberarchivistes, et quel doit être leur profil professionnel? Jean-Daniel Zeller To cite this version: Jean-Daniel Zeller. Faut-il des cyberarchivistes, et quel doit être leur profil professionnel?.
Routine testing to reduce late HIV diagnosis in France. Cyrille Delpierre, Lise Cuzin, France Lert To cite this version: Cyrille Delpierre, Lise Cuzin, France Lert. Routine testing to reduce late HIV diagnosis
Journal of Antimicrobial Chemotherapy Advance Access published May 10, 2011 J Antimicrob Chemother doi:10.1093/jac/dkr164 Drug resistance mutations in patients infected with HIV-2 living in Spain Ana Treviño
State of the Art Testing for HIV Drug Resistance Victor S.B. Jorden, MD, MPH Sindy M. Paul, MD, MPH Today, many patients with HIV infection are able to live longer and better lives, owing to the use of
ANIMATED PHASE PORTRAITS OF NONLINEAR AND CHAOTIC DYNAMICAL SYSTEMS Jean-Marc Ginoux To cite this version: Jean-Marc Ginoux. ANIMATED PHASE PORTRAITS OF NONLINEAR AND CHAOTIC DYNAMICAL SYSTEMS. A.H. Siddiqi,
Paediatric HIV Drug Resistance in African Settings Dr Cissy Kityo Mutuluuza INTEREST Meeting May 5-9, 2014 Lusaka, Zambia Background: ART for children in sub- Saharan Africa 2.3 million children with HIV
M42-Determinants M19 of HIV Sustained Viral Suppression in HIV/HCV-Coinfected Patients: role of the HCV sustained viral suppression F. Bani-Sadr 1-2, M-A Loko 2, E. Pambrun 2, M. Winnock 2, P. Carrieri
Expanding Renewable Energy by Implementing Demand Response Stéphanie Bouckaert, Vincent Mazauric, Nadia Maïzi To cite this version: Stéphanie Bouckaert, Vincent Mazauric, Nadia Maïzi. Expanding Renewable
Data Mining Analysis of HIV-1 Protease Crystal Structures Gene M. Ko, A. Srinivas Reddy, Sunil Kumar, and Rajni Garg AP0907 09 Data Mining Analysis of HIV-1 Protease Crystal Structures Gene M. Ko 1, A.
Managing Risks at Runtime in VoIP Networks and Services Oussema Dabbebi, Remi Badonnel, Olivier Festor To cite this version: Oussema Dabbebi, Remi Badonnel, Olivier Festor. Managing Risks at Runtime in
Therapeutic Drug Monitoring of Antiretroviral Drugs with PLC-M Ursula Gutteck-Amsler, Katharina M. Rentsch Abstract Prospective and retrospective studies have provided some evidence of the clinical and
Minkowski Sum of Polytopes Defined by Their Vertices Vincent Delos, Denis Teissandier To cite this version: Vincent Delos, Denis Teissandier. Minkowski Sum of Polytopes Defined by Their Vertices. Journal
Effets du monoxyde d azote inhalé sur le cerveau en développement chez le raton Gauthier Loron To cite this version: Gauthier Loron. Effets du monoxyde d azote inhalé sur le cerveau en développement chez
TREATMENT FAILURE AND PATTERNS OF GENOTYPIC DRUG RESISTANCE MUTATIONS AMONG HAART EXPERIENCED HIV-1 PATIENTS AT KCMC Theonest Ndyetabura KILIMANJARO CHRISTIAN MEDICAL CENTRE / KILIMANJARO CLINICAL RESERCH
Knowledge based tool for modeling dynamic systems in education Krassen Stefanov, Galina Dimitrova To cite this version: Krassen Stefanov, Galina Dimitrova. Knowledge based tool for modeling dynamic systems
ANALYSIS OF SNOEK-KOSTER (H) RELAXATION IN IRON J. San Juan, G. Fantozzi, M. No, C. Esnouf, F. Vanoni To cite this version: J. San Juan, G. Fantozzi, M. No, C. Esnouf, F. Vanoni. ANALYSIS OF SNOEK-KOSTER
Chapter 36 Media Directory Drugs for Viral Infections Slide 23 Slide 27 Slide 29 Zidovudine Animation Saquinavir Mesylate Animation Acyclovir Animation Upper Saddle River, New Jersey 07458 All rights reserved.
Discussion on the paper Hypotheses testing by convex optimization by A. Goldenschluger, A. Juditsky and A. Nemirovski. Fabienne Comte, Celine Duval, Valentine Genon-Catalot To cite this version: Fabienne
DOI: 10.1111/j.1468-1293.2008.00561.x r 2008 Merck & Co., Inc. HIV Medicine (2008), 9, 285 293 ORIGINAL RESEARCH The prevalence of transmitted antiretroviral drug resistance in treatment-naïve patients
Guidance for Industry Antiviral Product Development Conducting and Submitting Virology Studies to the Agency U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation
Comparative Drug Ranking for Clinical Decision Support in HIV Treatment Emiliano Mancini University of Amsterdam 1 Prevalence of HIV 2 Global Overview HIV Infection People living with HIV: 34 million (2010
QASM: a Q&A Social Media System Based on Social Semantics Zide Meng, Fabien Gandon, Catherine Faron-Zucker To cite this version: Zide Meng, Fabien Gandon, Catherine Faron-Zucker. QASM: a Q&A Social Media
Population Pharmacokinetics of Atazanavir in Naïve HIV Infected Patients using Medication Events Monitoring System (MEMS) for drug intake timing ANRS -COPHAR clinical trial Céline Verstuyft Pharmacologie,
Guidance for Industry Role of HIV Resistance Testing in Antiretroviral Drug Development U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research
Online vehicle routing and scheduling with continuous vehicle tracking Jean Respen, Nicolas Zufferey, Jean-Yves Potvin To cite this version: Jean Respen, Nicolas Zufferey, Jean-Yves Potvin. Online vehicle
review article medical progress HIV Drug Resistance François Clavel, M.D., and Allan J. Hance, M.D. the use of combinations of antiretroviral drugs has proven remarkably effective in controlling the progression
An update on acoustics designs for HVAC (Engineering) Ken MARRIOTT To cite this version: Ken MARRIOTT. An update on acoustics designs for HVAC (Engineering). Société Française d Acoustique. Acoustics 2012,
Additional mechanisms for rewriting on-the-fly SPARQL queries proxy Arthur Vaisse-Lesteven, Bruno Grilhères To cite this version: Arthur Vaisse-Lesteven, Bruno Grilhères. Additional mechanisms for rewriting
From Microsoft Word 2003 to Microsoft Word 2007: Design Heuristics, Design Flaws and Lessons Learnt Yin-Leng Theng, Eng Kiat Ting, Xuehong Tao To cite this version: Yin-Leng Theng, Eng Kiat Ting, Xuehong
VR4D: An Immersive and Collaborative Experience to Improve the Interior Design Process Amine Chellali, Frederic Jourdan, Cédric Dumas To cite this version: Amine Chellali, Frederic Jourdan, Cédric Dumas.
Study on Cloud Service Mode of Agricultural Information Institutions Xiaorong Yang, Nengfu Xie, Dan Wang, Lihua Jiang To cite this version: Xiaorong Yang, Nengfu Xie, Dan Wang, Lihua Jiang. Study on Cloud
FP-Hadoop: Efficient Execution of Parallel Jobs Over Skewed Data Miguel Liroz-Gistau, Reza Akbarinia, Patrick Valduriez To cite this version: Miguel Liroz-Gistau, Reza Akbarinia, Patrick Valduriez. FP-Hadoop:
L exercice du théâtre à l école Mathilde Patteyn To cite this version: Mathilde Patteyn. L exercice du théâtre à l école. Éducation. 2013. HAL Id: dumas-00861849 http://dumas.ccsd.cnrs.fr/dumas-00861849
Chinese Journal of New Drugs 2002,Vol. 11 No. 11 2002 11 11 toxicity in CEM cells treated with carbovir [J ]. A ntivi ral Res, 1997,34 131-136. [ 29 ] Parese2Di GA,Rouquayrol M, Greiner J, et al. Synthesis
SELECTIVELY ABSORBING COATINGS J. Vuletin, P. Kuli ik, M. Bosanac To cite this version: J. Vuletin, P. Kuli ik, M. Bosanac. SELECTIVELY ABSORBING COATINGS. Journal de Physique Colloques, 1981, 42 (C1),
New implementions of predictive alternate analog/rf test with augmented model redundancy Haithem Ayari, Florence Azais, Serge Bernard, Mariane Comte, Vincent Kerzerho, Michel Renovell To cite this version:
Template Based MDE Matthieu Allon, Gilles Vanwormhoudt, Bernard Carré, Olivier Caron To cite this version: Matthieu Allon, Gilles Vanwormhoudt, Bernard Carré, Olivier Caron. Template Based MDE. 4ème Conférence
Full-fledged work is in progress towards construction and cloning of codon optimized envelope with subsequent aims towards immunization of mice to study immune responses. 1 2 4 5 6 Figure 4.1: Gel picture
Aligning subjective tests using a low cost common set Yohann Pitrey, Ulrich Engelke, Marcus Barkowsky, Romuald Pépion, Patrick Le Callet To cite this version: Yohann Pitrey, Ulrich Engelke, Marcus Barkowsky,
Information Technology Education in the Sri Lankan School System: Challenges and Perspectives Chandima H. De Silva To cite this version: Chandima H. De Silva. Information Technology Education in the Sri
Pricing access to the Internet with partial information Ilaria Brunetti, Eitan Altman, Majed Haddad To cite this version: Ilaria Brunetti, Eitan Altman, Majed Haddad. Pricing access to the Internet with
The CHI 2013 Interactive Schedule Arvind Satyanarayan, Daniel Strazzulla, Clemens Klokmose, Michel Beaudouin-Lafon, Wendy E. Mackay To cite this version: Arvind Satyanarayan, Daniel Strazzulla, Clemens
Australian Federation of AIDS Organisations PO Box 51 Newtown NSW 2042 www.afao.org.au July 2009 Information on adherence and hints to help manage your HIV medications HIV TREATMENT ADHERENCE What is adherence?
Electronic Theses and Dissertations UC San Diego Peer Reviewed Title: Computational structure-based methods to anticipate HIV drug resistance evolution and accelerate inhibitor discovery Author: Chang,
BRIEF REPORT Longitudinal Analysis of Lymphocyte Ratios and HIV-1 Intracellular DNA Levels in Children Akihiko Saitoh, 1 Christine A. Powell, 4 Terence Fenton, 4 Steven D. Douglas, 5 Stuart E. Starr, 5
GDS Resource Record: Generalization of the Delegation Signer Model Gilles Guette, Bernard Cousin, David Fort To cite this version: Gilles Guette, Bernard Cousin, David Fort. GDS Resource Record: Generalization
What Development for Bioenergy in Asia: A Long-term Analysis of the Effects of Policy Instruments using TIAM-FR model Seungwoo Kang, Sandrine Selosse, Nadia Maïzi To cite this version: Seungwoo Kang, Sandrine
Développement d un procédé de traitement de matrices d origine viticole polluées par des herbicides par couplage bioaugmentation/phytoremédiation : sélection d un triplet bactéries - sorbant - plante testé
Territorial Intelligence and Innovation for the Socio-Ecological Transition Jean-Jacques Girardot, Evelyne Brunau To cite this version: Jean-Jacques Girardot, Evelyne Brunau. Territorial Intelligence and
AIDS Rev. 2011;13:77-108 Anne-Mieke Vandamme, et al.: European HIV Drug Resistance Guidelines European Recommendations for the Clinical Use of HIV Drug Resistance Testing: 2011 Update Anne-Mieke Vandamme
1 Read verbatim. 2 The Infectious Diseases Society of America (IDSA) Hepatitis C Knowledge Network offers monthly, 1 hour webinars to educate IDSA members on current recommended practices and treatments
Protocol for the systematic review of virological outcomes after 12 Months of antiretroviral therapy in low and middle income countries 1. Authors James H. McMahon Alfred Hospital, Melbourne, Australia
Cracks detection by a moving photothermal probe J. Bodnar, M. Egée, C. Menu, R. Besnard, A. Le Blanc, M. Pigeon, J. Sellier To cite this version: J. Bodnar, M. Egée, C. Menu, R. Besnard, A. Le Blanc, et
1 Lessons from the Stanford HIV Drug Resistance Database Bob Shafer, MD Department of Medicine and by Courtesy Pathology (Infectious Diseases) Stanford University Outline 2 Goals and rationale for HIVDB
Application-Aware Protection in DWDM Optical Networks Hamza Drid, Bernard Cousin, Nasir Ghani To cite this version: Hamza Drid, Bernard Cousin, Nasir Ghani. Application-Aware Protection in DWDM Optical
DEM modeling of penetration test in static and dynamic conditions Quoc Anh Tran, Bastien Chevalier, Pierre Breul To cite this version: Quoc Anh Tran, Bastien Chevalier, Pierre Breul. DEM modeling of penetration
International AIDS Society - Industry Liaison Forum Meeting 5 March 2012 Treating HIV in children with tuberculosis Helen McIlleron, Division of Clinical Pharmacology University of Cape Town Challenges
Options for Doing Cost-Effectiveness Analysis Decision Analysis Example after Occupational Exposure to Clinical trial Mathematical modeling Clinical Trial Incremental Cost-Effectiveness Ratio Conduct a
Antiretroviral Treatment Options for Patients on Directly Acting Antivirals for Hepatitis C PIs: atazanavir PIs: other Simeprevir with ritonavir- or cobicistat boosted PIs (significant simeprevir AUC).
Performance Evaluation of Encryption Algorithms Key Length Size on Web Browsers Syed Zulkarnain Syed Idrus, Syed Alwee Aljunid, Salina Mohd Asi, Suhizaz Sudin To cite this version: Syed Zulkarnain Syed
èmes journées du Site ANRS-Cameroun Yaoundé, -4 juin 201 ANRS-122 Le sang total séché sur papier filtre, DBS (Dried Blood Spot), est-il utilisable pour le suivi virologique en routine des patients VIH+
Bloodborne Pathogens Exposure Policy and Procedures Employees of the State of South Dakota Department of Health Bloodborne Pathogens (HIV, HBV, and HCV) Exposure Management PEP Hotline 1-888-448-4911 DOH
Rehabilitation in the Context of HIV: An Interprofessional Course for Occupational Therapists, Physiotherapists, Speech-Language Pathologists and Audiologists Presented by: Canadian Working Group on HIV
Demand Readiness Level (DRL), a new tool to hybridize Market Pull and Technology Push approaches. Introspective analysis of the new trends in Technology Transfer practices. Florin Paun To cite this version:
Non-linear mixed-effects models for tests of interaction or of lack of interaction in cross-over and parallel pharmacokinetic studies: application to the test of interaction between protease inhibitors
Interlibrary loan and document supply in France the Montpellier meeting Joachim Schöpfel To cite this version: Joachim Schöpfel. Interlibrary loan and document supply in France the Montpellier meeting.
Running an HCI Experiment in Multiple Parallel Universes,, To cite this version:,,. Running an HCI Experiment in Multiple Parallel Universes. CHI 14 Extended Abstracts on Human Factors in Computing Systems.
Applies to all products administered or underwritten by Blue Cross and Blue Shield of Louisiana and its subsidiary, HMO Louisiana, Inc.(collectively referred to as the Company ), unless otherwise provided
Noam Danenberg CEO N. Danenberg Holding Ltd firstname.lastname@example.org Experience CEO at N. Danenberg Holding (2000) Ltd) 2000 - Present (13 years) Investment Consulting Firm Consultant at Bonzai Holding Ltd.
Information behaviour and practices of PhD students Thea Marie Drachen, Asger Væring Larsen, Eystein Gullbekk, Hilde Westbye, Karin Lach To cite this version: Thea Marie Drachen, Asger Væring Larsen, Eystein
Core Competencies: HIV/AIDS: HIV Basics HIV/AIDS JEOPARDY* ABOUT THIS ACTIVITY Time: 60 minutes Objectives: By the end of this session, participants will be able to: Reviewed their knowledge of HIV/AIDS
The Effectiveness of non-focal exposure to web banner ads Marc Vanhuele, Didier Courbet, Sylvain Denis, Frédéric Lavigne, Amélie Borde To cite this version: Marc Vanhuele, Didier Courbet, Sylvain Denis,
HIV/AIDS REVIEW ARTICLE Antiretroviral Drug Resistance Testing in Adult HIV-1 Infection: 2008 Recommendations of an International AIDS Society USA Panel Martin S. Hirsch, 1 Huldrych F. Günthard, 9 Jonathan
TUPE089 Virologic suppression outcomes of second-line antiretroviral therapy in a Nigerian cohort. Authors: Adedotun A. Adetunji 1, MBChB, MSc; Chad Achenbach 2, MD, MPH; Joseph Feinglass 3, PhD; Kristin