D. Francis, J. Curran, and M. Essex, Epidemic acquired immune deficiency syndrome: epidemiologic evidence for a transmissible agent, J Natl Cancer Inst, vol.71, pp.1-4, 1983.

R. Gallo, P. Sarin, and E. Gelmann, Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS), Science, vol.220, issue.4599, pp.865-872, 1983.
DOI : 10.1126/science.6601823

F. Barre-sinoussi, J. Chermann, and F. Rey, Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS), Science, vol.220, issue.4599, pp.868-71, 1983.
DOI : 10.1126/science.6189183

A. Basavapathruni and K. Anderson, Reverse transcription of the HIV-1 pandemic, The FASEB Journal, vol.21, issue.14, pp.3795-808, 2007.
DOI : 10.1096/fj.07-8697rev

A. Fauci, HIV and AIDS: 20 years of science, Nature Medicine, vol.9, issue.7, pp.839-882, 2003.
DOI : 10.1038/nm0703-839

P. Sharp and B. Hahn, AIDS: Prehistory of HIV-1, Nature, vol.74, issue.7213, pp.605-611, 2008.
DOI : 10.1038/455605a

M. Worobey, M. Gemmel, and D. Teuwen, Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960AIDS (UNAIDS) and world health organization (WHO); 2009. 11 Human Immunodeficiency Virus Pathogenesis Basics of the virology of HIV-1 and its replication, Principles of Virology, pp.661-4653, 1987.

M. Stevenson, Basic science summary, Top HIV Med, vol.17, pp.30-34, 2009.

S. Goff, Retroviral reverse transcriptase: synthesis, structure, and function, J Acquir Immune Defic Syndr, vol.3, pp.817-848, 1990.

A. Jacobo-molina, E. Arnold, T. Copeland, and A. Devico, HIV reverse transcriptase structure-function relationships Characterization of highly immunogenic p66/p51 as the reverse transcriptase of HTLV-III/LAV, Biochemistry Science, vol.30231, issue.17, pp.6351-61289, 1986.

L. Kohlstaedt, J. Wang, J. Friedman, P. Rice, S. Tamolina et al., Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor Crystal structure of human immunodeficiency virus type 1 reverse transcriptase complexed with double-stranded DNA at 3.0 A resolution shows bent DNA The structure of unliganded reverse transcriptase from the human immunodeficiency virus type 1 Fidelity of HIV-1 reverse transcriptase, Menendez-Arias L. Targeting HIV: antiretroviral therapy and development of drug resistance, pp.1783-906320, 1988.

L. Mansky and H. Temin, Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase Coffin JM. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy, J Virol Science, vol.69267, issue.24, pp.5087-94483, 1995.

F. Gao, Y. Chen, D. Levy, J. Conway, T. Kepler et al., Unselected mutations in the human immunodeficiency virus type 1 genome are mostly nonsynonymous and often deleterious The accuracy of reverse transcriptase from HIV-1 Lethal mutagenesis of HIV, J Virol Science Virus Res, vol.78242107, issue.27, pp.2426-331171, 1988.

J. Julias, V. Pathak, R. Chen, H. Wang, and L. Mansky, Deoxyribonucleoside triphosphate pool imbalances in vivo are associated with an increased retroviral mutation rate Roles of uracil-DNA glycosylase and dUTPase in virus replication, J Virol J Gen Virol, vol.7283, issue.29, pp.7941-92339, 1998.

S. Goff, Death by Deamination, Cell, vol.114, issue.3, pp.281-284, 2003.
DOI : 10.1016/S0092-8674(03)00602-0
URL : http://doi.org/10.1016/s0092-8674(03)00602-0

M. Stevenson, HIV-1 pathogenesis, Nature Medicine, vol.9, issue.7, pp.853-60, 2003.
DOI : 10.1038/nm0703-853

L. Margolis, R. Shattock, L. Picker, and R. Koup, Selective transmission of CCR5-utilizing HIV-1: the 'gatekeeper' problem resolved? T cell dynamics in HIV-1 infection, Nat Rev Microbiol Annu Rev Immunol, vol.421, pp.312-7265, 2003.

D. Douek, T. Hiv-disease-progression-chun, D. Engel, M. Berrey, T. Shea et al., ed: Library of Congress Cataloging-in-Publication Data; 1997. 36 Early establishment of a pool of latently infected, resting CD4(+) T cells during primary HIV-1 infection, 35. Coffin JM, Hughes SH, Varmus HE, pp.114-78869, 1998.

T. Igarashi, C. Brown, and Y. Endo, Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans, Proceedings of the National Academy of Sciences, vol.98, issue.2, pp.658-63, 2001.
DOI : 10.1073/pnas.98.2.658

S. Aquaro, R. Calio, J. Balzarini, M. Bellocchi, E. Garaci et al., Macrophages and HIV infection: therapeutical approaches toward this strategic virus reservoir The challenge of finding a cure for HIV infection, Antiviral Res Science, vol.55323, issue.39, pp.209-251304, 2002.

S. Gartner, P. Markovits, D. Markovitz, M. Kaplan, R. Gallo et al., The role of mononuclear phagocytes in HTLV-III/LAV infection, Science, vol.233, issue.4760, pp.215-224, 1986.
DOI : 10.1126/science.3014648

S. Koenig, H. Gendelman, and J. Orenstein, Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy, Science, vol.233, issue.4768, pp.1089-93, 1986.
DOI : 10.1126/science.3016903

J. Weinberg, T. Matthews, B. Cullen, and M. Malim, Productive human immunodeficiency virus type 1 (HIV-1) infection of nonproliferating human monocytes, Journal of Experimental Medicine, vol.174, issue.6, pp.1477-82, 1991.
DOI : 10.1084/jem.174.6.1477

T. Chun, L. Carruth, and D. Finzi, Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection, Nature, vol.387, issue.6629, pp.183-191, 1997.
DOI : 10.1038/387183a0

C. Gavegnano and R. Schinazi, Antiretroviral therapy in macrophages: implication for HIV eradication, Antiviral Chemistry & Chemotherapy, vol.20, issue.2, pp.63-78, 2009.
DOI : 10.3851/IMP1374

C. Wiley, R. Schrier, J. Nelson, P. Lampert, M. Oldstone et al., Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients Twenty years of therapy for HIV-1 infection, Proc Natl Acad Sci U S A Nat Med, vol.839, issue.46, pp.7089-93867, 1986.

R. Rothenberg, M. Woelfel, R. Stoneburner, J. Milberg, R. Parker et al., Survival with the Acquired Immunodeficiency Syndrome, New England Journal of Medicine, vol.317, issue.21, pp.1297-302, 1987.
DOI : 10.1056/NEJM198711193172101

R. Schinazi, B. Hernandez-santiago, S. Hurwitz, H. Mitsuya, K. Weinhold et al., 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro7096-100. 51. Mitsuya H, Broder S. Inhibition of the in vitro infectivity and cytopathic effect of human Tlymphotrophic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) by 2',3'- dideoxynucleosides Yarchoan R, Perno CF, Thomas RV, et al. Phase I studies of 2',3'-dideoxycytidine in severe human immunodeficiency virus infection as a single agent and alternating with zidovudine (AZT), Pharmacology of current and promising nucleosides for the treatment of human immunodeficiency viruses vivo activity against HIV and favorable toxicity profile of 2',3'-dideoxyinosine M. Both 2',3'- dideoxythymidine and its 2',3'-unsaturated derivativedideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitro, pp.322-341911, 1985.

R. Schinazi, C. Chu, and A. Peck, Activities of the four optical isomers of 2',3'-dideoxy-3'- thiacytidine (BCH-189) against human immunodeficiency virus type 1 in human lymphocytes Probing the mechanistic consequences of 5-fluorine substitution on cytidine nucleotide analogue incorporation by HIV-1 reverse transcriptase, Antimicrob Agents Chemother Antivir Chem Chemother, vol.3614, pp.672-6115, 1992.

S. Daluge, S. Good, and M. Faletto, 1592U89, a novel carbocyclic nucleoside analog with potent, selective anti-human immunodeficiency virus activity Anti-human immunodeficiency virus activity and cellular metabolism of a potential prodrug of the acyclic nucleoside phosphonate 9-R- (2-phosphonomethoxypropyl)adenine (PMPA), Bis(isopropyloxymethylcarbonyl)PMPA, Antimicrob Agents Chemother Antimicrob Agents Chemother, vol.4142, issue.58, pp.1082-93612, 1997.

C. Tsai, K. Follis, and A. Sabo, Prevention of SIV Infection in Macaques by (R)-9-(2-Phosphonylmethoxypropyl)adenine, Science, vol.270, issue.5239, pp.1197-1206, 1995.
DOI : 10.1126/science.270.5239.1197

P. Furman, J. Jeffrey, and L. Kiefer, Mechanism of action of 1-beta-D-2,6-diaminopurine dioxolane, a prodrug of the human immunodeficiency virus type 1 inhibitor 1-beta-D-dioxolane guanosine, Antimicrob Agents ChemotherTriangle Pharmaceuticals Curr Opin Investig Drugs, vol.452, issue.61, pp.158-65348, 2001.

Z. Gu, M. Wainberg, and N. Nguyen-ba, Mechanism of action and in vitro activity of 1',3'- dioxolanylpurine nucleoside analogues against sensitive and drug-resistant human immunodeficiency virus type 1 variants, Antimicrob Agents Chemother, vol.43, pp.2376-82, 1999.

M. Thompson, H. Kessler, J. Eron, and . Jr, Short-term safety and pharmacodynamics of amdoxovir in HIV-infected patients The use of antibiotics: a clinical review of antibacterial, antifungal and antiviral drugs. Avon: The Bath Press; 2009. 65 Antiviral activity and tolerability of amdoxovir in combination with zidovudine in a randomized double-blind placebo controlled study in HIV-1 infected persons, AIDS Antiviral therapy, vol.1915, issue.642, pp.1607-15185, 2005.

J. Narayanasamy, M. Pullagurla, A. Sharon, J. Wang, R. Schinazi et al., Synthesis and anti-HIV activity of (???)-??-d-(2R,4R)-1,3-dioxolane-2,6-diamino purine (DAPD) (amdoxovir) and (???)-??-d-(2R,4R)-1,3-dioxolane guanosine (DXG) prodrugs, Antiviral Research, vol.75, issue.3, pp.198-209, 2007.
DOI : 10.1016/j.antiviral.2007.03.005

S. Menne, G. Asif, and J. Narayanasamy, Antiviral Effect of Orally Administered ( )-??-D-2-Aminopurine Dioxolane in Woodchucks with Chronic Woodchuck Hepatitis Virus Infection, Antimicrobial Agents and Chemotherapy, vol.51, issue.9, pp.3177-84, 2007.
DOI : 10.1128/AAC.00325-07

Y. Mehellou, D. Clercq, E. Twenty, E. Gifford, X. Tan et al., ADMET in silico modelling: towards prediction paradise? Development and optimization of anti-HIV nucleoside analogs and prodrugs: A review of their cellular pharmacology, structure-activity relationships and pharmacokinetics Nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase Nucleoside and nucleobase transport in animal cells Cell entry and export of nucleoside analogues MRP4: A previously unidentified factor in resistance to nucleoside-based antiviral drugs Emtricitabine: Inhibitor and substrate of multidrug resistance associated protein Combination of tenofovir and emtricitabine plus efavirenz: in vitro modulation of ABC transporter and intracellular drug accumulation, J Med Chem Nat Rev Drug Discov Adv Drug Deliv Rev Curr Top Med Chem Plagemann PG, Wohlhueter RM Biochim Biophys Acta Virus Res Nat Med Eur J Pharm Sci Antimicrob Agents Chemother, vol.53239494710753553, issue.76, pp.521-38192, 1988.

P. Furman, J. Fyfe, S. Clair, and M. , Phosphorylation of 3'-azido-3'-deoxythymidine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase., Proceedings of the National Academy of Sciences, vol.83, issue.21, pp.8333-8340, 1986.
DOI : 10.1073/pnas.83.21.8333

P. Furman and D. Barry, Spectrum of antiviral activity and mechanism of action of zidovudine

A. Overview-stein, D. Moore, K. Feng, J. Parker, W. Krajewski et al., Phosphorylation of nucleoside analog antiretrovirals: a review for clinicians Anabolism of amdoxovir: phosphorylation of dioxolane guanosine and its 5'-phosphates by mammalian phosphotransferases, Am J Med Pharmacotherapy Biochem Pharmacol, vol.852168, issue.80, pp.176-8111, 1988.

K. Moore, J. Barrett, and S. Shaw, The pharmacokinetics of lamivudine phosphorylation in peripheral blood mononuclear cells from patients infected with HIV-1, AIDS, vol.13, issue.16, pp.2239-50, 1999.
DOI : 10.1097/00002030-199911120-00006

J. Bourdais, R. Biondi, and S. Sarfati, Cellular phosphorylation of anti-HIV nucleosides Role of nucleoside diphosphate kinase Cellular metabolism of (-) enantiomeric 2'-deoxy-3'- thiacytidine, J Biol Chem Biochem Pharmacol, vol.27143, issue.84, pp.7887-902059, 1992.

P. Krishnan, Q. Fu, W. Lam, J. Liou, G. Dutschman et al., Phosphorylation of Pyrimidine Deoxynucleoside Analog Diphosphates: SELECTIVE PHOSPHORYLATION OF L-NUCLEOSIDE ANALOG DIPHOSPHATES BY 3-PHOSPHOGLYCERATE KINASE, Journal of Biological Chemistry, vol.277, issue.7, pp.5453-5462, 2002.
DOI : 10.1074/jbc.M109025200

B. Schneider, R. Sarfati, D. Deville-bonne, and M. Veron, Role of nucleoside diphosphate kinase in the activation of anti-HIV nucleoside analogs, Journal of Bioenergetics and Biomembranes, vol.32, issue.3, pp.317-341, 2000.
DOI : 10.1023/A:1005501432684

B. Schneider, R. Biondi, and R. Sarfati, The mechanism of phosphorylation of anti-HIV D4T by nucleoside diphosphate kinase, Mol Pharmacol, vol.57, pp.948-53, 2000.

S. Eriksson, B. Kierdaszuk, B. Munch-petersen, B. Oberg, and N. Johansson, Comparison of the substrate specificities of human thymidine kinase 1 and 2 and deoxycytidine kinase toward antiviral and cytostatic nucleoside analogs, Biochemical and Biophysical Research Communications, vol.176, issue.2, pp.586-92, 1991.
DOI : 10.1016/S0006-291X(05)80224-4

B. Eriksson, R. Schinazi, A. Lavie, I. Schlichting, I. Vetter et al., -deoxythymidine (zidovudine) and phosphonoformate (foscarnet) against human immunodeficiency virus type 1 and cytomegalovirus replication in vitro The bottleneck in AZT activation Structure of thymidylate kinase reveals the cause behind the limiting step in AZT activation Intracellular metabolism of 3'-azidothymidine in isolated human peripheral blood mononuclear cells, Antimicrob Agents Chemother Nat Med Nat Struct Biol AIDS Res Hum Retroviruses, vol.33347, issue.90, pp.663-9922, 1989.
URL : https://hal.archives-ouvertes.fr/hal-00212160

S. Kewn, L. Wang, and P. Hoggard, Enzymatic Assay for Measurement of Intracellular DXG Triphosphate Concentrations in Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus Type 1-Infected Patients, Antimicrobial Agents and Chemotherapy, vol.47, issue.1, pp.255-61, 2003.
DOI : 10.1128/AAC.47.1.255-261.2003

P. Meyer, S. Matsuura, A. Mian, A. So, and W. Scott, A Mechanism of AZT Resistance, Molecular Cell, vol.4, issue.1, pp.35-43, 1999.
DOI : 10.1016/S1097-2765(00)80185-9

D. Clercq and E. , STRATEGIES IN THE DESIGN OF ANTIVIRAL DRUGS, Nature Reviews Drug Discovery, vol.1, issue.1, pp.13-25, 2002.
DOI : 10.1038/nrd703

M. Gotte, J. Rausch, B. Marchand, S. Sarafianos, L. Grice et al., Reverse transcriptase in motion: Conformational dynamics of enzyme-substrate interactions The influence of natural substrates and inhibitors on the nucleotidedependent excision activity of HIV-1 reverse transcriptase in the infected cell, Biochim Biophys Acta Curr Pharm Des, vol.180412, issue.5, pp.1202-121827, 2006.

J. Jeffrey, J. Feng, C. Qi, K. Anderson, and P. Furman, Dioxolane Guanosine 5'-Triphosphate, an Alternative Substrate Inhibitor of Wild-type and Mutant HIV-1 Reverse Transcriptase: STEADY STATE AND PRE-STEADY STATE KINETIC ANALYSES, Journal of Biological Chemistry, vol.278, issue.21, pp.18971-18980, 2003.
DOI : 10.1074/jbc.M210113200

S. Staszewski, C. Loveday, and J. Picazo, Safety and efficacy of lamivudine-zidovudine combination therapy in zidovudine-experienced patients. A randomized controlled comparison with zidovudine monotherapy. Lamivudine European HIV Working Group, JAMA: The Journal of the American Medical Association, vol.276, issue.2, pp.111-118, 1996.
DOI : 10.1001/jama.276.2.111

L. Ruiz, J. Romeu, and J. Martinez-picado, Efficacy of triple combination therapy with zidovudine (ZDV) plus zalcitabine (ddC) plus lamivudine (3TC) versus double (ZDV+3TC) combination therapy in patients previously treated with ZDV+ddC Drug resistance and virologic response in NUCA 3001, a randomized trial of lamivudine (3TC) versus zidovudine (ZDV) versus ZDV plus 3TC in previously untreated patients The triple combination of tenofovir, emtricitabine and efavirenz shows synergistic anti-HIV-1 activity in vitro: a mechanism of action study, AIDS AIDS Retrovirology, vol.10106, issue.102, pp.61-6975, 1996.

Z. Gu, M. Wainberg, P. Nguyen-ba, L. Heureux, L. De-muys et al., Anti-HIV-1 Activities of 1,3-Dioxolane Guanine and 2,6-Diaminopurine Dioxolane, Nucleosides and Nucleotides, vol.7, issue.4-5, pp.891-893, 1999.
DOI : 10.1016/S0960-894X(00)80014-1

. Dapd, DXG against zidovudine-and lamivudine-drug resistant mutants: a molecular modelling approach

K. Borroto-esoda, J. Vela, F. Myrick, A. Ray, M. Miller et al., In vitro evaluation of the anti-HIV activity and metabolic interactions of tenofovir and emtricitabine Role of purine nucleoside phosphorylase in interactions between 2',3'-dideoxyinosine and allopurinol, ganciclovir, or tenofovir Lack of a metabolic and antiviral drug interaction between tenofovir, abacavir and lamivudine, Antivir Chem Chemother Antivir Ther Antimicrob Agents Chemother Antivir Ther AIDS Rev, vol.131148107, issue.107, pp.115-28377, 2002.

J. Balzarini, P. Hoggard, S. Sales, and S. Kewn, Effect of antimetabolite drugs of nucleotide metabolism on the anti-human immunodeficiency virus activity of nucleoside reverse transcriptase inhibitors Correlation between intracellular pharmacological activation of nucleoside analogues and HIV suppression in vitro, Pharmacol Ther Antivir Chem Chemother, vol.8711, issue.110, pp.175-87353, 2000.

W. Tong, C. Lu, S. Sharma, S. Matsuura, A. So et al., Nucleotide-induced stable complex formation by HIV-1 reverse transcriptase Mechanisms associated with HIV-1 resistance to acyclovir by the V75I mutation in reverse transcriptase HIV-1 drug resistance mutations: an updated framework for the second decade of HAART, Biochemistry J Biol Chem AIDS Rev, vol.3628410, issue.113, pp.5749-5721496, 1997.

V. Johnson, F. Brun-vezinet, and B. Clotet, Update of the drug resistance mutations in HIV-1

T. Cihlar, A. Ray, U. Parikh, D. Koontz, C. Chu et al., Nucleoside and nucleotide HIV reverse transcriptase inhibitors: 25 years after zidovudine In vitro activity of structurally diverse nucleoside analogs against human immunodeficiency virus type 1 with the K65R mutation in reverse transcriptase, Antiviral Res Antimicrob Agents Chemother, vol.8549, issue.116, pp.39-581139, 2005.

K. White, N. Margot, T. Wrin, C. Petropoulos, M. Miller et al., Molecular Mechanisms of Resistance to Human Immunodeficiency Virus Type 1 with Reverse Transcriptase Mutations K65R and K65R+M184V and Their Effects on Enzyme Function and Viral Replication Capacity, Antimicrobial Agents and Chemotherapy, vol.46, issue.11, pp.3437-3483, 2002.
DOI : 10.1128/AAC.46.11.3437-3446.2002

K. Rapp, M. Ruckstuhl, M. Schinazi, R. Hurwitz, S. Asif et al., The combination of zidovudine and amdoxovir prevents the selection of thymidine analogue mutations in primary human lymphocytes Development of an optimized dose for coformulation of zidovudine with drugs that select for the K65R mutation using a population pharmacokinetic and enzyme kinetic simulation model Dioxolane guanosine, the active form of the prodrug diaminopurine dioxolane, is a potent inhibitor of drug-resistant HIV-1 isolates from patients for whom standard nucleoside therapy fails, In: Antiviral therapy. Barbados, West Indies: IHL Antimicrob Agents Chemother J Acquir Immune Defic Syndr, vol.1195229, issue.120, pp.1304241-5011, 2002.

C. Klaassen, Casarett and Doull's Toxicology: The Basic Science of Poisons: Ovid, 2009.

A. Johnson, A. Ray, and J. Hanes, Toxicity of Antiviral Nucleoside Analogs and the Human Mitochondrial DNA Polymerase, Journal of Biological Chemistry, vol.276, issue.44, pp.40847-57, 2001.
DOI : 10.1074/jbc.M106743200

P. Anderson, T. Kakuda, K. Lichtenstein, M. Spiga, D. Weidner et al., The cellular pharmacology of nucleoside-and nucleotide-analogue reverse-transcriptase inhibitors and its relationship to clinical toxicities Inhibition of beta-globin gene expression by 3'-azido-3'-deoxythymidine in human erythroid progenitor cells The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial, Clin Infect Dis Antiviral Res N Engl J Med, vol.3844317, issue.125, pp.743-53167, 1987.

A. Collier, S. Bozzette, and R. Coombs, A pilot study of low-dose zidovudine in human immunodeficiency virus infection Correlates of zidovudine phosphorylation with markers of HIV disease progression and drug toxicity, N Engl J Med AIDS, vol.3238, issue.127, pp.1015-21763, 1990.

S. Hetherington, S. Mcguirk, and G. Powell, Hypersensitivity reactions during therapy with the nucleoside reverse transcriptase inhibitor abacavir, Clinical Therapeutics, vol.23, issue.10, pp.1603-1617, 2001.
DOI : 10.1016/S0149-2918(01)80132-6

J. Walsh, M. Reese, and L. Thurmond, The metabolic activation of abacavir by human liver cytosol and expressed human alcohol dehydrogenase isozymes, Chemico-Biological Interactions, vol.142, issue.1-2, pp.135-54, 2002.
DOI : 10.1016/S0009-2797(02)00059-5

J. Uetrecht, New Concepts in Immunology Relevant to Idiosyncratic Drug Reactions:?? The ???Danger Hypothesis??? and Innate Immune System, Chemical Research in Toxicology, vol.12, issue.5, pp.387-95, 1999.
DOI : 10.1021/tx980249i

C. Chen, M. Vazquez-padua, and Y. Cheng, Effect of anti-human immunodeficiency virus nucleoside analogs on mitochondrial DNA and its implication for delayed toxicity, Mol Pharmacol, vol.39, pp.625-633, 1991.

J. Kohler and W. Lewis, A brief overview of mechanisms of mitochondrial toxicity from NRTIs, Environmental and Molecular Mutagenesis, vol.69, issue.3-4
DOI : 10.1002/em.20223

N. Venhoff, B. Setzer, K. Melkaoui, and U. Walker, Mitochondrial toxicity of tenofovir, emtricitabine and abacavir alone and in combination with additional nucleoside reverse transcriptase inhibitors, Environ Mol Mutagen Antivir Ther, vol.4812, issue.133, pp.166-721075, 2007.

P. Reichard, Interactions Between Deoxyribonucleotide and DNA Synthesis, Annual Review of Biochemistry, vol.57, issue.1, pp.349-74, 1988.
DOI : 10.1146/annurev.bi.57.070188.002025

M. Meuth, The molecular basis of mutations induced by deoxyribonucleoside triphosphate pool imbalances in mammalian cells, Experimental Cell Research, vol.181, issue.2, pp.305-321, 1989.
DOI : 10.1016/0014-4827(89)90090-6

R. Murray, . Bd, K. Botham, P. Kennelly, V. Rodwell et al., Metabolism of Purine & Pyrimidine Nucleotides In: Harper's Illustrated Biochemistry, 28e: Mc Graw Hill Medical Macrophage tropism of HIV-1 depends on efficient cellular dNTP utilization by reverse transcriptase, J Biol Chem, vol.279, pp.51545-53, 2004.

M. Sandrini and J. Piskur, Deoxyribonucleoside kinases: two enzyme families catalyze the same reaction, Trends in Biochemical Sciences, vol.30, issue.5, pp.225-233, 2005.
DOI : 10.1016/j.tibs.2005.03.003

J. Balzarini, C. Lee, P. Herdewijn, D. Clercq, and E. , Mechanism of the potentiating effect of ribavirin on the activity of 2',3'-dideoxyinosine against human immunodeficiency virus, J Biol Chem, vol.266, pp.21509-21523, 1991.

R. Pesi, M. Turriani, and S. Allegrini, The Bifunctional Cytosolic 5???-Nucleotidase: Regulation of the Phosphotransferase and Nucleotidase Activities, Archives of Biochemistry and Biophysics, vol.312, issue.1, pp.75-80, 1994.
DOI : 10.1006/abbi.1994.1282

J. Spychala, V. Madrid-marina, and I. Fox, High Km soluble 5'-nucleotidase from human placenta. Properties and allosteric regulation by IMP and ATP, J Biol Chem, vol.263, pp.18759-65, 1988.

N. Hartman, G. Ahluwalia, and D. Cooney, Inhibitors of IMP dehydrogenase stimulate the phosphorylation of the anti-human immunodeficiency virus nucleosides 2',3'-dideoxyadenosine and 2',3'- dideoxyinosine In vitro combination of amdoxovir and the inosine monophosphate dehydrogenase inhibitors mycophenolic acid and ribavirin demonstrates potent activity against wild-type and drug-resistant variants of human immunodeficiency virus type 1, Mol Pharmacol Antimicrob Agents Chemother, vol.4048, issue.144, pp.118-244387, 1991.

N. Margot and M. Miller, In vitro combination studies of tenofovir and other nucleoside analogues with ribavirin against HIV-1, Antivir Ther, vol.10, pp.343-351, 2005.

E. Vispo, P. Barreiro, and J. Pineda, Low response to pegylated interferon plus ribavirin in HIVinfected patients with chronic hepatitis C treated with abacavir The use of beta-D-2,6-diaminopurine dioxolane with or without mycophenolate mofetil in drug-resistant HIV infection Effects of 3'-azido-3'- deoxythymidine on the deoxynucleotide triphosphate pools of cultured human cells, Antivir Ther AIDS Biochem Biophys Res Commun, vol.1321154, issue.148, pp.429-372025, 1988.

W. Gao, R. Agbaria, J. Driscoll, and H. Mitsuya, Divergent anti-human immunodeficiency virus activity and anabolic phosphorylation of 2',3'-dideoxynucleoside analogs in resting and activated human cells, J Biol Chem, vol.269, pp.12633-12641, 1994.

G. Morris, T. Iams, K. Slepchenko, E. Mckee, M. Lynx et al., Origin of pyrimidine deoxyribonucleotide pools in perfused rat heart: implications for 3'-azido-3'-deoxythymidine-dependent cardiotoxicity Effect of AZT on thymidine phosphorylation in cultured H9c2, U-937, and Raji cell lines Effect of nucleoside and nucleotide reverse transcriptase inhibitors of HIV on endogenous nucleotide pools, Metabolism of carbovir, a potent inhibitor of human immunodeficiency virus type 1, and its effects on cellular metabolism, pp.513-201610, 1993.

Q. Meng, D. Walker, and O. Olivero, Zidovudine-didanosine coexposure potentiates DNA incorporation of zidovudine and mutagenesis in human cells, Proceedings of the National Academy of Sciences, vol.97, issue.23, pp.12667-71, 2000.
DOI : 10.1073/pnas.220203197

S. Kewn, P. Hoggard, and J. Henry-mowatt, Intracellular Activation of 2',3'-Dideoxyinosine and Drug Interactions in Vitro, AIDS Research and Human Retroviruses, vol.15, issue.9, pp.793-802, 1999.
DOI : 10.1089/088922299310692

H. Cote, Possible ways nucleoside analogues can affect mitochondrial DNA content and gene expression during HIV therapy, M3-11. 157. Saada A. Mitochondrial deoxyribonucleotide pools in deoxyguanosine kinase deficiency, pp.169-73, 2005.

N. Gattermann, M. Dadak, and G. Hofhaus, Severe impairment of nucleotide synthesis through inhibition of mitochondrial respiration Cytotoxicity of 3'-azido-3'- deoxythymidine correlates with 3'-azidothymidine-5'-monophosphate (AZTMP) levels, whereas antihuman immunodeficiency virus (HIV) activity correlates with 3'-azidothymidine-5'-triphosphate (AZTTP) levels in cultured CEM T-lymphoblastoid cells Zidovudine phosphorylation and mitochondrial toxicity in vitro, Nucleosides Nucleotides Nucleic Acids Biochem Pharmacol Toxicol Appl Pharmacol, vol.2349177, issue.160, pp.1275-9829, 1995.

V. Dolce, G. Fiermonte, M. Runswick, F. Palmieri, J. Walker et al., The human mitochondrial deoxynucleotide carrier and its role in the toxicity of nucleoside antivirals Uridine abrogates mitochondrial toxicity related to nucleoside analogue reverse transcriptase inhibitors in HepG2 cells, Proc Natl Acad Sci U S A Antivir Ther, vol.988, pp.2284-8463, 2001.

B. Setzer, D. Lebrecht, U. Walker, N. Venhoff, D. Lebrecht et al., Pyrimidine nucleoside depletion sensitizes to the mitochondrial hepatotoxicity of the reverse transcriptase inhibitor stavudine Oral uridine supplementation antagonizes the peripheral neuropathy and encephalopathy induced by antiretroviral nucleoside analogues Effects of zidovudine and stavudine on mitochondrial DNA of differentiating 3T3-F442a cells are not associated with imbalanced deoxynucleotide pools The effects of dNTP pool imbalances on frameshift fidelity during DNA replication, Am J Pathol AIDS Lynx MD Antimicrob Agents Chemother J Biol Chem, vol.1722453267, issue.165, pp.681-90345, 1992.

Y. Sidi and B. Mitchell, 2'-deoxyguanosine toxicity for B and mature T lymphoid cell lines is mediated by guanine ribonucleotide accumulation Guanine nucleosides and Jurkat cell death: roles of ATP depletion and accumulation of deoxyribonucleotides, J Clin Invest Batiuk TD Am J Physiol Cell Physiol, vol.74281, issue.168, pp.1640-1648, 1984.

L. Bisset, T. Lung, M. Kaelin, E. Ludwig, R. Dubs et al., Reference values for peripheral blood lymphocyte phenotypes applicable to the healthy adult population in Switzerland Importance of ribonucleotide availability to proliferating T-lymphocytes from healthy humans. Disproportionate expansion of pyrimidine pools and contrasting effects of de novo synthesis inhibitors, Eur J Haematol J Biol Chem, vol.72270, issue.170, pp.203-1229682, 1995.

B. Jacobsson, S. Britton, Y. Tornevik, S. Eriksson, and A. Cohen, Decrease in thymidylate kinase activity in peripheral blood mononuclear cells from HIV-infected individuals Purine nucleotide metabolism in resident and activated rat macrophages in vitro, Biochem Pharmacol Barankiewicz J Eur J Immunol, vol.5615, issue.172, pp.389-95627, 1985.

J. Balzarini, Y. Van-herrewege, and G. Vanham, Metabolic activation of nucleoside and nucleotide reverse transcriptase inhibitors in dendritic and Langerhans cells, AIDS, vol.16, issue.16, pp.2159-63, 2002.
DOI : 10.1097/00002030-200211080-00008

S. Aquaro, C. Perno, and E. Balestra, Inhibition of replication of HIV in primary monocyte/macrophages by different antiviral drugs and comparative efficacy in lymphocytes Cell cycle effect on the activity of deoxynucleoside analogue metabolising enzymes, 176. Saada A. Fishing in the (deoxyribonucleotide) pool, pp.138-43847, 1997.

L. F. Bello, P. Roepstorff, R. L. Hines, J. Mora, V. Berkel et al., Regulation of thymidine kinase synthesis in human cells Mass Spectrometry of Nucleic Acids Molecular beams of macroions Electrochemical processes in electrospray ionization mass spectrometry, Exp Cell Res Nordhoff EK, Mass Spectrometry Reviews Dole MM, L.L. The Journal of Chemical Physics J Mass Spectrom, vol.89154935, issue.180, pp.263-7467, 1968.

P. Kebarle, A brief overview of the present status of the mechanisms involved in electrospray mass spectrometry, Journal of Mass Spectrometry, vol.113, issue.187, pp.804-821, 2000.
DOI : 10.1002/1096-9888(200007)35:7<804::AID-JMS22>3.0.CO;2-Q

P. Kebarle and U. Verkerk, Electrospray: From ions in solution to ions in the gas phase, what we know now, Mass Spectrometry Reviews, vol.107, issue.14, pp.898-917, 2009.
DOI : 10.1002/mas.20247

J. Roboz, Mass Spectrometry in cancer research, 2002.

F. Mclafferty, Tandem mass spectrometry, Science, vol.214, issue.4518, pp.280-287, 1981.
DOI : 10.1126/science.7280693

S. Dresen, N. Ferreiros, H. Gnann, R. Zimmermann, and W. Weinmann, Detection and identification of 700 drugs by multi-target screening with a 3200 Q TRAP?? LC-MS/MS system and library searching, Analytical and Bioanalytical Chemistry, vol.49, issue.7, pp.2425-2459, 2003.
DOI : 10.1007/s00216-010-3485-2

E. Debenedetti and M. Tsvet, HPLC Separation Modes, Minerva Med, vol.47, issue.2010, pp.536-544, 1956.

J. Fritz, Factors affecting selectivity in ion chromatography, Journal of Chromatography A, vol.1085, issue.1, pp.8-17, 2005.
DOI : 10.1016/j.chroma.2004.12.087

J. Stahlberg, Retention models for ions in chromatography, Journal of Chromatography A, vol.855, issue.1, pp.3-55, 1999.
DOI : 10.1016/S0021-9673(99)00176-4

J. Ståhlberg, B. Bidlingmeyer, S. Deming, W. Price, B. Sachok et al., How Theory and Practice Meet in Ion Pair Chromatography Retention mecanism for reversed-phase ion-pair liquid chromatography, EAS meeting. Sweden. www.academyofchromatography, pp.419-453, 1979.

J. Chen, S. Weber, L. Glavina, F. Cantwell, R. Kostiainen et al., Electrical double-layer models of ion-modified (ion-pair) reversed-phase liquid chromatography Effect of eluent on the ionization process in liquid chromatographymass spectrometry, J Chromatogr J Chromatogr A, vol.6561216, pp.549-76685, 1993.

R. Schinazi, D. Cannon, B. Arnold, and D. Martino-saltzman, Combinations of isoprinosine and 3'-azido-3'-deoxythymidine in lymphocytes infected with human immunodeficiency virus type 1., Antimicrobial Agents and Chemotherapy, vol.32, issue.12, pp.1784-1791, 1988.
DOI : 10.1128/AAC.32.12.1784

S. Hurwitz, G. Asif, E. Fromentin, P. Tharnish, and R. Schinazi, Lack of Pharmacokinetic Interaction between Amdoxovir and Reduced- and Standard-Dose Zidovudine in HIV-1-Infected Individuals, Antimicrobial Agents and Chemotherapy, vol.54, issue.3, pp.1248-55, 2010.
DOI : 10.1128/AAC.01209-09

A. A. Hayter, E. Fromentin, C. Gavegnano, A. Obikhod, and R. Schinazi, Kramer Multiple Comparisons Procedure is Conservative. The Annals of Simultaneous Quantification of Intracellular Natural and Antiretroviral Nucleosides and Nucleotides by Liquid Chromatography-Tandem Mass Spectrometry, Statistics Anal Chem, vol.12, issue.82, pp.61-75, 1982.

R. Jansen, H. Rosing, J. Schellens, J. Beijnen, B. Hernandez-santiago et al., Retention studies of 2'-2'-difluorodeoxycytidine and 2'-2'-difluorodeoxyuridine nucleosides and nucleotides on porous graphitic carbon: development of a liquid chromatography-tandem mass spectrometry method Short communication cellular pharmacology of 9-(beta-D-1,3-dioxolan-4-yl) guanine and its lack of drug interactions with zidovudine in primary human lymphocytes, J Chromatogr A Antivir Chem Chemother, vol.121618, issue.200, pp.3168-74343, 2007.

R. Jansen, H. Rosing, C. De-wolf, and J. Beijnen, Development and validation of an assay for the quantitative determination of cladribine nucleotides in MDCKII cells and culture medium using weak anion-exchange liquid chromatography coupled with tandem mass spectrometry, Rapid Communications in Mass Spectrometry, vol.667, issue.24, pp.4049-59, 2007.
DOI : 10.1002/rcm.3318

G. Shi, J. Wu, and Y. Li, Novel direct detection method for quantitative determination of intracellular nucleoside triphosphates using weak anion exchange liquid chromatography/tandem mass spectrometry Solute attributes and molecular interactions contributing to "U-shape" retention on a fluorinated high-performance liquid chromatography stationary phase, 203. Bell DS, Jones AD, pp.1092-999, 2002.

M. Gilar, Y. Yu, J. Ahn, J. Fournier, and J. Gebler, Mixed-mode chromatography for fractionation of peptides, phosphopeptides, and sialylated glycopeptides, Journal of Chromatography A, vol.1191, issue.1-2, pp.162-70, 2008.
DOI : 10.1016/j.chroma.2008.01.061

G. Hennere, F. Becher, A. Pruvost, C. Goujard, J. Grassi et al., Liquid chromatography-tandem mass spectrometry assays for intracellular deoxyribonucleotide triphosphate competitors of nucleoside antiretrovirals Improved method to quantify intracellular zidovudine mono-and triphosphate in peripheral blood mononuclear cells by liquid chromatographytandem mass spectrometry Specificity enhancement with LCpositive ESI-MS/MS for the measurement of nucleotides: application to the quantitative determination of carbovir triphosphate, lamivudine triphosphate and tenofovir diphosphate in human peripheral blood mononuclear cells, J Chromatogr B Analyt Technol Biomed Life Sci J Mass Spectrom J Mass Spectrom, vol.7894243, issue.207, pp.273-81389, 2003.

Y. Asakawa, N. Tokida, C. Ozawa, M. Ishiba, O. Tagaya et al., Suppression effects of carbonate on the interaction between stainless steel and phosphate groups of phosphate compounds in high-performance liquid chromatography and electrospray ionization mass spectrometry1198-1199:80-6. 209. Espada A, Rivera-Sagredo A. Ammonium hydrogencarbonate, an excellent buffer for the analysis of basic drugs by liquid chromatography-mass spectrometry at high pH Simultaneous quantification of free nucleotides in complex biological samples using ion pair reversed phase liquid chromatography isotope dilution tandem mass spectrometry, J Chromatogr A J Chromatogr A Seifar RM Anal Biochem, vol.987388, issue.210, pp.211-20213, 2003.

R. Claire, J. Vela, L. Olson, A. Huang, A. Fridland et al., Positive ion electrospray ionization tandem mass spectrometry coupled to ionpairing high-performance liquid chromatography with a phosphate buffer for the quantitative analysis of intracellular nucleotides Simultaneous quantitation of the nucleotide analog adefovir, its phosphorylated anabolites and 2'-deoxyadenosine triphosphate by ion-pairing LC/MS/MS Stainless steel electrospray probe: a dead end for phosphorylated organic compounds? Intracellular pharmacokinetics of tenofovir diphosphate, carbovir triphosphate, and lamivudine triphosphate in patients receiving triple-nucleoside regimens, Rapid Commun Mass Spectrom J Chromatogr B Analyt Technol Biomed Life Sci J Chromatogr A J Acquir Immune Defic Syndr, vol.14848110439, issue.214, pp.1625-34335, 2000.

R. Cordell, S. Hill, C. Ortori, D. Barrett, R. Bas et al., Quantitative profiling of nucleotides and related phosphate-containing metabolites in cultured mammalian cells by liquid chromatography tandem electrospray mass spectrometry Simultaneous quantitative analysis of metabolites using ion-pair liquid chromatography-electrospray ionization mass spectrometry, J Chromatogr B Analyt Technol Biomed Life Sci Anal Chem, vol.87178, pp.115-246573, 2006.

C. Crauste, I. Lefebvre, and M. Hovaneissian, Development of a sensitive and selective LC/MS/MS method for the simultaneous determination of intracellular 1-beta-D- arabinofuranosylcytosine triphosphate (araCTP), cytidine triphosphate (CTP) and deoxycytidine triphosphate (dCTP) in a human follicular lymphoma cell line Influence of the hofmeister series on the retention of amines in reversed-phase liquid chromatography, J Chromatogr B Analyt Technol Biomed Life Sci Anal Chem, vol.87774, issue.218, pp.1417-254927, 2002.

Y. Zhang and P. Cremer, Interactions between macromolecules and ions: the Hofmeister series, Current Opinion in Chemical Biology, vol.10, issue.6
DOI : 10.1016/j.cbpa.2006.09.020

D. Mccalley, Rationalization of Retention and Overloading Behavior of Basic Compounds in Reversed-Phase HPLC Using Low Ionic Strength Buffers Suitable for Mass Spectrometric Detection, Analytical Chemistry, vol.75, issue.14, pp.3404-3414, 2003.
DOI : 10.1021/ac020715f

C. Gavegnano, E. Fromentin, R. Schinazi, G. Chandrasena, R. Ho et al., Anti-HIV-1 Nucleoside Analogue Triphosphate Levels are Significantly Lower in Primary Human Macrophages Than in Lymphocytes In: Press I, ed. 4th International Workshop on HIV-1 Persistence St Comparison of rates of intracellular metabolism of zidovudine in human and primate peripheral blood mononuclear cells, Antimicrob Agents Chemother, vol.38, pp.2398-403, 1994.

C. Perno, V. Svicher, D. Schols, M. Pollicita, J. Balzarini et al., Therapeutic strategies towards HIV-1 infection in macrophages, Antiviral Research, vol.71, issue.2-3, pp.293-300, 2006.
DOI : 10.1016/j.antiviral.2006.05.015

P. Plagemann, Na+-Dependent, concentrative nucleoside transport in rat macrophages, Biochemical Pharmacology, vol.42, issue.2
DOI : 10.1016/0006-2952(91)90710-M

C. Soler, J. Garcia-manteiga, and R. Valdes, Macrophages require different nucleoside transport systems for proliferation and activation, The FASEB Journal, vol.15, issue.11, pp.1979-88, 2001.
DOI : 10.1096/fj.01-0022com

S. Aquaro, V. Svicher, and D. Schols, Mechanisms underlying activity of antiretroviral drugs in HIV-1-infected macrophages: new therapeutic strategies, Journal of Leukocyte Biology, vol.80, issue.5, pp.1103-1113, 2006.
DOI : 10.1189/jlb.0606376

S. Hunsucker, B. Mitchell, and J. Spychala, The 5???-nucleotidases as regulators of nucleotide and drug metabolism, Pharmacology & Therapeutics, vol.107, issue.1, pp.1-30, 2005.
DOI : 10.1016/j.pharmthera.2005.01.003

. Aminopurine-dioxolane, beta-D-2-amino-6-chloropurine dioxolane and their antiviral metabolite (-beta-D-dioxolane e guanine in rhesus monkeys, Antimicrob Agents Chemother, vol.40, pp.2332-2338, 1996.

H. Chen, R. Schinazi, and P. Rajagopalan, Pharmacokinetics of (-)-beta-D-Dioxolane Guanine and Prodrug (-)-beta-D-2,6-Diaminopurine Dioxolane in Rats and Monkeys, AIDS Research and Human Retroviruses, vol.15, issue.18, pp.1625-1655, 1999.
DOI : 10.1089/088922299309667

K. Manouilov, L. Manouilova, F. Boudinot, R. Schinazi, C. Chu et al., Biotransformation and pharmacokinetics of prodrug 9-(??-d-1,3-dioxolan-4-yl)-2-aminopurine and its antiviral metabolite 9-(??-d-1,3-dioxolan-4-yl)guanine in mice, Antiviral Research, vol.35, issue.3, pp.187-93, 1997.
DOI : 10.1016/S0166-3542(97)00028-4

E. Fromentin, G. Asif, A. Obikhod, S. Hurwitz, R. Schinazi et al., Simultaneous quantification of 9- (beta-D-1,3-dioxolan-4-yl)guanine, Amdoxovir and Zidovudine in human plasma by liquid chromatography-tandem mass spectrometric assay Rapid human immunodeficiency virus decay in highly active antiretroviral therapy (HAART)-experienced children after starting mega-HAART Inhibitory activity of dioxolane purine analogs on wild-type and lamivudine-resistant mutants of hepadnaviruses Development and validation of a liquid chromatographic/tandem mass spectrometric assay for the quantitation of nucleoside HIV reverse transcriptase inhibitors in biological matrices, J Chromatogr B Analyt Technol Biomed Life Sci J Virol Hepatology J Mass Spectrom, vol.877783640, issue.235, pp.3482-811272, 2002.

V. Bezy, P. Morin, P. Couerbe, G. Leleu, L. Agrofoglio et al., Simultaneous analysis of several antiretroviral nucleosides in rat-plasma by high-performance liquid chromatography with UV using acetic acid/hydroxylamine buffer Test of this new volatile medium-pH for Measurement of ribavirin and evaluation of its stability in human plasma by high-performance liquid chromatography with UV detection Simple rapid method for quantification of antiretrovirals by liquid chromatography-tandem mass-spectrometry Sensitive and rapid liquid chromatography-tandem mass spectrometry method for the determination of stavudine in human plasma Simultaneous determination of zidovudine and lamivudine in human serum using HPLC with tandem mass spectrometry, J Chromatogr B Analyt Technol Biomed Life Sci J Chromatogr B Analyt Technol Biomed Life Sci Clin Biochem J Chromatogr B Analyt Technol Biomed Life Sci J Pharm Biomed Anal, vol.8218563577322, issue.239, pp.132-43358, 2000.

A. Gehrig, G. Mikus, W. Haefeli, J. Burhenne, M. Salvadori et al., Electrospray tandem mass spectroscopic characterisation of 18 antiretroviral drugs and simultaneous quantification of 12 antiretrovirals in plasma A rapid and sensitive method for simultaneous determination of lamivudine and zidovudine in human serum by on-line solid-phase extraction coupled to liquid chromatography/tandem mass spectrometry detection Simultaneous measurement of intracellular triphosphate metabolites of zidovudine, lamivudine and abacavir (carbovir) in human peripheral blood mononuclear cells by combined anion exchange solid phase extraction and LC-MS, Rapid Commun Mass Spectrom Rapid Commun Mass Spectrom, vol.2118, issue.243, pp.2704-161147, 2004.

L. Wang, J. W. Brosnan-cook, M. Sista, N. D. Rousseau, F. Cremieux et al., and the DAPD-101 Clinical Trial Group. . The Disposition of DAPD and Its Active Metabolite DXG in Therapy Naïve and Experienced HIV-Infected Subjects A comparison of the steady-state pharmacokinetics and safety of abacavir, lamivudine, and zidovudine taken as a triple combination tablet and as abacavir plus a lamivudine-zidovudine double combination tablet by HIV-1- infected adults, Conference of Retroviruses and Opportunistic Infections, pp.424-454, 2001.

J. Marier, M. Dimarco, and R. Guilbaud, Pharmacokinetics of lamivudine, zidovudine, and nevirapine administered as a fixed-dose combination formulation versus coadministration of the individual products The effect of zidovudine dose on the formation of intracellular phosphorylated metabolites, J Clin Pharmacol AIDS, vol.4710, issue.247, pp.1381-91361, 1996.

E. Kennedy, R. Schinazi, C. Gavegnano, E. Fromentin, and B. Kim, Elevated rNTP incorporation by HIV-1 RT with dNTP/rNTP pools found in human macrophages, Palm Springs Symposium on HIV/AIDS, CA, 2010.

S. Aquaro, V. Svicher, D. Schols, M. Pollicita, A. Antinori et al., Mechanisms underlying activity of antiretroviral drugs in HIV-1-infected macrophages: new therapeutic strategies, Journal of Leukocyte Biology, vol.80, issue.5, pp.1103-1110, 2006.
DOI : 10.1189/jlb.0606376

A. Alexaki, Y. Liu, and B. Wigdahl, Cellular Reservoirs of HIV-1 and their Role in Viral Persistence, Current HIV Research, vol.6, issue.5, pp.388-400, 2008.
DOI : 10.2174/157016208785861195

R. F. Schinazi, B. I. Hernandez-santiago, and S. J. Hurwitz, Pharmacology of current and promising nucleosides for the treatment of human immunodeficiency viruses, Antiviral Research, vol.71, issue.2-3, pp.322-334, 2006.
DOI : 10.1016/j.antiviral.2006.03.012

. Balzarini, Metabolism and mechanism of antiretroviral action of purine and pyrimidine derivatives, Pharmacy World & Science, vol.37, issue.Suppl 2A, pp.113-126, 1994.
DOI : 10.1007/BF01880662

. Balzarini, Effect of antimetabolite drugs of nucleotide metabolism on the anti-human immunodeficiency virus activity of nucleoside reverse transcriptase inhibitors, Pharmacology & Therapeutics, vol.87, issue.2-3, pp.175-187, 2000.
DOI : 10.1016/S0163-7258(00)00050-4

P. A. Furman, J. A. Fyfe, . St, M. H. Clair, K. Weinhold et al., Phosphorylation of 3'-azido-3'-deoxythymidine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase., Proceedings of the National Academy of Sciences, vol.83, issue.21, pp.8333-8337, 1986.
DOI : 10.1073/pnas.83.21.8333

L. Durand-gasselin, K. K. Van-rompay, J. E. Vela, I. N. Henne, W. A. Lee et al., Nucleotide Analogue Prodrug Tenofovir Disoproxil Enhances Lymphoid Cell Loading following Oral Administration in Monkeys, Molecular Pharmaceutics, vol.6, issue.4, pp.1145-1151, 2009.
DOI : 10.1021/mp900036s

G. J. Yuen, S. Weller, and G. E. Pakes, A Review of the Pharmacokinetics of Abacavir, Clinical Pharmacokinetics, vol.16, issue.2, pp.351-371, 2008.
DOI : 10.2165/00003088-200847060-00001

S. J. Hurwitz, G. Asif, N. M. Kivel, and R. F. Schinazi, Development of an Optimized Dose for Coformulation of Zidovudine with Drugs That Select for the K65R Mutation Using a Population Pharmacokinetic and Enzyme Kinetic Simulation Model, Antimicrobial Agents and Chemotherapy, vol.52, issue.12, pp.4241-4250, 2008.
DOI : 10.1128/AAC.00054-08

S. D. Sales, P. G. Hoggard, D. Sunderland, S. Khoo, C. A. Hart et al., Zidovudine Phosphorylation and Mitochondrial Toxicity in Vitro, Toxicology and Applied Pharmacology, vol.177, issue.1, pp.54-58, 2001.
DOI : 10.1006/taap.2001.9288

R. S. Jansen, H. Rosing, J. H. Schellens, and J. H. Beijnen, Retention studies of 2???-2???-difluorodeoxycytidine and 2???-2???-difluorodeoxyuridine nucleosides and nucleotides on porous graphitic carbon: Development of a liquid chromatography???tandem mass spectrometry method, Journal of Chromatography A, vol.1216, issue.15, pp.3168-3174, 2009.
DOI : 10.1016/j.chroma.2009.02.002

T. L. Diamond, M. Roshal, V. K. Jamburuthugoda, H. M. Reynolds, A. R. Merriam et al., Macrophage Tropism of HIV-1 Depends on Efficient Cellular dNTP Utilization by Reverse Transcriptase, Journal of Biological Chemistry, vol.279, issue.49, pp.51545-51553, 2004.
DOI : 10.1074/jbc.M408573200

B. I. Hernandez-santiago, A. Obikhod, E. Fromentin, S. J. Hurwitz, and R. F. Schinazi, Cellular Pharmacology of 9-(??-D-1,3-dioxolan-4-yl) Guanine and its Lack of Drug Interactions with Zidovudine in Primary Human Lymphocytes, Antiviral Chemistry and Chemotherapy, vol.7, issue.6, pp.343-346, 2007.
DOI : 10.1177/095632020701800606

R. S. Jansen, H. Rosing, and C. De-wolf, Development and validation of an assay for the quantitative determination of cladribine nucleotides in MDCKII cells and culture medium using weak anion-exchange liquid chromatography coupled with tandem mass spectrometry, Rapid Communications in Mass Spectrometry, vol.667, issue.24, pp.4049-4059, 2007.
DOI : 10.1002/rcm.3318

G. Shi, J. T. Wu, Y. Li, R. Geleziunas, K. Gallagher et al., Novel direct detection method for quantitative determination of intracellular nucleoside triphosphates using weak anion exchange liquid chromatography/tandem mass spectrometry, Rapid Communications in Mass Spectrometry, vol.647, issue.11, pp.1092-1099, 2002.
DOI : 10.1002/rcm.684

D. S. Bell, H. M. Cramer, and A. D. Jones, Rational method development strategies on a fluorinated liquid chromatography stationary phase: Mobile phase ion concentration and temperature effects on the separation of ephedrine alkaloids, Journal of Chromatography A, vol.1095, issue.1-2, pp.113-118, 2005.
DOI : 10.1016/j.chroma.2005.08.004

G. Hennere, F. Becher, A. Pruvost, C. Goujard, J. Grassi et al., Liquid chromatography???tandem mass spectrometry assays for intracellular deoxyribonucleotide triphosphate competitors of nucleoside antiretrovirals, Journal of Chromatography B, vol.789, issue.2, pp.273-281, 2003.
DOI : 10.1016/S1570-0232(03)00099-0

S. Compain, L. Durand-gasselin, J. Grassi, and H. Benech, Improved method to quantify intracellular zidovudine mono- and triphosphate in peripheral blood mononuclear cells by liquid chromatography-tandem mass spectrometry, Journal of Mass Spectrometry, vol.11, issue.18, pp.389-404, 2007.
DOI : 10.1002/jms.1176

A. Pruvost, F. Theodoro, L. Agrofoglio, E. Negredo, and H. Benech, Specificity enhancement with LC-positive ESI-MS/MS for the measurement of nucleotides: application to the quantitative determination of carbovir triphosphate, lamivudine triphosphate and tenofovir diphosphate in human peripheral blood mononuclear cells, Journal of Mass Spectrometry, vol.39, issue.2, pp.224-233, 2008.
DOI : 10.1002/jms.1294

R. M. Seifar, C. Ras, J. C. Van-dam, W. M. Van-gulik, J. J. Heijnen et al., Simultaneous quantification of free nucleotides in complex biological samples using ion pair reversed phase liquid chromatography isotope dilution tandem mass spectrometry, Analytical Biochemistry, vol.388, issue.2, pp.213-219, 2009.
DOI : 10.1016/j.ab.2009.02.025

R. L. Claire, R. Tuytten, F. Lemiere, E. Witters, W. Van-dongen et al., Positive ion electrospray ionization tandem mass spectrometry coupled to ion-pairing high-performance liquid chromatography with a phosphate buffer for the quantitative analysis of intracellular nucleotides, Rapid Communications in Mass Spectrometry, vol.63, issue.17, pp.1625-1634, 2000.
DOI : 10.1002/1097-0231(20000915)14:17<1625::AID-RCM72>3.0.CO;2-0

T. Hawkins, W. Veikley, . St, R. L. Claire, B. Guyer et al., Acquired Immune Defic. Syndr, pp.406-411, 2005.

R. L. Cordell, S. J. Hill, C. A. Ortori, and D. A. Barrett, Quantitative profiling of nucleotides and related phosphate-containing metabolites in cultured mammalian cells by liquid chromatography tandem electrospray mass spectrometry, Journal of Chromatography B, vol.871, issue.1, pp.115-124, 2008.
DOI : 10.1016/j.jchromb.2008.07.005

L. Coulier, R. Bas, S. Jespersen, E. Verheij, M. J. Van-der-werf et al., Simultaneous Quantitative Analysis of Metabolites Using Ion-Pair Liquid Chromatography???Electrospray Ionization Mass Spectrometry, Analytical Chemistry, vol.78, issue.18, pp.6573-6582, 2006.
DOI : 10.1021/ac0607616

C. Crauste, I. Lefebvre, M. Hovaneissian, J. Y. Puy, B. Roy et al., Development of a sensitive and selective LC/MS/MS method for the simultaneous determination of intracellular 1-beta-d-arabinofuranosylcytosine triphosphate (araCTP), cytidine triphosphate (CTP) and deoxycytidine triphosphate (dCTP) in a human follicular lymphoma cell line, Journal of Chromatography B, vol.877, issue.14-15, pp.1417-1425, 2009.
DOI : 10.1016/j.jchromb.2009.02.071

J. Y. Feng, W. B. Parker, M. L. Krajewski, D. Deville-bonne, M. Veron et al., Anabolism of amdoxovir: phosphorylation of dioxolane guanosine and its 5???-phosphates by mammalian phosphotransferases, Biochemical Pharmacology, vol.68, issue.9, pp.1879-1888, 2004.
DOI : 10.1016/j.bcp.2004.06.019

B. Seigneres, C. Pichoud, P. Martin, P. Furman, C. Trepo et al., Inhibitory activity of dioxolane purine analogs on wild-type and lamivudine-resistant mutants of hepadnaviruses, Hepatology, vol.46, issue.3, p.710, 2002.
DOI : 10.1053/jhep.2002.35070

A. Volosov, C. Alexander, L. Ting, and S. J. Soldin, Simple rapid method for quantification of antiretrovirals by liquid chromatography???tandem mass-spectrometry, Clinical Biochemistry, vol.35, issue.2, p.99, 2002.
DOI : 10.1016/S0009-9120(02)00286-2

A. K. Gehrig, G. Mikus, W. E. Haefeli, and J. Burhenne, Electrospray tandem mass spectroscopic characterisation of 18 antiretroviral drugs and simultaneous quantification of 12 antiretrovirals in plasma, Rapid Communications in Mass Spectrometry, vol.16, issue.16, p.2704, 2007.
DOI : 10.1002/rcm.3138

B. L. Robbins, P. A. Poston, E. F. Neal, C. Slaughter, and J. H. Rodman, Simultaneous measurement of intracellular triphosphate metabolites of zidovudine, lamivudine and abacavir (carbovir) in human peripheral blood mononuclear cells by combined anion exchange solid phase extraction and LC???MS/MS, Journal of Chromatography B, vol.850, issue.1-2, p.310, 2007.
DOI : 10.1016/j.jchromb.2006.12.015

C. Estrela-rde, M. C. Salvadori, and G. Suarez-kurtz, A rapid and sensitive method for simultaneous determination of lamivudine and zidovudine in human serum by on-line solid-phase extraction coupled to liquid chromatography/tandem mass spectrometry detection, Rapid Communications in Mass Spectrometry, vol.18, issue.10, p.1147, 2004.
DOI : 10.1002/rcm.1446

H. Chen, R. F. Schinazi, P. Rajagopalan, Z. Gao, C. K. Chu et al., Pharmacokinetics of (-)-beta-D-Dioxolane Guanine and Prodrug (-)-beta-D-2,6-Diaminopurine Dioxolane in Rats and Monkeys, AIDS Research and Human Retroviruses, vol.15, issue.18, p.1625, 1999.
DOI : 10.1089/088922299309667

L. H. Wang, J. W. Bigley, M. Brosnan-cook, N. D. Sista, and F. , Rousseau and the DAPD-101 Clinical Trial Group, Conference of Retroviruses and Opportunistic Infections, 2001.