Novel therapies based on mechanisms of HIV-1 cell entry

New England Journal of Medicine

Volumn 348, Issue 22, 2003, Pages 2228-2238

  Kilby, J Michael ^a,c   Eron, Joseph J ^b  

^a University of Alabama at Birmingham   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,1' [1,4 PHENYLENEBIS(METHYLENE)]BIS(1,4,8,11 TETRAAZACYCLOTETRADECANE); 4 BENZOYL 1 [(4 METHOXY 1H PYRROLO[2,3 B]PYRIDIN 3 YL)OXOACETYL] 2 METHYLPIPERAZINE; ABACAVIR; AMPRENAVIR; CD4 IMMUNOGLOBULIN G2; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CXCR4; CYANOVIRIN N; DELAVIRDINE; DEXTRAN SULFATE; DIDANOSINE; EFAVIRENZ; ENFUVIRTIDE; INDINAVIR; LAMIVUDINE; LOPINAVIR PLUS RITONAVIR; NELFINAVIR; NEVIRAPINE; PRO 140; PRO 2000; RITONAVIR; SAQUINAVIR; SOLUBLE CD4 ANTIGEN; STAVUDINE; T 1249; TENOFOVIR; TNX 355; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZALCITABINE; ZIDOVUDINE;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; BINDING AFFINITY; BINDING KINETICS; CLINICAL TRIAL; CRYSTALLIZATION; DRUG HALF LIFE; ERYTHEMA; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INHIBITION KINETICS; INJECTION SITE; MEMBRANE FUSION; MOLECULAR DYNAMICS; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; PRURITUS; REVIEW; SIDE EFFECT; SKIN NODULE; VIRUS ADSORPTION; VIRUS CELL INTERACTION; VIRUS ENVELOPE; VIRUS ETIOLOGY; VIRUS ISOLATION; VIRUS PATHOGENESIS;

AMINO ACID SEQUENCE; ANTIGENS, CD4; CD4-POSITIVE T-LYMPHOCYTES; HIV ENVELOPE PROTEIN GP120; HIV ENVELOPE PROTEIN GP41; HIV FUSION INHIBITORS; HIV PROTEASE INHIBITORS; HIV-1; HUMANS; MEMBRANE FUSION; MOLECULAR SEQUENCE DATA; PEPTIDE FRAGMENTS; RECEPTORS, CHEMOKINE; REVERSE TRANSCRIPTASE INHIBITORS; VIRAL ENVELOPE PROTEINS;

EID: 0038187684     PISSN: 00284793     EISSN: None     Source Type: Journal    
DOI: 10.1056/NEJMra022812     Document Type: Review

References (98)

1. Barre-Sinoussi F, Chermann JC, Rey F, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983;220:868-71.
2. Gallo RC, Sarin PS, Gelmann EP, et al. Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science 1983;220:865-7.
3. Klatzmann D, Champagne E, Chamaret S, et al. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 1984;312:767-8.
4. Dalgleish AG, Beverley PCL, Clapham PR, et al. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 1984;312:763-7.
5. Earl PL, Doms RW, Moss B. Oligomeric structure of the human immunodeficiency virus type 1 envelope glycoprotein. Proc Natl Acad Sci U S A 1990;87:648-52.
6. Weiss CD, Levy JA, White JM. Oligomeric organization of gp120 on infectious human immunodeficiency virus type 1 particles. J Virol 1990;64:5674-7.
7. Wyatt R, Sullivan N, Thali M, et al. Functional and immunologic characterization of human immunodeficiency virus type 1 envelope glycoproteins containing deletions of the major variable regions. J Virol 1993;67-4557-65.
8. Moore JP, Sattentau QJ, Wyatt R, Sodroski J. Probing the structure of the human immunodeficiency virus surface glycoprotein gp120 with a panel of monoclonal antibodies. J virol 1994;68:469-84.
9. Peterson A, Seed B. Genetic analysis of monoclonal antibody and HIV binding sites on the human lymphocyte antigen CD4. Cell 1988;54:65-72.
10. Lasky LA, Nakamura G, Smith DH, et al. Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor. Cell 1987;50:975-85.
11. Kowalski M, Potz J, Basiripour L, et al. Functional regions of the envelope glyco-protein of human immunodeficiency virus type 1. Science 1987;237:1351-5.
12. Skinner MA, Langlois AJ, McDanal CB, McDougal JS, Bolognesi DP, Matthews TJ. Neutralizing antibodies to an immunodominant envelope sequence do not prevent gp120 binding to CD4. J Virol 1988;62:4195-200.
13. Freed EO, Myers DJ, Risser R. Identification of the principal neutralizing determinant of human immunodeficiency virus type 1 as a fusion domain. J Virol. 1991;65:190-4.
14. Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science 1995;270:1811-5.
15. Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 1996;272:872-7.
16. Dragic T, Litwin V, Allaway GP, et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 1996;381:667-73.
17. Deng H, Liu R, Ellmeier W, et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature 1996;381:661-6.
18. Hoxie JA, LaBranche CC, Endres MJ, et al. CD4-independent utilization of the CXCR4 chemokine receptor by HIV-1 and HIV-2. J Reprod Immunol 1998;41:197-211.
19. Wyatt R, Sodroski J. The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 1998;280:1884-8.
20. Koot M, Keet IP, Vos AH, et al. Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med 1993;118:681-8.
21. Richman DD, Bozzette SA. The impact of the syncytium-inducing phenotype of human immuno deficiency virus on disease progression. J Infect Dis 1994;169:968-74.
22. Singh A, Collman RG. Heterogeneous spectrum of coreceptor usage among variants within a dualtropic human immunodeficiency virus type 1 primary-isolate quasispecies. J Virol 2000;74:10229-35.
23. Choe H, Farzan M, Sun Y, et al. The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 1996;85:1135-48.
24. Cocchi F, DeVico AL, Garzino-Demo A, Cara A, Gallo RC, Lusso P. The V3 domain of the HIV-1 gp120 envelope glycoprotein is critical for chemokine-mediated blockade of infection. Nat Med 1996;2:1244-7.
25. Clapham PR, McNight A. Cell surface receptors, virus entry and tropism of primate lentiviruses. J Gen Virol 2002;83:1809-29.
26. Liu R, Paxton WA, Choe S, et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 1996;86:367-77.
27. Dean M, Carrington M, Winkler C, et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele o the CKR5 structural gene. Science 1996;273:1856-62. (Erratum, Science 1996;274:1069.]
28. Michael NL, Nelson JA, KewalRamani VN, et al. Exclusive and persistent use of the entry coreceptor CXCR4 by human immunodeficiency virus type 1 from a subject homozygous for CCR5 delta32. J Virol 1998;72:6040-7.
29. Gallaher WP, Ball JM, Garry RF, Griffin MC, Montelaro RC. A general model of the transmembrane proteins of HIV and other retroviruses. AIDS Res Hum Retroviruses 1989;5:431-40.
30. Delwart EL, Mosialos G, Gilmore T. Retroviral envelope glycoproteins contain a "leucine zipper"-like repeat. AIDS Res Hum Retroviruses 1990;6:703-6.
31. Dubay JW, Roberts SJ, Brody B, Hunter E. Mutations in the leucine zipper of the human immunodeficiency virus type 1 transmembrane glycoprotein affect fusion and infectivity. J Virol 1992;66:4748-56.
32. Carr C, Kim PS. A spring-loaded mechanism for the conformational change of influenza hemagglutinin. Cell 1993;73:823-32.
33. Chen CH, Matthews TJ, McDanal CB, Bolognesi DP, Greenberg ML. A molecular clasp in the human immunodeficiency virus (HIV) type 1 TM protein determines the anti-HIV activity of gp41 derivatives: implication for viral fusion. J Virol 1995;69:3771-7.
34. Fisher RA, Bertonis JM, Meier W, et al. HIV infection is blocked in vitro by recombinant soluble CD4. Nature 1988;331:76-8.
35. Hussey RE, Richardson NE, Kowalski M, et al. A soluble CD4 protein selectively inhibits HIV replication and syncytium formation. Nature 1988;331:78-81.
36. Schooley RT, Merigan TC, Gaut P, et al. Recombinant soluble CD4 therapy in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex: a phase I-II escalating dosage trial. Ann Intern Med 1990;112:247-53.
37. Schacker T, Collier AC, Coombs R, et al. Phase I study of high-dose, intravenous rsCD4 in subjects with advanced HIV-1 infection. J Acquir Immune Defic Syndr Hum Retrovirol 1995;9:145-52.
38. O'Brien WA, Chen IS, Ho DD, Daar ES. Mapping genetic determinants for human immunodeficiency virus type 1 resistance to soluble CD4. J Virol 1992;66:3125-30.
39. Moore JP, McKeating JA, Huang YX, Ashkenazi A, Ho DD. Virions of primary human immunodeficiency virus type I isolates resistant to soluble CD4 (sCD4) neutralization differ in sCD4 binding and glycoprotein gp120 retention from sCD4-sensitive isolates. J Virol 1992;66:235-43.
40. Meng T-C, Fischl MA, Cheeseman SH, et al. Combination therapy with recombinant human soluble CD4-immunoglobulin G and zidovudine in patients with HIV infection: a phase I study. J Acquir Immune Defic Syndr Hum Retrovirol 1995;8:152-60.
41. Trkola A, Pomales AB, Yuan H, et al. Cross-clade neutralization of primary isolates of human immunodeficiency virus type 1 by human monoclonal antibodies and tetrameric CD4-IgG. J Virol 1995;69:6609-17.
42. Jacobson JM, Lowy I, Fletcher CV, et al. Single-dose safety, pharmacology, and antiviral activity of the human immunodeficiency virus (HIV) type 1 entry inhibitor PRO 542 in HIV-infected adults. J Infect Dis 2000;182:326-9.
43. Shearer WT, Israel RJ, Starr S, et al. Recombinant CD4-IgG2 in human immunodeficiency virus type 1-infected children: phase 1/2 study. J Infect Dis 2000;182:1774-9.
44. Shearer MH, Timanus DK, Benton PA, Lee DR, Kennedy RC. Cross-clade inhibition of human immunodeficiency virus type I primary isolates by monoclonal anti-CD4. J Infect Dis 1998;177:1727-9.
45. Moreland LW, Bucy RP, Koopman WJ. Regeneration of T cells after chemotherapy. N Engl J Med 1995;332:1651-2.
46. Wofsy D. Treatment of murine lupus with anti-CD4 monoclonal antibodies. Immunol Set 1993;59:221-36.
47. Kuritzkes DR, Jacobson JM, Powderly WG, et al. Safety and preliminary anti-HIV activity of an anti-CD4 mAb (TNX-355; formerly Hu5A8) in HIV-infected patients. In: Programs and abstracts of the 10th Conference on Retroviruses and Opportunistic Infections, Boston, February 10-14, 2003. Alexandria, Va.: Foundation for Retrovirology and Human Health, 2003:62. abstract.
48. Lin P-F, Guo K, Fridell R, Ho H-T, Yamanaka G, Colonno R, Identification and characterization of a novel inhibitor of HIV-1 entry. II. Mechanism of action. In: Programs and abstracts of the Ninth Conference on Retroviruses and Opportunistic Infections, Seattle, February 24-28, 2002. Alexandria, Va.: Foundation for Retrovirology and Human Health, 2001:56. abstract.
49. Lin P-F, Gong YF, Rose B, et al. Generation and characterization of HIV-1 variants resistant to BMS 806, a novel HIV-1 entry inhibitor. Antiviral Ther 2002;7:Suppl 1:S8. abstract.
50. Mitsuya H, Looney DJ, Kuno S, Ueno R, Wong-Staal F, Broder S. Dextran sulfate suppression of viruses in the HIV family: inhibition of virion binding to CD4+ cells. Science 1988;240:646-9.
51. Moulard M, Lortat-Jacob H, Mondor I, et al. Selective interactions of polyanions with basic surfaces on human immunodeficiency virus type 1 gp120. J Virol 2000;74:1948-60.
52. Este JA, Schols D, De Vreese K, et al. Development of resistance of human immunodeficiency virus type 1 to dextran sulfate associated with the emergence of specific mutations in the envelope gp120 glycoprotein. Mol Pharmacol 1997;52:98-104.
53. Meylan P, Kombluth RS, Zbinden I, Richman DD. Influence of host cell type and V3 loop of the surface glycoprotein on susceptibility of human immunodeficiency virus type 1 to polyanion compounds. Antimicrob Agents Chemother 1994;38:2910-6.
54. Flexner C, Barditch-Crovo PA, Kornhauser DM, et al. Pharmacokinetics, toxicity, and activity of intravenous dextran sulfate in human immunodeficiency infection. Antimicrob Agents Chemother 1991;35:2544-50.
55. Rusconi S, Moonis M, Merrill DP, et al. Naphthalene sulfonate polymers with CD4-blocking and anti-human immunodeficiency virus type 1 activities. Antimicrob Agents Chemother 1996;40:234-6.
56. Van Damme L, Wright A, Depraetere K, et al. A phase I study of a novel potential intravaginal microbicide, PRO 2000, in healthy sexually inactive women. Sex Transm Infect 2000;76:126-30.
57. Mori T, Boyd MR, Cyanovirin-N, a potent human immunodeficiency virus-inactivating protein, blocks both CD4-dependent and CD4-independent binding of soluble gp120 (sgp120) to target cells, inhibits sCD4-induced binding of sgp120 to cell-associated CXCR4, and dissociates bound sgp120 from target cells. Antimicrob Agents Chemother 2001;45:664-72.
58. Dragie T, Trkola A, Thompson DA, et al. A binding pocket for a small molecule inhibitor of HIV-1 entry within the transmembrane helices of CCR5. Proc Natl Acad Sci U S A 2000;97:5639-44.
59. Rusconi S, La Seta Catamancio S, Citterio P, et al. Combination of CCR5 and CXCR4 inhibitors in therapy of human immunodeficiency virus type 1 infection: in vitro studies of mixed virus infections. J Virol 2000;74:9328-32.
60. Simmons G, Clapham PR, Picard L. Potent inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist. Science 1997;276:276-9.
61. Cairns JS, D'Souza MP. Chemokines and HIV-1 second receptors: the therapeutic connection. Nat Med 1998;4:563-8.
62. Mosier DE, Picchio GR, Gulizia RJ, et al. Highly potent RANTES analogues either prevent CCR5-using human immunodeficiency virus type 1 infection in vivo or rapidly select for CXCR4-using variants. J Virol 1999;73:3544-50.
63. Strizki JM, Xu S, Wagner NE, et al. SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo. Proc Natl Acad Sci U S A 2001;98:12718-23.
64. Reyes G. Development of CCR5 antagonists as a new class of anti-HIV therapeutic. In: Programs and abstracts of the Eighth Conferenee on Retroviruses and Opportunistic Infections, Chicago, February 4-8, 2001. Alexandria, Va.: Foundation for Retrovirology and Human Health, 2001:285. abstract.
65. Trkola A, Ketas TJ, Nagashima KA, et al. Potent broad-spectrum inhibition of human immunodeficiency virus type 1 by the CCR5 monoclonal antibody PRO 140. J Virol 2001;75:579-88.
66. Reynes J, Rouzier R, Kanouni T, et al. Safety and antiviral effects of a CCR5 receptor antagonist in HIV-1 infected subjects. In: Programs and abstracts of the Ninth Conference on Retroviruses and Opportunistic Infections, Seattle, February 24-28, 2002. Alexandria, Va.: Foundation for Retrovirology and Human Health, 2002:53. abstract.
67. Trkola A, Kuhmann SE, Strizki JM, et al. HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use. Proc Natl Acad Sci U S A 2002;99:395-400.
68. Nagasawa T, Hirota S, Tachibana K, et al. Defects of B-cell lymphopoiesis and bone-marrow myclopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 1996;382:635-8.
69. Doranz BJ, Filion LG, Diaz-Mitoma F, et al. Sale use of the CXCR4 inhibitor ALX40-4C in humans. AIDS Res Hum Retroviruses 2001;17:475-86.
70. Donzella GA, Schols D, Lin SW. AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor. Nat Med 1998;4:72-7.
71. Hendrix CW, Flexner C, MacFarland RT, et al. Pharmacokinetics and safety of AMD-3100, a novel antagonist of the CXCR4 chemokine receptor, in human volunteers. Antimicrob Agents Chemother 2000;44:1667-73.
72. Schols D, Claes S, De Clercq E, et al. AMD-3100, a CXCR4 antagonist, reduced HIV viral load and X4 levels in humans. In: Programs and abstracts of the Ninth Conference on Retroviruses and Opportunistic Infections, Seattle, February 24-28, 2002. Alexandria, Va.: Foundation for Retrovirology and Human Health, 2002:53. abstract.
73. de Vreese K, Kofler-Mongold V, Leutgeb C, et al. The molecular target of bicyclams, potent inhibitors of human immunodeficiency virus replication. J Virol 1996;70:689-96.
74. Zhang L, Yu W, He T, et al. Contribution of human alpha-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor. Science 2002;298:995-1000.
75. Eckert DM, Malashkevich VN, Hong LH, Carr PA, Kim PS. Inhibiting HIV-1 entry: discovery of D-peptide inhibitors that target the gp41 coiled-coil pocket. Cell 1999;99:103-15.
76. Ferrer M, Kapoor TM, Strassmaier T, et al. Selection of gp41-mediated HIV-1 cell entry inhibitors from biased combinatorial libraries of non-natural binding elements. Nat Struct Biol 1999;6:953-60.
77. Judice JK, Tom JY, Huang W, et al. Inhibition of HIV type 1 infectivity by constrained alpha-helical peptides: implications for the viral fusion mechanism. Proc Natl Acad Sci U S A 1997;94:13426-30.
78. Wild C, Greenwell T, Matthews T. A synthetic peptide from HIV-1 gp41 is a potent inhibitor of virus-mediated cell-cell fusion. AIDS Res Hum Retroviruses 1993;9:1051-3.
79. Kilby JM, Hopkins S, Venetta TM, et al. Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat Med 1998;4:1302-7.
80. Kilby JM, Lalezari JP, Eron J, et al. The safety, plasma pharmacokinetics, and antiviral activity of subcutaneous enfuvirtide (T-20), a peptide inhibitor of gp41-mediated virus fusion, in HIV-infected adults. AIDS Res Hum Retroviruses 2002;18:685-93. [Erratum, AIDS Res Hum Retroviruses 2003;19:83.]
81. Greenberg M, Sista P, Miralles G, et al. Enfuvirtide (T-20) and T-1249 resistance: observations from phase II clinical trials of enfuvirtide in combination with oral antiretrovirals and a phase I/II dose-ranging monotherapy trial of T-1249. Antiviral Ther 2002;7:Suppl:S14O. abstract.
82. Lalezari JP, Bron JJ, Carlson M, et al. A phase II clinical study of the long-term safety and antiviral activity of enfuvirtide-based antiretroviral therapy. AIDS 2003;17:691-8.
83. Lalezari J, Drucker J, Demasi R, Hopkins S, Salgo M. A controlled phase II trial assessing three doses of T-20 in combination with abacavir, amprenavir, low dose ritonavir, and efavirenz in non-nucleoside naive, protease inhibitor-experienced, HIV-1-infected adults: In: Programs and abstracts of the Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, February 4-8, 2001. Alexandria, Va.: Foundation for Retrovirology and Human Health, 2001:277. abstract.
84. Lalezari JP, Henry K, O'Heam M, et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N Engl J Med 2003;348:2175-85.
85. Lazzarin A, Clotet B, Gooper D, et al. Efficacy of enfuvirtide in patients infected with drug-resistant HIV-I in Europe and Australia. N Engl J Med 2003;348:2186-95.
86. Greenberg M, Davison D, Jin L, et al. In vitro antiviral activity of T-1249, a second generation fusion inhibitor. Antiviral Ther 2002;7:Suppl:S14. abstract
87. Bron J, Merigan T, Kilby M, et al. A 14-day assessment of the safety, pharmacokinetics, and antiviral activity of T-1249, a peptide inhibitor of membrane fusion. In: Programs and abstracts of the Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, February 4-8, 2001. Alexandria, Va.: Foundation for Retrovirology and Human Health, 2001:47. abstract.
88. Wei X, Decker JM, Liu H, et al. Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob Agents Chemother 2002;46:1896-905.
89. Rimsky LT, Shugars DC, Matthews TJ. Determinants of human immunodeficiency virus type 1 resistance to gp41-derived inhibitory peptides. J Virol 1998;72:986-93.
90. Derdeyn CA, Decker JM, Sfakianos JN, et al. Sensitivity of human immunodeficiency virus type 1 to the fusion inhibitor T-20 is modulated by coreceptor specificity defined by the V3 loop of gp120. J Virol 2000;74:8358-67.
91. Lu J, Sista P, Cammack N, Kurtizkes D. Fitness of HIV-1 clinical isolates resistant to T-20 (enfuvirtide). Antiviral Ther 2002;7: Suppl:S74. abstract.
92. Miralles G, Lalezari J, Bellos N, et al. T-1249 demonstrates potent antiviral activity over 10-day dosing in most patients who have failed a regimen containing enfuvirtide: planned interim analysis of T1249-102, a phase I/II study. In: Programs and abstracts of the 10th Conference on Retroviruses and Opportunistic Infections, Boston, February 10-14, 2003. Alexandria, Va.: Foundation for Retrovirology and Human Health, 2003:63. abstract.
93. Derdeyn CA, Decker JM, Sfakianos JN, et al. Sensitivity of human immunodeficiency virus type 1 to fusion inhibitors targeted to the gp41 first heptad repeat involves distinct regions of gp41 and is consistently modulated by gp120 interactions with the coreceptor. J Virol 2001;75:8605-14.
94. Reeves JD, Gallo SA, Ahmad N, et al. Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics. Proc Natl Acad Sci U S A 2002;99:16249-54.
95. Greenberg ML, McDanal CB, Stanfield-Oakley SA, et al. Virus sensitivity to T-20 and T-1249 is independent of coreceptor usage. In: Programs and abstracts of the Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, February4-8, 2001. Alexandria, Va.: Foundation for Retrovirology and Human Health, 2001:194. abstract.
96. Tremblay C, Kollman G, Giguel F, Chou TC, Hirsch MS. Strong in vitro synergy observed between the fusion inhibitor T-20 and a CXCR4 blocker, AMD3100. In: Programs and abstracts of the Seventh Conference on Retroviruses and Opportunistic Infections, San Francisco, January 30-February 4, 2000. Alexandria, Va.: Foundation for Retrovirology and Human Health, 2001:170. abstract.
97. Nagashima KA, Thompson DA, Rosenfield SI, Maddon PJ, Dragic T, Olson WC. Human immunodeficiency virus type 1 entry inhibitors PRO 542 and T-20 are potently synergistic in blocking virus-cell and cell-cell fusion. J Infect Dis 2001;183:1121-5.
98. Tremblay CL, Giguel F, Kollmann C, et al. Anti-human immunodeficiency virus interactions of SCH-C (SCH 351125), a CCR5 antagonist, with other antiretroviral agents in vitro. Antimicrob Agents Chemother 2002;46:1336-9.