Daar ES, Kesler KL, Petropoulos CJ, et al. 2007. Hemophilia Growth and Development Study. Baseline HIV type 1 coreceptor tropism predicts disease progression. Clin Infect Dis, 45:643–9. Dalgleish AG, Beverley PC, Clapham PR, et al. 1984. The CD4 (T4) anti- gen is an essential component of the receptor for the AIDS retrovirus. Nature, 312:763–7. Dean M, Carrington M, Winkler C, et al. 1996. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene: Hemophilia Growth and Development Study, Multi- center AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science, 273:1856–62. Deeks SG. 2006. Challenges of developing R5 inhibitors in antiretroviral naive HIV-infected patients. Lancet, 367:711–3. Dorr P, Westby M, Dobbs S, et al. 2005. Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeﬁciency virus type 1 activity. Antimicrob Agents Chemother, 49:4721–32. Dragic T, Litwin V, Allaway GP, et al. 1996. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature, 381:667–73. Dragic T, Trkola A, Thompson DA, et al. 2000. A binding pocket for a small molecule inhibitor of HIV-1 entry within the transmembrane helices of CCR5. Proc Natl Acad Sci USA, 97:5639–44. Eckert DM, Kim PS. 2001. Mechanisms of viral membrane fusion and its inhibition. Annu Rev Biochem, 70:777–810. Fätkenheuer G, Pozniak AL, Johnson MA, et al. 2005. Efﬁcacy of short- term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1. Nat Med, 11:1170–2. Fischereder M, Luckow B, Hocher B, et al. 2001. CC chemokine receptor 5 and renal-tranplant survival. Lancet, 357:1758–61. Galvani AP, Slatkin M. 2003. Evaluating plague and smallpox as historical selective pressures for the CCR5-∆ 32 HIV-resistance allele. Proc Natl Acad Sci USA, 100:15276–9. Glass WG, McDermott DH, Lim JK, et al. 2006. CCR5 deﬁciency increases risk of symptomatic West Nile virus infection. J Exp Med, 203:35–40. Goetz MB, Leduc R, Kostman JR, et al. 2007. Prediction of disease progression by HIV coreceptor tropism in persons with untreated chronic HIV infec- tion. Program and abstracts of the 47th Interscience Conference on Anti- microbial Agents and Chemotherapy, Chicago, Ill. Abstract H-1027. Goodrich JM, Saag M, van der Ryst E, et al. 2007. 48-week safety and efﬁcacy of maraviroc, a novel ccr5 antagonist, in combination with optimized background therapy (OBT) for the treatment of antiretroviral- experienced patients infected with dual/mixed-tropic HIV-1. Program and abstracts of the 45th Annual Infectious Diseases Society of America, San Diego, CA, Abstract LB-2. Greaves W, Landovitz R, Fätkenheuer G, et al. 2006. Late Virologic break- through in treatment-naive patients on a regimen of combivir + vicrivi- roc. Program and abstracts of the 13th Conference on Retroviruses and Opportunistic Infections, Denver, CO, Abstract 161LB. Gulick R, Su Z, Flexner C, et al. 2007a. Phase II study of the safety and efﬁcacy of vicriviroc in HIV-infected treatment-experienced subjects: ACTG 5211. J Infect Dis, 196:304–12. Gulick R, Su Z, Flexner C, et al. for the ACTG 5211 Team. 2007b. ACTG 5211: phase II study of the safety and efﬁcacy of vicriviroc (VCV) in HIV-infected treatment-experienced subjects: 48 week results. Pro- gram and abstracts of the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Sydney, Australia, Abstract TUAB102. Gulick R, Haas D, Collier A, et al. 2007c. Two-year follow-up of treatment- experienced patients on vicriviroc (VCV). Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, Abstract H-1030. Gulick RM, van der Ryst E, Lampiris H, et al. 2007d. Efﬁcacy and safety of once- daily (QD) compared with twice-daily (BID) maraviroc plus optimized background therapy (OBT) in treatment-experienced patients infected with CCR5-tropic-HIV-1: 24-week combined analysis of the MOTIVATE 1 and 2 studies. Program and abstracts of the 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Abstract WEPEB116LB. Therapeutics and Clinical Risk Management 2008:4(2) CCR5 antagonists of HIV-1 infection Guo Q, Ho HT, Dicker I, et al. 2003. Biochemical and genetic characterizations of a novel human immunodeﬁciency virus type 1 inhibitor that blocks gp120-CD4 interactions. J Virol, 77:10528–36. Hammer SM, Saag MS, Schechter M, et al. 2006. International AIDS Society- USA panel. Treatment for adult HIV-1 infection: 2006 recommendations of the International AIDS Society-USA panel. JAMA, 296:827–43. Hartley O, Gaertner H, Wilken J, et al. 2004. Medicinal chemistry applied to a synthetic protein: development of highly potent HIV entry inhibitors. Proc Natl Acad Sci USA, 101:16460–5. Holmberg SD, Hamburger EM, Moorman AC, et al. 2003. Factors associ- ated with maintenance of long-term plasma human immunodeﬁciency virus RNA suppression. Clin Infect Dis, 37:702–7. Huang Y, Paxton WA, Wolinsky SM, et al. 1996. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med, 2:1240–3. Jacobson JM, Israel RJ, Lowy I, et al. 2004. Treatment of advanced human immunodeﬁciency virus type 1 disease with the viral entry inhibitor PRO 542. Antimicrob Agents Chemother, 48:423–9. Jacobson JM, Thompson M, Saag MS, et al. 2007. Antiretroviral Activity and Pharmacodynamics of PRO 140, a CCR5 Monoclonal Antibody, in HIV-Infected Individuals. Program and abstracts of the 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, Abstract H-716. Ji C, Zhang J, Dioszegi M, et al. 2007. CCR5 small-molecule antagonists and monoclonal antibodies exert potent synergistic antiviral effects by cobinding to the receptor. Mol Pharmacol, 72:18–28. Jouvenot Y, Perez E, Urnov FD, et al. 2005. Towards Gene Knock Out Therapy for AIDS/HIV: Targeted Disruption of CCR5 Using Engi- neered Zinc Finger Protein Nucleases (ZFNs). Program and abstracts of the 45th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, Abstract H-1084. Kadow J, Wang HG, Lin PF. 2006. Small-molecule HIV-1 gp120 inhibitors to prevent HIV-1 entry: an emerging opportunity for drug development. Curr Opin Investig Drugs, 7:721–6. Koot M, Keet IP, Vos AH, et al. 1993. Prognostic value of HIV-1 syncytium- inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med, 118:681–8. Kuhmann SE, Pugach P, Kunstman KJ, et al. 2004. Genetic and pheno- typic analyses of human immunodeﬁciency virus type 1 escape from a small-molecule CCR5 inhibitor. J Virol, 78:2790-807. Erratum in: J Virol, 2005. 78:6706. Kwong PD, Wyatt R, Robinson J, et al. 1998. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutral- izing human antibody. Nature, 393:648–59. Lalezari J, Thompson M, Kumar P, et al. 2005. Antiviral activity and safety of 873140, a novel CCR5 antagonist, during short-term monotherapy in HIV-infected adults. AIDS, 19:1443–8. Lalezari J, Lederman M, Yadavalli G, et al. 2006. A phase 1, dose-escalation, placebo-controlled study of a fully human monoclonal antibody (CCR5mAb004) against CCR5 in patients with CCR5-tropic HIV-1 infection. Program and abstracts of the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA, Abstract H-1668. Lalezari J, Goodrich J, DeJesus E, et al. 2007. MOTIVATE 1. USA and Canada. Efﬁcacy and safety of maraviroc plus optimized background therapy in viremic, ART-experienced patients infected with CCR5- tropic HIV-1: 24-week results of phase 2b/3 studies. Program and abstracts of the 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, CA, Abstract 104bLB. Lapidot T. 2001. Mechanism of human stem cell migration and repopula- tion of NOD/SCID and B2mnull NOD/SCID mice. The role of SDF- 1/CXCR4 interactions. Ann NY Acad Sci, 938:83–95. Liu R, Paxton WA, Choe S, et al. 1996. Homozygous defect in HIV-1 core- ceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell, 86:367–77. Luther SA, Cyster JG. 2001. Chemokines as regulators of T cell differentiation. Nat Immunol, 2:102–7. 483