Schlecht et al Maeda K, Yoshimura K, Shibayama S, et al. 2001. Novel low molecular weight spirodiketopiperazine derivatives potently inhibit R5 HIV-1 infection through their antagonistic effects on CCR5. J Biol Chem, 276:35194–200. Maeda K, Nakata H, Koh Y, et al. 2004. Spirodiketopiperazine-based CCR5 inhibitor which preserves CC-chemokine/CCR5 interactions and exerts potent activity against R5 human immunodeﬁciency virus type 1 in vitro. J Virol, 78:8654–62. Mani M, Kandavelou K, Dy FJ, et al. 2005. Design, engineering, and characterization of zinc finger nucleases. Biochem Biophys Res Commun, 335:447–57. Markowitz M, Mohri H, Mehandru S, et al. 2005. Infection with multidrug resistant, dual-tropic HIV-1and rapid progression to AIDS: a case report. Lancet, 365:1031–8. Marozsan AJ, Kuhmann SE, Morgan T, et al. 2005. Generation and prop- erties of a human immunodeﬁciency virus type 1 isolate resistant to the small molecule CCR5 inhibitor, SCH-417690 (SCH-D). Virology, 338:182–99. Melby T, Despirito M, Demasi R, et al. 2006. HIV-1 coreceptor use in triple- class treatment-experienced patients: baseline prevalence, correlates, and relationship to enfuvirtide response. J Infect Dis, 194:238–46. Mocroft A, Phillips AN, Friis-Moller N, et al. 2002. Response to antiretroviral therapy among patients exposed to three classes of antiretrovirals: results from the EuroSIDA Study. Antivir Ther, 1:21–30. Mori J, Mosley M, Lewis M, et al. 2007. Characterization of maraviroc resis- tance in patients failing treatment with CCR5-tropic virus in MOTIVATE 1 and MOTIVATE 2. Program and abstracts of the 16th International HIV Drug Resistance Workshop, Barbados, West Indies. Abstract 10. Mosley M, Smith-Burchnell C, Mori J, et al. 2006. Resistance to the CCR5 antagonist maraviroc is characterized by dose-response curves that display a reduction in maximal inhibition. Program and abstracts of the 13th Conference on Retroviruses and Opportunistic Infections, Denver, Colorado. Abstract 598. Moyle GJ, Wildﬁre A, Mandalia S, et al. 2005. Epidemiology and predic- tive factors for chemokine receptor use in HIV-1 infection. J Infect Dis, 191:866–72. Moyle GJ, DeJesus E, Bofﬁ to M, et al. 2007. CXCR4 antagonism: proof of activity with AMD11070. Program and abstracts of the 14th Con- ference on Retroviruses and Opportunistic Infections, Los Angeles, CA, Abstract 511. Murga JD, Franti M, Pevear DC, et al. 2006. Potent antiviral synergy between monoclonal antibody and small-molecule CCR5 inhibitors of human immunodeﬁciency virus type 1. Antimicrob Agents Chemother, 50:3289–96. Nakata H, Maeda K, Miyakawa T, et al. 2005. Potent anti-R5 human immunodeﬁciency virus type 1 effects of a CCR5 antagonist, AK602/ ONO4128/GW873140, in a novel human peripheral blood mononuclear cell nonobese diabetic-SCID, interleukin-2 receptor gamma- chain-knocked-out AIDS mouse model. J Virol, 79:2087–96. Nelson M, Fatkenheuer G, Konourina I, et al. 2007. MOTIVATE 2. Europe, Australia and USA. 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 104aLB. Oldﬁeld V, Keating GM, Plosker G. 2005. Enfuvirtide: a review of its use in the management of HIV infection. Drugs, 65:1139–60. Olson WC, Rabut GE, Nagashima KA, et al. 1999. Differential inhibition of human immunodeﬁciency virus type 1 fusion, gp120 binding, and CC-chemokine activity by monoclonal antibodies to CCR5. J Virol, 735:4145–55. Oppermann M. 2004. Chemokine receptor CCR5: insights into structure, function, and regulation. Cell Signal, 16:1201–10. Palella FJ Jr, Delaney KM, Moorman AC, et al. 1998. Declining morbidity and mortality among patients with advanced human immunodeﬁciency virus infection. HIV-1 Outpatient Study Investigators. N Engl J Med, 338:853–60. 484 Pastore C, Nedellec R, Ramos A, et al. 2006. Human immunodeﬁciency virus type 1 coreceptor switching: V1/V2 gain-of-ﬁtness mutations compensate for V3 loss-of-ﬁtness mutations. J Virol, 80:750–8. Philpott SM. 2003. HIV-1 coreceptor usage, transmission, and disease progression. Curr HIV Res, 1:217–27. Prahalad S. 2006. Negative association between the chemokine receptor CCR5-[Delta]32 polymorphism and rheumatoid arthritis: a meta- analysis. Genes Immun, 7:264–8. Pugach P, Marozsan AJ, Ketas TJ, et al. 2007. HIV-1 clones resistant to a small molecule CCR5 inhibitor use the inhibitor-bound form of CCR5 for entry. Virology, 361:212–28. Qin XF, An DS, Chen IS, et al. 2003. Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5. Proc Natl Acad Sci USA, 100:183–8. Reynes J, Rouzier R, Kanouni T, et al. 2002. SCH C: Safety and antiviral effects of a CCR5 receptor antagonist in HIV-1-infected subjects. Program and abstracts of the 9th Conference on Retroviruses and Opportunistic Infections. Seattle, WA, Abstract 1. Roschke V, Clark S, Branco L, et al. 2004. Characterization of a panel of novel human monoclonal antibodies that speciﬁcally antagonize CCR5 and Block HIV-1 entry. Program and abstracts of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, D.C., Abstract #2871. Rufﬁng N, Sullivan N, Sharmeen L, et al. 1998. CCR5 has an expanded ligand-binding repertoire and is the primary receptor used by MCP-2 on activated T cells. Cell Immunol, 189:160–8. Saag M, Ive P, Heera J, et al. 2007. A multicenter, randomized, double-blind, comparative trial of a novel CCR5 antagonist, maraviroc versus efavirenz, both in combination with Combivir (zidovudine [ZDV]/lamivudine [3TC]), for the treatment of antiretroviral naive patients infected with R5 HIV 1: Week 48 results of the MERIT study. Program and abstracts of the 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Sydney, Australia, Abstract WESS104. Sabeti PC, Walsh E, Schaffner SF, et al. 2005. The case for selection at CCR5-Delta32. PLoS Biol, 3:e378. Samson M, Libert F, Doranz BJ, et al. 1996. Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature, 382:722–5. Schooley RT, Mellors JW. 2007. No cure yet for HIV-1-1, but therapeutic research presses on. J Infect Dis, 195:770–2. Schurmann D, Fätkenheuer G, Reynes J, et al. 2007. Antiviral activity, phar- macokinetics and safety of vicriviroc, an oral CCR5 antagonist, during 14-day monotherapy in HIV-infected adults. AIDS, 21:1293–9. Shet A, Berry L, Mohri H, et al. 2006. Tracking the prevalence of transmitted antiretroviral drug-resistant HIV-1-1: a decade of experience. J Acquir Immune Deﬁc Syndr, 41:439–46. Signoret N, Hewlett L, Wavre S, et al. 2005. Agonist-induced endocytosis of CC chemokine receptor 5 is clathrin dependent. Mol Biol Cell, 16:902–17. Simmons G, Clapham PR, Picard L, et al. 1997. Potent inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antago- nist. Science, 276:276–9. Starr-Spires LD, Collman RG. 2002. HIV-1 entry and entry inhibitors as therapeutic agents. Clin Lab Med, 22:681–701. Steigbigel R, Kumar P, Eron J, et al. 2007. Results from BENCHMRK-2, a phase III study evaluating the efﬁcacy and safety of MK-0518, a novel HIV-1integrase inhibitor, in patients with triple-class resistant virus. Program and abstracts of the 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, CA, Abstract 105bLB. Stephens JC, Reich DE, Goldstein DB, et al. 1998. Dating the origin of the CCR5-Delta32 AIDS-resistance allele by the coalescence of haplotypes. Am J Hum Genet, 62:1507–15. Strizki JM, Xu S, Wagner NE, et al. 2001. 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 USA, 98:12718–23. Therapeutics and Clinical Risk Management 2008:4(2)