1. The Role of Maraviroc in Antiretroviral Therapy for Treatment-Experienced Patients Daniel R. Kuritzkes, MD Section of Retroviral Therapeutics Brigham and Women’s Hospital Harvard Medical School

2. Risk of Virologic Failure and HIV-1 Drug Resistance after starting ART Phillips et al AIDS 2005; 19:487-94

3. Prevalence of antiretroviral drug resistance in US patients in care (1998) Richman et al AIDS 2004; 18:1393-1401

4. Prevalence of multidrug-resistant HIV ~270,000 patients receiving ART in US 1 ~10%-15% of treated patients are viremic and have triple-class drug resistance 2 At least 25,000-40,000 patients could benefit from better options for treating drug-resistant HIV-1 3 1 Teshale E, et al. 12th CROI, Boston, 2005 (Abstract 167). 2 Napravnik S, et al. Antivir Ther. 2006;11:S88. Abstract 78. 3 Chase M. Wall Street Journal, February, 2007.

5. Changing goals of therapy in highly antiretroviral-experienced patients Goals of therapy—2003 1 –Preserve immune function –Maximize reduction in plasma HIV-1 RNA –Minimize toxicity Goals of therapy—2006 2,3 –Full viral suppression is an achievable goal Newer drugs Drugs in new classes –Use multiple active drugs to achieve full suppression –Minimize toxicity 1 Kuritzkes D. JAIDS 2003; 34 (suppl 2):103-10. 2 DHHS Guidelines, www.aidsinfo.nih.gov, October 10, 2006.www.aidsinfo.nih.gov 3 Hammer S et al JAMA. 2006;296:827-843.

6. Why are CCR5 antagonists needed? Many highly treatment-experienced patients have extensive resistance to drugs in existing classes No single new drug is likely to have durable activity without additional active agents Use of several new/active drugs necessary to achieve and maintain full suppression

7. Changing goals of antiretroviral therapy in treatment-experienced patients Percent achieving >1-log reduction in plasma HIV-1 RNA level (wk 24) Percent with plasma HIV-1 RNA <50 copies/mL (wk 24) Percent achieving endpoint Source: Nelson et al JAIDS 2005;40:404-12; Hicks et al Lancet 2006;368:466-75; Lazzarin et al XVIth Intl AIDS Conf, Toronto, 2006, abstr ThAB0104; Nelson et al, 14 th CROI, Los Angeles, 2007, abstr 104aLB; Lalezari et al, 14 th CROI, Los Angeles, 2007, abstr 104bLB

8. Potential benefits of maraviroc Potent inhibitor of R5 HIV-1 in highly treatment- experienced patients when combined with OBR Safe and well-tolerated in studies to date No demonstrated adverse consequences of administration to patients with D/M or X4 virus

9. How should maraviroc be used? Maraviroc should be used in combination with other active drugs in antiretroviral treatment- experienced patients with R5 virus