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

Risk of Virologic Failure and HIV-1 Drug Resistance after starting ART

Phillips et al AIDS 2005; 19:487-94

Prevalence of antiretroviral drug resistance in US patients in care (1998)

Richman et al AIDS 2004; 18:1393-1401

Prevalence of multidrug-resistant HIV

~270,000 patients receiving ART in US1

~10%-15% of treated patients are viremic

and have triple-class drug resistance2

At least 25,000-40,000 patients could

benefit from better options for treating

drug-resistant HIV-13

1Teshale E, et al. 12th CROI, Boston, 2005 (Abstract 167).2Napravnik S, et al. Antivir Ther. 2006;11:S88. Abstract 78.3Chase M. Wall Street Journal, February, 2007.

Changing goals of therapy in highly antiretroviral-experienced patients

Goals of therapy—20031

– Preserve immune function– Maximize reduction in plasma HIV-1 RNA – Minimize toxicity

Goals of therapy—20062,3

– Full viral suppression is an achievable goal• Newer drugs• Drugs in new classes

– Use multiple active drugs to achieve full suppression– Minimize toxicity

1Kuritzkes D. JAIDS 2003; 34 (suppl 2):103-10.2DHHS Guidelines, www.aidsinfo.nih.gov, October 10, 2006.3Hammer S et al JAMA. 2006;296:827-843.

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

Changing goals of antiretroviral therapy in treatment-experienced patients

0

5

10

15

20

25

30

35

40

45

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10

20

30

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60

70

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Percent achieving >1-log reduction in plasma HIV-1 RNA level (wk 24)

Percent with plasma HIV-1 RNA<50 copies/mL (wk 24)

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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, 14th CROI, Los Angeles, 2007, abstr 104aLB; Lalezari et al, 14th CROI, Los Angeles, 2007, abstr 104bLB

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

How should maraviroc be used?

Maraviroc should be used in combination with other active drugs in antiretroviral treatment-experienced patients with R5 virus