1. National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Division of HIV/AIDS Prevention High maraviroc concentrations in rectal secretions after oral dosing do not prevent rectal SHIV transmission in macaques Ivana Massud, Wutyi Aung, Amy Martin, Shanon Bachman, James Mitchell, Frank Deyounks, Ellen Kersh, Chou-Pong Pau, Walid Heneine, J. Gerardo García-Lerma Disclaimer: The findings and conclusions in this presentation are those of the author(s) and do not necessarily represent the views of the Centers for Disease Control and Prevention Laboratory Branch, Division of HIV/AIDS Prevention, CDC

2. National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Division of HIV/AIDS Prevention Pharmacokinetic profile of maraviroc in rhesus macaques Single dose PK -12 rhesus macaques -MVC (44 mg/kg) given orally by gavage -Blood and secretions collected over time Macaques Humans* T max 24 n.a C max 12,748 n.a AUC 0-24h 131,164 n.a AUC 0-48h 339,772 n.a T max 2 1.6 2 C max 451 412 503 AUC 0-24h 1,685 1,680 1,950 Blood plasmaRectal secretions *PK parameters in human studies measured over 12h. Brown et al., JID 2010; Dumond et al., J AIDS 2009

3. National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Division of HIV/AIDS Prevention Historical controls (n = 35) Real-time controls (n = 4) N. of rectal exposures 02468101214 0 25 50 75 100 Percent survival Efficacy of MVC against rectal SHIV transmission Design Treated (n=6) SHIV162p3 MVC -24h +2h Weekly rectal exposures to low doses (10 TCID 50 ) of SHIV162p3 (R5 tropic) Untreated controls (n=4) Results Maraviroc (n = 6)

4. Summary Similar PK profile with 44 mg/kg MVC in macaques and 300 mg in humans No prophylactic efficacy with the doses and regimen used Poster WEPDC0105 Long (2.5 days) half-life of MVC bound to CCR5 in PBMCs Similar IC 50 in rhesus and human PBMCs No evidence of selection of low frequency X4 variants from the infecting pool Low (10-20%) protein binding in rectal secretions High stability of protein-bound and free MVC in secretions