Adherence in TLC+: The Sticky Wicket

1. Adherence in TLC+:  The Sticky Wicket Michael S. Saag, MD Center for AIDS Research University of Alabama at Birmingham USA

2. One Man’s Journey to Adherence: Lessons from a Career Path in HIV Research Michael S. Saag, MD Center for AIDS Research University of Alabama at Birmingham USA

3. Ardea Avexa Boehringer-Ingelheim Bristol-Myers Squibb Gilead Sciences GlaxoSmithKline /ViiV Merck Pain Therapeutics Pfizer / ViiV Progenics Tibotec / Virco Tobria Disclosures Grant Support / Consulting

4. Translational Research

5. M Saag, UAB

6. Piatak, et al, Science, 1993

9. Latently Infected CD4+ Lymphocytes HIV Infected Cells HIV virions Antiretroviral Rx Uninfected Activated CD4+ Lymphocytes Uninfected Resting CD4+ Lymphocytes M Saag, UAB

11. At steady state, when an actively producing cell dies, it is replaced by how many newly infected cells? • One • Twenty – Five • One Hundred • One Thousand • It depends on the viral load

12. M Saag, UAB

13. VL = 100,000

14. VL < 50

23. Clinical Trials

24. How Did We Get Here? ZDV NVP 3TC EFVLPV ddI SQVRTV ABC TDF d4T IDVNFV Sequential exposure to effective “monotherapy” in a population of largely adherent, aggressively treated patients created a cohort of individuals with highly-resistant HIV 1996 1997 1998 1999 2000

25. New HAART Era T20TPVDRVMaraviroc, RaltegravirEtravirine After years of sequential “monotherapy” many patients with MDR are now entering a period where more than one new medication may be readily available 2004 2005 2006 2007 2008 2009

26. 0 10 20 30 40 60 70 50 80 90 100 % RESPONSE Bartlett, JA, et al Abst # 586 CROI 2005

27. Outcomes Research

28. The FUTURE: MEDICAL INFORMATICS

31. 8 Year Survival in HAART Era Updated from Chen, et al, 8th CROI, 2001

32. CD4 Count at HAART Initiation

33. Most New Infections Transmitted by Persons who Do Not Know Their Status account for… ~25% Unaware of Infection ~54% New Infections ~75% Aware of Infection ~46% of New Infections Source: G. Marks et al. AIDS 2006

34. <400 <400 <400 >50 000 >50 000 >50 000 400-3499 400-3499 400-3499 3500-9999 3500-9999 3500-9999 10 000-49 999 10 000-49 999 10 000-49 999 TNT: Based on the association of viral load and HIV transmission risk 30 Female-to-Male Transmission Male-to-Female Transmission All subjects 25 20 15 Transmission rate per 100 Person-Years 10 5 0 Viral load (HIV-1 RNA copies/ml) and HIV transmission Quinn TC, et al.NEJM 2000; also Fideli U, et al. AIDS Res Hum Retrovir 2001

35. 2009 WHO model Lancet 2009; 373:48-57

36. 21% of HIV-infected individuals in the U.S. are undiagnosed Role in reducing HIV transmission …don’t forget Engagement Test and Treat Campsmith M et al. MMWR 2008;57:1073-76, Gardner et al. AIDS 2005;19:423-431,Marks et al. AIDS 2006;20: 1447-50, Fleming et al. 9th CROI 2002, abstract 11, Metsch et al. Clin Infect Dis 2008;47:577-584, Cohen at al. Ann Intern Med 2007;146:591-601, Diffenbach & Fauci. JAMA 2009;301:2380-82

37. 33% with known HIV NOT in regular care 24-44% fail to enter care w/in 6 mos. 21% of HIV-infected individuals in the U.S. are undiagnosed Role in reducing HIV transmission …don’t forget Engagement Test and Treat Campsmith M et al. MMWR 2008;57:1073-76, Gardner et al. AIDS 2005;19:423-431,Marks et al. AIDS 2006;20: 1447-50, Fleming et al. 9th CROI 2002, abstract 11, Metsch et al. Clin Infect Dis 2008;47:577-584, Cohen at al. Ann Intern Med 2007;146:591-601, Diffenbach & Fauci. JAMA 2009;301:2380-82

38. New Challenges Identify a Need Emerge Name It Make a plan Celebrate Empower Others to Join You Project CONNECT Client- Oriented New Patient Navigationto Encourage Connectionto Treatment

39. CONNECT: Program Evaluation a Multivariable model controls for age, race, sex, insurance, location of residence and time from call to scheduled visit. Wylie et al. 4th International Conference on HIV Treatment Adherence 2009

40. Mugavero, Davila, Nevin & Giordano; 4th International Conference on HIV Treatment Adherence 2009

41. Missed Visits and Mortality a Cox proportional hazards (PH) analysis also adjusts for sex, insurance, race/ethnicity, depression, anxiety, alcohol abuse, and substance abuse. Mugavero et al. Clin Infect Dis 2009;48:248-56

42. Retention in Care: Challenge to Survival Giordano et al. Clin Infect Dis 2007;44:1493-1499

43. Expanding the Spectrum of Adherence Mugavero. Top HIV Med 2008;16:156-61.

44. Expanding the Spectrum of Adherence Mugavero. Top HIV Med 2008;16:156-61.

45. Summary • Expanded spectrum of HIV adherence • Engagement in care includes distinct steps: Linkage, Retention and Re-engagement • Engagement in care vital for HIV treatment success at individual & population level • Early missed visits may identify patients at risk for poor long-term health outcomes • Engagement worse in groups bearing a disproportionate burden of US HIV epidemic

46. What Can We Do? • Incorporate adherence to care counseling into patient encounters as a matter of routine • Evaluate “no show” phenomenon at the clinic level & revise new patient orientation • Develop partnerships with local HIV testing, clinical & supportive service providers • Integrate HIV testing and linkage activities • Coordinate activities around retention and re-engagement for shared patients

47. Thanks UAB 1917 Clinic Cohort supported by UAB CFAR (P30AI27767), CNICS (R24AI067039), and the Mary Fisher CARE Fund; MJM supported by NIMH (K23MH082641) & CDC