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

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

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

Translational Research

M Saag, UAB

Piatak, et al, Science, 1993

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

At steady state, when an actively producing cell dies, it is replaced by how many newly infected cells? 1.One 2.Twenty – Five 3.One Hundred 4.One Thousand 5.It depends on the viral load

M Saag, UAB

VL = 100,000

VL < 50

Clinical Trials

Slide #24 How Did We Get Here? Sequential exposure to effective monotherapy in a population of largely adherent, aggressively treated patients created a cohort of individuals with highly-resistant HIV ZDV NVP 3TC EFV LPV ddI SQVRTV ABC TDF d4T IDVNFV

Slide #25 New HAART Era After years of sequential monotherapy many patients with MDR are now entering a period where more than one new medication may be readily available T20 TPVDRV Maraviroc, Raltegravir Etravirine

Slide # % RESPONSE Bartlett, JA, et al Abst # 586 CROI 2005

Outcomes Research

MEDICAL INFORMATICS The FUTURE:

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

CD4 Count at HAART Initiation Median CD4 % CD4 < % % % % % % % % % Median CD4 % CD4 < % % % %

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

TNT: Based on the association of viral load and HIV transmission risk Viral load (HIV-1 RNA copies/ml) and HIV transmission Transmission rate per 100 Person-Years < > Quinn TC, et al. NEJM 2000; also Fideli U, et al. AIDS Res Hum Retrovir 2001 < > < > All subjects Male-to-Female Transmission Female-to-Male Transmission

Lancet 2009; 373: WHO model

Slide #36 Test and Treat 21% of HIV-infected individuals in the U.S. are undiagnosed Role in reducing HIV transmission Campsmith M et al. MMWR 2008;57: , Gardner et al. AIDS 2005;19: , Marks et al. AIDS 2006;20: , Fleming et al. 9th CROI 2002, abstract 11, Metsch et al. Clin Infect Dis 2008;47: , Cohen at al. Ann Intern Med 2007;146: , Diffenbach & Fauci. JAMA 2009;301: …dont forget Engagement

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

Slide #38 Celebrate Make a plan Identify a Need Name It Empower Others Join You to Emerge Challenges New Client- Oriented New Patient Navigation to Encourage Connection to Treatment Project CONNECT

Slide #39 CONNECT: Program Evaluation Time PeriodNo ShowUnadjusted OR (95%CI) Adjusted OR (95%CI) a Pre-CONNECT (n=522) Post-CONNECT (n=361) 30.7% 17.7% ( ) ( ) a Multivariable model controls for age, race, sex, insurance, location of residence and time from call to scheduled visit. Wylie et al. 4 th International Conference on HIV Treatment Adherence 2009

Slide #40 Mugavero, Davila, Nevin & Giordano; 4th International Conference on HIV Treatment Adherence 2009 Missed Visits Appt. Adherence Visit Constancy Gap in Care HRSA HAB Measure Patient AYes; 180%100%NoYes Patient BYes; 433%50%Yes Patient CNo; 0100%75%NoYes Patient DYes; 167%25%YesNo

Slide #41 Missed Visits and Mortality CharacteristicHR (95%CI) a Missed visit in 1 st year2.90 ( ) Age (HR per 10 years)1.58 ( ) CD4 count <200 cells/mm ( ) Log 10 plasma HIV RNA1.02 ( ) ART started in 1 st year0.64 ( ) 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

Slide #42 Retention in Care: Challenge to Survival Giordano et al. Clin Infect Dis 2007;44: Quarters w/ visit (Visit Constancy) N (%) of Sample Adjusted HR (95%CI) for Mortality (64%)1.0 (Referent) 3479 (18%)1.41 ( ) 2286 (11%)1.68 ( ) 1169 (7%)1.94 ( )

Slide #43 Expanding the Spectrum of Adherence Mugavero. Top HIV Med 2008;16:

Slide #44 Expanding the Spectrum of Adherence Mugavero. Top HIV Med 2008;16:

Slide #45 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 Summary

Slide #46 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 What Can We Do?

Slide #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