1 Meet the Author Webinar March 15, 2012

2 Ground Rules for Webinar Participation Actively participate and write your questions into the chat area during the presentation(s) Do not put us on hold Mute your line if you are not speaking (press *6, to unmute your line press #6) Slides and other resources are available on our website at incareCampaign.org All webinars are being recorded

3 Agenda Welcome & Introductions, 5min Meet the Author: Dr. Michael Mugavero, 30min Q & A Session, 20min Campaign Next Steps, 5min

4 Michael J. Mugavero, 1 K. Rivet Amico, 2 Andrew O. Westfall, 1 Heidi M. Crane, 3 Anne Zinski, 1 James H. Willig, 1 Julie Dombrowski, 3 Wynne E. Norton, 4 James L. Raper, 1 Mari M. Kitahata, 3 Michael S. Saag 1 1 Department of Medicine, University of Alabama at Birmingham (UAB), 2 University of Connecticut, 3 Department of Medicine, University of Washington, 4 Department of Health Behavior, UAB Supported by grants 1R21AI , 3K23MH S1 and 1R24AI

5 HPTN 052 Press release, May 12, 2011, Cohen et al. N Engl J Med 2011;365 96% reduction in new HIV infections

6 Background  Considerable enthusiasm for ‘test and treat’ or ART treatment as prevention approaches Suppression of plasma HIV viral load (VL) significantly reduces likelihood of transmission  Implicit to TnT success is the need for prompt linkage and sustained retention in HIV care  Numerous initiatives to expand HIV testing and efficacious intervention for linkage exists However, a paucity of evidence for the period immediately following entry to outpatient HIV care Diffenbach & Fauci. JAMA 2009;301, Cohen et al. N Engl J Med 2011;365, Quinn et al. N Engl J Med 2000;342, Gardner et al. AIDS 2005;19

7 Adapted from: Gardner et al. Clin Infect Dis 2011;52, Greenberg et al. Health Affairs 2009;28, Marks et al. AIDS 2010;24 21% Undiagnosed31% Not linked / delayed41% Not retained19% VL<50 c/mL

8 Ulett et al. AIDS Pt Care STDS 2009;23, Mugavero et al. Clin Infect Dis 2011;52(S2) Blueprint for HIV treatment success

9 Background  The first year in outpatient HIV medical care is a dynamic, formative & vulnerable time  Poor early retention in care associated with: Delayed / failed antiretroviral therapy (ART) receipt Increased sexual risk transmission behaviors Increased risk of long-term adverse clinical events  This study: early retention & VL suppression Evaluation of both time to plasma VL suppression and cumulative VL burden Ulett et al. AIDS Pt Care STDS 2009;23, Giordano et al. JAIDS 2003;32, Metsch et al. Clin Infect Dis 2008;47, Mugavero et al. Clin Infect Dis 2009;48, Giordano et al. Clin Infect Dis 2007;44

10 Methods  Hypotheses: Early missed clinic visits associated with delayed plasma HIV VL suppression Greater cumulative VL burden over first 2 years in HIV medical care among patients with worse early retention in care  Design: Cohort study supported by CNICS UAB 1917 Clinic Cohort (BHM, AL) and UW HIV Cohort (Seattle, WA) Kitahata et al. Int J Epi 2008;37

11 Methods  Study period: January 2007 – October 2010  Eligibility criteria: Initial outpatient HIV care visit during study period No previous outpatient HIV medical care at another treatment facility For analyses of cumulative VL burden, ≥2 years potential f/u from initial visit and no gap ≥12 months between VL measures

12 Mugavero, Davila, Nevin & Giordano. AIDS Pt Care STDs 2010;24 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

13 Methods  Principal outcomes & exposures of interest: Time to VL suppression (<50 copies/mL) Time-varying count of “no show” visits Cumulative VL burden: viremia copy-years (VCY) Visit adherence: Proportion of kept / scheduled visits  Statistical analyses: Time to VL suppression: KM plots, Cox PH models 2-year VCY: ANOVA, linear regression & ANCOVA MV models: demographic, clinical & site variables Sensitivity analyses: pts w/ initial CD4 <350 cells/mL Cole et al. Am J Epidemiology 2010;171, Mugavero, Davila, Nevin & Giordano. AIDS Pt Care STDs 2010;24

14 Methods: Viremia Copy-Years (VCY)

15 Methods: Viremia Copy-Years (VCY)

16 Methods: Viremia Copy-Years (VCY)  Estimate of cumulative HIV burden over time  Example: 10,000 copy-years 1,000 c/mL per day for 10 years 10,000 c/mL per day for 1 year  VCY approximated as time-weighted sum using trapezoidal rule: Cole et al. Am J Epidemiology 2010;171

17 Methods: Viremia Copy-Years (VCY) Cole et al. Am J Epidemiology 2010;171

18 Characteristic Overall sample (N=676) Age (years) 35.8 ± 10.8 Non-white female Non-white male White female White male 88 (13%) 289 (44%) 31 (5%) 253 (38%) Private insurance Public insurance Uninsured 245 (38%) 174 (27%) 232 (36%) UAB 1917 clinic UW Harborview clinic 417 (62%) 259 (38%) Baseline plasma HIV VL (log 10 c/mL)4.56 (0.97) Baseline CD4 count (cells/  L) 337 ± 255 Zero “no show” visits One “no show” visit ≥ Two “no show” visits 363 (54%) 144 (21%) 169 (25%) Initiate antiretroviral therapy536 (79%) Achieve plasma HIV VL <50 c/mL425 (63%) 2-year visit adherenceN/A 2-year VCY(log 10 copy x years/mL)N/A Data presented as n (%) or mean ± standard deviation

19 Characteristic Overall sample (N=676) Sample w/ 2-years f/u (N=258) Age (years) 35.8 ± ± 10.3 Non-white female Non-white male White female White male 88 (13%) 289 (44%) 31 (5%) 253 (38%) 31 (12%) 109 (43%) 15 (6%) 99 (39%) Private insurance Public insurance Uninsured 245 (38%) 174 (27%) 232 (36%) 96 (40%) 62 (26%) 83 (34%) UAB 1917 clinic UW Harborview clinic 417 (62%) 259 (38%) 147 (57%) 111 (43%) Baseline plasma HIV VL (log 10 c/mL) 4.56 ± ± 0.94 Baseline CD4 count (cells/  L) 337 ± ± 250 Zero “no show” visits One “no show” visit ≥ Two “no show” visits 363 (54%) 144 (21%) 169 (25%) 80 (31%) 53 (21%) 125 (48%) Initiate antiretroviral therapy536 (79%)224 (87%) Achieve plasma HIV VL <50 c/mL425 (63%)208 (81%) 2-year visit adherenceN/A0.84 ± year VCY(log 10 copy x years/mL)N/A4.31 ± 0.76 Data presented as n (%) or mean ± standard deviation

20 Characteristic Unadjusted HR (95% CI) Adjusted HR (95% CI) “No show” visits (per additional “no show”)0.91 (0.83, 0.98)*0.83 (0.76, 0.92)** Age (per 10 years)1.01 (0.92, 1.10)0.92 (0.84, 1.02) Non-white Female Non-white Male White Female White Male 0.82 (0.58, 1.14) 1.24 (1.01, 1.53)* 0.73 (0.44, 1.20) (0.53, 1.09) 1.10 (0.88, 1.37) 0.91 (0.55, 1.52) 1.0 Private insurance Public insurance Uninsured 1.28 (1.02, 1.61)* 1.09 (0.85, 1.40) (1.08, 1.73)** 1.17 (0.88, 1.56) 1.0 Baseline plasma HIV VL (per 50,000 c/mL)1.01 (1.00, 1.03)0.97 (0.96, 0.99)** Baseline CD4 count <200 cells/mL Baseline CD4 count cells/mL Baseline CD4 count >350 cells/mL 2.97 (2.35, 3.76)** 2.73 (2.12, 3.50)** (2.82, 4.93)** 2.96 (2.26, 3.86)** 1.0 Table. Factors associated with more expeditious suppression of plasma HIV RNA (<50 c/mL) among 676 HIV-infected patients initiating outpatient HIV medical care; UAB 1917 and UW Harborview Clinics, Jan 2007 – Oct 2010 Hazard ratio: HR, 95% Confidence interval: 95% CI. * P<0.05, ** P<0.01 Unadjusted and adjusted Cox PH models. Adjusted model controls for variables included in table and site.

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22 Characteristic Adjusted β (95% CI) Visit adherence (β per 10%)-0.11 (-0.17, -0.04)** Age (per 10 years)0.04 (-0.06, 0.13) Non-white female Non-white male White female White male (-0.37, 0.25) 0.13 (-0.08, 0.34) 0.10 (-0.29, 0.49) Ref Private insurance Public insurance Uninsured (-0.27, 0.17) 0.08 (-0.33, 0.18) Ref Baseline CD4 count <200 cells/  L Baseline CD4 count cells/  L Baseline CD4 count >350 cells/  L (-0.24, 0.21) (-0.40, 0.08) Ref Table. Factors associated with 2 year log 10 VCY among 258 patients initiating outpatient HIV care; UAB 1917 & UW Harborview Clinics, Jan 2007 – Oct % Confidence interval: 95% CI. * P<0.05, ** P<0.01 ANCOVA model controls for variables included in table and site

23 Figure. Relationship between 2 year visit adherence and viremia copy-years (VCY) among 258 patients initiating outpatient HIV care; UAB 1917 & UW Harborview Clinics, Jan 2007 – Oct 2008 Visit adherence 0-79% (n=83): mean VCY=143,038; 80-99% (n=95): mean VCY=56,894; 100% (n=80): mean VCY=35, %CI generated by repeated measures ANOVA

24 Conclusions  Early retention in HIV care associated with: Faster time to viral load suppression (<50 c/mL) and Lower 2-year cumulative viral load burden (VCY)  Each “no show” clinic visit conveyed a 17% increased risk of delayed VL suppression  Significantly greater 2-year VCY accumulated among patients with worse visit adherence Four-fold increase in mean VCY among patients with 0-79% vs. 100% visit adherence

25 Limitations  Observational study: cannot ascribe causality due to potential for uncontrolled confounding  Heterogeneity in number and timing of VL measures may result in imprecision in VCY Prior VCY studies using IPW to account for heterogeneity yielded similar findings to 1 o analyses  As ART receipt, persistency and adherence on causal pathway, not evaluated in this study Future studies with all 8 CNICS sites planned using methods of causal inference

26 Implications  Early retention in HIV care associated with time to VL suppression and cumulative HIV burden  Others identified 50% reduced odds of sexual risk behavior in pts w/ better early retention  Clear implications of early retention for HIV prevention, esp. in context of ‘test & treat’  Interventions needed for the vulnerable period immediately following entry into care Metsch et al. Clin Infect Dis 2008;47

27 “Significant barriers impede the efficient movement of a patient infected with HIV from diagnosis to care…As with voluntary testing, a public health–systems research agenda will be needed to define efficient and effective means of entering and retaining patients in care”

28 Our next steps: Integrated studies to assess risk behaviors during short-duration VCY segments, and in relation to other modifiable factors

29 Acknowledgments K. Rivet Amico Andrew O. Westfall Heidi M. Crane Anne Zinski James H. Willig Julie Dombrowski Wynne E. Norton James L. Raper Mari M. Kitahata Michael S. Saag Supported by grants 1R21AI , 3K23MH S1 and 1R24AI Stephen R. Cole Sonia Napravnik Joseph J. Eron Bryan Lau Thomas P. Giordano UAB & UW patients UAB & UW cohort teams CNICS staff

30 Questions?

31 Campaign Headquarters: National Quality Center (NQC) 90 Church Street, 13 th floor New York, NY Phone incareCampaign.org youtube.com/incareCampaign