1. Clinical Care: 2010 Institute of Medicine Committee on HIV Screening and Access to Care Michael Saag, MD, FIDSA University of Alabama, Birmingham Director, Center for AIDS Research Chair, HIV Medicine Association (HIVMA)

2. Survival Data – Years After AIDS Diagnosis MMWR Weekly June 2, 2006 / 55(21);589-592

3. 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 1996 1997 1998 1999 2000 ZDV NVP 3TC EFV LPV ddI SQVRTV ABC TDF d4T IDVNFV

4. 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 2004 2005 2006 2007 2008 2009 T20 TPVDRV Maraviroc, Raltegravir Etravirine

5. Improved Life Expectancy with Modern ARV Therapy Hogg, et al. Lancet, 2008

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

7. CD4 Count at HAART Initiation Median CD4 % CD4 < 200 1996115 62.8% 1997180 53.8% 1998221 47.8% 1999212 49.3% 2000197 50.1% 2001277 39.5% 2002210 48.8% 2003220 47.2% 2004207 49.1% Median CD4 % CD4 < 200 2005278 39.6% 2006300 35.4% 2007296 35.2% 2008310 29.4%

8. Key Point: Many (? Most) HIV infected patients in the US dont know they are infected Universal, opt-out testing is needed

9. Slide 9 When To Start Treatment? – Summary of Current Guidelines Guidelines symptoms or CD4 <200 CD4 200- 350 CD4 >350 IAS-USA: JAMA 2008 treat Therapy should be considered and decision individualized DHHS: <www.aidsinfo. nih.gov> treat treat* * Split opinion > 500 symptoms

10. Slide 10 Cohort Study Results (NA-ACCORD / ART-CC) Consequences of unchecked viral replication (Inflammation / Harm) Improved tolerability / convenience of newer ARV regimens Treatment reduces transmission of HIV Cost Savings Reasons for Earlier Initiation of Therapy

11. Slide 11 Inverse Probability Weighted Cox Regression Multivariate Analysis *Stratified by Cohort and Year Relative Hazard (RH)* 95% Confidence Interval P-value Deferral of HAART at 351-5001.71.4, 2.1<0.001 Female Sex1.10.9, 1.50.290 Older Age (per 10 years)1.61.5, 1.8<0.001 Baseline CD4 count (per 100 cells/mm 3 ) 0.90.7, 1.00.083 Results were similar when restricting the analysis to the 77% of participants with baseline HIV RNA data Adjusted RH for deferral vs. immediate treatment was also 1.7 95% C.I. 1.4, 2.2; p <0.0001 HIV RNA was not an independent predictor of mortality

12. Slide 12 Relative Time on Treatment… 30 35 40 45 50 55 60 65 70 AGE (years) CD4 650/ul CD4 500/ul 40 years on Rx35 years on Rx 5 years

13. Slide 13 Relative Time on Treatment… 30 35 40 45 50 55 60 65 70 AGE (years) CD4 650/ul CD4 500/ul 40 years on Rx35 years on Rx 5 years HARM?

14. Slide 14 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

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

16. Slide 16 Prevention of Transmission TEST and TREAT –Testing and Linkage to Care (TLC+) National AIDS Strategy…

17. ARV Receipt Retention in Care Outcome s HIV Dx Linkage to Care ARV Adherence Adapted from: Giordano et al. Curr HIV/AIDS Rep 2005;2:177-183, Samet et al. AIDS 2001;15:77-85, Eldred & Malitz. AIDS Pt Care STDs 2007;21:S1-2; Tobias et al. AIDS Pt Care STDs 2007;21:S3-8 Blueprint for HIV Treatment Success Adherence research has traditionally focused on ARV medications Growing interest in expanding HIV adherence to include linkage & retention in care

18. ARV Receipt Retention in Care Outcome s HIV Dx Linkage to Care ARV Adherence Expanding the spectrum of adherence 25% of HIV-infected individuals in the U.S. are undiagnosed 20-40% of newly diagnosed pts. fail to establish care w/in 6 mos. One-third of pts. w/ known HIV infection are not engaged in care Glynn & Rhodes. National HIV Prevention Conference 2005, Abstract 595, Gardner et al. AIDS 2005;19:423-431, Mugavero et al. Clin Infect Dis 2007;45:127-130, Fleming et al. 9th CROI 2002, abstract 11

19. Mean Annual Total Patient Costs by CD4 Count (cells/ul)

20. Mean Annual Total Patient Costs by Component

21. CD4 strata (cells/ L) TotalARVNon- ARV HospitalOther Outpt. Physician/c linic < 50$36,532$10,885$14,882$8,353$1,909$533 50-199$23,864$11,862$6,685$3,369$1,416$532 200-349$18,274$11,935$3,452$1,186$1,365$336 > 350$13,885$9,407$1,855$1,408$930$285 All $18,640 $10,500$4,240$2,342$1,199$359 Patients with CD4 counts 350 (P<0.001) Overall expenditures

22. Change in clinical status $0 $5,000 $10,000 $15,000 $20,000 $25,000 $30,000 $35,000 $40,000 $45,000 CD4 <50 CD4 50-199CD4 200-349CD4 >=350 CD4 Category (cells/ul) Mean Annual Cost CD4 Declined CD4 Unchanged CD4 Improved * * * * P=0.003

23. Major Focus of Appropriations: Provision of medications The majority of the new dollars in the current iteration of the RW appropriation of the Presidents budget is targeted for Part B Over the last 8 years most increases in the RW Care Act have gone to ADAP

24. Policy implications Provision of antiretroviral and other essential medications Funding for ADAPs

25. Reality Check Operating budget of our clinic: $4.2 M / yr (1800 active pts) Third party payment ~ $ 800,000/yr RW Title III $495,000/yr –Flat Funded for > 10 years –2.5% cut in 2006 –Despite 120% increase in patient volume over last 8 years Part B funds ~ $1.0 M since 2007 Annual Deficit ~ $1.8 M per year

26. Key Points Mortality is much higher when patients are diagnosed late in the course of infection (CD4 < 200 /ul) The majority (> 50%) of newly diagnosed patients are diagnosed late (except preg Women) Many (? Most) HIV infected patients in the US dont know they are infected Universal, opt-out testing is needed With more universal testing, a 25 -50% increase in patient volume will occur

27. Who will take care of these patients ?

28. Policy implications Provision of antiretroviral and other essential medications –Funding for ADAPs Need dramatic increase in funding to increase clinic capacity Increase Part C funding Provide incentives for younger MDs to go into HIV Medicine

29. Provision of medications Every American who needs HIV treatment and care should have access to it People who are HIV-positive need essential medications Without the drugs, providing care is difficult to impossible PACHA. Achieving and HIV-Free Generation; IDSAnews 2006;16(1):7

30. Provision of HIV CARE Every American who needs HIV treatment and care should have access to it People who are HIV-positive need essential medications Without the drugs, providing care is difficult to impossible Without qualified HIV care providers and clinics, HIV drugs mean nothing PACHA. Achieving and HIV-Free Generation; IDSAnews 2006;16(1):7

31. EDITORIAL COMMENTARY Which Policy to ADAP-T: Waiting Lists or Waiting Lines? Michael S. Saag University of Alabama at Birmingham Center for AIDS Research Clinical Infectious Diseases 2006;43:1365-1367 © 2006 by the Infectious Diseases Society of America. All rights reserved.

32. Thanks UAB 1917 Clinic Cohort supported by UAB CFAR (grant P30-AI27767), CNICS (grant 1 R24-AI067039-1), and the Mary Fisher CARE Fund