1. Paul E. Sax, MD Professor of Medicine Harvard Medical School Clinical Director Brigham and Women’s Hospital Infectious Diseases Practical Strategies to Engage HIV Patients in Timely Care This program is supported by an educational grant from Image: Polka Dot Images/Copyright©2013 Thinkstock. All Rights Reserved

2. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care Faculty and Disclosures Paul E. Sax, MD Clinical Director HIV Program and Division of Infectious Diseases Brigham and Women’s Hospital Professor of Medicine Harvard Medical School Boston, Massachusetts Paul E. Sax, MD, has disclosed that he has received consulting fees from Bristol-Myers Squibb, Gilead, GlaxoSmithKlein, Janssen, and Merck and other grant support from Bristol-Myers Squibb, Gilead, and GlaxoSmithKlein.

3. Please review the slide notes for analysis of each study by expert faculty Paul E. Sax, MD

4. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care DHHS Definition: Early HIV Infection  Acute HIV infection is the phase of HIV disease immediately after infection during which the initial burst of viremia in newly infected patients occurs; anti-HIV antibodies are undetectable at this time, while HIV RNA or p24 antigen are present.  Recent infection generally is considered the phase up to 6 months after infection, during which anti-HIV antibodies are detectable.  Early HIV infection is the phrase used to refer to either acute or recent HIV infection. DHHS Guidelines. February 2013.

5. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care HIV Disease: Acute Infection Plasma viral titer by PCR or bDNA assay Number of CD+4 cells 10 6 10 5 10 4 10 3 10 2 10 1 1400 1200 1000 800 600 400 200 Plasma Viremia CD4 + Cell Count 12910 Time (Yrs)

6. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care FDA-Approved HIV Antibody Tests: Diagnosing HIV Infection a Reactive/positive specimens must be confirmed by Western blot or immunofluorescence. b Enzyme immunoassay (EIA) test method. c OraSure test. d 6 FDA-approved tests available. e 8- to 12-wk “window” after infection. Beckwith C, et al; Centers for Disease Control and Prevention. HIV Testing Implementation Guidance for Correctional Settings. Atlanta, GA: Centers for Disease Control and Prevention, US Department of Health & Human Services: January 2009:1-38.

7. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care Diagnostic Tests for Acute HIV Infection  HIV RNA (“viral load”) is test of choice –More sensitive than p24 Ag –Turns positive 10-15 days after HIV acquired (“eclipse” period) –Result very high (> 100,000 copies/mL) –False-positives may occur with low-level results (< 5,000 c/mL)  HIV Antibody –Window period with current tests averages 2-3 wks –Combined antibody/antigen test reduces window period further –Patients may still be symptomatic with Ab + –Western blot may be negative or indeterminate Ann Intern Med 2001;134:25. AIDS 2003;14:1871-9. Ann Intern Med 1999; 130:37. J Infect Dis 2004;190:598-604. J Acquir Immune Defic Syndr 2010;55:S102–S105.

8. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care The Problem of False-Negative Western Blot Tests Branson. J Acquir Immune Defic Syndr. 2010;55:S102–S105. Days Before Western Blot Positive 25201510 50 -2 RNA 4th-generation Ag/Ab assay 3rd-generation CIA 3rd-generation EIA Flow-through rapid testWB IndeterminateLateral flow rapid test 2nd-generation EIA WB positive 1st-generation EIA

9. EPIDEMIOLOGY

10. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care Diagnoses of HIV Infection Among Adults and Adolescents by Transmission Category, 2011: United States and 6 Dependent Areas N = 50,007 Male-to-male sexual contact Injection drug use – Males Injection drug use – Females Male-to-male sexual contact and IDU Heterosexual contact a – Males Heterosexual contact a – Females Other b < 1% 3% 5% 10% 18% 62% Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically adjusted to account for reporting delays and missing transmission category, but not for incomplete reporting. a Heterosexual contact with a person known to have, or to be at high risk for, HIV infection. b Includes hemophilia, blood transfusion, perinatal exposure, and risk factor not reported or not identified.

11. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care Diagnoses of HIV Infection Among Adults and Adolescents by Sex and Race/Ethnicity, 2011: United States and 6 Dependent Areas Males N = 39,495 Females N = 10,512 2% <1% American Indian/Alaska Native Asian Black/African American Hispanic/Latino a Native Hawaiian/other Pacific Islander White Multiple races 42% 30% 23% 1% <1% 63% 17% Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically adjusted to account for reporting delays but not for incomplete reporting. a Hispanics/Latinos can be of any race.

12. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care HIV in the United States Overall HIV Prevalence 1  HIV+ population in the United States –1,106,400  HIV+ and unaware of their diagnosis –232,700 (21%) –Source of > 50% of new infections New Infections and Total Number of People Living With HIV: 1980-2010 2 1. Campsmith M, et al. J Acquir Immune Defic Syndr. 2010 Apr;53:619-24. 2. CDC Fact Sheet. New HIV Infections in the United States. 2012. 1,200,000 1,000,000 800,000 600,000 400,000 200,000 19801983 198619891992199519982001 200420072010 People living with HIV New HIV infections using back-calculation methodology New HIV infections using original incidence surveillance methodology New HIV infections using updated incidence surveillance methodology

13. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care US Trends in HIV Testing: 2000-2010  Identification of HIV infection through testing acts as an entry to social services and healthcare –Associated with improved outcomes, including survival; in 2010: –19% of HIV-infected unaware of infection –32% progressed to AIDS within 1 yr of diagnosis, indicating long-standing infection –Suppression of HIV-1 RNA associated with reduced morbidity/mortality and HIV transmission  National HIV/AIDS Strategy and the Division of HIV/AIDS Prevention Strategic Plan –Increase knowledge of serostatus to 90% by 2015 (currently at 79%)  Adults without reported risk ever tested increased from 36.6% in 2000 to 45% in 2010 CDC. HIV testing trends in the United States, 2000-2011. 2013.

14. Testing and the Initiation of Care

15. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care Importance of Testing and the Initiation of Therapy in Tx-Naive Patients  Early initiation of therapy is a fundamental recommendation of DHHS 2013 guidelines –Currently, median CD4+ cell count at diagnosis < 350 cells/mm 3 –Recommendations intended to reduce disease progression and prevent transmission  ART is indicated regardless of baseline CD4+ cell count –Strength of recommendation depends upon CD4+ cell count at diagnosis  HIV diagnoses more often delayed in nonwhites, IDUs, and older patients DHHS Guidelines. February 2013.

16. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care Knowing HIV+ Status Reduces High-Risk Behavior  Meta-analysis of sexual behavior studies in patients aware and unaware of their HIV infection –High-risk sexual behavior declined significantly (68%) after learning of HIV status –Unprotected anal or vaginal (UAV) intercourse with seronegative partners –Analysis limited by unknown number of partners at risk, self- reported sexual behaviors, UAV differences may not reflect actual transmission rates Marks G, et al. J Acquir Immune Defic Syndr. 2005;39:446-453.

17. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care Barriers to Implementing Testing  Systemic Barriers –Survey of Washington state providers 1 –Only 5% (11/221) routinely offer HIV testing –57% (119/221) perceived their patient population at low risk –Legislative 2 –Requiring separate consent form may reduce testing –Continued use of “opt-in” policies –Limited funding for testing  Patient-Based Barriers 3 –Most common reason: fear –Lack of awareness of: –Improved treatment options –Personal risk –Availability of low-cost/free care 1. Shirreffs A, et al. PLoS ONE. 2012;7: e44417. 2. Ping D, et al. Sex Transm Dis. 2011;38:858-864. 3. Schwarcz S, et al. AIDS Care. 2011;23:892-900.

18. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care Strategies to Overcome Testing Barriers  Systemic approaches 1 –Expand “opt-out” testing programs –No separate consent form requirement –Educate practitioners on current testing guidelines –Increase public health funding for testing –Increase healthcare access/utilization –Expand rural outreach  Patient education 2 –Risk for serodiscordant couples –Behavioral risk factors –Testing privacy policies –Messaging: –Effective, tolerable treatments –Low-income assistance programs 1. Ping D, et al. Sex Transm Dis. 2011;38:858-864. 2. Schwarcz S, et al. AIDS Care. 2011;23:892-900.

19. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care When to Start Therapy: View in Early 2000s  Drug toxicity  Preservation of limited Rx options  Risk of resistance (and transmission of resistant virus) Delayed ART

20. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care When to Start Therapy: Balance Now Favors Earlier Antiretroviral Therapy  Drug toxicity  Preservation of limited Rx options  Risk of resistance (and transmission of resistant virus)  ↑ potency, durability, simplicity, safety of current regimens  ↓ emergence of resistance  ↓ toxicity with earlier therapy  ↑ subsequent treatment options  Risk of uncontrolled viremia at all CD4+ cell count levels  ↓ transmission Early ARTDelayed ART

21. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care Considerations for Initiating ART in Treatment-Naive Patients  Lasting viral suppression improves immune function, prolongs and improves quality of life, and reduces complications due to AIDS-defining and non- AIDS  defining diseases  Pts must be ready, willing, and able to commit to treatment –Exhibit an understanding of risks and benefits of therapy –Importance of adherence  Choice to defer therapy may be made by pts or providers due to clinical and/or psychosocial issues DHHS Guidelines. February 2013.

22. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care Early ART Limits HIV Reservoir in Long-lived Central Memory T Cells (T CM )  Infected T CM act as HIV reservoir and inhibit cure, contributing to HIV persistence –ART during acute HIV infection may limit reservoir seeding  Pts (N = 68) with acute HIV infection (Fiebig stage I-III) evaluated for 96 wks after ART initiation –90% of pts undetectable HIV DNA in PBMCs after 1 yr –Findings mimic characteristics of elite and posttreatment controllers –Reservoir size low and primarily in transitional and effector CD4+ T cells Ananworanich J, et al. 20th CROI meeting. Atlanta, GA: 2013. Abstract 47.

23. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care Early ART Enhances Recovery of CD4+ Cell Counts  HIV-1-infected pts (N = 468) followed for 48 mos Median time to CD4+ < 500 in those not treated: 12 mos  64% of pts treated ≤ 4 mos after infection achieved CD4+ cell count ≥ 900 cells/mm 3 –34% in those deferring therapy  Early ART resulted in higher final CD4+ cell counts Le T, et al. N Engl J Med. 2013;368:218-230. CD4+ Cell Count at ART Initiation Group (Est. Time to ART Initiation After HIV Infection [mos]) High (> 500 cells/mm 3 )1 (≤ 4); 2 (4-12); 3 (> 12) Low (< 500 cells/mm 3 )4 (≤ 4); 5 (4-12); 6 (> 12) 100 80 60 40 20 0 0 1224 36 48 CD4+ ≥ 900 Cells/mm 3 (% of Participants) Months Since Initiation of ART Group 2 Group 1 Group 3 Group 4 Group 5 Group 6

24. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care Nadir CD4+ May Increase Risk for Both HIV and non-HIV Complications  Lower CD4+ nadir identified as: –A predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy 1 –Independently associated with worsening endothelial function if < 350 cells/mL 2 –Stronger predictor than current CD4+ cell count –An independent risk factor for greater BMD decrease during first 96 weeks after ART initiation 3 1. Ellis R, et al. AIDS. 25:1747-1751. 2. Ho JE, et al. CROI 2012. Abstract 813. 3. Grant P, et al. CROI 2013. Abstract 823.

25. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care Early ART Reduces Risk of Transmission  Early ART associated with 96% reduction of sexual HIV transmission in serodiscordant couples  Linked HIV transmissions to HIV- negative partner (n = 28) –Early therapy (n = 1): 0.1/100 PYs –Delayed therapy (n = 27): 7/100 PYs  Median follow-up: 1.7 yrs  HIV-1 RNA < 400 copies/mL –Early ART: 90% –Delayed ART: 93% Cumulative Probability Linked HIV Transmission Early ART Delayed ART Cohen MS, et al. N Engl J Med. 2011;365:493-505. Years HR: 0.04 (95% CI 0.01-0.27; P <.001) 0.2 0.15 0.1 0.05 0 012345

26. HIV Care Access and Retention

27. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care HIV Care Cascade: Local Influence King County, Washington vs US Dombrowski J, et al. 20 th CROI. Atlanta, 2013. Abstract 1027. People Living With HIV/AIDS (%) HIV Diagnosed 25% 57% Linked to Care Retained in Care Prescribed ART HIV-1 RNA < 200 Copies/mL 81% 85% 65% 78% 71% 31% 37% 66% US (2009; n = 1,148,200) King County (2011, n = 7169) King County estimates account for in- and out-migration of persons living with HIV/AIDS. Linkage to care: CD4/HIV-1 RNA report or confirming a completed medical appointment. 100 80 60 40 20 0

28. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care HIV Care Cascade: Steady-State Evolution British Columbia, Canada People Living With HIV/AIDS (%) 2% 32% Linked to Care Retained in Care Prescribed ART HIV-1 RNA Suppressed 53% 86% 46% 79% 55% ~ 20% ~ 30% 43% 1996 2009 HIV RNA suppressed: 1996 (< 500 copies/mL), 2009 (< 50 copies/mL). Montaner J, et al. 20 th CROI. Atlanta, 2013. Abstract 1029. HIV Care in Canada: Single-Payer Health Service, Free Access to ART (1996-2010) 100 80 60 40 20 0 HIV Diagnosed

29. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care HIV Care Cascade: Implications of Multiple Studies  Critical to analyze different methodologies –How is population defined? –What is the denominator of interest?  Local HIV care cascades may provide more useful information than national data  Goal of studies should be to improve delivery of care Howard A and Williams I. Discussants. 20 th CROI. Atlanta, 2013. Session 31.

30. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care Access to Care Starts With Testing: Current CDC Testing Guidelines  All patients should be screened for HIV –Follow an “opt-out” screening model  Annual testing for high-risk groups  Separate written consent for HIV testing should not be required  Pretest counseling should not be required with HIV diagnostic testing or as part of HIV screening programs in healthcare settings  Last updated, September 2006 CDC. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5514a1.htm. Accessed March 26, 2013.

31. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care ARTAS: Case-Management Linkage Intervention  Goal: facilitate entry into HIV care  Intensive, short duration, time limited –Up to 5 sessions with ARTAS case manager within 90 days –Clients transitioned to ongoing Ryan White case management –Compared with SOC passive referral to HIV provider  Interventions client centered/strengths based –Strengths assessment –Individual goal setting –Fostered empowerment and self-efficacy Craw JA, et al. J Acquir Immune Defic Syndr. 2008;47:597-606.

32. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care ARTAS-II (Community-Based Intervention): Summary of Findings  79% (497/626) entered medical care within first 6 mos –Comparable to results of ARTAS-I trial (university setting) –Higher than previous CDC and HRSA “in care” estimates –Sites with HIV care providers located in the same building or complex where case management intervention was delivered had highest percentage of participants entering into care within 6 mos (P <.00001)  On average, time needed to link patients to care was moderate –Median number of case management sessions: 2 (mean: 2.3) –Median time spent per client: 5.8 hrs (mean: 7.2 hrs) Craw JA, et al. J Acquir Immune Defic Syndr. 2008;47:597-606.

33. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care SPNS Model for Opportunities to Improve Adherence to Care Rajubiun S, et al. AIDS Patient Care STDS. 2007;21(suppl 1):S9-S19. Interventions to Engage in Care Interventions to Prevent Falling Out of Care Persons Unstable in Care Persons in Care Pivotal Points Opportunities

34. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care Techniques Used to Improve Retention  Case management (eg, strengths model)  Clinic appointment reminders  Help with appointment scheduling and rescheduling  Service coordination via a “system navigator” or “buddy”  Mental health counseling and treatment  Substance abuse counseling and treatment  Housing assistance  Food and nutrition support  Transportation

35. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care Components of Improved HIV Care  Care coordination and communication –Nonjudgmental, supportive, culturally sensitive  Multidisciplinary team addressing housing, insurance, financial issues, and emotional support (eg, peer educators) –Team includes but not limited to nurses, nutritionists, social workers, case managers  Primary-care practitioner coordinates all aspects of care  Individual office visits should be timed to allow thorough evaluation –Issues identified should be address at that visit –Co-locate laboratory, mental health, medical services Bidwell R. Available at http://hab.hrsa.gov/deliverhivaidscare/clinicalguide11/. Accessed June 5, 2013.

36. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care “You Are Not Alone”: Improving Motivation and Reducing Social Isolation Peer Educators  Trained HIV-infected individuals  Provide unique, patient- centered approach  Often “seasoned” pts motivated to help others  Reduce anxiety in newly diagnosed and still adjusting pts Patient Advisory Groups  “Voice of the people” in the clinic  Program takes input seriously to improve delivery of care  Individualized educators  Allows pts to act as a cohesive unit  Often required for program funding Bidwell R. Available at http://hab.hrsa.gov/deliverhivaidscare/clinicalguide11/. Accessed June 5, 2013.

37. clinicaloptions.com/hiv Practical Strategies to Engage HIV Patients in Timely Care Now Take the Test...  To earn CME credit for this activity, please click the “Claim Credit” button on the right of your screen

38. Go Online for More Educational Programming on Retention in Care! Downloadable slideset Online Textbook inPractice — HIV Special Considerations in the Management of HIV-Infected Patients From Minority Communities: Challenges to Treating Minorities Living With HIV/AIDS CME Topic — Improving Engagement for HIV Patients in Primary Care clinicaloptions.com/firstline2013