1. Washington D.C., USA, 22-27 July 2012www.aids2012.org Treatment as Prevention: It is complex: Let us work on it Kenneth H. Mayer Fenway Health Beth Israel Deaconess Hospital Harvard Medical School Boston, Mass July 23 rd, 2012 Session Room 2

2. Is Treatment as Prevention Utopian?

3. Percentage of women and men who received an HIV test and test results in last 12 months, 2003–2010 (WHO/UNAIDS) Most PLHIV are unaware that they are infected Successful TasP requires massive ↑Testing

4. Still a long way to go to reach 15 million on ART, let alone treating everyone Estimated gap: CD4 cell count ≤ 350/mm 3 but not on ART Patients receiving ART 47% 3% WHO, 2011 53% 97%

5. Effective prevention interventions have not been brought to scale Goal: ~ 20 million by 2016 Total MCs through 2011: ~1.35 million, 6.5% of target # Source: WHO Male circumcisions performed annually in 14 priority countries in eastern and southern Africa

6. Major inequities persist in access to treatment and prevention PROPORTION OF PEOPLE WHO INJECT DRUGS RECEIVING ART IN LOW AND MIDDLE INCOME COUNTRIES IN EECA REGION 2002-10 2002200520062010 Number of reporting countries among 26 low- and middle-income countries surveyed 17212319 HIV cases among people who inject drugs (% among cumulative reported HIV cases with a known transmission route) 46,052 (71%) 221,849 (77%) 249,982 (77%) 185,565 (62%) People who inject drugs receiving antiretroviral therapy (% among the total reported people receiving ART with a known route of transmission) 130 (20%) 4,670 (26%) 5,275 (26%) 7,646 (22%) Source: Global HIV/AIDS Response. Epidemic update and health sector progress towards Universal Access. Progress Report 2011. WHO/UNAIDS/UNICEF. Table 6.9, p. 137.

7. Who is Prescribed ART and Who Achieves Viral Suppression in the USA (MMP)? CharacteristicPrescribed ART % (95% CI) Virally suppressed % (95% CI) Race/ethnicity Non-Hispanic White92 (90-94)80 (76-83) Non-Hispanic Black86 (83-88)*64 (60-68)* Hispanic89 (86-92)74 (71-78) Other87 (81-94)69 (63-76) Sexual risk behavior MSM89 (87-91)76 (72-79) MSW91 (88-93)70 (66-75) WSM86 (83-89)66 (62-70)* * P value <0.05 Skarbinski, CROI, 2012

8. 80% 77% 51% 89% 77% MMWR (60), 2011 850,000 with HIV do not have virus under control (72%) Clinical Care System Considerations Addressing the HIV Continuum of Care

9. Early retention in care (Mugavero et al)  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  Delayed time to VL suppression and greater cumulative HIV burden  Increased sexual risk transmission behaviors  Increased risk of clinical events & mortality  Worse ART adherence, CD4 & VL response and increased long-term mortality following ART start 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, Tripathi et al. AIDS Res Hum Retrovirus 2011;e-pub, Giordano et al. Clin Infect Dis 2007;44

10.  Outcome: 1 o HIV provider visit attended w/in: Case Management Standard of Care P-value 6 months 78%60%<0.01 Gardner et al. AIDS 2005;19  Intervention is efficacious, but additional steps needed to promote linkage to care… 12 months 64%49%<0.01 Linkage to Care: CDC ARTAS

11. Clinical Care System Considerations Linkage, retention, and effectiveness (USA) Linkage to care and preventive services – Only 69% of persons with HIV attend clinic within 12 months of diagnosis – Case management improves linkage by 32% at cost of $1,200 per person – Interventions focused on adherence increase likelihood of undetectable viral load by 15% Effectiveness depends on coverage during entire cascade from testing to care – Transmission reductions can vary from 15% to 44% Walensky ClD 2010, Marks AIDS 2010; Crepaz AIDS 2006 11

12. Looking Ahead: Challenging Times for HIV Prevention Picture in the United States especially grim: – Federal deficit ~$1.3 trillion for FY 2011 – 5-year freeze on federal discretionary spending – Reductions in HIV prevention by health departments ~45,000 state and local public health jobs lost Staff furloughs, hiring freezes, pay cuts – Many community organizations closed or struggling Similar picture being observed in other Western Industrialized settings, driven by economic downturn *Total includes HIV and viral hepatitis prevention programs, but majority of funds cut were from HIV Kaiser Family Foundation; NASTAD; Center on Budget and Policy Priorities

13. Social Cognitive Model: TasP Needs to Consider Concomitant Issues Self efficacy Safer Sex Adherence Pleasure reduction Disease prevention Social Models Depression, anxiety, mental health problems Wulfert, Safren, et al., 1999; Journal of Applied Social Psychology

14. Total HIV-1 Transmission Events: 39 HPTN 052: Lots of “Uncoupled” Transmissions Linked Transmissions: 28 Unlinked or TBD Transmissions: 11 p < 0.001 Immediate Arm: 1 Delayed Arm: 27 Up to 30% of new infections in couples occur outside the primary relationship (Campbell et al PLoS One 2011; Hughes et al. J Infect Dis 2011)

15. Source: Tim Hallett, personal communication A combination of interventions has more impact than the interventions delivered alone

16. 16 Decrease in HIV Transmission Decrease in HIV Transmission Maintain Viral Suppression Suppression TreatTreat Enroll in Care Address concomitant concerns, e.g. depression, substance use, relationship dynamics Combination Antiretroviral Prevention HIV Negative TestTest Interventions to Increase Testing PositivePreventionPositivePrevention Linkage To Care Linkage Adherence to ART ART Initiation. Risk Assessment PrEP, Adherence Counseling Counseling HIV Positive

17. Thank You Kevin Fenton Gottfried Hirnschall Tim Hallett Steven Safren Jacek Skarbinski Michael Mugavero Wafaa El-Sadr NIAID, NIMH, NIDA, NICHD, CDC, HRSA, Mass DPH, Gilead www.thefenwayinstitute.org