Highly Active HIV Prevention: Eight Targets of Opportunity

1. Highly Active HIV Prevention: Eight Targets of Opportunity Steve Morin, Ph.D. Center for AIDS Prevention Studies AIDS Research Institute University of California, San Francisco

2. Highly Active HIV Prevention

3. National HIV/AIDS Strategy White House initiative with three objectives � Reducing number of new infections Increasing access to care Reducing HIV-related health disparities HIV Research should be directly related to these planning objectives Research should be coordinated across all federal agencies New review mechanisms should be developed in keeping with these objectives

4. Test & Treat Hypothesis Test Adoption of safer behaviors by HIV(+) persons Treat with ART + Adherence Maintain viral suppression

5. A Policy Cocktail for Fighting HIV New modeling research suggests that implementing a voluntary "test and treat" approach could dramatically reduce new HIV cases beginning within a decade and ultimately halt the pandemic. Before this approach can be implemented, however, we must pursue a research agenda that includes studies of feasibility, efficacy, the benefits to individual patients vs. the benefits to society, and cost-effectiveness.

6. Testing, Linkage and Care Plus (TLC+) National think tank to develop an integrated approach to HIV testing, linkage and care plus treatment (TLC+) Group expressed concern that �test & treat� may be viewed as involving universal, even compulsory testing and treatment While promising in terms of reducing the number of new infections, need to stress approach is voluntary and involves informed consent

9. A Conceptual Model

10. Target 1

12. Routine Testing CDC Recommendations Routinely screen all patients for HIV, unless patient population has HIV prevalence of 0.1% or less High risk persons should be screened at least annually High risk = MSM, IDU, IDU sex partners, sex workers, sex partners of HIV+ individuals, heterosexuals with more than one partner People being treated for TB or STDs should receive HIV testing. Demonstrated cost-effectiveness for testing every 5 years in populations with prevalence of 0.45% (Paltiel et al., 2006) More intensive routine screening programs likely to be cost-effective only when focused on higher risk populations or in higher risk settings

13. Routine Testing in 6 Southeastern Community Health Centers

14. Routine Testing in Emergency Departments High percentage of late testers seen in Emergency Departments = lost opportunity for earlier diagnosis Findings from study in SF Bay Area: Lack of consistently-defined protocols �Routine� HIV testing looks different in different EDs Numbers of patients offered testing is affected by nature of presenting acute condition, language, time of day High acceptance of routine testing among ED patients Most common reason for declining: been tested recently

16. NIMH Project Accept(HIV Prevention Trials Network 043) Phase III randomized controlled trial to determine the efficacy of a community-level behavioral intervention in reducing HIV seroincidence. Randomizing 48 communities: 8 in rural Zimbabwe 10 in rural Tanzania 8 in Soweto, South Africa 8 in rural KwaZulu Natal, South Africa 14 in Northern Thailand

17. Project Accept Intervention

18. Community Mobilization This component of the intervention is based on diffusion of innovation theory and uses community outreach to increase awareness of HIV status through HIV testing, education and encouraging discussion in the community. Endpoints: increased HIV/AIDS-related awareness increased rate of HIV testing increased frequency of discussions about HIV reduced HIV/AIDS-related stigma at community level

19. Results

20. HIV Detection

21. Target 2

22. Targeted Community-LevelCDC 2008 Compendium of Evidence-Based HIV Prevention Interventions Best Evidence Interventions can assist in the development of HIV-prevention strategic plans 14 new evidence-based interventions from 2000-2004 focus on HIV uninfected persons 8 heterosexual adults 2 high-risk youth 2 MSM 2 drug users

23. Target 3

25. Mean Number of Unprotected Vaginal and Anal Sex Acts per Week, Stratified by Partner Serostatus

26. Rapid Ag+Ab Test Kits

27. Target 4

28. Linkage to Care

29. Antiretroviral Treatment Access Study (ARTAS) CDC sponsored trial of a 5 session strengths based case management intervention At 6 months, 78% in intervention arm kept an HIV provider appointment (v. 60% in control) At 12 months, 64% in intervention arm kept an HIV provider appointment (v. 49%) 25% of sample not newly diagnosed (past 6 months)

30. Outreach Initiative HRSA sponsored project � 10 demonstration sites with different approaches to linkage to care Range of strategies from peer-based to case management 1 in 5 of new diagnoses not retained in care � 1 visit in each of 2 consecutive six month periods

31. Target 5

32. Treatment Engagement Defined as seen at least once in over 6 mos. in past year using San Francisco surveillance registry 16,988 mean viral load of those engaged (52%) 28,026 mean viral load for those not engaged (48%) *p<0.001 using Kruskal-Wallis test to test the null hypothesis of the different means of the levels of the categorical variables

33. Engagement & Retention in Care: What can we do? Linkage and retention are distinct processes Engagement in care is vital for HIV treatment success at the individual and population levels Early missed visits can identify at risk persons Engagement in care is worse for disproportionately affected populations Ancillary services (mental health & substance abuse care) have a crucial role in engagement and retention

34. Target 6

35. Treatment Guidelines Treatment has been recommended for individuals with CD4 < 350 Revised guidelines now recommend treatment for individuals with CD4 < 500 Some recommend treatment for all HIV+ for improved health outcomes and public health Modeling suggests more widespread ART would result in a large number of incident cases averted

36. Target 7

37. Target 8

38. Retention in Care Survival Advantage

39. Retention in Care Missed visits in the first year of care is associated with increased mortality No controlled trials No consistent definition � one visit in 3 months or 6 months Not linked to the content of the visit Some retrospective analyses of clinic cohort data Difficult to assess reasons for �loss to follow-up�

40. Prevention with Positives: Interventions Effective in Reducing Sexual Risk Clinic-Based: Partnership for Health, Options, Video Doctor, Positive STEPS, KHARMA Project Group Sessions: Healthy Relationships, WILLOW, Together Learning Choices (TLC), Holistic Health Recovery Program (HRPP) One-on-one counseling: Healthy Living, CLEAR, SUMIT

41. Enhancing Prevention with Positives Evaluation Center

43. HIV Transmission Risk Sex in the Last 6 Months

44. Intervention Provider Type

46. Incremental Cost Effectiveness of Intervention by Delivery Mode

47. Medication Adherence Adherence interventions Should include practical approaches Pill boxes, reminders, calendars, etc Should address complex structural and individual barriers Stigma, access, cultural beliefs, economic constraints, depression Approaches include cognitive behavioral, social support, contingency management, home visits and directly observed therapy

48. Linkage to Mental Health and Substance Abuse Care High prevalence of substance abuse and depression found in clinical samples Detection and linkage to treatment are challenges in HIV care. Short computer-based screening in waiting rooms could be combined with transmission risk assessment Innovative use of electronic medical records

50. Prevention Social Marketing Key strategies in prevention social marketing campaigns include: Targeting audiences effectively Multi-channel exposure (TV, radio, print, transit, etc) Using behavior change as a theme Strengthening research designs for outcome evaluation utilizing behavioral measures There is a greater need for cost-effectiveness analysis to be integrated in prevention social marketing outcome assessments.

54. A population-based measurement of a community�s viral burden reflective of the aggregate HIV transmission risk Community Viral Load is a biologic indicator: Antiretroviral treatment effectiveness HIV Prevention effectiveness Engagement and retention in care Passive surveillance of clinical laboratories and active surveillance of care providers We propose a population-based approach to measuring a community�s viral burden or overall level of infectiousness Community Viral Load A population-based biologic health indicator of: HIV Prevention effectiveness Antiretroviral Treatment effectiveness (access, adherence, engagement ) CVL is a biologic marker at the nexus of prevention and treatment: transmission We propose a population-based approach to measuring a community�s viral burden or overall level of infectiousness Community Viral Load A population-based biologic health indicator of: HIV Prevention effectiveness Antiretroviral Treatment effectiveness (access, adherence, engagement ) CVL is a biologic marker at the nexus of prevention and treatment: transmission

56. We mapped mean cVL (mCVL) by neighborhood to visually explore spatial differences. As shown in the map (Figure 1), mean cVL varied by neighborhood. Historically, the two areas with highest AIDS case density have been among MSM in the relatively upper-income Castro and among low-income IDU in the Tenderloin. Noe Valley, Bayview and Visitacion Valley have not historically had high AIDS case density but have high mCVLs. It is notable that four of the five neighborhoods with the highest mcVL (Tenderloin, South of Market, Bayview, and Visitacion Valley) have the lowest median incomes in San Francisco. Homeless mean cVL was twice the overall mean cVL (43,818 copies/mL)(p<0.001).4 Overall SF mCVL was 20, 563 +/- 81,793 4/5 neighborhoods with highest mCVL have the lowest median incomes in San Francisco Tenderloin, South of Market, Bayview and Visitacion Valley Homeless mCVL was twice the SF mCVL (43,818 +/-103,492) Disparities by: Race/ethnicity Transmission group Insurance status Engagement in care Geography/Neighborhood We mapped mean cVL (mCVL) by neighborhood to visually explore spatial differences. As shown in the map (Figure 1), mean cVL varied by neighborhood. Historically, the two areas with highest AIDS case density have been among MSM in the relatively upper-income Castro and among low-income IDU in the Tenderloin. Noe Valley, Bayview and Visitacion Valley have not historically had high AIDS case density but have high mCVLs. It is notable that four of the five neighborhoods with the highest mcVL (Tenderloin, South of Market, Bayview, and Visitacion Valley) have the lowest median incomes in San Francisco. Homeless mean cVL was twice the overall mean cVL (43,818 copies/mL)(p<0.001).4 Overall SF mCVL was 20, 563 +/- 81,793 4/5 neighborhoods with highest mCVL have the lowest median incomes in San Francisco Tenderloin, South of Market, Bayview and Visitacion Valley Homeless mCVL was twice the SF mCVL (43,818 +/-103,492) Disparities by: Race/ethnicity Transmission group Insurance status Engagement in care Geography/Neighborhood

57. Conclusion Highly Active HIV Prevention shows promise -- Requires extensive both testing and treatment related behavior change A multi-level intervention should be feasible � could be organized around eight targets of opportunity Outcomes can be measured by trends in community viral load