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

Highly Active HIV Prevention Coates, Lancet, 2008

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

Test & Treat Hypothesis Test Adoption of safer behaviors by HIV(+) persons Treat with ART + Adherence Maintain viral suppression Decrease in HIV Transmission + Sten Vermund, HPTN

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. Anthony S. Fauci, Washington Post, April 16, 2009

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

Eight Targets of Opportunity

Table A Conceptual Model

Table Target 1

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

Routine Testing in 6 Southeastern Community Health Centers Est. Unduplicated patients aged 13 to 64 seen at health centers 58,619 Offered HIV test (% of patients)16,291 (28%) Received HIV test (% of those offered)11,309 (69%) False positives19 Confirmed as newly diagnosed HIV-infected17 Confirmed linked to care14 Myers et al., JGIM, 2009

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

Table

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

Project Accept Intervention Community Mobilization Community Preparedness Support at the highest levels Testimonials from early adopters Event testing Linkage to other community goals Voluntary Counseling and Testing Mobile Vans Free, Rapid Testing Individualized Risk Assessment Motivational Interviewing Post Test Support Services Information sharing Support groups Coping Effectiveness Workshops Stigma Reduction Workshops Linkage to services

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

Results

HIV Detection

Table Target 2

Targeted Community-Level CDC 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 focus on HIV uninfected persons –8 heterosexual adults –2 high-risk youth –2 MSM –2 drug users Lyles et al., American Journal of Public Health, 2007

Table Target 3

HIV RNA in Semen (Log 10 copies/ml) Acute Infection 3 wks AsymptomaticInfection HIV Progression AIDS / /10,000 1/ /2000 1/100-1/1000 Risk of Transmission Reflects Genital Viral Burden 1/30-1/200 Sexual Transmission of HIV Cohen & Pilcher, JID, 2005

Mean Number of Unprotected Vaginal and Anal Sex Acts per Week, Stratified by Partner Serostatus Steward et al., AIDS & Behavior, 2009

Rapid Ag+Ab Test Kits Determine® HIV-1/2 Ag/Ab Combo

Table Target 4

Linkage to Care Ulett et al., AIDS Patient Care STDs, 2008

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) Gardner, et. al. AIDS, 2005

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

Table Target 5

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 Das-Douglas, CROI, 2009

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 Mugavero et al., Topics in HIV Medicine, 2008

Table Target 6

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

Table Target 7

Table Target 8

Retention in Care Survival Advantage Quarters in Care Adjusted Hazard Ratio of Death P-value 11.9< < < (reference) - Controlled for in model: baseline CD4, age, non-HIV co-morbidities, HCV co-infection Giordano et al., CID, 2007

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”

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

Enhancing Prevention with Positives Evaluation Center

Sites

HIV Transmission Risk Sex in the Last 6 Months Morin et al., AIDS and Behavior, 2007

Intervention Provider Type Site Primary Care Provider Intervention Specialist Peer Johns Hopkins University, Baltimore  University of Alabama, Birmingham  St. Luke’s Roosevelt Hospital, New York  (Social Worker) El Rio/Special Immunology Health Ctr., Tucson  (Health Educator) University of Washington, Seattle  (Social Worker)  Mt. Sinai Hospital, Chicago  Fenway Community Health Center  University of Miami  Drexel University, Philadelphia  (Health Educator)  DeKalb County Board of Health, Decatur  (Specialist) University of North Carolina, Chapel Hill  (Specialist) University of California, San Diego  (Health Educator) University of California, Davis  (Social Worker)

Change in Risk Behavior by Intervention Delivery Mode P=.03 P=.04 Myers, et al, under review

Incremental Cost Effectiveness of Intervention by Delivery Mode Provider (N=2) Specialist (N=6) Mixed (N=5) Time per Patient 1.7 minutes13 minutes7.6 Minutes Cost per Patient $1,004$3,201$3,468 Incremental Cost- Effectiveness $107,656Provider dominates Marseille et al., under review

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 Simoni et al., 2008 and Stirratt & Gordon, 2008

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

Table

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. Noar et al., Journal of Health Communications, 2009

How Can We Measure Outcome at a Biological Level?

Das-Douglas, CROI 2009 Spatial Distribution of AIDS in San Francisco

Montaner et al., 2008, XVII International AIDS Conference Cohort VL Predicts HIV Incidence

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 Community Viral Load Das-Douglas, CROI 2009

N(%)Mean CVL San Francisco 8,625(100) 20,563 Race/Ethnicity* White7,432(66.8)18,742 Latino1,606(14.4)19,471 Black1,474(13.3)31,489 Other613(5.5)18,509 *p<0.001 using Kruskal-Wallis test to test the null hypothesis of the different means of the levels of the categorical variables Das-Douglas, CROI 2009 Race/Ethnic Variations in Mean CVL

Das-Douglas, CROI 2009 Spatial Distribution of Mean CVL in San Francisco,

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