Jonathan Mermin, MD, MPH - PowerPoint Presentation

Jonathan Mermin, MD, MPHNational Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Centers for Disease Control and Prevention DC CFAR City-Wide SeminarGeorge Washington UniversitySeptember 13, 2016 HIV prevention today: what are the big unanswered questions? National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Office of Director

HIV Prevalence and Incidence United StatesNumber of people living with HIV has grown because incidence is relatively stable and survival has increasedHall HI et al. JAMA 2008 Aug 6;300(5): 520-9; Prejean J et al PLoS One 2011;6(8): e17502; MMWR 2012 Mar 2;61(8):133-8 .

Health InequityAfrican Americans 8 times and Latinos 3 times more likely to have HIV than whites Women estimated to be diagnosed with HIV in their lifetime ranges from about 1 in 32 among African American women to 1 in 526 among white or Asian women HIV prevalence is associated with population density, region of residence, poverty, education, employment, and homelessness MSM lifetime risk of HIV ~80 times higher than other men and women CDC, HIV Surveillance Report, 2009; www.cdc.gov/hiv/surveillance/resources/reports. Denning, International AIDS Society, 2010; Purcell D et al. The Open AIDS Journal, 2012, 6 (Suppl 1: M6) 98-107.

Current Lifetime Risk of HIV Diagnosis Among MSM Source: Centers for Disease Control and Prevention

Why are we here when these are 100% effective?

Vaccine Ultimate prevention for negativesCureUltimate prevention for positives

Big kahuna questionsWhat is the best use of resources to reduce HIV incidence? What are the scientific breakthroughs that will make the healthy choice an easy choice?Can wearing a condom feel better than alternative?What is new generation of risk messaging? Can we implement truly routine HIV screening?How can viral load suppression be maximized on a population level?

What is the best use of resources?

Prevention with Positives HIV testing, linkage to care and prevention services Antiretroviral therapyRetention in care and adherencePartner services Risk reduction interventions and condoms STD screening and treatment Perinatal transmission Sexual health education and social mobilization Condom availability Substance use, mental health, and social support Prevention with Negatives Behavioral risk reduction interventions and condoms Pre-exposure prophylaxis ( PrEP ) Syringe services Male circumcision STD screening and treatment Post-exposure prophylaxis Not focused on HIV status

Combination preventionMultiple disciplines and approaches Community interventions Biomedical interventions Structural interventions HIV testing and linkage to care Individual and small group Interventions HIV prevention

Combination preventionMultiple disciplines and approaches Combining interventions is not enough Community interventions Biomedical interventions Structural interventions HIV testing and linkage to care Individual and small group Interventions HIV prevention All effective interventions are not equal All interventions are not effective

Potential interventions Assess efficacy and effectiveness Establish cost and cost effectiveness per infections averted and life-years saved Determine feasibility of full scale implementation Develop epidemic models to project impact of interventions Implement and evaluate programs Prioritize interventions HIGH-IMPACT PREVENTION Strategy

Good care saves lives and moneyIntervention Cost per QALY SavedContinuum of Care: Testing in clinical settings Cost Saving Linkage to care Cost Saving Adherence to ART Cost Saving Retention in care $13,460 Other Interventions: Partner services Cost saving PrEP MSM $59,000 Lin, et al., Am J Prev Med 2016

Antiretroviral treatment worksSTART trialART at CD4 count >500 fewer severe adverse events and mortality than delaying therapy 68% of primary endpoints occurred in persons with CD4>500ART reduces transmission of HIV by >96% NEJM, August 27, 2015

Expanding treatment and reducing HIV incidence? Hontelez PLOS Med 2013; Tanser Science 2013 Elimination t heoretically possible New HIV infections can be eliminated (<1 per 1,000 person-years) in South Africa with annual screening and universal or CD4-guided ART And empirically possible In rural KwaZulu-Natal, a person living in a community with 30-40% ART coverage was 38% less likely to acquire HIV than person in community with <10% coverage

Aligning resources with the epidemic Proportion of Americans Diagnosed with HIV Who Live in Each State (2008)Proportion of CDC Core HIV Prevention Funding—FY20162

Implementation of High Impact PreventionProgram shifts Most activities focused on priority interventionsDoubling of jurisdictions with integrated HIV prevention and care planningIncreased activities with PLWHV and MSM, especially black MSMFunding for behavioral risk reduction mostly for negatives reduced from 34% to 11% Focus on use of ACA and billing capacity About 50% of jurisdictions receive no state HIV prevention resources NASTAD National HIV Prevention Inventories 2013, 2014

2010-14, annual new HIV diagnoses decreased 9%6% reduction in men; 21% in women32% decrease in infections attributed to injection drug use Proportion of persons with HIV aware of status increased, so decreases not due to less testing2010-2013, 9% less mortality--seen in all race/ethnic groups2008-12, mortality among African Americans diagnosed with HIV decreased 28%Hispanic/Latinos have lowest mortality among people living with HIV Some indicators of successHIV Surveillance Report , Volume 26, 2014, CDC

Trends in HIV disparities

Major disparities persist CDC surveillance report

What are the scientific breakthroughs that will make the healthy choice the easy choice?

Can a condom feel better than alternative? In national sample, >70% of adolescents reported condom use during last sex However, 22% of women and 25% of men of all ages reported condom useUse more than twice as likely with casual than “relationship” partnerCouples stop using condoms over timeMen and women >5 times less likely to use condom if had sex >10 times previously Among MSM, 68% of HIV transmission from main partnerHigher number of sex acts, more frequent receptive role, and lower condom use Reece J Sex Med 2010; 7 ( suppl 5); Sanders J Sex Med 2010; 7 ( suppl 5); Sullivan AIDS 2009

Need for improved technologyGates foundation awarded $1 million in research grants to develop a condom that “significantly preserves or enhances pleasure”Photograph: Niall Carson/PA

Can healthy choice be easy choice? Andrews Science 2014; Smith PNAS, 2013 Oral PrEP reduced HIV acquisition among heterosexuals, MSM, IDUs Some trials failed More effective with better adherence Long-acting GSK744 monthly injections protected macaques from rectal and vaginal SHIV TDF ring protected macaques from vaginal SHIV infection Should lubricants routinely contain tenofovir /PREP?

PrEP in practiceRandomized trialsWhen taken as directed, PrEP prevents >90% of sexually transmitted HIVPrEP Demonstration Project2 HIV infections with moderate adherence among MSM and transgender womenPrEP Use, Kaiser Permanent, San Francisco No HIV infections despite high rates of STIs, risk behaviorHIV PrEP demonstration project for YMSM 56% of participants had protective drug level at first visit, but adherence declined4 HIV infections; all had undetectable drug levelsPrEP empowersIAS 2015; Volk CID 2015

Prevention as healthcare – Healthcare as preventionHow do we make HIV prevention services, including PrEP, a normative part of healthcare?HIV testing as routine as cholesterol testing Risk reduction as common as nutrition counseling, foot care for people with diabetesEnsure reimbursement systems support routine HIV prevention services within clinics and by community-based organizations

What is new generation of sexual risk messaging?

What is the new generation of risk messaging?“Protection” is no longer restricted to condomsNo studies have assessed effectiveness of risk reduction for HIV-negative persons incorporating ART by partner, PrEP, nPEP, male circumcision, and serosortingFew studies have assessed new approaches for persons with HIV and their partners

HIV Risk Reduction Tool User-friendly tool for different audiences of risk estimates and HIV prevention messages incorporating ART, PrEP and new prevention toolsContent structured to enable tailoring by user

Sexual health educationGood sex education is a counter measure to false information School Health Policies and Practices Study, 2014

MSM accounted for 61% of reported syphilis cases in 2014 Among syphilis cases in which HIV status is known, 51% of cases are in MSM with HIV, compared to 11% among MSW and 6% among womenSyphilis increasing among MSM Primary and secondary syphilis cases, reported cases by sex and sexual behavior, 27 areas, 2007-2014 CDC. 2014 STD Surveillance Report; MMWR May 13, 2014

How can we implement truly routine screening?

HIV prevalence and diagnosis

Estimated HIV Transmission Rate CDC. MMWR 2012; 61 ( Suppl; June 15, 2012): 57-64 . Holtgrave et al. Updated Annual HIV Transmission Rates in the United States, 1978-2006. J Acquir Immune Defic Syndr 2009; 50 (2): 236-38; Holtgrave et al. HIV Transmission Rates in the United States, 2006-2008. The Open AIDS Journal 2012; 6:20-22., Bonacci , Holtgrave, AIDS and Behavior, July 2016. Number living with diagnosed HIV infection Transmission rate

HIV testing exampleVeterans Health Administration revised national HIV policy to routinely offer HIV testing to all veteransEliminated required written informed consent and pre- and post-test counselingIn 2009, 9.2% of outpatients had ever been tested for HIV, by 2011, 20% had--1.2 million more veterans Very few hospitals or clinics have routine clinical decision support systems that flag blood drawn for other tests, e.g., CBC or chemistries and request HIV testing

New HIV testing algorithm71-84% of RNA +/ 3rd generation-negative specimens detected by 4th generation assay 4 days after RNA positive New algorithm will diagnose majority of acute infections, allows for PCR confirmation rather than WB, and detects HIV-2 * Cunningham P, HIV Diagnostics Conf 2007 ** Patel P, CROI 2009 *** Owen M, CROI 2009

Return on investment: Expanded Testing Initiative $102 million over 3 years HIV testing and linkage to care in clinical and non-clinical settings:2.8 million persons tested for HIV18,432 persons newly diagnosed with HIV70% African American, 12% Latino3,381 HIV infections were averted $1.1 billion in direct medical costs were saved For each dollar the health system1 invested, $1.97 in medical costs was saved Hutchinson AB, et al. JAIDS 2012 Mar 1;59(3):281-6. Return on public health investment: CDC's Expanded HIV Testing Initiative.

Testing in health care and at homeIn Kampala, Uganda, 98% of 50,000 in-patients and clinic attendees agreed to HIV testing 29% never tested previously were infected In eastern Uganda, 99% of 2,300 family members of people taking ART accepted HIV testing37% of adults and 10% of children <5 years infected\ 74% of HIV-infected never previously tested--of these, 39% eligible for ART 43 % of spouses positive and 99% not previously tested Wanyenze WHO Bulletin 2008; Basset JAIDS 2007; Bebell CROI 2008

Door-to-door testing 111,700 (98% of those present) counseled and tested in Bushenyi District, UgandaPrevalence 5.8% >7,000 people In Nairobi with 96% uptake Prevalence 13% 85% of people with HIV had never had an HIV test Median CD4 count 450 cells/ml All testing was cost-effectiveCost-saving if averted infections included: $1,800-$51,000 saved per 1,000 tested Nuwaha IAS 2006 ; Delal 2012

How can viral load suppression be maximized on a population level?

Prescribed ART All diagnosed persons Any HIV care All persons with HIV Regular HIV care PUBLIC HEALTH CLINICAL MEDICINE How can surveillance be used to improve care ? Clinical Medicine, Community, and Public Health Reduce Risk Behavior COMMUNITY

HIV transmission at each step of care continuum, United States 9 of 10 new infections transmitted by HIV-infected people who are undiagnosed or diagnosed but not in medical care Frieden NEJM 2015

Linkage, retention, ART adherenceLinkage to care and preventive services 82% of persons with newly diagnosed HIV linked to care within 90 daysCase management improves linkage by 32% at cost of $1,200 per personInterventions focused on adherence increase likelihood of undetectable viral load by 15%Overall impact depends on coverage during entire continuum from testing to care Magnitude of improved transmission reduction can vary from 15% to 44% Walensky ClD 2010, Marks AIDS 2010; Crepaz AIDS 2006; CDC, Monitoring and Evaluation Report, PS12-1201

Data to Care StrategyUsing CD4 count and viral load surveillance data to identify people who are not engaged in care or not receiving optimal care Never linked to care, dropped out of carePersistently low CD4 count or detectable viral loadData are used for public health follow upContinuum of Care uses aggregate data for monitoringData to Care helps people with HIV get the care, prevention, mental health, behavioral health, and social services they need Sweeney P et al Milbank Quarterly 2013

Molecular epidemiology:Helping with the basicsART resistance testing routinely performed for new diagnoses Reporting by 27 jurisdictionsAllows for rapid response to outbreaks and clusters including providing needed social, prevention, treatment services to sexual and drug using networks Precedent with TB where 95% of all TB isolates tested and outbreaks rapidly identified

HIV Diagnoses by Week, Indiana HIV Outbreak (N=188) Retesting “blitz” Peters P et al., under review and Indiana State Department of Health Detect and confirm Not tested previously Deploy emergency command, HIV testing, contact tracing, services Consolidate case management, HIV treatment, prevention services

Impact of Syringe Exchange in Scott County Reductions in sharing syringes and injection equipment (n=148) p <0.001p <0.001 p <0.001 Patel et al. IDWeek 2015, abstract: Open Forum Infect Dis (Fall 2015) 2 (supplement 1): S69-S70 (median 10 weeks after first visit)

Vulnerability to HIV/HCV outbreaks and presence of syringe service programs

Achieving the prevention goals of National HIV/AIDS Strategy would avert tens of thousands of new infections and save billions of dollars Unpublished CDC Data, 2015291,309 infections prevented, $127 billion saved in health care costsThink bigger, act faster

Racial Disparities in HIV-Associated Mortality Levin et al. AJPH. 2010 Nov. 100 (11) 2176-2184.

Conclusions The U.S. has turned the corner on HIV, but we are far from achieving successPrioritizing the tools and programs that will have the greatest impact is essentialNew science, creative education, sound policy, and innovative programs can make easier, more effective choices Future includes integration of clinical practice and public healthTreatment, PrEP, molecular epidemiology, and use of data to improve programsThink bigger, act faster

Acknowledgments Sara BinghamRich WolitskiEugene McCray Stephanie SansomIrene HallJanet ClevelandDavid Purcell Nick DeLuca Dawn Smith Evin Jacobson Patty Dietz Norma Harris Alexa Oster John Brooks The findings and conclusions in this presentation do not necessarily represent official position of CDC