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Why an HIV vaccine?

Why an HIV vaccine?. Catherine Hankins MD MSc FRCPC Chief Scientific Adviser to UNAIDS Office of the Deputy Executive Director. Journalist training, HIV vaccine research National Press Foundation and Global HIV Vaccine Enterprise Atlanta, Georgia, September 27 th , 2010.

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Why an HIV vaccine?

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  1. Why an HIV vaccine? Catherine Hankins MD MSc FRCPC Chief Scientific Adviser to UNAIDS Office of the Deputy Executive Director Journalist training, HIV vaccine research National Press Foundation and Global HIV Vaccine Enterprise Atlanta, Georgia, September 27th, 2010

  2. Why an HIV Vaccine? • Global epidemic (facts and figures) • Know Your Epidemic/Know your Response • Economic burden • Funding trends and resource needs • New prevention technologies • Male circumcision, microbicides, pre-exposure prophylaxis

  3. Global estimates for adults and children, 2008 • People living with HIV33.4 million[31.1 – 35.8] • New HIV infections in 20082.7 million [ 2.4 – 3.0] • Deaths due to AIDS in 20082.0 million[1.7 – 2.4] • Almost half of people living with HIV are women • Of the 7400 new infections per day in 2008, about 1200 were in children under 15 years of age

  4. HIV: a stabilized epidemic (incidence/deaths) • spread of HIV peaked in 1996 at 3.5 new infections (2008: 2.7 million) • new infections have dropped by 17% since 2001 • deaths peaked in 2004 at 2.2 million (2008: 2 million) Number of patients newly infected with HIV UNAIDS epidemic update 2009 * National household surveys 4

  5. HIV: a stabilized epidemic (prevalence) Adult HIV prevalence • Almost 60 million people have been infected by HIV and 25 million have died of HIV-related causes • 2008: stabilized HIV prevalence is the result of reduced new infections and the effect of antiretroviral therapy UNAIDS epidemic update 2009 5

  6. Know your epidemic and response synthesis process ANALYSIS OF EPIDEMIC Incidence data (modelled or otherwise) Epidemiological Review: Drivers/ country specificity SYNTHESIS Prevention policies, response and strategic info review Review of resources for prevention ANALYSIS OF RESPONSE

  7. Incidence by mode of HIV transmission in East and Southern Africa Source: MOT country reports available at http://www.unaidsrstesa.org/hiv-prevention-modes-of-transmission

  8. Collectively we’ve made remarkable progress in many aspects of the response to HIV… … incidence of new infections, antiretroviral treatment, human rights

  9. Treatment benefits are clear…. The number of AIDS-related deaths has declined by over 10% over the past five years… Since 1996 the availability of effective treatment, has saved some 2.9 million lives…

  10. People in the poorest places have access to life-prolonging medicines

  11. Why we need a prevention revolution • # people accessing antiretroviral treatment has increased 12-fold in just 6 years • 2010 WHO guidelines for treatment initiation (CD4 count of 350 cells) increased # in need by 50% • Globally, 2 of every 3 people who need treatment are not accessing it - 10 million people are waiting now • Globally, new infections are outstripping expansion of treatment availability - for every 2 people who start taking antiretroviral drugs, another 5 are newly infected • Great progress but not only are we not keeping up, we are increasingly behind • Need a prevention revolution to break the trajectory of the epidemic

  12. Young people are leading the prevention revolution by taking definitive action toprotect themselves from HIV • HIV prevalence in young people aged 15-24 has declined in 22 high burden countries in sub-Saharan Africa: • delaying onset of sex • fewer partners • correct & consistent condom use

  13. Human rights issues and the AIDS movement • Recent advances include the decision of the Delhi high court to strike down an anti-sodomy law dating back to the early days of the British Raj • China’s launching of needle exchange and methadone programmes for people who inject drugs need to be multiplied • Lifting of travel restrictions: USA, China “Gay couple freed by Malawi presidential pardon return to home villages” Human rights campaigner says men have not been reunited amid fears for their safety

  14. One of the biggest human rights issues facing the AIDS movement is funding

  15. TOTAL annual resources available for AIDS in low and middle income countries, 1996-2009

  16. Spending per capita for HIV > $10 per capita $1 - $10 per capita $0.10 - $1 per capita < $0.10 per capita Source: UNAIDS global report 2008, Annex 2

  17. International AIDS Assistance: Trends in G8/EC & Other Donor Government Assistance, 2002-2009 USD billions Disbursements Commitments(Enacted Amounts) Sources: KFF and UNAIDS, Financing the response to AIDS in low- and middle- income countries: International assistance from the G8, European Commission and other donor Governments in 2009, July 2010

  18. Assessing Fair Share 2: Donor Rank by Disbursements for AIDS per US$1 Million GDP*, 2009 Sources: KFF and UNAIDS, Financing the response to AIDS in low- and middle- income countries: International assistance from the G8, European Commission and other donor Governments in 2009, July 2010

  19. International Assistance for HIV, domestic spending, and financing gaps Eastern Europe and Central Asia DONOR 2 BILLION DONOR 3.5 BILLION South East Asia and the Pacific DONOR 21 MILLION Latin America and the Caribbean DONOR 8 MILLION Sub-Saharan Africa

  20. Resources needed to provide ART under two CD4 eligibility criteria (New WHO ART guidelines) 12,000 10,000 8,000 6,000 4,000 CD4 <350 CD4 <200 2,000 Millions US$ 0 2010 2011 2012 2013 2014 2015 23

  21. Investing in AIDS: • linked to individual and societal benefits • essential for attainment of MDG 3, 4, 5, 6 • saves money in the long term • Millennium development goals (AIDS+MDGs) • Eradicate extreme poverty and hunger • Achieve universal primary education • Promote gender equality and empower women • Reduce child mortality • Improve maternal health • Combat HIV/AIDS, malaria and other diseases • Ensure environmental sustainability • Develop a global partnership for development 24

  22. Worst case scenarios if funding decreases: • Increased mortality and morbidity • Greater transmission risks • Treatment interruption • Increased burden on health systems • Reversal of economic and social gains

  23. Bilateral Aid for AIDS in 2008 Bonus paid to London Financial staff at Christmas 2006 Amounts spent on Valentine's day Cost of war in Iraq in 2008 - 25 50 75 100 125 150 175 200 US$ billion How much is too much? 2010 estimated need: 26.8 billion US$. Available: 15.9 billion US$ Is the 11 billion USD gap that we are trying to close too much?

  24. Resource mobilization action! Financing options Increase domestic funding Fair share from bilaterals Corporate Partnerships Framework Agreement on Debt2Health Airline ticket tax BRICS governments becoming donors Huge accumulation of wealth (Sovereign Wealth Funds, HNI) Robin Hood Tax (take a look at the videos on http://robinhoodtax.org.uk/) 27

  25. Why an HIV Vaccine? • Global epidemic (facts and figures) • Know Your Epidemic/Know your Response • Economic burden • Funding trends and resource needs • New prevention technologies • Male circumcision, microbicides, pre-exposure prophylaxis

  26. HIV Prevention at the Crossroads Behaviour change can be effective need tailored, sustainable strategies Structural interventions need better understanding of underlying determinants Biomedical interventions with partial efficacy male circumcision in HIV- heterosexual men (clinical trial) antiretroviral therapy (observational & ecologic data) pre-exposure prophylaxis trials underway modest protective efficacy in the Thai RV144 vaccine trial proof of concept for antiretroviral-containing topical microbicides in CAPRISA 004 No single strategy will work alone: multi-component, integrated, biomedical, behavioural, and structural approaches: rights-based, evidence-informed combination HIV prevention approaches

  27. What works for HIV prevention:Results from randomised controlled trials with HIV incidence endpoints Review of 37 HIV prevention RCTs on 39 interventions: PrEP : 1 Behavioural: 7 Microfinance:1 Diaphragm: 1 STI treatment: 9 Vaccines: 4 Microbic: 12 Male Circ: 4 Study Effect size (CI) HIV Vaccine (Thai RV144) 31% (1; 51) STD treatment (Mwanza) 42% (21; 58) 57% (42; 68) : M-A Circumcision (Orange Farm, Rakai, Kisumu) CAPRISA 004 39% (6;60) Efficacy 0% 10 20 30 40 50 60 70 80 90 100% Padian NS, et al. Weighing the gold in the gold standard: challenges in HIV prevention research. AIDS 2010, 24:621–635

  28. Develop, implement & evaluate setting-appropriate combination prevention Scale-up of proven effective prevention strategies  Research for new biomedical, behavioural & structural prevention strategies Magic Bullet Technology HIV prevention Crossroads Courtesy Q. Abdool Karim

  29. Impact on HIV incidence: Evidence from observational studies and RCTs Weiss & Hayes Effect size Study (95% CI) Overall 0.42 ( 0.34, 0.52) High-risk groups 0.29 ( 0.20, 0.42) General Population 0.56 ( 0.44, 0.71) South Africa 0.40 ( 0.24, 0.67) Kenya 0.41 ( 0.24, 0.70) Uganda 0.49 ( 0.28, 0.86) .15 .2 .3 .4 .5 1 1.5 Effect size

  30. Weiss et al. AIDS 2008

  31. Snapshot of Country Progress, Jan 2010 Situation Analysis Policy Quality Service Assurance Delivery Training National Coordinator Task Force M&E

  32. Population-level Impacts by Coverage Hankins et al.Male circumcision for HIV prevention in high HIV prevalence settings: What can mathematical modelling contribute to informed decision making? PLoS Medicine 2009;6, September 8

  33. Communicating about partial protection

  34. Develop, implement & evaluate setting-appropriate combination prevention Scale-up of proven effective prevention strategies  Research for new biomedical, behavioural & structural prevention strategies Magic Bullet Technology HIV prevention Crossroads Courtesy Q. Abdool Karim

  35. Pre-exposure prophylaxis (PrEP) PrEP is a strategy for HIV-negative individuals to reduce or prevent their risk of infection by: taking oral antiretroviral drugs used for HIV treatment or applying microbicides containing the active antiretroviral agent in the vagina or rectum Dosing can be: daily intermittently (e.g. Fridays & Mondays) episodically (i.e. before & after sex) PMTCT, PEP, animal studies promising

  36. Completed/ongoing PrEP studies - safety

  37. Characteristics of ongoing PrEP efficacy trials • HIV seroconversion is 1° endpoint = event-driven trials • Studies continue until a pre-defined number of endpoints achieved (=timeline uncertain) • Safety is co-1° endpoint • Given sample sizes, will provide large amount of safety data • Distinct trials • Population/route of exposure: IDUs, heterosexual women & men, MSM • Agent: TDF, FTC/TDF, vaginal tenofovir gel • Location: Africa, Americas, Asia • Follow-up: 1-3 years per person • Trials designed to detect ~50-70% efficacy • Larger trials are designed so that lower limit of 95% confidence bound will exclude low efficacy (25-30%) • Seroconverters followed for ≥1 year • CD4, HIV-1 RNA, resistance testing

  38. Ongoing PrEP studies - efficacy

  39. Systemic versus topical administration in women

  40. 67 Past & Current Microbicide Clinical Trials (courtesy of CAPRISA, Durban) 1st class: Surfactants eg. N9, SAVVY 2nd class: Polymers eg. PRO2000, Carraguard, Cellulose Sulfate (CS) 3rd class: ARVs eg. Tenofovir gel, Dapivirine gel/ring 4th class: Co-receptor Blockers eg. CD4 blocker, CCR5 Blockers Kenya N-9 sponge trial CONRAD CS trial FHI CS Trial CAPRISA Tenofovir gel trial FHI N-9 film trial PopCouncil Carraguard trial Zena Stein publishes seminal article “HIV prevention: the need for methods women can use” UNAIDS COL-1492 trial MTN 003 VOICE trial HPTN PRO2000 & BufferGel trial IPM Dapivirine gel & ring trial FHI SAVVY trial MDP 0.5% PRO2000 trial 2% PRO2000 ‘90 ‘92 ’98 ’00 ‘03 ‘04 ‘04 ’05 ’05 ’07 ‘10 Safe but not effective Increased HIV infection Stopped for futility

  41. CAPRISA 004 dosing strategy (BAT 24) – based on nevirapine in childbirth BAT 24 Insert 1 gel up to 12 hours Before sex, insert 1 gel as soon as possible within 12 hours After sex, no more than Two doses in 24 hours HIVNET 012 nevirapine regimen CAPRISA 004 tenofovir gel regimen asap 72 hrs asap 12 hrs Onset of labour Delivery 44

  42. CAPRISA Vulindlela Clinic KwaZulu-Natal Midlands CAPRISA eThekwini Clinic Durban City Centre CAPRISA 004: Urban and Rural sites

  43. Effectiveness of tenofovir gel in preventing HIV infection Incidence rate ratio: 0.61 (CI: 0.4 to 0.94); p = 0.017 39% lower HIV incidence in tenofovir gel group 46

  44. Impact of adherence on effectiveness of tenofovir gel (overall 39% [6,60]) 47

  45. HIV infection rates in the Tenofovir and placebo gel groups: Kaplan-Meier survival probability Tenofovir Placebo p=0.017 After 12 months of gel use: HIV endpoints: 65 Effectiveness: 50% P-value: 0.007 (0.017)

  46. Tenofovir gel – Next steps Moral obligation and public health imperative to confirm whether tenofovir gel is a viable HIV prevention option for women • VOICE trial reports in 2013: daily dosing, powered to provide strength of evidence to support licensure of tenofovir gel if it shows at least 58% effectiveness • FACTS 001: proposed South African trial 16 to 30 years BAT24 • MDP 302: proposed trial in other African countries: BAT24 plus single dose arm • CAPRISA 008: implementation trial in HIV-negative women • CAPRISA 009: seroconverter study Funding need: US$100 million over 3 years ( US$33 million/year) Committed: US$58 million Gap: US$42 million In comparison: US $868 million invested in HIV vaccines in 2009 of US$1.165 billion invested in HIV prevention R& D

  47. Carlos Avila Salim Abdool Karim Helen Weiss Richard Hayes Jared Baeton Connie Celum Quarraisha Abdool Karim Eleanor Gouws Alexandra Calmy Tim Hallett Lynn Paxton Dawn Smith Myron Cohen Toby Kasper Kim Dickson John Stover Tim Farley Elizabeth McGrory Acknowledgements

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