WWhy an HIV vaccine?hy an HIV vaccine?

Catherine Hankins MD MSc FRCPCChief Scientific Adviser to UNAIDS

Office of the Deputy Executive Director

Journalist training, HIV vaccine researchNational Press Foundation and Global HIV Vaccine Enterprise

Atlanta, Georgia, September 27th, 2010

Why an HIV Vaccine?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

Global estimates for adults and children, 2008

• People living with HIV 33.4 million [31.1 – 35.8]

• New HIV infections in 2008 2.7 million [ 2.4 – 3.0]

• Deaths due to AIDS in 2008 2.0 million [1.7 – 2.4]

Almost half of people living with HIV are womenOf the 7400 new infections per day in 2008, about 1200

were in children under 15 years of age

UNAIDS epidemic update 2009 * National household surveys

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 5

HIV: a stabilized epidemic (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

Adult HIV prevalence

Know your epidemic and Know your epidemic and response synthesis processresponse synthesis process

Epidemiological Review: Drivers/

country specificity

Incidence data (modelled or otherwise)

Prevention policies, response and strategic info

review

Review of resources for prevention

SYNTHESIS

ANALYSIS OF EPIDEMIC

ANALYSIS OF RESPONSE

7April

2010

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

0%

20%

40%

60%

80%

100%

Kenya Lesotho Swaziland Uganda Zambia

Per

cen

t new

infe

ctio

ns

Stable heterosexual couples Partners (casual heterosexual sex)Casual heterosexual sex Men having sex with menPrison population (measured only in Kenya) Injecting drug usersPartners of clients of female sex workers Clients of female sex workersFemale sex workers Other

Collectively we’ve made remarkable Collectively we’ve made remarkable

progress in many aspects of the progress in many aspects of the

response to HIV…response to HIV…

… incidence of new … incidence of new

infections, antiretroviral treatment, infections, antiretroviral treatment,

human rightshuman rights

ART Scale up Progression in Resource Limited Settings (2003 - 2008)

0

1,000,000

2,000,000

3,000,000

4,000,000

5,000,000

6,000,000

Dec-03 Jun-04 Dec-04 Jun-05 Dec-05 Jun-06 Dec-06 Jun-07 Dec-07 Jun-08 Dec-08 Dec-09

Cu

mu

lati

ve N

um

ber

of

Pati

en

ts o

n A

RT

0

20,000

40,000

60,000

80,000

100,000

120,000

Nu

mb

er

of

Pati

en

ts o

n A

RT

/Mo

nth

Cumulative Number of PatientsReceiving ART

Mean Rate of Increase (patients onART/month)

2009 AIDS epidemic update

Estimated number of Life- years added due to antiretroviral therapy, by region, 1996–2008

8

7

6

4

5

3

(mill

ions)

2

1

Sub-SaharanAfrica

Asia Caribbean MiddleEast

and NorthAfrica

WesternEurope

and NorthAmerica

LatinAmerica

EasternEurope

and CentralAsia

Oceania0

Figure VII

7.2 million

2.3 million

1.4 million

590 000

73 000 40 000 49 000 7500

2009 AIDS epidemic update

Estimated number of AIDS- related deaths with and without antiretroviral therapy, globally, 1996–2008

2.5

2.0

1.5

0.5

1.0

3.0

0

Num

ber

(mill

ions

)

Year

1996 1998 2000 2002 2004 2006 20081997 1999 2001 2003 2005 2007

Figure V

No antiretroviral therapy

At current levels of antiretroviral therapy

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…

Treatment benefits are clear….

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

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

Young people are leading the prevention Young people are leading the prevention revolution by taking definitive action torevolution by taking definitive action toprotect themselves from HIVprotect 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

Human rights issues Human rights issues

and the AIDS movementand the AIDS movement

“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

• 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

One of the biggest human rights issues One of the biggest human rights issues

facing the AIDS movement is fundingfacing the AIDS movement is funding

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

$15.9

$15.6

$11.4

$8.9

$8.3

$6.1

$5.0

$0.3 $0.5 $0.5$0.9

$1.4 $1.6

$3.2

0.0

2.5

5.0

7.5

10.0

12.5

15.0

17.5

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

US

$ b

illio

n

UNAIDS Gates Foundation

World Bank MAP launch

Signing of Decleration of Commitment on HIV/AIDS, UNGASS

PEPFAR

The Global Fund

$12,8

$09,9

$14,3

$17,0

UNITAID

HIP+

$14.4

$17.4

$0.10 - $1 per capita

> $10 per capita $1 - $10 per capita

< $0.10 per capita

Spending per capita for HIV

Source: UNAIDS global report 2008, Annex 2

International AIDS Assistance: Trends in G8/EC & International AIDS Assistance: Trends in G8/EC & Other Donor Government Assistance, 2002-2009Other Donor Government Assistance, 2002-2009

USD billions

Commitments(Enacted Amounts)

Disbursements

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

$1.6$2.0

$3.6$4.3

$5.6

$6.6

$8.7 $8.7

2002 2003 2004 2005 2006 2007 2008 2009

Assessing Fair Share 2: Donor Rank by Assessing Fair Share 2: Donor Rank by Disbursements for AIDS per US$1 Million GDP*, Disbursements for AIDS per US$1 Million GDP*,

20092009

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

Eastern Europe and Central Asia

Latin America and the Caribbean

Sub-Saharan Africa

South East Asia and the Pacific

DONOR 3.5 BILLION

DONOR 2 BILLION

DONOR 21 MILLION

DONOR 8 MILLION

119

518

1,600

ReceivedAid

Domesticspending

Needed Aid

3,7721,306

12,000

ReceivedAid

Domesticspending

Needed Aid

International Assistance for HIV, domestic International Assistance for HIV, domestic spending, and financing gapsspending, and financing gaps

Resources needed to provide ART under two Resources needed to provide ART under two CD4 eligibility criteria (New WHO ART CD4 eligibility criteria (New WHO ART guidelines)guidelines)

23

0

2,000

4,000

6,000

8,000

10,000

12,000

2010 2011 2012 2013 2014 2015

US

$

Mill

ion

s

CD4 <350

CD4 <200

24

Investing in AIDS: 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)Millennium development goals (AIDS+MDGs)

1. Eradicate extreme poverty and hunger 2. Achieve universal primary education 3. Promote gender equality and empower women 4. Reduce child mortality 5. Improve maternal health 6. Combat HIV/AIDS, malaria and other diseases 7. Ensure environmental sustainability8. Develop a global partnership for development

Worst case scenarios if funding Worst case scenarios if funding decreases:decreases:

• Increased mortality and morbidity• Greater transmission risks• Treatment interruption• Increased burden on health systems• Reversal of economic and social

gains

How much is too much?How much is too much?

- 25 50 75 100 125 150 175 200

Cost of war in Iraq in 2008

Amounts spent on

Valentine's day

Bonus paid to London

Financial staff at Christmas

2006

Bilateral Aid for AIDS in

2008

US$ billion

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?

Resource mobilization action! Financing Resource mobilization action! Financing optionsoptions• 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

Why an HIV Vaccine?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

HIV Prevention at the Crossroads

Behaviour change can be effective• need tailored, sustainable strategiesStructural 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 004No single strategy will work alone:• multi-component, integrated, biomedical, behavioural, biomedical, behavioural,

and structural approachesand structural approaches: rights-based, evidence-informed combination HIV prevention approaches

What works for HIV prevention:What works for HIV prevention:Results from randomised controlled trials Results from randomised controlled trials

with HIV incidence endpointswith HIV incidence endpoints

Efficacy

Study Effect size (CI)

STD treatment (Mwanza)

42% (21; 58)

Circumcision (Orange Farm, Rakai, Kisumu)

57% (42; 68) : M-A

HIV Vaccine (Thai RV144) 31% (1; 51)

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

Review of 37 HIV prevention RCTs on 39 interventions:PrEP : 1PrEP : 1 Behavioural: 7 Microfinance:1 Diaphragm: 1 Behavioural: 7 Microfinance:1 Diaphragm: 1 STI treatment: 9 Vaccines: 4 Microbic: 12 Male Circ: 4STI treatment: 9 Vaccines: 4 Microbic: 12 Male Circ: 4

CAPRISA 004 39% (6;60)

Courtesy Q. Abdool Karim

Impact on HIV incidence: Evidence from observational studies and

RCTs Weiss & Hayes

Effect size .15 .2 .3 .4 .5 1 1.5

Study

Effect size

(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)

Weiss et al. AIDS 2008

CROI 2010CROI 201017th Conference on Retroviruses and 17th Conference on Retroviruses and

Opportunistic InfectionsOpportunistic Infections

Snapshot of Country Progress, Jan 2010Snapshot of Country Progress, Jan 2010

               

               

               

               

               

               

               

               

               

               

               

               

               

Botswana

Kenya

Lesotho

Malawi

Mozambique

Namibia

Rwanda

South Africa

Swaziland

Tanzania

Uganda

Zambia

Zimbabwe

National

Coordinator Task Force

Situation

Analysis Policy Training

Quality Service

Assurance Delivery M&E

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

Communicating about partial protection

Courtesy Q. Abdool Karim

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

Completed/ongoing PrEP studies - safety

Location Sponsor/Funder

Population / Primary Goal

PrEP Agent Status

Cameroon, Ghana, Nigeria

FHI / BMGF 936 high-risk women safety

TDF Completed 2006Safety demonstrated.

United States Extended Safety Trial

CDC 400 MSM safety

TDF Completed Results Q3 2010

Botswana TDF2 Study

CDC 1200 heterosexual men and women safety and behaviour

FTC/TDF Fully enrolledResults Q4 2010

Kenya, Uganda E001/002

IAVI 150 MSM, high-risk women, HIV discordant couples safety, acceptability

FTC/TDF (daily &

intermittent)

Fully enrolledResults Q4 2010

United States ATN 082

ATN / NIH 99 young MSM safety, acceptability

FTC/TDF EnrollingResults 2011

United States HPTN 066

HPTN / NIH 60 MSM PK

FTC/TDF (different dosing strategies)

Planning

TBD (Thailand, Africa) HPTN 067

HPTN / NIH 360 MSM, women safety, behavior

FTC/TDF (intermittent)

Planning

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

Ongoing PrEP studies - efficacy

Location Sponsor/Funder

Population PrEP Agent Status

Thailand Bangkok Tenofovir Study

CDC 2400 IDU TDF >95% enrolledResults Q4 2011?

South Africa CAPRISA 004

CAPRISA / USAID

900 women Vaginal TDF gel(coitally dep)

Completed.Results Q3 2010

Brazil, Ecuador, Peru, S. Africa, Thailand, US iPrEX

UCSF/NIH& BMGF

2499 MSM FTC/TDF Fully enrolled.Results end 2010

Kenya, Uganda Partners PrEP Study

UW / BMGF

4700 HIV discordant couples

TDF, FTC/TDF ~75% enrolledResults Q4 2012

Kenya, South Africa (Malawi, Tanzania Zambia) FEM-PrEP

FHI / USAID& BMGF

3900 high-risk women FTC/TDF ~20% enrolled Results 2013

South Africa, Uganda, Zimbabwe (Malawi, Zambia) VOICE / MTN 003

MTN / NIH

4200 ( 4950) women TDF, FTC/TDF,Vaginal TDF gel

(daily)

~10% enrolled Results 2013

Systemic versus topical administration in Systemic versus topical administration in womenwomen

Past & Current Microbicide Clinical Trials(courtesy of CAPRISA, Durban)

Stopped for futility Safe but not effective Increased HIV infection

Zena Stein publishes seminal article “HIV prevention: the need for methods women can use”

KenyaN-9 sponge

trial

FHIN-9 film trial

UNAIDSCOL-1492

trial

CONRADCS trial

FHI SAVVY trial

PopCouncilCarraguard trial

HPTN PRO2000 &

BufferGel trial

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

CAPRISATenofovir gel trial

MDP 0.5%PRO2000

trial

‘‘90 ‘92 ’98 ’00 ‘03 ‘04 ‘04 ’05 ’05 ’07 90 ‘92 ’98 ’00 ‘03 ‘04 ‘04 ’05 ’05 ’07 ‘10 ‘10

FHI CSTrial

2% PRO2000

67

MTN 003VOICE trial

IPMDapivirinegel & ring

trial

44

CAPRISA 004 dosing strategy (BAT 24) CAPRISA 004 dosing strategy (BAT 24) – based on nevirapine in childbirth– 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

asapasap72 hrs12 hrs

Onset of labour

Delivery

CAPRISA Vulindlela Clinic

KwaZulu-Natal Midlands

CAPRISA eThekwini Clinic

Durban City Centre

CAPRISA 004: Urban and Rural sites CAPRISA 004: Urban and Rural sites

Effectiveness of tenofovir gel in Effectiveness of tenofovir gel in preventing HIV infection preventing HIV infection

46

Tenofovir Placebo

# HIV infections 38 60

Women-years (# women) 680.6 (445) 660.7 (444)

HIV incidence(per 100 women-years)

5.6 9.1

Incidence rate ratio: 0.61 (CI: 0.4 to 0.94); p = 0.017

39% lower HIV incidence in tenofovir gel group

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

47

# HIV N

HIV incidence

EffectTFV Placebo

High adherers(>80% gel adherence)

36 336 4.2 9.3 54%

Intermediate adherers (50-80% adherence)

20 181 6.3 10.0 38%

Low adherers(<50% gel adherence)

41 367 6.2 8.6 28%

HIV infection rates in the Tenofovir and HIV infection rates in the Tenofovir and placebo gel groups: Kaplan-Meier survival placebo gel groups: Kaplan-Meier survival

probabilityprobabilityP

rob

ab

ilit

y o

f H

IV i

nfe

cti

on

0.0 0.5 1.0 1.5 2.0 2.5

Years

Months of follow-up 6 12 18 24 30

Cumulative HIV endpoints 37 65 88 97 98

Cumulative women-years 432 833 1143 1305 1341

HIV incidence rates(Tenofovir vs Placebo)

6.0 vs 11.2 5.2 vs 10.5 5.3 vs 10.2 5.6 vs 9.4 5.6 vs 9.1

Effectiveness (p-value)

47%

(0.069)

50%

(0.007)

47%

(0.004)40%

(0.013)39%

(0.019)

p=0.019

Tenofovir

Placebo

0.20

0.18

0.16

0.14

0.12

0.10

0.08

0.06

0.04

0.02

0.00

p=0.017

(0.017)

After 12 months of gel use:

HIV endpoints: 65

Effectiveness: 50%

P-value: 0.007

TenofovirPlacebo

Tenofovir gel – Next stepsTenofovir gel – Next steps

• 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

Moral obligation and public health imperative to confirm whether tenofovir gel is a viable HIV prevention option for women

Funding need: US$100 million over 3 years ( US$33 million/year)Committed: US$58 million Gap: US$42 millionGap: US$42 millionIn comparison: US $868 million invested in HIV vaccines in 2009 of US$1.165 billion invested in HIV prevention R& D

Acknowledgements

• 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

hivthisweek.unaids.org

Zero new HIV infections

Zero discrimination

Zero HIV-related deaths