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
 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 women

Of the 7400 new infections per day in 2008, about 1200
were in children under 15 years of age
 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 4

 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

 Know your epidemic and
response synthesis process
ANALYSIS OF EPIDEMIC
Epidemiological
Review: Incidence data
Drivers/ (modelled or
country specificity otherwise)

SYNTHESIS

Prevention
policies, Review of
response and resources for
strategic info prevention
review ANALYSIS OF RESPONSE
Incidence by mode of HIV transmission in East
and Southern Africa
100%

80%
Percent new infections

60%

40%

20%

0%
April Kenya
Source: MOT country reports available at Lesotho S waziland Uganda 7
2010 http://www.unaidsrstesa.org/hiv-prevention-modes-of-transmission
Collectively we’ve made remarkable
progress in many aspects of the
response to HIV…

… incidence of new infections,

antiretroviral treatment, human rights
 ART Scale up Progression in Resource Limited
Settings (2003 - 2008)

6,000,000 120,000
Cumulative Number of Patients
Receiving ART
Cumulative Number of Patients on ART

Mean Rate of Increase (patients on

Number of Patients on ART/Month

ART/month)
5,000,000 100,000

4,000,000 80,000

3,000,000 60,000

2,000,000 40,000

1,000,000 20,000

0 0
Dec-03 Jun-04 Dec-04 Jun-05 Dec-05 Jun-06 Dec-06 Jun-07 Dec-07 Jun-08 Dec-08 Dec-09
Treatment benefits are clear….

The number of AIDS-related Estimated number of Life- years ad

deaths has declined by over 10% by region,
over the past five years…

8
7.2 million
7

Estimated number of AIDS - related deaths with and

(millions)
5

without antiretroviral therapy,

4 globally, 1996
–2008
3
2.3 million
2
3.0
Since 1996 the availability of
1.4 million

effective treatment, has

1 590 0
2.5
saved
0 some 2.9 million lives…
Western Sub- Latin Asia
mber (millions)

2.0 Europe Saharan America

and North Africa
1.5 America

1.0
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
revolution by taking definitive action to
protect 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
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
“Gay couple freed by Malawi presidential
pardon return to home villages”
be multiplied Human rights campaigner says men have not been reunited amid fears for their safety

• Lifting of travel
restrictions: USA, China
One of the biggest human rights issues
facing the AIDS movement is funding
TOTAL annual resources available for AIDS in low and
middle income countries, 1996-2009
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

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

USD billions

Commitments Disbursements
(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
 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
 International Assistance for HIV, domestic
spending, and financing gaps
Eastern Europe and
Central Asia 1,600

518
119

DONOR
DONOR 2 BILLION
Received Domestic Needed Aid
3.5 BILLION Aid spending South East Asia and the
Pacific
DONOR
21 MILLION

Latin America and the

Caribbean

Sub-Saharan DONOR
8 MILLION
Africa

12,000

3,772
1,306

Re ce iv e d Dome stic Ne e de d Aid

Aid sp e n d in g
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
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)

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 sustainability
8. Develop a global partnership for development

24
 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
 How much is too much?
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

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 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
 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 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:
approaches rights-based, evidence-informed
combination HIV prevention approaches
 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 42% (21; 58)
(Mwanza)
Circumcision 57% (42; 68) : M-A
(Orange Farm, Rakai, Kisumu)

CAPRISA 004 39% (6;60)

0% 10 20 30 40 50 60 70 80 90 100% Efficacy

Padian NS, et al. Weighing the gold in the gold standard: challenges in HIV prevention research. AIDS 2010, 24:621–635
 

Courtesy Q. Abdool Karim

 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
Weiss et al. AIDS 2008
 Snapshot of Country Progress, Jan 2010
Situation Quality Service
National Analysis Policy Training Assurance Delivery M&E
Coordinator Task Force
Botswana
Kenya

Lesotho

Malawi

Mozambique

Namibia

Rwanda
South Africa

Swaziland

Tanzania

Uganda
Zambia

Zimbabwe

CROI 2010
17th Conference on Retroviruses and
 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/ Population / PrEP Agent Status
Funder Primary Goal

Cameroon, Ghana, FHI / 936 high-risk TDF Completed 2006

Nigeria BMGF women Safety
safety demonstrated.

United States CDC 400 MSM TDF Completed

Extended Safety safety Results Q3 2010
Trial
Botswana CDC 1200 heterosexual FTC/TDF Fully enrolled
TDF2 Study men and women Results Q4 2010
safety and
behaviour

Kenya, Uganda IAVI 150 MSM, high-risk FTC/TDF Fully enrolled

E001/002 women, HIV (daily & Results Q4 2010
discordant couples intermitte
safety, nt)
acceptability

United States ATN / NIH 99 young MSM FTC/TDF Enrolling

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 Population PrEP Agent Status
/
Funder

Thailand CDC 2400 IDU TDF >95% enrolled

Bangkok Tenofovir Results Q4 2011?
Study
South Africa CAPRISA 900 women Vaginal TDF Completed.
CAPRISA 004 / USAID gel Results Q3 2010
(coitally dep)

Brazil, Ecuador, Peru, UCSF/ 2499 MSM FTC/TDF Fully enrolled.

S. Africa, Thailand, NIH& Results end 2010
US BMGF
iPrEX
Kenya, Uganda UW / 4700 HIV discordant TDF, FTC/TDF ~75% enrolled
Partners PrEP BMGF couples Results Q4 2012
Study
Kenya, South Africa FHI / 3900 high-risk FTC/TDF ~20% enrolled
(Malawi, Tanzania USAID& women Results 2013
Zambia) BMGF
FEM-PrEP
Systemic versus topical administration in
women
 67
Past & Current Microbicide Clinical Trials
(courtesy of CAPRISA, Durban)
1st class: 2nd class: 3rd class: 4th class:
Surfactants Polymers ARVs Co-receptor
Blockers
eg. N9, SAVVY eg. PRO2000, eg. Tenofovir gel,
Carraguard, Dapivirine gel/ring eg. CD4 blocker,
Cellulose Sulfate (CS) CCR5 Blockers
Kenya
N-9 sponge CONRAD FHI CS
trial CS trial Trial
CAPRISA
Tenofovir
FHI
N-9 film trial
PopCouncil gel trial
Zena Stein Carraguard trial
publishes
UNAIDS MTN 003
seminal article HPTN
COL-1492 PRO2000 & VOICE trial
“HIV trial BufferGel trial
prevention: the
need for IPM
FHI SAVVY
methods women Dapivirine
trial MDP 0.5%
can use” gel & ring
PRO2000
trial
trial
2% PRO2000

‘90 ‘92 ’98 ’00 ‘03 ‘04 ‘04 ’05 ’05 ’07
‘10
Safe but not effective Increased HIV infection Stopped for futility
 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
12 hrs 72 hrs asap

Onset of Delivery
labour

44
CAPRISA 004: Urban and Rural sites
CAPRISA Vulindlela Clinic CAPRISA eThekwini Clinic
KwaZulu-Natal Midlands Durban City Centre
 Effectiveness of tenofovir gel in
preventing HIV infection
Tenofovir Placebo

# HIV infections 38 60
Women-years (# women) 680.6 (445) 660.7 (444)

HIV incidence 5.6 9.1

(per 100 women-years)

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

39% lower HIV incidence in tenofovir gel group

46
 Impact of adherence on effectiveness of
tenofovir gel
(overall 39% [6,60])
# HIV N HIV incidence Effect
TFV Placebo

High adherers 36 336 4.2 9.3 54%

(>80% gel adherence)

Intermediate adherers (50- 20 181 6.3 10.0 38%

80% adherence)

Low adherers 41 367 6.2 8.6 28%

(<50% gel adherence)

47
 HIV infection rates in the Tenofovir and
placebo gel groups: Kaplan-Meier survival
probability
0.20
0.18
Tenofovir
0.16
Placebo Placebo
0.14 p=0.019
0.12 p=0.017
0.10 Tenofovir
0.08
0.06
0.04
fH
IV P

0.02
n
c
e b
ro
ilty
a

0.00
0.0-up 0.5 1.0 1.5
After
2.0
12 2.5months of gel
Months of follow 6 12 18 24 30
Cumulative HIV endpoints 37 65 Years 88 97 use:
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 HIV endpoints:
5.6 vs 9.4 5.6 vs 9.1 65
Effectiveness 47% 50% 47% 40% 39%
(p-value) (0.069) (0.007) (0.004) Effectiveness:
(0.013) (0.019) 50%
P-value: 0.007
(0.017)
 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
 Acknowledgements

• Carlos Avila • Tim Hallett

• Salim Abdool Karim
• Helen Weiss
• •
Richard Hayes
• Jared Baeton
• Connie Celum
• Quarraisha Abdool Karim
• Eleanor Gouws
• Alexandra Calmy
• 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