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AIDS World Day, Belgian Development Agency,
Brussels 30th November 2012
Prof Joseph Vyankandondera
Senior Women and Children Health Specialist
Burnet Institute, Melbourne, Australia
Outline
•
•
•
•
•
Basic facts
Prevalence and Incidence
Prevention
Cost
Burnet CD4 Point of Care
• Based on available samples from 1959 onwards
most likely location for transmission event from
chimpanzees to humans (Sharp Nature 2008)
First peer reviewed report – Lancet
• 8 men in NYC
HIV Entry into CD4+ Cells
WHO HIV/AIDS Classification
System
Stage I
Asymptomat
ic
Stage II
Minor
Symptoms
Stage III
Moderate
Symptoms
Stage IV
AIDS
Pattern of progression
to AIDS
Long-term Non-progressors
>10-15 years
No symptoms, stable CD4
<10%
Rapid progressors
<3 years
5%
Typical
progressors
7-10 years
90%
Type and subtype also
influence natural history
of disease
• HIV-1 vs HIV-2
• Clade D vs A
Infectious fluids
• Highly Infectious
• Not infectious
–
Blood, bloody fluids, body tissue
–
Semen, vaginal secretions
–
Urine
–
Fluid around the brain, spinal
cord, unborn baby, heart, lungs,
intestines, joints
–
Faeces
–
nasal secretions
–
saliva
(cerebrospinal, amniotic,
pericardial, peritoneal, pleural,
synovial fluids…….
–
gastric fluid
–
sputum
NB: these fluids are not normally
shared!)
–
tearsa
–
sweat
• Moderately
infectious
–
Breast milk
(unless visibly bloody)
Transmission needs an infectious fluid to
come into contact with a mucous
membrane
HIV Transmission: rare routes
• Open-mouth kissing
One possible case
• Oral sex
Few possible cases
• Women having sex with women
Few possible cases
• Using sex toys
No documented cases
• Tattoos and body piercing
Documented cases
• Human bite
Few possible cases
• Household contact
Few possible cases
• From health care workers
One case
Exposure
HIV transmission
per exposure
RECEPTIVE ANAL INTERCOURSE
1:125 to 1:31
RECEPTIVE VAGINAL INTERCOURSE
1:2000 to 1:667
INSERTIVE ANAL
OR
VAGINAL INTERCOURSE
1:3333 to 1:1111
PUNCTURE OF HEALTH CARE WORKER
BY CONTAMINATED NEEDLE
1:313
USE OF CONTAMINATED
INJECTING DRUG EQUIPMENT
1:149
http://www.ashm.org.au/default2.asp?active_page_id=25
Prevalence and Incidence
Regional HIV and AIDS statistics and features  2010
22.9 million
Adults and children
newly infected with
HIV
1.9 million
[21.6 million – 24.1 million]
[1.7 million – 2.1 million]
Adults and children
living with HIV
Sub-Saharan Africa
Middle East and North Africa
South and South-East Asia
East Asia
Latin America
5.0%
Adult & child
deaths due to
AIDS
1.2 million
[4.7% – 5.2%]
[1.1 million – 1.4 million]
Adult prevalence
(15‒49) [%]
470 000
59 000
0.2%
35 000
[350 000 – 570 000]
[40 000 – 73 000]
[0.2% – 0.3%]
[25 000 – 42 000]
4.0 million
270 000
0.3%
250 000
[3.6 million – 4.5 million]
[230 000 – 340 000]
[0.3% – 0.3%]
[210 000 – 280 000]
790 000
88 000
0.1%
56 000
[580 000 – 1.1 million]
[48 000 – 160 000]
[0.1% – 0.1%]
[40 000 – 76 000]
1.5 million
100 000
0.4%
67 000
[1.2 million – 1.7 million]
[73 000 – 140 000]
[0.3% – 0.5%]
[45 000 – 92 000]
200 000
12 000
0.9%
9000
[170 000 – 220 000]
[9400 – 17 000]
[0.8% – 1.0%]
[6900 – 12 000]
million
Eastern Europe and Central Asia [1.3 million1.5
– 1.7 million]
160 000
0.9%
90 000
[110 000 – 200 000]
[0.8% – 1.1%]
[74 000 – 110 000]
Caribbean
Western and Central Europe
North America
Oceania
TOTAL
840 000
30 000
0.2%
9900
[770 000 – 930 000]
[22 000 – 39 000]
[0.2% – 0.2%]
[8900 – 11 000]
1.3 million
58 000
0.6%
20 000
[1.0 million – 1.9 million]
[24 000 – 130 000]
[0.5% – 0.9%]
[16 000 – 27 000]
54 000
3300
0.3%
1600
[48 000 – 62 000]
[2400 – 4200]
[0.2% – 0.3%]
[1200 – 2000]
34.0 million
2.7 million
0.8%
1.8 million
[31.6 million – 35.2 million]
[2.4 million – 2.9 million]
[0.8% - 0.8%]
[1.6 million – 1.9 million]
The ranges around the estimates in this table define the boundaries within which the actual numbers lie, based on the best available
information.
Over 7000 new HIV infections a day in 2010
 About 97% are in low and middle income countries
 About 1000 are in children under 15 years of age
 About 6000 are in adults aged 15 years and older, of
whom:
─ almost 48% are among women
─ about 42% are among young people (15-24)
World HIV Prevalence and incidence
beetween 1990-2010 Unaids report 2011
Mortality due to AIDS and impact of
Antiretroviral therapy
HIV prevalence and incidence in Asia
(1990-2010)
HIV prevalence and incidence in
Eastern Europe and Central Asia
(1990-2010)
HIV prevalence in women
2015 target in ARV coverage
2015 Target: new infection in adults
PREVENTION
Why Prevention?
(HIV Prevention working group)
• An estimated 7,000 new HIV infections each
day,
• Number of new HIV infections was more than
2.5 greater than the number under ARV (in
2007)
•
Access to proven prevention strategies:
– half of new infection averted
– In Sub-Saharan Africa, 55% of the 53 million new infections projected to
occur 2003-2020
•
In Asia, the epidemic will push an additional 6 million people into
poverty by 2015
the need for sustained
investment in prevention
“We must not forget: for every two people who start antiretroviral
treatment, five are newly infected with HIV. To break this vicious
circle, there is only one solution to stop new HIV infections.
Prevention must become our watchword, the banner we raise in this
critical stage of the response.”
Michel Sidibé, Executive Director of
Preventing Sexual Transmission (1)
• Behavior Change Programs
Behavioral interventions in well-defined populations at risk of HIV
infection:
–
–
–
–
–
Sex workers
Men who have sex with men
Substance users
Women
Young people
• remain sexually abstinent (?)
• delay initiating sexual activity
• decreasing the number of sex partners, or using condoms
consistently if sexually active
Preventing Sexual transmission(2)
• Condoms
– Effectiveness: 85% on individual level, limited on population
level
• HIV Testing
– Timely diagnosis of HIV infection promotes HIV prevention.
– 80% of people living with HIV in low- and middle-income
countries remain undiagnosed
– in 70% of countries reporting data to UNAIDS, HIV testing is
not widely available
– When undiagnosed HIV infection: 3.5 times more likely to
transmit HIV than individuals tested HIV-positive
• Prompt Diagnosis and Treatment of Other STIs
– Sexually transmitted infections (STIs) increase the risk of HIV
acquisition and transmission by 2 to 5 times.
Treating STIs
Pre exposure prophylaxis with Anti
retrovirals
Preventing sexual transmission
Medical Male Circumcision (MMC)
• Clinical trials in Kenya, South Africa and
Uganda: MMC lowers by approximately 60%
the risk of female-to-male sexual HIV
transmission.
• But
– risk of transmission may increase if a newly-circumcised male
engages in sexual intercourse before wounds have healed.
– No proof that MMC benefit for women during heterosexual
intercourse
Male circumcision
Preventing Blood-BorneTransmission (1)
Injection Drug Users
Injection drug use is
– a primary driver of the epidemic in many parts of Asia
– >60% of new reported HIV diagnoses in Eastern Europe and Central
Asia in 2006
• Harm Reduction Programs access to clean syringes and
injection equipment,
• substitution drug treatment therapy,
• programs to reduce demand for drugs
Preventing BloodBorneTransmission (2)
• Blood Supply Safety
–
–
–
–
routine screening of the blood supply,
reduce unnecessary transfusions
preclude high-risk donors,
can virtually eliminat the risk of HIV transmission (developed
countries)
– >1 million units of blood still not properly screened in 2008 (WHO)
Preventing BloodBorneTransmission (3)
•
•
•
•
Infection Control in Health Care Settings
Adopt “universal precautions”
Every patient as potentially infectious,
workers to wear protective gear, to use syringes properly sterilize
all equipment and surfaces.
• equipment used to administer injections are automatically
disposed of safely.
• In 2000, unsafe injection practices were estimated to be
responsible for 5% of new HIV infections
“We can prevent mothers from dying and babies
from becoming infected with HIV. That is why I
am calling for a virtual elimination of mother to
child transmission of HIV by 2015,” said Michel
Sidibé, Executive Director of UNAIDS.
“This is one of the main priority areas for UNAIDS,
UNICEF, WHO and UNFPA to act on.”
Preventing MTCT and keeping Mother
alive
• Transmission during gestation, birth or via breastfeeding.
• With no intervention and prolonged Breastfeeding:
45% of MTCT
• If Comprehensive package for PMTCT: less than
1%
– Antiretroviral Drugs
– Safe Breast-feeding (exclusive combined with
ARVs) or formula feeding
– Caesarean Delivery (where available)
– Reducing women vulnerability.
How children become infected?
Most during pregnancy, at delivery or
through breastfeeding
Some
through
sexual
abuse
A small
proportion through blood
transfusions and unsafe injections
100 pregnant HIV positive women
On average 35 babies will be infected with HIV
About 7
become
infected during
the pregnancy
About 15
become
infected at
the time
of delivery
About 13
become
infected
through
breastfeeding –
most in the
early weeks
HIV and infant feeding
– weighing the risks in different circumstances
Savage-King
Risk of HIV if
breastfed
Risk of
diarrhoea, URTI
and malnutrition
if not breastfed
Holmes
Other preventive methods
• Vaccines
• Microbicides
• HSV-2 Treatment
• HIV Treatment as Prevention
COST MODELLING FOR HIV
MITIGATION AND ELIMINATION
Women & Child Health Costs
Demand side
Consultation fees
Facility charges
Laboratory fees
Transport costs
Food costs
Costs associated with accompanied persons
Supply side
Human resources – all types of providers
Drug costs
Medical supplies
Other recurrent costs
AUSAID KNOWLEDGE HUBS FOR HEALTH
Principal Financing
Mechanisms
Women & child health care can be funded in a number of ways
Direct payments: User charges
Tax revenue
Social health insurance
Private insurance
Community financing
External funders (e.g. donor funding)
AUSAID KNOWLEDGE HUBS FOR HEALTH
• Sub-Saharan Africa spent more per
capita (19 % vs 2%) than any other
region on HIV and less per capita (80 %
vs 98 %) than any other region on
health.
Figure: HIV Spending as a Share of Total Health Spending.
PLoS ONE | www.plosone.org September 2010 | Volume 5 | Issue 9 |
HIV expenditure
• from 1996-2007: 33 fold especially in Sub Saharan Africa
• in 2007: 10 billion
• If test and treat strategy for elimination of HIV:4 fold
= 41-58 billion by 2015
• Elimination by 2050 in combination with comprehensive
preventive methods
ART scale up – where are we now?
Is the 15 million target achievable?
<350 CD4
but not on ART
<200 CD4
but not on ART
6%
47 |
The Strategic Use of ARVs | IAC Satellite, July 22, 2012
54%
WHO’s ARV-related guidance in 2012
Treatment as Prevention (TasP)
TasP in sero-discordant couples
Lifelong ART for pregnant women (“B/B+”)
TasP in key populations (SW, IDU, MSM)
Pre-Exposure Prophylaxis (PrEP)
Demonstration projects
in sero-discordant couples and MSM
48 |
The Strategic Use of ARVs | IAC Satellite, July 22, 2012
Infectiveness
Reuben M Granich, Charles F Gilks, Christopher Dye, Kevin M De Cock, Brian G Williams Lancet 2009; 373: 48–57
Scenarios for the incremental expansion of ARV
provision to treat and prevent HIV
51 |
The Strategic Use of ARVs | IAC Satellite, July 22, 2012
Treating HIV infection earlier rather than later
Likely benefits of earlier initiation
–should prevent AIDS and non-AIDS related disease
–decreases risk of TB
–offers medium and long-term cost saving opportunities
but
–could increase toxicities and risk of drug resistance
–could limit future treatment options
–will increase upfront costs
52 |
The Strategic Use of ARVs | IAC Satellite, July 22, 2012
Towards elimination of HIV?
Lancet 2009; 373: 48–57
CD4 T-cells - need for point-of-care
• Essential monitoring tool for management of HIV
– < 350 CD4+ T-cells/µl to initiate therapy
– > 350 – re-test in 6 months, or in pregnancy give prophylaxis
• ≈ 2 million infected patients in the developed world
– Flow cytometry is “standard of care”
– Access to Flow counts widely available, if not convenient
• ≈ 30-34 million infected in the developing world
– Little access to Flow cytometry
– Some low-throughput microscopy tests, at moderate cost
– Roadblock to effective HIV drug treatment – 15 million eligible
patients lacking access to treatment (UNAIDS 2010)
• Need for simple, robust, cheaper tests
Priority Diagnostics Roadmap
UNMET MEDICAL NEEDS
• Access to treatment,
control of disease
spread, targeting of
vaccines or drugs
Develop novel
(point-of-care)
tests
Laboratory
validation of
tests
Implementation
studies
PATIENT
BENEFITS
Outlicensing for
manufacture and sale
Field validation
of tests
Target CD4 Rapid Test Specifications
1.
Simple, inexpensive and robust
2.
Semi-quantitative: cut off of 250 CD4 T-cells/microlitre
3.
Stable >12 months 40ºC with high humidity
5.
Use of whole blood from finger-prick
6.
Easy to perform and interpret – no, or minimal
instrumentation
7.
Less than 40 minutes from patient to result
8.
All components included in the kits
Preferable: Similar format to existing RPOC tests used for
initial diagnosis of HIV and other infectious diseases, etc.
CD4 Test incorporated into low-cost device
Add 40 L of whole blood
to Well A wait 3 minutes
Add 1 drop of buffer to Well A
and allow the sample to run
for 17 minutes.
Add 3 drops of buffer to
Well B, wait 20 minutes.
Read results after 20 minutes
(40 minutes total).
Step 1: blood to well A
Add 40 L of whole blood
to Well A wait 3 minutes
RBC and monocytes retained in
pad
Biotinylated anti-CD4 ecto
rehydrates & complexes with
intact T cells
Step 2: buffer to well A
Add 1 drop of buffer to Well A and
allow the sample to run for 17 minutes.
Soluble
CD4 not
captured
Capture of
exposed CD4
cytoplasmic tail
Cells lysed exposing full length
CD4 cytoplasmic domain
Step 4: Read Results
Read
results
after 20
minutes
.
“TREAT”
Test line equal or
weaker than 350
reference line
(≤350 CD4+ T-cells/µl).
“ NO TREAT”
Test line stronger than
350 reference line
(>350 CD4+ T-cells/µl).
CD4 Test – next steps
• 2012 - Lab validation trials in USA, UK
– CE mark
• Field validation trials in Zimbabwe, India,
and antenatal clinics in Kenya, South
Africa commencing Q4, 2012
– “Saving Lives at Birth” – Stanley Luchters et al
(Gates Foundation, USAID, DFID, Govt
Norway).
• India, South Africa, under current grant
applications (USAID, UNITAID)
• Studies for use in TB/HIV coinfection –
second “cutoff” of 50-100 CD4/µl
• Revised cutoff of 500 CD4/µl anticipated
Translational research – eg, Point of care testing
Control Reference Test
(350 or 200/µl)
“I saw at the Burnet Institute a simple CD4 count test that costs less than
US$ 1 and requires minimal expertise to use. If we were to measure the
baseline CD4 of the 10 million people worldwide with HIV who still need
treatment today, it would cost us $700 million. Using such low-cost,
easy-to-use tests, we could achieve the same for just $10 million in a
tiny fraction of the time.”
Michel Sidibé, Executive Director, UNAIDS (2010)
Duke University
Suzanne Crowe
David Anderson
James McMehon
Mary Garcia, Suzanne Crowe, Robyn Lloyd,
Jocelyn Diaz, Nadine Barnes, Pat Mottram,
Simone van de Waarsenburg, Joy Liu
Alan Landay
Tom Denny
Andrew Lysikatos, Gavin Ramanathan,
Bill Hopper,
Nolan, Anthony Lawlor
MRCF Australia
See-D4 Andrew
Ltd
Mitra Singhal, Cori Barfield, Chris Crudder,
Rebecca Barney, Matt Steele
THANK YOU