Transcript Early diagnosis and treatment options for children living with HIV

Early diagnosis and treatment
options for children living with
HIV
Dr Siobhan Crowley
Paediatric & Family HIV Care
World Heath Organization,
Email: [email protected]
http://www.who.int/hiv/paediatric/en/index.html
Overview
• Progress
• Rationale for early diagnosis and
treatment
• Ways forward
• Revised WHO recommendations
250,000
Children <15 receiving ART
200,000
 More children are
receiving ART
55% increase
from 2006-2007
 Increased from 75,000 in
2005 to almost 200,000 in
2007
 19 of 20 countries with
highest PMTCT burden are
in sub-Saharan Africa
90% of burden is in 20
countries
150,000
78% increase
from 2005-2006
100,000
50,000
0
Total=75,000
Total=127,300
Total=197,600
End 2005
End 2006
End 2007
East, South & South East Asia
Eastern Europe & Central Asia
Latin America & Caribbean
West and Central Africa
Eastern and Southern Africa
Towards Universal Access: Scaling up priority HIV/AIDS interventions in the health sector, WHO/UNAIDS/UNICEF 2008
ART outcomes - more good news
• National
programmes
reporting good
outcomes
• 1 year survival
estimated as 9395%
• 2 year survival
91%
Country
Treatment Outcomes
Malawi #
5% mortality overall @ 6 mo, 13% at 12 mo
> Death & default in younger kids
Zambia
Overall 6.6 mortality, good CD4 responses, higher mortality in
<18mo most early
Haiti #
81% in care @ 12 mo, 9% mortality
Kenya
Decreased hospitalisation; 6-9 % mortality
Cote d'Ivoire
3.5 - 12% mortality at 36 mo, RNA < 300 in 46-66%
Thailand #
Decreased hospitalisation; 5.7% mortality decreased to 0.6 after
24 wks
Tanzania
0% mortality (instutionalised orphans)
South Africa
8.6 % mortality most early; 80% RNA undetectable at 12 mo
15% mortality at 12 mo, 70% RNA < 400
MSF (Asia, Africa ) #
3% mortality/ 8% LFU at 12 mo;
7% still severe immunosuppression at 12mo
China
2% mortality, 55% RNA < 400 at 12 mo;
Cambodia #
92 % survival at 24 mo; 81% RNA undetectable
# programme reporting
Sutcliffe. Lancet Infect Dis 2008;8: 477–89
Children are Starting Treatment Late
Janssens/Cambodia
2007
53% >5 years of age,
70% severe immune
deficiency, 12% aged <
12 months
(KIDS-ART-LINC)
Arrive 2008
2007
4.4 yrs
6%
5.7 yrs
8%
7.7 yrs
5%
9.2 yrs
8.6%
6.5 yr
8%
N=250
Rouet/Cote d’Ivoire
2006
12%
N=107
Kamya/Uganda
2007
6.3 yrs
N=151
Puthanakit/Thailand
2007
6%
N=67
Reddi/S Africa
2007
6.0 yrs
N=100
Wamawala/Kenya
2007
Baseline
Median CD4
N=212
George/Haiti
Meta-analysis 1,195
children from 8
African clinical trials
Baseline
Median Age
N=78
Starting ART when severely immunodeficient
increases mortality
Months from
ART start
Probability of Death After Starting ART
Immune Deficient at Start
ART
6 months
12 months
7.8%
8.2%
Not Immune Deficient at
Start ART
6% excess mortality
1.8%
2.2%
Arrive E et al. 14th CROI, Los Angeles, CA, 2007 Abs. 727
73% median age > 5 years of age, > 50% start with severe immune
deficiency, most deaths within 6 months of starting ART.
Risk factors for death:
• low CD4
• < 18 months age
• WHO stage 3/4
• Viral load greater than 6·0 log
• severe malnutrition
Sutcliffe et al. Lancet Infect Dis 2008;8: 477–89
CHER STUDY : 76% Reduction in the Risk of Death
with Immediate Compared to Deferred ART
1.00
P = 0.0002
Immediate
0.40
0.60
Most deaths occurred within
first 6 months (i.e., before age 10 months)
16%
deferred
0.20
Failure Probability
0.80
Deferred
0.00
immediate
0
3
Patients at risk
6
Time to Death (months)
Month 0
Month 3
Month 6
Month 9
9
12
Month 12
Deferred
125
104
72
44
22
Immediate
252
213
145
99
52
4%
Entry points for children - Malawi
PMTCT
f/up
1%
Index
patient
Kenya -
1%
VCT
ART
care
IPD 69%
Cote D' Ivoire
Child
health
64% IPD
12% PMTCT
24% PLHA Index
18%
Wards
80%
<1%
Southern Africa – HIV prevalence in
population based surveys
9
HIV Prevalence (%)
8
7
6
5
Botswana
4
3
Swaziland
2
South Africa
1
0
2-4
5-9
10-14
Age
Source: CSO, Measure DHS. Swaziland Demographic and Health Survey 2006-7. Preliminary report, 2007. NACA, CSO.
Botswana AIDS Impact Survey II 2004. Central Statistics Office: Gaborone, Botswana, 2005. Shisana, O., et al., South
African National HIV Prevalence, HIV Incidence, Behaviour and Communication Survey, 2005. HSRC Press: Cape Town,
2005.
SLIDE courtesy of E Gouws UNAIDS
90
80
2005 n=79
76
78
2006 n=108
70
In 2007:
2007 n=109
60
47
50
40
30
30
20
• only 8% of HIV
exposed infants
tested in 1st 2 months
of life
• only 4 % started on
co-trimoxazole
23
17
10
0
Number of countries using dired blood
spots for virological testing
Number of countries with a policy on
provider initated testing and counselling for
infants and young children
Towards Universal Access: Scaling up priority HIV/AIDS interventions in the health sector,
WHO/UNAIDS/UNICEF 2008
Ways forward
•
•
•
•
Each infection can and should be prevented
Early diagnosis prior to disease progression
Earlier initiation of ART
Expand PITC and screening for HIV in health
care facilities
WHO recommendations for provider initiated
testing approaches infants & children
Population
Recommendation
Strength of
recommendation
HIV exposure unknown
Ask all about HIV exposure as
early as possible
Strong
Unknown HIV exposure Ensure /maternal/ infant testing
High HIV burden
within first 6 weeks or at first
contact with health system
Conditional –
(HIV prevalence)
HIV exposed
Virological testing at 4-6 weeks of Strong
age
Any signs or symptoms
suggestive of HIV
Age appropriate testing urgently
Strong
Sibling, parent or carer
has HIV (family)
Age appropriate testing
Strong
WHO -new recommendations for
starting ART in infants
All infants under 12 months of age with
confirmed HIV infection should be started on
antiretroviral therapy, irrespective of clinical or
immunological stage.
GRADE Evidence profile = Moderate
Strength of Recommendation = STRONG
http://www.who.int/hiv/pub/paediatric/WHO_Paediatric_ART_guideline_rev_mreport_2008.pdf
What ART to Start in infants –
2008 revision
NVP
triple
ART
No infant or maternal
ARV exposure
18%
34%
Sd NVP or NNRTI containing ART
PI
triple
ART#
Non NNRTI exposure
NVP
triple
ART
MTCT ARV
Exposure
Unknown infant
maternal MTCT
Exposure
# If no PI is available use NVP triple ART
Simplified weight based dosing availabe at;
http://www.who.int/hiv/paediatric/en/index.html
NVP
triple
ART
Immunological thresholds to start
ART
CD4/mm3 #
Age
%CD4
Infants < 1 yr
All- irrespective of CD4
12-35 months
<750
<20
36-59 months
<350
5 years or over <15
As in adults
# Absolute CD4 count is naturally less constant and more age-dependent than %CD4;
it is not therefore appropriate to define a single threshold.
Thank you
Please feel free to contact me if you need more information
Dr Siobhan Crowley
[email protected]
Acknowledgments:
HIV Care and treatment: Technical Reference group
Paediatric ARV dosing working group
WHO colleagues
Lynne Mofenson
Eleanor Gouws
F Dabis/V Leroy
Robert Gass/Patricia Doughty