Transcript The Effectiveness of generic Highly Active Antiretroviral

The Effectiveness of generic Highly
Active Antiretroviral Therapy for the
treatment of HIV infected Ugandan
children
Presenter: Linda Barlow-Mosha MD, MPH,
FAAP
Makerere University- Johns Hopkins University Research
Collaboration
3rd IAS Conference
July 27, 2005
Background
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90% of the 2.1million HIV infected children are in subSaharan Africa (UNAIDS, 2004)
Uganda has approximately 143,000 children living with
HIV and 20,000 children are infected each year through
mother to child transmission (MTCT) (MOH, 2001)
MU-JHU Research Collaboration has taken care of
over 3000 HIV infected children since 1988
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Death occurred in 30%,66%, 75% of the children at 1, 3, and
5 years respectively (Marum et al. July 1996)
Background
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Benefits of HAART have not yet been fully realized in
resource limited countries due to:
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High cost of drugs
Limited infrastructure to monitor patients
Access has recently been increased for patients in the
developing world through:
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Global funds
World Bank funds-MAP
PEPFAR (President Bush’s Initiative)
HAART in Uganda
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Approximately 64,000 individuals on HAART (Ministry of
Health,2005)
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< 4000 are children under 15 years of age (Ministry of
Health,2005)
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Majority of the children on HAART are in a few clinics
Children are often left out because of :
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Lack of infant HIV diagnostic tests
Limited appropriate drug formulation
Inadequate knowledge on ARV use in children
Triomune
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Fixed dose combination (d4T+3TC+NVP) - CIPLA
Reduced cost has made HAART more accessible
Clinical experience has documented satisfactory
response (Laurent et al, 2004)
In Uganda a study in adults documented a decline in
viral load and increase in CD4 count at 12 weeks into
therapy (Oyugi et al, Bangkok 2004)
Most of the fixed dose combinations available are in
tablet or capsule form and not in formulations
appropriate for young children
Objectives
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Primary Objective
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To determine the feasibility and effectiveness of a
generic fixed dose combination tablet (Triomune) in
HIV infected children
Secondary Objectives
To assess adherence to Triomune among HIV
infected children
 To document mortality rate of the children on
therapy
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Methods
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Screening
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HIV infected children from perinatal trials at MUJHU Research Collaboration and PIDC Mulago
Hospital were screened using WHO criteria for
antiretroviral therapy in resource limited settings and
CD4 count/percent
Methods
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Data collection
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Baseline
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Follow up 2 years
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CBC, CD4%/CD4 abs,Viral Load
Liver function test and Renal function test
CBC, CD4%/CD4 abs, and viral load – every 12 wks
Adherence assessment by self report and pill counts – at all routine
visits
Plasma storage for later NVP resistance testing
Sub-study for NVP pharmacokinetic (n=20)
Preliminary data after 48 weeks on therapy will be presented
Results
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Total number screened – 164 HIV infected children
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90 enrolled
81 given Triomune (d4T/3TC/NVP) as 1st line regime
72 remain on Triomune
14 are on alternative regimens
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8 due to weight <13kg
4 due to hypersensitivity to NVP
1 hepatitis
1 virologic failure
4 deaths
Results
At Enrollment
 Median age – 5yrs (1-14yrs)
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48% female
96% < 3rd percentile expected weight for age
67% < 5th percentile expected height for age
60% WHO stage II and 16% WHO stage III
26% with CD4 percent < 5%
67% with CD4 percent between 5-15%
Results
Median
CD4%
Median
Viral Load
(copies/mL)
Non-detectable
<400copies/ml
Baseline
n= 90
12 wks 24 wks 36 wks 48 wks
n= 78 n= 52 n=25 n=23
9%
17%
23%
27%
32%
(0.2-22)
(1-41)
(7-44)
(8-58)
(10-76)
p<0.0001
p<0.0001
p<0.0001
p<0.0001
284,391
121
141
190
190
(150->750,000)
(0->750,000) (0-133,469)
p<0.0001
p<0.0001
(0-140,418)
p<0.0001
(0-416,941)
p<0.0001
Results
Distribution Of Medain CD4 percent Over Time
35
30
Median CD4 %
25
20
n=23
15
n=25
n=52
10
n=78
5
n=90
0
Baseline
WK12
WK24
Time
WK36
WK48
Results
Viral Load vs Baseline, 12, 24,36, & 48 Weeks
Baseline
V 600000
I
R
R
N
A
A 400000
L
P
L
C
O 200000
R
A
D
12wks
12wks
24wks
36wks
48wks
12wks
0
Baseline
1
12 wks
2
24 3
wks
vi si t
36 4wks
48 5wks
t tests
1
Results
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48 weeks after therapy
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96% (22/23) of children have CD4% > 15
83% (19/23) of children have undetectable viral load
(<400copies/ml)
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42% (8/19) of the children with undetectable viral loads were NVP
exposed at birth
Adherence rate – 95% in 90% of the children
Majority of children with poor adherence were on syrups
Results- Toxicity and Mortality
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Side Effects
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skin rash - 4% (4/90)
hepatitis - 1% (1/90)
Mortality rate is 4% (4/90)
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2/4 children had an initial CD4 count less than 1%
3/4 children were severely immuno-suppressed or WHO
stage III
Causes of death include toxoplasmosis, malaria, and
pneumonia
Results
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Treatment Failure
Defined as viral load >400 copies/ml at 48 wks
 The 4 children with detectable viral loads
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history of poor/fair adherence to syrups
 exposure to single-dose Nevirapine at birth
 baseline viral loads >750,000 copies/ml
 viral rebound effect
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Results- Treatment Failure
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1/4 children with detectable viral loads has also shown
immunologic failure to therapy
Baseline
CD4%
12wk
CD4%
24wk
CD4%
36wk
48wk
CD4% CD4%
A
11.1
31.8
27.4
32.1
32.5
B
7.1
14.4
15.5
20.5
31.8
C
2.2
7.8
12.4
14.5
9.9
(4.5 at 60wk)
D
13.2
21.1
30.6
34.8
39.2
Conclusions
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The use of fixed dose combination in HIV infected
children is feasible and effective
Triomune led to a significant increase in CD4 count
and a decrease in viral load during the initial 48 weeks
of therapy
Adherence is better with a fixed dose combination than
syrups
We are still monitoring the effect of single-dose
Nevirapine exposure on response to future NVP
containing HAART regimens
Acknowledgments
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Elizabeth Glaser Pediatric AIDS Foundation
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Dr. Phillipa Musoke – Department of Pediatrics,
Makerere University Mulago / MU-JHU Research
Collaboration, Recipient of ILA
Program Staff – MU-JHU Research Collaboration
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International Leadership Award (ILA)
P. Ajuna, M. Luttajumwa, B. Musoke, J. Walabyeki, M. Owor,
M. Mubiru, M.G. Nalubega, M. Namawejje, E. Babirekere
MU-JHU Research Collaboration
Children and their caretakers
Thank You