Transcript a report to the who technical reference group on pediatric care and

EARLY CHILDHOOD OUTCOMES AT THE BOTSWANABAYLOR CHILDREN’S CLINICAL CENTRE OF
EXCELLENCE:
A REPORT TO THE WHO TECHNICAL REFERENCE GROUP
ON PEDIATRIC CARE AND TREATMENT, APRIL 2008
Gabriel M. Anabwani, Executive Director
Elizabeth Lowenthal, Associate Director
Michelle Eckerle, Pediatric AIDS Corps Doctor
Botswana - Background
Parameter
Total or Estimate
Population
1,719,996
HIV prevalence in pregnancy
32.4 % (2006)
HIV+ pregnant women delivering per yr
14,215 (2006)
± infant infections per yr without
PMTCT
4500
± Current new infant infections per year
900 (2005)
± HIV infected Children <15 yr on ART
6831
Neonatal/Infant/Child mortality rates
33/70/150 per 1000
Deaths Under Five Years of Age
Attributable to HIV/AIDS
Global
4.0%
Botswana
57.7%
Zimbabwe
42.2%
Swaziland
40.6%
Namibia
36.5%
Zambia
0%
10%
20%
33.6%
30%
40%
50%
60%
Percent of all HIV-positive pregnant women receiving antiretroviral drugs
during pregnancy, and changes to drug regimen
Botswana National PMTCT Program, 2002-2006
(Denominator=total number of deliveries x HIV prevalence from surveillance data)
100
Long-course AZT + SD NVP
Percent receiving drug
90
80
AZT (or HAART)
70
NVP (or HAART)
60
HAART*

50
40
Short-course AZT +
SD NVP
Short-course AZT
only
30
20
10
0
2002
2003
2004
2005
Year
*20-25% of pregnant women are eligible for ARV therapy during pregnancy (CD4<200)
Source: Situation Analysis (March 2006)
2006
Early Childhood Outcomes

Management According to Botswana National
ART Guidelines



All received AZT/d4T + 3TC + NVP
Criteria: all children <12 months with confirmed HIV
infection (DNA PCR) or >12 months with mild/moderate
or severe immune suppression or clinical manifestations
Children initiated on HAART at <36 months of age




Outcomes analyzed via database and manual chart
reviews
N = 377
Of these 56 patients had incomplete data (transferred
out, lost to follow-up, insufficient laboratory data)
Preliminary data analyzed for remaining 321
Virologic Suppression
By Baseline VL
Baseline VL
Suppressed by 6
Number
months on therapy
<750,000
122
112 (92%)
>750,000
180
147 (82%)

P= 0.02
Published Data Regarding Virologic Suppression
in Adults on NVP-based HAART by Baseline VL
(from Raffi et al, HIV Clin Trials 2001)
Virologic Suppression
By Age at Initiation
Age at Initiation
Number
VL Suppressed by 6
months on therapy
<6 months
19
13 (68%)
6-12 months
95
77 (81%)
>12-36 months
119
101 (85%)
Since baseline viral load is predictive
of virologic failure, can we predict
baseline VL on the basis of age and
baseline CD4 count?
Correlation Matrices
on BANA2 Trial Patients

Baseline VL >750,000 compared with
VL <750,000 with regards to:
Age
 CD4%
 CD4 absolute count
 CDC Immunologic category

No statistically significant correlations
Role of PMTCT
In Early Infant Outcomes
Standard program is:

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Maternal AZT started as early as 28 weeks (unless
mother on HAART)
sd-NVP to mother
sd-NVP to baby at birth
4 weeks of AZT to baby
Mothers rarely know whether sd-NVP was received

PMTCT is recorded as:




“yes” - some received
“no” - none known to have been received
Or “unknown”- not recorded
Based on reported excellent uptake of sd-NVP use by
national programme, it is assumed that most children
received sd-NVP if some PMTCT is reported
Virologic Suppression Among Children on
NNRTI-based 1st line by PMTCT status

112 infants/young children known to
have received PMTCT and initiated
HAART


187 infants/young children reported to
have received no PMTCTand initiated
HAART


85 (76%) achieved a VL<400 on 1st line
171 (91%) achieved VL<400 on 1st line
P=0.0003
Virologic Suppression Among Children on NNRTI-based 1st
Line by PMTCT Status and Age at Initiation

15 patients initiated HAART at <6 months of
age with a follow-up VL confirming virologic
suppression (VL <400 copies/ml) or nonsuppression at or after 6 months on HAART


10 (67%) suppressed
59 patients initiated HAART between 6 and
12 months of age with a follow-up VL
confirming virologic suppression (VL<400
copies/ml) at or after 6 months on HAART

44 (75%) suppressed
P=0.53
No difference between outcomes among patients
who initiated before 6 months and after 12 months

15 patients initiated HAART at <6 months of
age with a follow-up VL confirming virologic
suppression (VL <400 copies/ml) or nonsuppression at or after 6 months on HAART


42 patients initiated HAART between 1 and 3
years of age with a follow-up VL confirming
virologic suppression (VL<400 copies/ml) at or
after 6 months on HAART


10 (67%) suppressed
34 (81%) suppressed
P=0.29
Limitations of Data



Retrospective analysis
PMTCT status listed as “yes” or “no” and
may not necessarily be reflective of sdNVP status
Missing data
Benefits vs. Risks:
Early HAART Initiation

A recent chart review of 281 children who
initiated HAART >2 years ago at age <3 years at
the COE

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
235 confirmed alive
46 confirmed dead (16%)
93 were CDC category C3 at initiation


66 confirmed alive
27 confirmed dead (29%)
Benefit: children are more likely to live if you
initiate HAART before they are very sick and
immune suppressed
Note: Because we have liberal initiation criteria, we
do not have a comparison of death rates among
untreated children
Benefits vs. Risks:
Adverse Drug Reactions 1

The charts of the first 110 treatment naïve
children who had received HAART at the
COE for >52 w were reviewed for ADRs:


Mean age = 70 m; Male: female = 1:1
106 (96%) received ZVD+3TC+NVP
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4 with Hb<7.5 g/dl received d4T in lieu of ZVD
Median VL/CD4% were 310,000/15%
44 (40%) were in CDC immune category 3
Median Hb was:
9.4 g/dl in patients < 24 m
 10.6 g/dl in those > 24 m

Benefits vs. Risks:
Adverse Drug Reactions 2

Overall Median Hb increased by 52 w:

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
9.4 to 10.4 among those aged <24 m
10.6 to 11.2 g/dl in those aged >24 m
Median ALT unchanged at 19.0±0.5 u/L
over 52 weeks
ADR occurred in 23 (21%) patients:

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Rash in 17 (74%)
Severe anemia (Hb <3 g/dl) in 3 (13%)
Vomiting in 3 (13%)
Benefits vs. Risks:
Adverse Drug Reactions 3

Rash occurred in first three weeks of therapy:

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Severe anemia developed at 3 m in one and at 4 m
in 2 patients
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All were transfused and switched from ZVD to d4T
Vomiting was mild and resolved without therapy
Grade 3 lipase toxicity developed in 2 patients

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16/17 (94%) were mild or moderate
1 had Steven’s-Johnson syndrome requiring inpatient
care
Subsequently normalized without further intervention
Conclusion: HAART in naïve African children
using a regimen consisting of ZVD or d4T + 3TC +
NVP was both generally safe and well tolerated.