EARLY CHILDHOOD OUTCOMES AT THE BOTSWANA-BAYLOR CHILDREN

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EARLY CHILDHOOD OUTCOMES AT THE BOTSWANA-BAYLOR
CHILDRENS CLINICAL CENTRE OF EXCELLENCEA
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

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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 lt15 yr on ART 6831
Neonatal/Infant/Child mortality rates 33/70/150 per 1000
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Deaths Under Five Years of Age Attributable to
HIV/AIDS
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Source Situation Analysis (March 2006)
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(No Transcript)
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Early Childhood Outcomes

• Management According to Botswana National ART
  Guidelines
• All received AZT/d4T 3TC NVP
• Criteria all children lt12 months with confirmed
  HIV infection (DNA PCR) or gt12 months with
  mild/moderate or severe immune suppression or
  clinical manifestations
• Children initiated on HAART at lt36 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

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Virologic SuppressionBy Baseline VL
Baseline VL Number Suppressed by 6 months on therapy
lt750,000 122 112 (92)
gt750,000 180 147 (82)

• P 0.02

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Published Data Regarding Virologic Suppression in
Adults on NVP-based HAART by Baseline VL (from
Raffi et al, HIV Clin Trials 2001)
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Virologic SuppressionBy Age at Initiation
Age at Initiation Number VL Suppressed by 6 months on therapy
lt6 months 19 13 (68)
6-12 months 95 77 (81)
gt12-36 months 119 101 (85)
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Since baseline viral load is predictive of
virologic failure, can we predict baseline VL on
the basis of age and baseline CD4 count?
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Correlation Matriceson BANA2 Trial Patients

• Baseline VL gt750,000 compared with VL lt750,000
  with regards to
• Age
• CD4
• CD4 absolute count
• CDC Immunologic category
• No statistically significant correlations

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Role of PMTCT In Early Infant Outcomes

• Standard program is
• 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

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Virologic Suppression Among Children on
NNRTI-based 1st line by PMTCT status

• 112 infants/young children known to have received
  PMTCT and initiated HAART
• 85 (76) achieved a VLlt400 on 1st line
• 187 infants/young children reported to have
  received no PMTCTand initiated HAART
• 171 (91) achieved VLlt400 on 1st line
• P0.0003

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Virologic Suppression Among Children on
NNRTI-based 1st Line by PMTCT Status and Age at
Initiation

• 15 patients initiated HAART at lt6 months of age
  with a follow-up VL confirming virologic
  suppression (VL lt400 copies/ml) or
  non-suppression 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 (VLlt400 copies/ml) at or
  after 6 months on HAART
• 44 (75) suppressed
• P0.53

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No difference between outcomes among patients who
initiated before 6 months and after 12 months

• 15 patients initiated HAART at lt6 months of age
  with a follow-up VL confirming virologic
  suppression (VL lt400 copies/ml) or
  non-suppression at or after 6 months on HAART
• 10 (67) suppressed
• 42 patients initiated HAART between 1 and 3 years
  of age with a follow-up VL confirming virologic
  suppression (VLlt400 copies/ml) at or after 6
  months on HAART
• 34 (81) suppressed
• P0.29

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Limitations of Data

• Retrospective analysis
• PMTCT status listed as yes or no and may not
  necessarily be reflective of sd-NVP status
• Missing data

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Benefits vs. Risks Early HAART Initiation

• A recent chart review of 281 children who
  initiated HAART gt2 years ago at age lt3 years at
  the COE
• 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

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Benefits vs. Risks Adverse Drug Reactions 1

• The charts of the first 110 treatment naïve
  children who had received HAART at the COE for
  gt52 w were reviewed for ADRs
• Mean age 70 m Male female 11
• 106 (96) received ZVD3TCNVP
• 4 with Hblt7.5 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 lt 24 m
• 10.6 g/dl in those gt 24 m

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Benefits vs. Risks Adverse Drug Reactions 2

• Overall Median Hb increased by 52 w
• 9.4 to 10.4 among those aged lt24 m
• 10.6 to 11.2 g/dl in those aged gt24 m
• Median ALT unchanged at 19.00.5 u/L over 52
  weeks
• ADR occurred in 23 (21) patients
• Rash in 17 (74)
• Severe anemia (Hb lt3 g/dl) in 3 (13)
• Vomiting in 3 (13)

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Benefits vs. Risks Adverse Drug Reactions 3

• Rash occurred in first three weeks of therapy
• 16/17 (94) were mild or moderate
• 1 had Stevens-Johnson syndrome requiring
  inpatient care
• Severe anemia developed at 3 m in one and at 4 m
  in 2 patients
• All were transfused and switched from ZVD to d4T
• Vomiting was mild and resolved without therapy
• Grade 3 lipase toxicity developed in 2 patients
• 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.