EARLY CHILDHOOD OUTCOMES AT THE BOTSWANA-BAYLOR 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 DirectorElizabeth Lowenthal, Associate DirectorMichelle Eckerle, Pediatric AIDS Corps Doctor

Botswana - BackgroundParameterParameter Total or EstimateTotal 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

33.6%

36.5%

40.6%

42.2%

57.7%

4.0%

0% 10% 20% 30% 40% 50% 60%

Zambia

Namibia

Swaziland

Zimbabwe

Botswana

Global

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)

0

10

20

30

40

50

60

70

80

90

100

2002 2003 2004 2005 2006

Year

Per

cen

t re

ceiv

ing

dru

g

AZT (or HAART)

NVP (or HAART)

HAART*

*20-25% of pregnant women are eligible for ARV therapy during pregnancy (CD4<200)

Short-course AZT + SD NVP

Long-course AZT + SD NVP

Short-course AZT only

Source: Situation Analysis (March 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 SuppressionBy Baseline VL

Baseline VL NumberSuppressed by 6 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 SuppressionBy Age at Initiation

Age at Initiation NumberVL 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 Matriceson 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: 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 85 (76%) achieved a VL<400 on 1st line

187 infants/young children reported to have received no PMTCTand initiated HAART 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 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 (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 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 (VL<400 copies/ml) at or after 6 months on HAART 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 sd-NVP 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 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

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: 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: 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: 16/17 (94%) were mild or moderate 1 had Steven’s-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.