Transcript Mother-to-child transmission and infant diagnosis

Prevention of Mother-to-child
Transmission(PMTCT)
2011
Ashraf Coovadia
Department Of Paediatrics & Child Health
Rahima Moosa Mother and Child Hospital
University of The Witwatersrand
Overview
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Statistics
Timing of Transmission
Risk Factors for MTCT
History of pMTCT
Interventions
Revised SA pMTCT policy 2010
Antenatal Prevalence - SA
Antenatal Prevalence - SA
Just under a third of pregnant women (29.3%) in
South Africa are HIV Positive
Mother to Child Transmission
One out of four babies (25%)
born to all HIV positive mothers
will acquire HIV from their
mother ( if no intervention is
offered )
That means at least 75% of
babies are uninfected at birth!
Background
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55% of all HIV-1 positive adults are
women of child bearing age.
Seroprevalence rates among pregnant
women exceeds 30% in many urban
populations in sub-Saharan Africa
MTCT Rates
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~10 - 30% in non-breastfeeding
population of HIV-1 positive women
in more developed countries
25 -45% in breast-feeding
populations in Africa
Timing of transmission in Non breast-feeding
intrapartum
67%
in utero
33%
Timing of transmission Breastfeeding
Transmission in Children
breastfeeding
30%
intrapartum
60%
in utero
10%
Risk Factors for MTCT
Pregnancy
Labour and Delivery
Breastfeeding
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High maternal VL
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High maternal VL
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High maternal VL
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Placental infection
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ROM >4 hours before
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Duration of
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STIs
labour begins
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Maternal malnutrition
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Invasive delivery
procedures
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First infant in multiple
birth
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Chorioamnionitis
breastfeeding
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Early mixed feeding
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Breast abscesses, nipple
fissures, mastitis
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Poor maternal
nutritional status
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Oral disease in the baby
History of PMTCT and ARV
interventions
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ACTG 076
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Shorter course therapies sought
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1994, AZT to mother from 2nd trimester, IV
during labour and delivery, 6 weeks to infant;
transmission reduced from 25%-8%
Thai regimen
PETRA
HIVNET 012
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Nevirapine one dose to mother and one dose
to baby (transmission reduced to 13%)
What did we know and when did we know it?
Perinatal HIV Clinical Trial Results
1994
2004
1994 U.S. AZT Trial ACTG 076
• 67% reduction in transmission
1998 Thai Bangkok short AP/IP
AZT trial
• 50% reduction in transmission
1998 Cote d‘Ivoire short AP/IP
AZT trials
• 37% reduction in transmission
(breastfeeding)
1999 PETRA AZT/3TC trial (6 wk
results)
• 50% reduction with longest arm.
• 38% reduction with the IP/PP arm
2004 Thailand PHPT
• 1.9% AZT + NVP
2003 DITRAME + 1201.1
• 4.7% TR with AZT/3TC &
IP/PP NVP
2002 Cote d’Ivoire DITRAME +
• 6.2% TR with AZT & IP/PP NVP
2000 Thailand
Long vs short AZT regimens
• 4% TR in LL (non BF)
1999 Uganda 2-dose IP/PP NVP trial (HIVNET 012)
• 47% reduction in transmission (breastfeeding)
MTCT: The four-pronged strategy
• Primary prevention of HIV in
parents-to-be
• Prevention of unwanted
pregnancies
• Prevention of transmission
from HIV-infected mother to
infant
• Appropriate treatment and care
Interventions
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Before conception
Primary prevention of HIV in parents-to-be
Prevention of unwanted pregnancies
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Antenatal
Identification of women requiring HAART or PMTCT ARV course
Avoidance of unprotected sex with HIV+ partner
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Peripartum
Good obstetric practice
Elective Caesarian section
ARV – Nevirapine given in labour
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Postnatal
Avoidance of breastfeeding – where safe, feasible, acceptable
Standard ANC procedure
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Group pre-test counselling – PMTCT information
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Individual counselling
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Obtain verbal consent and proceed to test
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Test results
Post-test counselling and further PMTCT information
Screening HIV test
Screening HIV test
Screening Negative
Screening positive
Negative
Confirmatory HIV test
Confirmatory positive
Final result positive
Confirmatory negative
Indeterminate
Send for HIV ELISA
Indeterminate Elisa
send for PCR DNA
test (diagnostic PCR)
Positive /Negative final result
NB! Retest at 32
weeks
or
( 6 weeks after
initial test )
Staging – highly simplified
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Stage 1 - healthy
Stage 2 – skin conditions
Stage 3 – oral conditions and pulmonary TB
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Stage 4 – other opportunistic infections
Zidovudine (AZT)
Dual therapy – antenatal AZT and
intrapartum
sd-NVP – introduced in February 2008
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Addition of antenatal AZT further
decreases transmission to 5%
Timing of initiation of AZT changed
now to be in line with new WHO
AZT cont...
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According to president Zuma’s mandate on
1 December 2009, AZT for PMTCT should be
started from 14 weeks of pregnancy instead of
28 weeks
All HIV-infected pregnant women seen at
antenatal clinics at 14 weeks of pregnancy and
above must be started on AZT while awaiting
CD4 cell count result
AZT cont...
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If the CD4 cell count is above 350 cells/mm3, AZT
is continued until labour begins.
During labour, sd-NVP is issued in labour ward
together with AZT 300mg 3 hourly until delivery.
The women is then given TDF + FTC (acts as the
tail cover)
If the CD4 cell count is less than 350 cells/mm3,
the pregnant woman qualifies for ART).
AZT is stopped once ART is started, no
additional AZT during labour nor tail required.
Haemoglobin monitoring
AZT AND ANAEMIA IN
PREGNANCY
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Anaemia is common in pregnancy
Various causes: nutritional (iron deficiency),
HIV-related are common
AZT may exacerbate an existing anaemia, or
cause the haemoglobin to drop
Prescribe adequate doses of haematinics – for
all women and advise on how to take iron
Haematinics and monitoring
(BANC)
Iron Supplementation
Hb ≥ 11g/dl Ferrous
Sulphate 200mg
daily/
Folic acid 5mg daily
Hb >8g/dl <10g/dl
Ferrous Sulphate
200mg tds/Folic
acid 5mg daily
For women on AZT 4 weekly
Hb monitoring
Hb <8g/dl
Ferrous
sulphate
200mg
tds/Folic acid
5mg daily
Urgent referral
for
investigation
Repeat
Hb
weekly
Consider initiating ART
1st Visit – HIV Infected
Hb, TB screen,CD4, Stage, Start
FeSO4 and Folic Acid
>14weeks
<14
weeks
Return
1 week,
ART/AZT from
14weeks
Stage 3, 4
(any
gestation)
Hb > 8
Hb < 8
Start AZT
results 1
week
Refer for
anaemia
start AZT
when Hb >8
AZT
immediately
refer for ART
Management in labour
Single dose Nevirapine + AZT
300mg 3 hourly
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To reduce intrapartum
transmission (esp. unbooked
mothers presenting in labour)
Reduces transmission to around
10% by 6 weeks testing
TDF + FTC stat after delivery
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Combination therapy reduces
resistance due to sdNVP
Subsequent ANC visits
AZT started at 1st visit
Check CD4 cell count result
ALT if abnormal – HebBSag
U&E + Weight (creatinine clearance)
CD4 ≤ 350 or
stage 3 & 4
Same day referral to ARV
clinic for ART, AZT
stopped once ART
initiated
CD4 > 350
Stage 1 & 2
AZT 300 mg 12 hourly
Give 4 weeks supply
PMTCT and ART initiations
NEW
CD4>350
ANC
Booking
Case
finding
do a CD4
cell count
HIV
staging
CD4 result
within
1week
Start AZT
from 14
weeks
CD4
< 350
CD4 <350
Continue AZT
From 14 weeks,
•initiate ART
(EFV,TDF,3TC)
Less than 14 weeks
(NVP,TDF,3TC)
PMTCT and ART initiation
outline:
1.
2.
3.
4.
5.
6.
ANC booking visit
Rapid HIV test positive
HIV staging and CD4 cell count
Gestational age from 14 wks to 42 wks initiate AZT same day
CD4 count result within 1 week
A. CD4 >350 – continue AZT
B. CD4: <350 or stage 3 or 4 – initiate ART:
TDF, 3TC and NVP/EFV
Labour and delivery
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Minimize number of PV exams to
decrease risk of infection
Avoid prolonged labour
Avoid artificial rupture of membranes
Avoid traumatic vaginal delivery
Labour and delivery
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Avoid routine episiotomy
Suction baby only when indicated,
i.e. no routine suctioning
At onset of labour NEW
At onset of labour
HIV infected
mother on
PMTCT
regimen or
no
treatment
NVP stat
Tail cover FTC/TDF
stat dose post
delivery
AZT 300mg 3
hourly during
labour
Delivery
HIV infected
mother on
ART
Continue ART
regimen 12 hourly
throughout labour
Infant NVP
6 weeks*
Mother continue
ART lifelong
Caesarian section
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Routine C/S for HIV neither indicated nor
feasible in government hospitals.
Elective C/S (Obstetric indication):
 give sd NVP at least 4 hours before
surgery
 If patient on ART, continue medication at
usual times
Emergency C/S, antiretroviral treatment /
prophylaxis should be given stat
Tail cover post C/S
Feeding practices
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SAFE FEEDING PRACTICES
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For all HIV positive women
Either exclusive replacement feeding
or exclusive breast feeding
AFASS must be assessed on an individual
basis
Feeding choices for HIV
infected women
Mixed feeding strongly discouraged
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BREAST FEEDING: exclusive breastfeeding
recommended for 1st 6 months of life .
If she wants to stop at 6 months AFASS must be
reassessed
Cessation of breastfeeding before 6 months not
recommended.
Introduce complementary foods
from 6 months in addition to
continuing with breastfeeding
Feeding choices
for HIV infected
women
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REPLACEMENT FEEDING: If women
chose not to breast feed, exclusive
formula feeding (i.e. no breast milk)
should be practiced
Provision of free formula for
at least 6 months
Complementary foods should be
introduced from 6 months
If the mother is known to be
HIV positive – the infant is
referred to as HIV EXPOSED
AVOID MISLABELING
Post natal care
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All women of unknown HIV status should be
offered HIV testing and
counseling prior to discharge
All HIV exposed infants to receive NVP daily for 6
weeks
*All abandoned infants considered to be in their
first 72 hours of life, provide NVP daily for six
weeks or until HIV ELISA confirms no HIV
exposure
.
Exclusive formula fed
HIV negative
Stop CTX
*
Identify
HIV exposed
infant
6 weeks:
Start CTX
Do PCR
Stop NVP
PCR
negative
PCR
PCR positive
Prompt referral
for
ART. Continue
CTX
Switch to EBF if
possible
Infants of Breastfeeding mothers
Breastfeeding
mothers on ART
Stop infant
NVP at 6
weeks
Breastfeeding
mothers not on
ART
Continue infant
NVP until
breastfeeding
cessation or max
1year
Proposed Extended Simplified
Infant NVP Dosing Recommendations
(dosing required to sustain exposure in infant
of > 100 ng/ml with least dose changes)
50mg / 5 ml
Birth -6 weeks
•
Birth Weight < 2,500 gram 10 mg/daily = 1ml
•
Birth Weight >2,500 gram
15mg/daily =1,5ml
>6 weeks to 6 months
20mg/daily = 2ml
>6 to 9 months
30mg/daily =3ml
>9 months to end of BF
40mg/daily =4ml
Blood collection
CAPILLARY
VENOUS
V
500 ul
(0.5 ml)
1ml
Confirm HIV infection in
infants
.
Continue ART
VL ≥ 10000 copies/ml
(4log)
PCR
Positive
Do Viral load
on separate
blood sample
Initiate ART while
waiting for VL
results
VL ≤10000 copies/ml
Repeat DNA PCR
Testing breastfed
infants
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6 week PCR (as for all HIV-exposed infants)
BEFORE breastfeeding is stopped, do HIV test:
 if positive, continue breastfeeding,
refer for initiation
 if negative, stop breastfeeding
AFTER breastfeeding is stopped, do HIV test:
 if positive, try to re-initiate breastfeeding
refer for initiation
 if negative, currently HIV-uninfected
Rapid test at 18 months
" All HIV-exposed infants
should have a rapid test at
18 months to confirm their
status unless they are
already on ART"
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The provision of a “tail” to prevent
Nevirapine resistance for women
receiving sdNVP in labour
Dispensing daily NVP to the baby for 6
weeks (instead of AZT).
For breastfed infants NVP continues daily
for 1 week after breastfeeding stops
preferably no more than 12 months if
mother not on ART.
pMTCT and feeding choices
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HIV is present and transmitted via
breast milk
Formula feeding is difficult in many
areas especially rural
Women should be fully informed about
choices and supported in their decision
by health care workers (WHO)
Exclusive Breastfeeding
(for 4 months)
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BENEFITS
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Optimal nutrition
Saves time, money
and effort
Reduced exposure to
germs
Better immunity
Less allergy
Socially acceptable
Bonding
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RISKS
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Transmits HIV
Exclusive Formula feeding
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BENEFITS
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No transmission of
HIV through
breast milk
RISKS
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Cost- may have
higher risk of poor
growth
Infectious diseases,
such as diarrhoea
and pneumonia if
hygiene, sanitation
and access to clean
water is poor
PMTCT RATES
Of all HIV Infected Women
> 75
95%
% HIV
HIV Negative
Negative Babies
Babies !
25 % HIV Infected Babies
Where no intervention
< 5%
Infected
Take Home Messages
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All women have a right to receive PMTCT
All babies have a right to be protected through
PMTCT
Testing of all women is key to the realization of
these rights
Provision of appropriate and timely interventions is
critical to diminishing MTCT risk
Feeding choice needs to be an informed one
Paediatric Diagnosis is a key component of PMTCT
Paediatric HIV is ERADICABLE