1. 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

2. Overview Statistics Timing of Transmission Risk Factors for MTCT
History of pMTCT
Interventions
Revised SA pMTCT policy 2010

4. Antenatal Prevalence - SA

5. Antenatal Prevalence - SA

6. Just under a third of pregnant women (29
Just under a third of pregnant women (29.3%) in South Africa are HIV Positive

7. 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!

8. Background
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

9. MTCT Rates
~ % in non-breastfeeding population of HIV-1 positive women in more developed countries
25 -45% in breast-feeding populations in Africa

10. Timing of transmission in Non breast-feeding

11. Timing of transmission Breastfeeding

12. Risk Factors for MTCT Pregnancy Labour and Delivery Breastfeeding
High maternal VL
Placental infection
STIs
Maternal malnutrition
ROM >4 hours before labour begins
Invasive delivery procedures
First infant in multiple birth
Chorioamnionitis
Duration of breastfeeding
Early mixed feeding
Breast abscesses, nipple fissures, mastitis
Poor maternal nutritional status
Oral disease in the baby

13. History of PMTCT and ARV interventions
ACTG 076
1994, AZT to mother from 2nd trimester, IV during labour and delivery, 6 weeks to infant; transmission reduced from 25%-8%
Shorter course therapies sought
Thai regimen
PETRA
HIVNET 012
Nevirapine one dose to mother and one dose to baby (transmission reduced to 13%)

14. What did we know and when did we know it
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
2004 Thailand PHPT
1.9% AZT + NVP
1998 Thai Bangkok short AP/IP AZT trial
50% reduction in transmission
2003 DITRAME
4.7% TR with AZT/3TC & IP/PP NVP
1998 Cote d‘Ivoire short AP/IP AZT trials
37% reduction in transmission (breastfeeding)
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 PETRA AZT/3TC trial (6 wk results)
50% reduction with longest arm.
38% reduction with the IP/PP arm
1999 Uganda 2-dose IP/PP NVP trial (HIVNET 012)
47% reduction in transmission (breastfeeding)

15. 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

16. Interventions Before conception Antenatal Peripartum Postnatal
Primary prevention of HIV in parents-to-be
Prevention of unwanted pregnancies
Antenatal
Identification of women requiring HAART or PMTCT ARV course
Avoidance of unprotected sex with HIV+ partner
Peripartum
Good obstetric practice
Elective Caesarian section
ARV – Nevirapine given in labour
Postnatal
Avoidance of breastfeeding – where safe, feasible, acceptable

17. Standard ANC procedure
Group pre-test counselling – PMTCT information
Individual counselling
Obtain verbal consent and proceed to test
Test results
Post-test counselling and further PMTCT information

18. Screening HIV test NB! Retest at 32 weeks or
Screening Negative
Screening positive
Negative
Confirmatory HIV test
NB! Retest at 32 weeks or
( 6 weeks after initial test )
Confirmatory positive
Confirmatory negative
According to new protocol women diagnosed in pregnancy (window period) should be given ART immaterial to CD4 count due to increased viral load and risk of transmission. CD4 to be repeated at 6 wks post partum and ART will be stopped if CD4 >350.NB retest all negative women
Indeterminate
Final result positive
Send for HIV ELISA
Indeterminate Elisa send for PCR DNA test (diagnostic PCR)
Positive /Negative final result

19. HIV-infected pregnant women: 1ST visit
Haemoglobin
CD4 cell count
U&E (with weight)
ALT (if ALT abnormal do HepB Sag)
TB screening – clinical
HIV staging
WHO stage 1, 2 – PMTCT protocol
Stage 3 and 4, initiate AZT regardless of CD4 count – refer for urgent ART
Staging knowledge may be problematic
Those with stage III disease have advanced HIV disease and may need ART soon.

20. Staging – highly simplified
Stage 1 - healthy
Stage 2 – skin conditions
Stage 3 – oral conditions and pulmonary TB
Stage 4 – other opportunistic infections

21. Zidovudine (AZT) Dual therapy – antenatal AZT and intrapartum
sd-NVP – introduced in February 2008
Addition of antenatal AZT further decreases transmission to 5%
Timing of initiation of AZT changed now to be in line with new WHO guidelines – from 14 weeks gestation

22. AZT cont... 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

23. AZT cont...
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.
AZT 3hourly as per national protocol

24. AZT AND ANAEMIA IN PREGNANCY
Haemoglobin monitoring
AZT AND ANAEMIA IN PREGNANCY
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

25. Haematinics and monitoring (BANC)
Iron Supplementation
Hb <8g/dl Ferrous sulphate 200mg tds/Folic acid 5mg daily Urgent referral for investigation
Hb ≥ 11g/dl Ferrous Sulphate 200mg daily/
Folic acid 5mg daily
Hb >8g/dl <10g/dl Ferrous Sulphate 200mg tds/Folic acid 5mg daily
Repeat Hb weekly
For women on AZT 4 weekly Hb monitoring
Consider initiating ART

26. Hb, TB screen,CD4, Stage, Start FeSO4 and Folic Acid
1st Visit – HIV Infected
Hb, TB screen,CD4, Stage, Start FeSO4 and Folic Acid
>14weeks
<14 weeks
Stage 3, 4 (any gestation)
Hb > 8
Hb < 8
Stage 4 can start AZT at any stage preferably by 14 weeks but can be started earlier in special circumstances e.g.Karposis
Return
1 week,
ART/AZT from 14weeks
Start AZT results 1 week
Refer for anaemia start AZT when Hb >8
AZT immediately refer for ART

27. Management in labour Single dose Nevirapine + AZT 300mg 3 hourly
To reduce intrapartum transmission (esp. unbooked mothers presenting in labour)
Reduces transmission to around 10% by 6 weeks testing
TDF + FTC stat after delivery
Combination therapy reduces resistance due to sdNVP

28. Check CD4 cell count result
Subsequent ANC visits
AZT started at 1st visit
Check CD4 cell count result
ALT if abnormal – HebBSag
U&E + Weight (creatinine clearance)
CD4 > 350
Stage 1 & 2
CD4 ≤ 350 or stage 3 & 4
AZT 300 mg 12 hourly
Give 4 weeks supply
Same day referral to ARV clinic for ART, AZT stopped once ART
initiated

29. PMTCT and ART initiations NEW
ANC
Booking
Case finding
do a CD4 cell count
Less than 14 weeks
(NVP,TDF,3TC)
Continue AZT
CD4 <350
HIV staging
CD4 result within 1week
Start AZT from 14 weeks
From 14 weeks,
initiate ART
(EFV,TDF,3TC)
CD4
< 350
CD4>350

30. PMTCT and ART initiation outline:
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

31. Labour and delivery AZT 300mg 3 hourly plus 200mg sd NVP stat
If Nevirapine already taken with false labour do not repeat, neonate receives standard post exposure prophylaxis.
Continue AZT 300mg 3 hourly at the usual times until the neonate is delivered.
Mother on ART, continue treatment as usual during labour.
Gauteng administers 600mg of AZT stat during labour then reverts to 12hourly dosing . Nationally AZT 300mg 3hrly during labour

32. Labour and delivery Minimize number of PV exams to
decrease risk of infection
Avoid prolonged labour
Avoid artificial rupture of membranes
Avoid traumatic vaginal delivery

33. Labour and delivery Avoid routine episiotomy
Suction baby only when indicated,
i.e. no routine suctioning
Wipe baby clean immediately after
delivery to remove blood & liquor

34. Continue ART regimen 12 hourly throughout labour
At onset of labour NEW
HIV infected
mother on PMTCT regimen or no treatment
NVP stat
AZT 300mg 3 hourly during labour
Infant NVP
6 weeks*
Delivery
Tail cover FTC/TDF stat dose post delivery
At onset of labour
mother on ART
Continue ART regimen 12 hourly throughout labour
Mother continue
ART lifelong
. Truvada after delivery

35. Caesarian section
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
ARV ( can be given within an hour of C/S)

36. Feeding practices SAFE FEEDING PRACTICES For all HIV positive women
Either exclusive replacement feeding or exclusive breast feeding
AFASS must be assessed on an individual basis

37. Feeding choices for HIV infected women
Mixed feeding strongly discouraged
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

38. Feeding choices for HIV infected women
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

39. If the mother is known to be HIV positive – the infant is referred to as HIV EXPOSED
AVOID MISLABELING

40. Post natal care
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

41. Switch to EBF if possible.
Exclusive formula fed
Identify
HIV -exposed infant
6 weeks:
Start CTX
Do PCR
Stop NVP
Prompt referral for
ART. Continue
CTX
Switch to EBF if possible
PCR
PCR positive
PCR negative
*HIV negative
Stop CTX
If infant is ill test earlier. All HIV exposed infants not on ART should have an HIV ELISA or rapid test at 18 months of age to confirm HIV status conferred by the 6-week PCR test

42. Infants of Breastfeeding mothers
Breastfeeding mothers on ART
Breastfeeding mothers not on ART
Stop infant NVP at 6 weeks
Continue infant NVP until breastfeeding cessation or max 1year
Infants on NVP should continue with NVP for 1 week after breastfeeding has been stopped. All positive infants should continue breastfeeding and referred for ART within a week.

43. 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
Birth Weight >2,500 gram
10 mg/daily = 1ml
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

44. Blood collection CAPILLARY VENOUS V 500 ul (0.5 ml) 1ml
The old Guthrie card has been crossed out because it should no longer be in circulation (but may be at some clinics). The reason for the new card is that it is framed which is required for the automated punch in the laboratory to grip the card and punch out the blood spots automatically
The ‘adult’ EDTA tubes require a MINIMUM volume of 1ml (because there is EDTA diluent in the tube that will dilute out a smaller volume) and the microtainers a MINIMUM volume of half a ml. 44

45. Confirm HIV infection in infants.
PCR Positive
Do Viral load on separate blood sample
Repeat DNA PCR
Initiate ART while waiting for VL results
VL ≥ copies/ml
(4log)
Continue ART
If infant is ill test earlier. All HIV exposed infants not on ART should have an HIV ELISA or rapid test at 18 months of age to confirm HIV status conferred by the 6-week PCR test If VL test < copies per ml, repeat HIV DNA PCR
If can’t perform blood sampling for VL (not done on DBS), refer to CCMT site for confirmatory testing and treatment initiation
VL ≤10000 copies/ml

46. Testing breastfed infants
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
HIV test to be done is age-appropriate e.g. if younger than 18 months, do HIV PCR and if older than 18 months, use rapid test or ELISA

47. 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"
Traditionally we need TWO tests with the same results to confirm an HIV status.
In all cases, except for 2 positive PCR tests in HIV-infected infants, infants only have a single test to establish their HIV status therefore the 18 month rapid test acts as a confirmatory test month olds that are diagnosed on PCR for the first time will NOT be on HAART but will need their HIV status confirmed on rapids in case they slip through the gap on a confirmatory viral load test.
Final HIV tests will have to occur after 18 months in instances where infants are breastfed for longer than 18 months

48. 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.

49. pMTCT and feeding choices
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)

50. Exclusive Breastfeeding (for 4 months)
RISKS
Transmits HIV
BENEFITS
Optimal nutrition
Saves time, money and effort
Reduced exposure to germs
Better immunity
Less allergy
Socially acceptable
Bonding

51. Exclusive Formula feeding
BENEFITS
No transmission of HIV through breast milk
RISKS
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

52. PMTCT RATES Of all HIV Infected Women > 95% HIV Negative Babies !
25 % HIV Infected Babies
Where no intervention
< 5%
Infected

53. Take Home Messages 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