1. Prevention of Mother to Child Transmission (PMTCT) of HIV
HAIVN
Harvard Medical School AIDS Initiative in Vietnam
M2-15-Prevention of Mother to Child Transmission (PMTCT) of HIV-EN
HAIVN Module 2, Revised April 2012

2. Learning Objectives
By the end of this session, participants should be able to:
Describe modes of mother to child transmission (MTCT) of HIV
Explain the risk factors for MTCT
Describe ways to prevent MTCT
Explain use of ARVs in pregnancy and for PMTCT

3. Overview: HIV in Women (1)
Globally, 15.9 million adult women living with HIV
65% of PLHIV in sub-Saharan Africa are women
43% of PLHIV in Caribbean are women
Proportion of women living with HIV in Latin America, Asia and Eastern Europe is increasing

4. Overview: HIV in Women (2)
Percent of adults living with HIV who are female ( )
WHO and CDC. Prevention of mother-to-child transmission of HIV Generic Training Package, Draft. January 2008.
REVIEW this graph with participants.
MAKE SURE that they can see the Asia line clearly before moving on to the next slide.

5. Percentage of pregnant women who received an HIV test in low- and middle-income countries by region, 2005 and 2009–2012

6. Percentage of HIV + Pregnant Women Receiving ARVs for PMTCT 2005, 2008, 2009
Towards universal access: Scaling up priority HIV/AIDS interventions in the health sector by WHO, UNICEF, UNAIDS, 2010
32%
EXPLAIN that in addition to low HIV testing rates, pregnant women who are known to be HIV+ have low rates of PMTCT. Only 1/3 of HIV+ women in the region received ARVs to for prevention of mother to child transmission in 2009.

7. Mother to Child Transmission (MTCT) in Vietnam
National Sentinel Surveillance Data:
HIV prevalence in Vietnam 0.5%
HIV-1 prevalence in antenatal women 0.4% (0-1.9%)
1.5-2 million births per year
babies exposed to HIV at birth
EXPLAIN that in Vietnam, the prevalence of HIV in pregnant women is low. However because there are many babies born each year, there are babies exposed to HIV at birth every year.

8. Pathogenesis and Risk Factors for HIV MTCT

9. Question: What are the three main times that a mother can transmit HIV to her infant?
ASK participants the question on the slide.
ALLOW time for them to answer before moving on to the next slide.

10. Without intervention, the overall MTCT rate is 25-40%
MTCT Overview (1)
MTCT can occur during:
Pregnancy (5-10%)
Labor and delivery (10-20%)
Breastfeeding (10-15%)
Without intervention, the overall MTCT rate is 25-40%

11. MTCT Overview (2) 10-20% 5-10% 10-15% Pregnancy Breast feeding
Delivery
EXPLAIN this graphic to participants. It shows that while there is some (5-10%) risk of HIV transmission during pregnancy, the greatest risk for transmission occurs during delivery. After the baby is born, the mother can also transmit HIV to the infant through breastfeeding.

12. Pathogenesis: HIV Transmission in uterus During Pregnancy
Placenta's membrane separates mother ‘s uterus from fetus:
Can prevent at least 60% from HIV transmission
When structure of placenta’s membrane is destroyed , HIV crosses over the placenta
Transmission can occur from the first trimester until the end of gestation
EXPLAIN that HIV transmission may occur through the placenta to the fetus
This can occur from the first trimester until the end of gestation
EXPLAIN further that the mechanism of virus transmission through the placenta is very complex
One of the roles of the placenta is to protect the fetus by stopping pathogens, including HIV, from crossing over from the mother to the fetus.
It is this barrier which protects approximately 60 to 70% of children born to HIV infected mothers from HIV infection.
Unfortunately, the placental membrane may not function properly in a woman infected with HIV
During the first and second trimesters, the structure of the placental membrane is changed which lets the virus transmit more easily to the fetus.
During the later months of gestation, thinning of the membrane creates a more favorable condition for the virus to be transmitted.

13. Pathogenesis: HIV Transmission During Labor/Delivery
Bleeding increases quantity of HIV in vagina, increases risk of transmission:
Uterine contractions damages small vessel
Episiotomy, forceps or vacuum damage large blood vessels
Lesions caused by examination and operation on:
Vaginal and cervical excoriations of mothers
Skin, mucous membrane of baby
Baby contacts directly with wall of vagina (bleeding)
Baby swallows vaginal fluids containing HIV
EXPLAIN that there are a number of factors that work to facilitate HIV transmission during labor:
Uterine contractions cause cervical constriction and dilatation, which damages small blood vessels and leads to bleeding in the genital tract of the woman.
Manual examination may cause vaginal and cervical scratches resulting in bleeding in the genital tract.
In case of interventional delivery such as episiotomy, forceps or vacuum, the large blood vessels are damaged resulting in excessive bleeding
In vaginal delivery the fetus may swallow vaginal fluids containing HIV into the digestive tract.
Skin and mucous membrane scratches in the infant caused during manual examination or procedures may lead to vulnerability to viral entry into the infants' body

14. Pathogenesis: HIV Transmission During Breastfeeding
HIV from lymphocyte of mother penetrates into milk
Damaged nipple (inflamed, ulcerated, scratched,...) increases HIV transmission risk when baby breastfed
Mechanism of HIV transmission is unknown but maybe HIV penetrates to damaged intestine of baby
EXPLAIN that mixing breastfeeding and formula feeding leads to higher rates of HIV transmission from mother to child. The exact reason for this is not entirely clear.

15. Group Brainstorm: What are Some Risk Factors for MTCT?
ASK participants the question on the slide.
ALLOW time for them to answer.
WRITE down their answers on three separate pieces of flip chart paper entitled” Antepartum”, “Intrapartum” and “Postpartum”.
USE discussion to lead into the next few slides.

16. MTCT Risk Factors increasing risk(1)
Factor relates
High viral load, the HIV level in vagina is higher the risk of transmission is higher
Genotype of HIV may be responsible for high risk of transmission in different stages
Low CD4 cell or rate of CD4/CD8 decreases
High viral load in mothers
MTCT < 1% if maternal viral load < 1000
Viral load > 35,000 – higher in utero transmission
Viral load > 10,000 - higher intrapartum transmission

17. MTCT Risk Factors increasing rate (2)
Obstetric factor/mother’s clinical situation
Acute infection or advanced stage
STI, Illicit drug use
Vitamin A deficiency , nutritional status
Chorioamnionitis , Prolonged rupture of membrane
Invasive procedures
Episiotomy, forceps, scalp electrodes, etc

18. MTCT Risk Factors increasing rate (3)
Fetus/ infant
Pre-term
Breastfed Infant with oral lesions
Nourishment with:
Breastfeeding
Mixed feeding in first 6 months

19. MTCT Risk Factors reducing rate (4)
Scheduled Caesarean section delivery help to reduce approximately by 50% of risk
Some ARVs have effectiveness to reduce risk
Example AZT, 3TC, NVP, Aluvia,…
EXPLAIN that C section and the use of ARVs can reduce risk of transmission from mother to child.
However in Vietnam, the use of C section only does when having obstetric indications

20. PMTCT Interventions

21. Comprehensive intervention strategy in PMTCT
The comprehensive intervention strategy promoted by WHO:
Prevention of HIV transmission among women
Prevent unwanted pregnancy
Intervention for HIV women
Appropriate care and treatment for mothers and their children

22. Universal prevention: HIV, HBV,… HIV Counseling and testing
The use of ARV: reduce HIV viral load
Safe obstetric practice:
Avoid invasive procedures for mother and child
Considering C-section
Continuum services of post partum care

23. Small Group Activity: What are Some Ways to Prevent Mother to Child Transmission?
DIVIDE participants into small groups of 3-4 people. (if time is tight, you can just do this as a group brainstorm activity instead).
ASK them to discuss the question on the slide.
HAVE them write down their answers.
ALLOW 5-10 minutes for discussion.
RECONVENE the group and have each small group report back one or 2 prevention strategies.
WRITE down their answers on a flip chart, generating a list.
USE discussion to lead into the next few slides.

24. Timely PMTCT interventions save babies
PMTCT Strategies
Timely PMTCT interventions save babies
Category
General Approach
First Steps
Test for HIV during pregnancy
Antepartum interventions
HIV counseling and testing
ARVs for PMTCT
Intrapartum interventions
Rapid HIV testing
Avoid invasive procedures
Postpartum interventions
Provide ARVs to newborn
Avoid breastfeeding
PROVIDE an overview of MTCT strategies, as shown on the slide.
ASK participants what some tasks might be within each of the general categories.
ALLOW time for them to answer.
REFER participants to Handout M215.2: PMTCT Strategies for further detail on each of these strategies.
REVIEW the handout together before moving on to the next slide.

25. Antiretroviral Therapy in Pregnancy and PMTCT

26. Viral Load and the Risk of MTCT
High maternal viral load is a major risk factor for MTCT of HIV
This supports the idea that the risk of transmission is most related to the baby’s overall exposure to virus
Therefore, reducing maternal viral load by ARVs is an effective way to prevent MTCT

27. ARV in Pregnancy Status of Mother Action
If mother needs treatment for her own health (meets criteria for ARV)
Give 3-drug ARV regimen
If mother does not yet need treatment for her own health (does not meet criteria for ARV)
PMTCT with A or B regimen

28. What Are The Criteria For Starting Triple ART In A Pregnant Woman in Vietnam?
The criteria to start a woman on ARV treatment are the same for pregnant and non-pregnant women
NOTE that this slide is animated. Do not click through to the answer on the slide until after giving participants the opportunity to answer the question.
ASK participants the question on the slide.
ALLOW time for them to respond.
CLICK through the answer on the slide
EXPLAIN that the criteria for starting ART for treatment in a pregnant woman in Vietnam are the same as the criteria for starting ART in any patient.

29. Criteria for ART Initiation in Pregnant Women
CD4 ≤ 350 cells/mm³ irrespective of clinical stage
Clinical stage 3 or 4 irrespective of CD4 cell count
Modification and Supplement to the Guidelines for Diagnosis and Treatment of HIV/AIDS, MOH November 2011
* ART for pregnant woman is also doing
PMTCT

30. ARV Drugs Used in Pregnancy
Comment
AZT
safe and efficacious
longest track record for PMTCT
3TC
safe
easy to tolerate
low toxicity
NVP or a PI
(LPV/r in VN)
3 NRTIs
in special circumstances
EXPLAIN that the ARVs in this chart are the ones preferred in pregnancy.

31. ART Regimens Recommended in Pregnancy
Guidelines for the Diagnosis and Treatment of HIV/AIDS. Ministry of Health, 2009.
AZT + 3TC + NVP
Condition
Substitution
When AZT cannot be used
Replace AZT with d4T or ABC
When NVP cannot be used
AZT + 3TC + EFV
(if gestation age > 12 weeks) or
AZT + 3TC + LPV/r
AZT + 3TC + ABC
EXPLAIN that the preferred ART regimen for pregnant women in Vietnam is AZT, 3TC, NVP. When NVP cannot be used then EFV can be used but not if the women is in the 1st trimester of pregnancy.

32. Reminder: NVP Hypersensitivity
Most common side effects are rash and hepatic adverse events
Risk of symptomatic rash with hepatic toxicity is 9.8 times more common in women with CD4 > 250
Unknown whether risk is increased in pregnant women, though cases have been reported
REMIND participants about Nevirapine Hypersensitivity. It is more common in women and more common with higher CD4 counts.
EXPLAIN that:
Severe rash is times more common in women than men
Hepatic toxicity is 3.2 times more common in women than men

33. ARVs that Should be Avoided in Pregnancy
Efavirenz
May be teratogenic during 1st trimester (but not an indication for abortion)
Tenofovir
Bone demineralization seen in animals, but benefits may outweigh risks
EMPHASIZE that the risk of fetal malformation is small with EFV but that EFV should be avoided in the 1st trimester. However, if a woman is found to be pregnant while on EFV, it is not an indication to abort the pregnancy.
EXPLAIN that TDF safety data are lacking, but should not be stopped unless there are suitable alternatives.
Patients on TDF as part of their second line therapy should continue TDF.
Patients on TDF due to D4T toxicity can consider switching to ABC.

34. PMTCT Regimens in Vietnam
Pregnant woman does not meet criteria to treat ARV for her own
EXPLAIN that now we will discuss the use of ARVs for the prevention of mother to child transmission. In other words, for a pregnant woman who does not meet criteria for ART for her own health.

35. PMTCT Regimen A: Mother
During pregnancy
AZT 300mg bid from week 14 (or whenever diagnosed with HIV after week 14) until labor
During labor
NVP 200mg + AZT 600mg + 3TC 150mg
Then AZT 300mg + 3TC 150mg every 12 hours
Post-partum
AZT 300mg + 3TC 150mg every 12 hours for 7 days
EXPLAIN that there are 2 regimens for PMTCT recommended in the Vietnam MOH Guidelines.
Maternal AZT plus infant ARV prophylaxis (regimen A)
Maternal triple ARV prophylaxis (regimen B)
This slide and the next show the Maternal AZT plus infant ARV prophylaxis regimens.

36. PMTCT Regimen A: Infant
A single dose of NVP 6 mg, immediately after birth
PLUS
AZT 4mg/kg twice daily for 4 weeks

37. PMTCT Regimen B: Mother
During pregnancy
AZT 300mg + 3TC 150mg + LPV/r 400/100 twice daily
From week 14 (or whenever diagnosed with HIV after week 14)
During labor
Continue triple ARV prophylaxis
Post-partum
Continue triple ARV prophylaxis until one week after all exposure to breast milk has ended
EXPLAIN that this slide shows the regimen if using triple therapy for PMTCT.

38. PMTCT Regimen B: Infant
AZT 4mg/kg twice daily for 4 weeks

39. Triple ART in PMTCT
Triple ARV treatment, if available, may be safely started any time after the first trimester
Benefits:
Lowers VL most effectively in mother
Reduces transmission to < 2%
Decreases risk of viral resistance
Downsides:
More expensive
Higher pill burden
More monitoring required
EXPLAIN that triple ART can be used in pregnant women for the purposes of PMTCT. The WHO and Vietnam MOH now recommend the use of either regimen: triple ART or AZT-based. The benefits and downsides of triple ART for PMTCT are listed on this slide.

40. Single-Dose Nevirapine at Delivery
Benefits
Inexpensive
Easy to implement
Effective for women who present late to care
Transmission rate reduced from 30% to 12%
Downsides
Less effective than other regimens
Risk of NNRTI resistance
EXPLAIN that another strategy for PMTCT is to give only a single dose of NVP at delivery. However, this is no longer recommended because of the lower efficacy of this regimen and the high risk of developing NNRTI resistance.

41. ARV Treatment in Pregnancy: Some Scenarios

42. What is the appropriate course of action in this scenario?
Nga has been taking ARVs for the past 6 months, and recently found out that she is pregnant.
What is the appropriate course of action in this scenario?
ASK for a volunteer to read the scenario and question on the slide.
FACILITATE a short discussion to try to answer the question.
USE the discussion to lead into the next slide.

43. Scenario 1: Action
First, review her ARV regimen, then use chart below to determine course:
If….
Then….
Patient is on EFV
switch from Efavirenz to either Nevirapine or Lopinavir/ritonavir depending on CD4 count
or continue EFV if in 2nd or 3rd trimester
Patient is on D4T/DDI
switch to AZT/3TC
Hgb <7.5gm/dl
TDF can be used in place of AZT

44. Scenario 2
Trang is pregnant and HIV positive. She is eligible for ARVs, but has not yet started to take them. What is the appropriate course of action in this scenario?

45. Scenario 2: Action: Start ART
Regimen
Comments
Preferred first line
AZT + 3TC + NVP
Alternate regimen (1)
AZT + 3TC + EFV
If pregnant > 12 weeks and have contraindication to using NVP*
Alternate regimen (2)
AZT + 3TC + LPV/r
If pregnant < 12 weeks and have contraindication to using NVP* or > 12 weeks and have contraindication to using both NVP and EFV
*Contraindications to NVP: CD4 > 250 cells/mm3, allergy to NVP, or history of NVP hepatotoxicity

46. What is the appropriate course of action in this scenario?
Lan Anh is pregnant and HIV positive, but is not yet eligible for ARVs.
What is the appropriate course of action in this scenario?

47. Scenario 3: Answer Follow PMTCT protocol Prescribe ARVs for PMTCT When
What
twice a day from week 14 until labor
AZT 300mg
at start of labor
NVP 200mg
AZT 600mg
3TC 150mg
every 12 hours during labor
every 12 hours for 7 days after delivery

48. ARVs in Pregnancy: Summary
Antenatal Care
Assess HIV status
Mother needs
ART
Mother does not
need ART
AZT-3TC-NVP
Antepartum
AZT from 14 weeks
Intrapartum
AZT + 3TC
+ single dose NVP
Post partum
for 7 days
For
newborn
Single dose
NVP
immediately
Followed
by AZT
4 weeks
EXPLAIN that this summary slides includes the PMTCT regimen A: Maternal AZT plus infant ARV prophylaxis.

49. Post partum continuum care (1)
Counseling for mother on:
Family planning, safe sex: condom use
Prevention of transmission for partner
Options and practices to nourish her child: breastfeeding, formula feeding
Refer to continuum care and treatment service

50. Post partum continuum care (2)
To her child :
Continue ARV regimen of MOH guideline for PMTCT
Refer the child to a suitable Ped OPC to be followed up and treated continuously

51. PCR results at Pasteur of HCMC
PCR pos
PCRNeg
Total
Complete PMTCT
Non PMTCT
Incomplete PMTCT
Source : Pasteur/ the South 2012

52. Key Points
Increasing number of women in Vietnam with HIV; more babies potentially exposed
MTCT can occur during:
Pregnancy
Labor and delivery
Breastfeeding
PMTCT strategies include:
HIV counseling and testing
Safe obstetrics
ART
Avoid breastfeeding
Post partum continuum care for pair of mother and child

53. Thank you
Questions?