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

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

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

Overview: HIV in Women (2) Percent of adults living with HIV who are female (1990-2007) 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.

Percentage of Pregnant Women Receiving an HIV Test, 2005, 2008, 2009 Towards universal access: Scaling up priority HIV/AIDS interventions in the health sector by WHO, UNICEF, UNAIDS, 2010 REFER participants to Handout M215.1: Pregnant Women, HIV, and ART so that they can follow along with the slide. EXPLAIN that only a small portion of pregnant women living in Asia are tested for HIV. The percentage of pregnant women receiving an HIV test in Asia is the lowest among all regions except for the Middle East and North Africa 17%

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.

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 6000-7000 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 6000-7000 babies exposed to HIV at birth every year.

Pathogenesis and Risk Factors for HIV MTCT

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.

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%) Reference: N. Abdulsalami and O. Tekena, “The epidemiology of HIV/AIDS in Nigeria,” in AIDS in Nigeria: A Nation on the Threshold, O. Adeyi, P. Kanki, O. Odutolu, and J. Idoko, Eds., Havard Center for Population and Development Studies, Cambridge, Mass, USA, Without intervention, the overall MTCT rate is 25-40%

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.

Pathogenesis: HIV Transmission During Pregnancy HIV can cross from mother's blood through placenta's membrane to fetus Thinning of membrane during later months of gestation facilitates HIV crossing over CD4 cells containing HIV virus can also infiltrate through placenta to fetus 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.

Pathogenesis: HIV Transmission During Labor/Delivery Factors facilitating transmission: Uterine contractions and bleeding Vaginal and cervical excoriations, ulcerative STDs  bleeding Fetal injury or excoriations  bleeding due to episiotomy, forceps or vacuum 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

Pathogenesis: HIV Transmission During Breastfeeding Transmission risk during breastfeeding depends on: Use of safer breastfeeding practices avoidance of mixed feeding Duration of breastfeeding: 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. Duration Overall Transmission Rate Six months 20-35% 18-24 months 30-45%

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.

MTCT Risk Factors (1) Antepartum Advanced maternal HIV disease 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

MTCT Risk Factors (2) Intrapartum Prolonged rupture of membrane > 4 hours Chorioamnionitis Vaginal delivery compared to caesarean section when viral load > 1000 Invasive procedures scalp electrodes, etc

MTCT Risk Factors (3) Postpartum Breastfeeding, risk is higher with: Long duration Mixed feeding in first 6 months Breast infection Infant with oral lesions Pre-term, low birth weight infants

MTCT Risk Factors (4) Other STDs, especially ulcerative Illicit drug use Nutritional status EXPLAIN that risk factors such as illicit drug use and nutritional status have not been shown to be independently increase the risk of transmission, but they affect the mother’s and therefore the child’s overall health.

PMTCT Interventions

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.

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.

The Use of Caesarean Sections to Reduce MTCT A scheduled C-section at 38 weeks decreases risk of transmission by approximately 50% However, surgical risks may outweigh potential benefits in areas where this procedure is not performed often Not recommended unless obstetrically indicated EXPLAIN that the use of c-section if the mother’s HIV viral load is > 1000 c/ml can reduce the risk of transmission. However, the overall risks and benefits of the procedure must be weighed.

Antiretroviral Therapy in Pregnancy and PMTCT

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) Give PMTCT with single or dual ARVs to reduce exposure of fetus to maternal HIV

Triple ART For Pregnant Women

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.

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

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.

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.

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 5.5-7.3 times more common in women than men Hepatic toxicity is 3.2 times more common in women than men

ARVs that Should be Avoided in Pregnancy Efavirenz May be teratogenic during 1st trimester (but not an indication for abortion) D4T + DDI in combination Lactic acidosis with hepatic steatosis, can be fatal Tenofovir Bone demineralization seen in animals, but benefits may outweigh risks Indinavir Theoretical increased risk of hyperbilirubinemia in baby 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.

PMTCT Regimens in Vietnam 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.

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

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.

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

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.

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

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.

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.

ARV Treatment in Pregnancy: Some Scenarios

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.

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

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?

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

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?

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

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.

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 ART Avoid breastfeeding

Thank you Questions?