Prevention of mother to child transmission of viral hepatitis Dr. Lawrence Mbuagbaw MD, MPH, PhD, FRSPH 2nd International HIV/Viral Hepatitis Co-infection Meeting Friday July 17th, 2015

Outline 1.Background 2.When can transmission occur? 3.At what levels can we stop transmission? 4.Current recommendations 5.Take home messages

Background Prevalence of HIV in females and children 1 An estimated 35 million people were living with HIV worldwide in –3.2 million were children under 15 years of age. –17.6 million were women and girls. The annual number of newly infected children in 2013 was –Over 90% of these children live in sub-Saharan Africa

Background Incidences of HIV, HBV, HCV co-infections 2 * Shown are estimated numbers (in millions) of patients singly or doubly infected.

Background HIV & HBV co-infection In areas of low endemicity of HIV/HBV co-infection 3 : –Prevalence of co-infection is 5-7% among HIV-infected individuals –Mode of transmission is mainly in adulthood via sexual or percutaneous transmission In areas of high endemicity of HIV/HBV co-infection 4 : –Prevalence of co-infection is 10-20% –Mode of transmission is mainly perinatal or in early childhood.

Background Prevalence of hepatitis B infection, adults (19-49 years),

Background Prevalence of hepatitis B infection, children (4-9 years),

Background Prevalence of HIV infection, adult (15-49 years),

Background What is particular about a pregnant woman? 1.Potential teratogenicity of antivirals 2.Physiological changes associated with pregnancy have an impact on how the body processes HBV medication 3.Impact of chronic hepatitis B on pregnancy outcomes

Background Potential teratogenicity 7 Drug 1 st trimester birth defects (% live births) 2 nd /3 rd trimester birth defects (% live births) Lamivudine 127/4088 (3.1%)186/6635 (2.5%) Tenofovir 31/137018/782 (2.3%) Telbivudine 0/9 Entecavir 1/420/2 Adefovir 0/480/0 Antiretroviral pregnancy registry

Background Physiological changes caused by pregnancy 8,9,10 Pregnancy has been shown to alter pharmacokinetics of drugs metabolized by cytochrome P450 3A4. Aweeka et al. showed increases in the urinary ratio of 6- β hydroxycortisol to cortisol (a marker of CYP3A4 induction) during pregnancy compared with postpartum 8. Consequently, the dosage of corresponding antiretroviral medication may need to be altered during pregnancy.

Background Impact of CHB on maternal and fetal-neonatal outcomes 11,12 Lao et al. reported a significantly higher prevalence of gestational diabetes mellitus in mothers with HBsAg positivity when compared to those without chronic hepatitis B. Maternal HBsAg positivity is also associated wth increased antepartum hemorrhage, and threatened preterm labor.

Background Risk factors for perinatal transmission HBV DNA Level 13 : Zou et al. demonstrated a linear correlation between immunoprophylaxis failure rates and maternal HBV DNA levels in 1043 mother-infant pairs HBV replicative status 14 : 85-90% transmission rates in infants born to HBeAg-positive mothers and 32% in infants born to HBeAg-negative mothers

When can maternal-infant HBV transmission occur? Infection rate among infants born to HBeAg- positive mothers who do not receive any form of prophylaxis is as high as 90% 15, During Pregnancy: A.Antepartum B.Intrapartum: majority of total transmission 16. Postulated mechanisms are: Exposure of the baby’s mucocutaneous surface to maternal blood and cervical secretions.

When can maternal-infant HBV transmission occur? 17 2.After Delivery Breast Feeding: does NOT increase risk of MTCT of HBV –Hill et al. compared the rate of HBV transmission from chronic HBV carrying mothers in 101 breast-fed infants with 268 formula-fed infants. Infants received HBIG and full course of hepatitis B vaccine series. –MTCT of HBV was 0% when breast-fed vs. 3% when formula-fed.

At what levels can we stop antepartum transmission? Current immunoprophylaxis is less efficacious in mothers with high serum levels of HBV DNA > 6 log 10 copies/mL 13. Antiviral treatment in third trimester may reduce risk of HBV MTCT 18, 19, 20 –In a randomized, placebo-controlled study, lamivudine was administered to highly viremic mothers (HBV DNA >1000 mEq/mL) starting at 32 weeks gestation until 4 weeks postpartum. Rate of MTCT was 18% in lamivudine group vs. 39% in control group at 52 weeks.

At what levels can we stop intrapartum transmission? Currently, both HBIG and hepatitis B vaccine is given to the infant immediately after birth. Early RCT by Beasley et al. showed that HBIG administration can reduce rate of HBV transmission from more than 90% from HBeAg-positive mothers down to about 26% 21 When combined with the hepatitis B vaccine, the rates of transmission fell to 3% from 7% 22

Recommendations Antiviral therapy for mothers with active CHB 15

Recommendations Antiviral therapy for mothers without active CHB 15

Issues with current recommendations Gap in literature with regards to the benefits of antiviral therapy for mothers with HBV DNA levels <200,000 IU/mL. More data are needed regarding the long- term safety of fetal exposure to antiviral therapy. –The lack of access to HBV DNA level testing may prohibit women from receiving needed treatment.

The way forward Further research Do what we know works – Screening – Immunisation – Chemoprophylaxis Share our experiences working with co- infected women

Take home messages 1.Screen all HIV-infected pregnant women for Hep B&C 2.All –ve should receive Hep B vaccine 3.All co-infected pregnant women should receive cART (tenofovir, lam, emtricitabine) 4.Frequent monitoring of liver function tests & Hep B DNA 5.Children born to women with HBV infection should receive HBIG and HBV vaccination series 6.Mode of delivery is based on standard OB/HIV considerations 7.Mgt is complex and requires specialist consultation

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