Prevention of Mother to Child Transmission of HIV

HIV in children is predominantly acquired as a vertically transmitted disease. Without intervention the transmission rate from mother to child has varied from 20%-40%. However, this risk can be reduced to less than 2% with effective PPTCT (Prevention of parent to child transmission of HIV) programmes.

Vertical transmission of HIV can occur in-utero through placental transmission, intrapartum through contact with infected birth canal secretions or postpartum through breast feeding. It is estimated that of the 30% of babies who get infected vertically, 2% get infected in early gestation, 3% get infected in late gestation, 15% get infected intrapartum and 10% get infected via breast feeding.

Risk factors for increased maternal to child transmission of HIV

• Primary HIV infection in the mother due to high viremia
• Advanced HIV disease in the mother with high maternal viral load

• Prolonged rupture of membranes

• Chorioamnionitis
• Premature delivery

Prevention Modalities

Elective caesarean section (ECS)
 Elective caesarean section has been found to decrease transplacental hemorrhage during labor, reduce the length of exposure of baby to vagino-cervical secretions and reduces chances of ascending infection of HIV transmission. Studies have found that among HIV-1 infected women not taking ARV during pregnancy, ECS was efficacious for prevention of mother to child transmission (MTCT) of HIV-1, and decreased transmission by approximately 50 percent as compared to other modes of delivery.
 
 However, elective caesarean section is associated with post-partum morbidity in form of fever, urinary tract infection, endometritis and thromboembolism. Also it is more expensive and not universally available especially in resource limited settings. When ARV prophylaxis to mother and child are available and replacement feeding can be issued, the added advantage of ECS is not seen and vaginal delivery may be a safe and inexpensive option in this setting.

 In industrialized countries, elective caesarean section at 38 weeks of gestation is recommended when viral load is not totally suppressed at the end of pregnancy (i.e. HIV viral load is >1000 copies/ml).

Antiretroviral Prophylaxis

  The first trial PACTG-076 in 1994 demonstrated efficacy of antiretrovirals to decrease mother to child transmission of HIV. Subsequently many trials have demonstrated gradual reduction of the in-utero and intra-partum transmission rates with an increasing length and potency of drug combinations used during pregnancy and at delivery.

The 3 most commonly used regimes are :

• Zidovudine (AZT) monotherapy starting at the end of first trimester of pregnancy in the mother and for 4 weeks in the infant, with one maternal and infant perinatal single dose Nevirapine (NVP) plus AZT + Lamivudine (3TC) during labor and for 7 days post-partum was administered. (AZT+ 3TC for one week helps to reduce risk of NVP resistance in the mother and infant). With replacement feeds, this regime decreased transmission rate to < 2%.

• In industrialized countries, HAART (Triple drug therapy) is used in pregnant women as prophylaxis. For women with higher CD4 counts, protease inhibitor based regimens are recommended. Efavirenz (EFV) is now recommended for use in women even in first trimester (animal studies had initially found teratogenic effects of EFV and hence it was not recommended initially in the first trimester

• Now with maternal HAART taken throughout the pregnancy and even later on while breastfeeding, there is a greatly reduced HIV transmission rate of 2 percent. But there must be 100 percent adherence to taking the drugs correctly, otherwise there is a risk that the baby will become infected with HIV or resistant to the medication. This approach offers new hope for mothers with HIV infection who cannot safely feed their babies with replacement.

 The most appropriate infant feeding option for an HIV-infected mother depends on her individual circumstances, including her health status and the local situation.

Antiretroviral prophylaxis and breast feeding 

 It has been clearly shown that when antiretrovirals are taken through the pregnancy and breastfeeding stage, there is a greatly reduced HIV infection rate of 2 percent. But there must be 100 percent adherence to taking the drugs correctly, otherwise there is a risk that the baby will become infected with HIV or resistant to the medication. There needs to be good support for mothers to help them adhere to an extended drug regimen as well as keeping to 6 months of exclusive breastfeeding. This approach offers new hope for mothers with HIV infection who cannot safely feed their babies with replacement. It will improve the chances of infants remaining healthy and free of HIV infection as breast milk provides optimal nutrition and protects against other fatal childhood diseases such as pneumonia and Diarrhea. This led to recommendations by WHO in 2013 as follows:
 
 World Health Organization Rapid Advise for Use of antiretrovirals for treating pregnant women and preventing HIV infection in infants. 2013:

In pregnant women with confirmed HIV serostatus, initiation of antiretroviral therapy is recommended irrespective of gestational age and continued throughout pregnancy, delivery and thereafter. Infant born to these women should receive daily nevirapine (NVP) or zidovudine (AZT) from birth until 4 to 6 weeks of age. These women can then deliver their babies vaginally and also breast feed their babies. A once-daily fixed-dose combination of TDF + 3TC (or FTC) + EFV is recommended as first-line ART in pregnant and breastfeeding women, including pregnant women in the first trimester of pregnancy and women of childbearing age.

US guidelines for recommended first line ART in pregnant women (2015): In general, the same regimens as recommended for treatment of non-pregnant adults should be used in pregnant women unless there are known adverse effects for women, fetuses or infants that outweigh benefits. Preferred two-NRTI backbone are:

•  ABC/3TC
• TDF/FTC or 3TC
• ZDV/3TC

The 3rd drug that is to be given can be a PI or an NNRTI. The preferred PI is ATV/r (once a day) or LPV/r (twice a day). The preferred NNRTI is EFV.

1. A boosted PI-based regimen (two NRTIs plus ritonavir-boosted lopinavir) for prophylaxis, with the drugs stopped postpartum
2. Zidovudine prophylaxis alone during pregnancy and intrapartum
3. All infants should receive the standard 6-week AZT prophylaxis
4. No breast feeding

Conclusion :

While interventions to prevent mother to child transmission of HIV can dramatically reduce the risk of pediatric infections to less than 2%, a wide array of options exists to fit individual circumstances at various settings. Choice of PPTCT regime should be individualized as per needs with minimum risk to infant and mother in form or adverse effects and resistance.

References :

1. Shah Ira. Is Elective Caesarian Section Really Essential for Prevention of Mother to Child Transmission of HIV in the Era of Antiretroviral Therapy and Abstinence of Breast Feeding? J Trop Pediatr. 2006;52:163-5.
2. Shah Ira. HIV and Pregnancy- Is Vaginal Delivery a Safe and Viable Option? Indian Pediatrics. 2008; 45:603-604.
3. Shah Ira. Lactic Acidosis in HIV Exposed Infants with Perinatal Exposure to Antiretroviral therapy. Annals Trop Pediatr. 2009; 29: 257-261
4. Shah Ira, Dhabe H, Lala M. Prevention of Maternal to Child Transmission of HIV: A Profile in Indian Children”. 42nd National Conference of IAP (PEDICON - 2005), Kolkata, January 2005; JF/08(P).
5. Rouzioux C, Costagliola D, Burgard M, Blancke S, Mayaux MJ, Griscelli C et al. Estimated timing of mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission by use of a Markov Model. Am J Epidemiol 1995;142 (12):1330-1337.
6. Read JS, Newell MK. Efficacy and safety of caesarean delivery for prevention of mother-to-child transmission of HIV-1. Cochrane Database Syst Rev. 2005;4:CD 005479.
7. The International perinatal HIV Group. The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1 – a meta analysis of 15 prospective cohort studies. N Engl J Med 1999;340:977-987.
8. World Health Organization (WHO). Rapid Advice: Use of antiretroviral drugs for treating pregnant women and preventing HIV infection in infants. 2010. WHO.
9. Perinatal HIV Guidelines Working Group. Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. April 29, 2009; pp 1–90. Supplement Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy. By the Perinatal HIV Guideline Working Group. Available at http://aidsinfo.nih.gov/ContentFiles/PerinatalGL.pdf.
10. McIntyre JA, Martinson N, Gray GE, Hopley M. Addition of short course Combivir (CBV) to single dose Viramune (sdNVP) for the prevention of mother to child transmission (pMTCT) of HIV-1 can significantly decrease the subsequent development of maternal and pediatric NNRTI-resistant virus., 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, Brazil, July 24-27, 2005. Abstract TuFo0204.
11. Lallemant M. Prevention of MTCT. Prevention of mother to child transmission. Available from Tr@inforPedHIV 2011.