Preventing Mother-to-Baby transmission

If you are pregnant and HIV infected, there are three stages during which the baby can become infected:

1. At any stage while growing in the uterus
2. During delivery (peri-natal, or “around birth”)
3. While breastfeeding

If we take 100 pregnant HIV infected women, about 10 babies will become infected while growing in the uterus, about 20 will be infected during delivery and about another 15 will be infected through breastfeeding. Put a different way, about 30% of babies born to HIV infected women will be infected at birth, while another 15% of babies who were not infected at birth will become infected through breastfeeding. Infection can be prevented in some or all of these babies.

1. HIV infection of a baby in the uterus
Preventing infection of a baby in utero (growing in the uterus) requires that the mother be on effective antiretroviral treatment throughout pregnancy.

It has been shown that the higher the level of HIV in the blood, the more likely it is that a pregnant woman will give birth to an infected baby. Antiretroviral drugs cause a lowering of virus levels in a person’s blood and so lower the chances of the baby becoming infected.

In developed countries, a pregnant woman would be treated with antiretroviral drugs through pregnancy. However, there are concerns about ill-effects to the baby if antiretroviral drugs are taken throughout pregnancy, especially in early pregnancy.

A drug such as AZT has been used to treat hundreds of pregnant women at all stages of pregnancy and appears to be safe for the baby. With ongoing experience it will become clear which other antiretroviral drugs can be safely taken during pregnancy.

If antiretroviral drugs are not available for use in pregnancy, there are a few measures that can be taken to help prevent infection of the baby in utero, for example:

• Sexually transmitted diseases should be treated to avoid inflammation of the membranes of the uterus (chorioamnionitis).
• There has been some evidence that vitamin A supplements in pregnancy reduce the risk of HIV transmission to the baby.

2. HIV infection during birth
Most HIV infections in babies take place during delivery (peri-natal infections), and this is mainly where efforts to intervene have focused. The following three methods have been shown to be effective in preventing babies becoming infected with HIV during delivery:

• Caesarean section before labour starts
• Antiretroviral treatment of the mother starting some time before labour or at the beginning of labour
• Antiretroviral treatment of the baby after birth (Other simpler possibilities, such as washing the birth canal with a disinfectant, have unfortunately not proven effective.)

Caesarean section
An “elective” caesarean section, that is a caesarean section that is planned in advance and is done before labour starts, reduces peri-natal HIV infection by about half (50%).

However, in developing countries numbers of surgeons and operating theatres are insufficient to perform caesarean sections on all pregnant women with HIV. Also, a caesarean section is an operation that has risks for the mother, and complications such as infection of the wound are increased in women with HIV.

If a caesarean section is not done when a woman with HIV is in labour, care must be taken to avoid certain problems, such as early rupture of the membranes and the use of instruments to deliver the baby.

Antiretroviral treatment
The first study to show that antiretroviral drugs could reduce mother to child transmission of HIV was called the “PACTG 076 trial”. In this study women took AZT tablets daily from 14 weeks of pregnancy and were given intravenous AZT during delivery. Their babies were also given AZT syrup daily for the first six weeks of life.

The results of this study became known in 1994 and showed that babies who were in the AZT treatment group had a two thirds' (67%) lower rate of infection than babies who were in the “control group” (mothers and babies who did not receive AZT). In other words, where it was expected that three babies would be born infected with HIV, only one was infected when the mothers and babies were treated with AZT.

Since then, two routes have been followed. In developed countries, mothers and babies have been treated more intensively and for longer periods to try to reduce transmission rates even further. On the other hand, in developing countries researchers have been trying shorter and cheaper treatments, in order to make it practical and affordable to give such treatment to all pregnant women with HIV.

Of the many trials that have been conducted, the most important for African women was the “HIVNET 012 trial” in Uganda. This trial compared very short treatment using the drug nevirapine to very short treatment using AZT, with two groups of women and their babies taking one or the other drug. Each drug was given to the mother once only, at the beginning of labour. Then, in the case of nevirapine, the baby was given one dose after birth, and in the case of AZT, the baby received a dose every day for one week after birth.

The results showed that babies in the AZT group had a high rate of HIV infection, but in the nevirapine group this rate was cut by almost one half (47%). The reason that nevirapine is much more effective than AZT when the drugs are given as a very short course is because nevirapine starts to work against the virus much more quickly than AZT, and because nevirapine lasts much longer in the body, so it continues to work against the virus for longer.

To sum up, options for preventing peri-natal HIV infection start with very simple and cheap treatments, such as short course nevirapine, which will reduce infections in babies by at most 50%. At the other end of the range are complex, longer drug treatments for mother and baby, combined with elective caesarean section, which can avoid HIV infection during labour in almost every case.

Is nevirapine safe?
All drugs, including antiretroviral drugs, have side-effects. The two common side-effects of nevirapine are rash and hepatitis (liver inflammation). These side-effects can occur in people who have been taking nevirapine daily for several weeks. This sometimes means that a person will need to stop taking nevirapine and change to another antiretroviral drug.

However, these side-effects are extremely unlikely to occur when only one dose of nevirapine is taken, as in women who take nevirapine at the beginning of labour to protect the baby from HIV infection during delivery, or in babies who have one dose after birth.

One concern is that HIV becomes resistant to nevirapine very easily. It has been shown that in a significant number of women nevirapine-resistant virus appears in the blood after only one dose of nevirapine. This means that these women might not be able to use nevirapine as one of the treatment drugs when their time comes to take antiretroviral treatment for themselves when they develop Aids. (Although there are other choices of antiretroviral drugs that can be used, nevirapine is often an inexpensive first choice in developing countries.)

Also, there is concern that if a woman has a second baby, treatment with nevirapine will be less effective or ineffective for preventing infection during delivery.

3. HIV infection of a baby during breastfeeding
Breastfeeding is the third stage during which a baby can be infected by an HIV infected mother. There is no doubt that babies are infected through breastfeeding, and the longer breastfeeding continues the greater the final risk of infection.

However, the results of one study in South Africa suggest that it is not breastfeeding alone that leads to infection of the baby, but the practice of using both breast and other feeds (“mixed feeding”), which puts the baby at risk of infection. It is thought that possibly non-breast milk feeding in young babies causes damage to the gut lining, which then allows virus present in breast milk to penetrate the gut. The results of this study and the theory that it has generated urgently need to be proven by more studies.

At this time, there are two important options to prevent or reduce HIV infection through breastfeeding:

1. Exclusive formula feeding from birth. (“Exclusive formula feeding” is when a baby only receives milk formula by bottle and is never breast-fed.)
   

   This option completely excludes the possibility of infection through breastfeeding, and is practised in developed countries. However, milk formula is expensive and many people in developing countries cannot afford this option unless the formula is provided by the government or sold at subsidised prices. Also, if the family lives under conditions where it is difficult to prepare clean bottle feeds, this option can lead to other serious diseases in the baby, such as gastroenteritis. A mother’s desire to bottlefeed may be opposed by fear of exposure in certain communities, since it is known that women with HIV use this method of feeding.

2. Exclusive breastfeeding until early weaning (three months). (“Exclusive breastfeeding” is when a baby only receives breast milk and no other feeds.)
   

   This second option carries a risk of HIV infection to the baby, but the risk is limited to the time that the baby is on the breast. This option gives the baby the benefits of breastfeeding in early life, including the transfer of the mother’s protective antibodies in the breast milk and feeds that are safe from contamination by disease organisms. Breastfeeding is stopped as soon as possible after three months and replaced with milk substitutes and other suitable foods. This may be the best option in developing countries.

A healthcare worker should explain the risks and benefits of these two options to the mother very carefully, and then support her in whatever choice she makes.