Prevention of Transmission of HIV From Mother to Fetus

Following the clinical trial (ACTG 076) which showed that AZT could reduce the risk of transmission of HIV from mother to infant, the change in clinical practice has confirmed the trial result. Whereas transmission rates used to be over 20%, recent reports show rates of 5% or less.

However, this trial leaves many unanswered questions:

1. The trial design covered possible transmission during late pregnancy, around the time of birth and during breast feeding. Therefore we do not know which parts of therapy are most important.
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2. There was a trend towards less risk of transmission with lower maternal HIV RNA load but some mothers with relatively low levels still had infected infants. However, the risk of transmission when the virus load is below detection is not known.

3. AZT reduced the virus load only modestly. Clearly, a current aim is to reduce the maternal virus load to below detection limits.
4. Showing that an alternative treatment is better is very difficult. For example, a trial comparing AZT plus/minus HIV antibody was stopped early as the transmission rates were under 5%. Only a greatly enlarged trial could show a difference.

5. Monitoring for long-term effects. Over 1000 children (from trials ACTG 076, 185 and 219) are being followed. With many children now over 3 years old, there are no differences between the AZT and placebo groups in growth, neurodevelopment or CD4 count. No tumors have been seen.

Further investigations with other anti-HIV agents are hampered by lack of information, for lack of pharmacokinetic data - how well do the drugs pass from mother to fetus. For the protease inhibitors, that are metabolised in the liver, we may expect drug levels to be maintained in the fetus for a long time as the fetal liver is immature. In spite of these difficulties, several international trials are ongoing, including:

1. AZT and 3TC comparing treatment during various stages of pregnancy and after birth.

2. AZT, 3TC and nevirapine.

In conclusion, AZT therapy gives a large improvement in reducing the risk of maternal transmission. The ongoing trials with AZT and 3TC will, hopefully, give us a further step forward. Testing triple therapy with a protease inhibitor, HIV RNA load down to undetectable levels, remains a future goal.