Aids is one of the principal causes of infant mortality in many developing countries. Viral transmission takes place during pregnancy (in utero), at the moment of childbirth or even during breastfeeding. If no treatment is given, the virus is transmitted to about 35% of children of infected mothers.
The use of a preventive treatment with zidovudine (AZT) has, since the 1990s, cut this risk to a third. However, access to these treatments remains scarcely possible for seropositive women living in developing countries, because of their duration, complexity and cost.
A clinical trial conducted in Thailand by a team of Thai, American and French researchers (1), as part of the international programme Perinatal HIV Prevention Trial (PHPT-2), showed that it is now possible to reduce the risk of mother-child HIV transmission to below the 2% threshold. This is possible using a combination of a short AZT treatment and a single dose of another antiretroviral, nevirapine (NVP).
In Thailand, the short treatment usually prescribed for prevention of mother-child HIV transmission is based on the administration of AZT in the course of the last three months of pregnancy and during labour and childbirth, and for one week in the newborn child. Bottle-feeding is also recommended, in order to avoid the child’s contamination by its mother’s milk. The researchers suggested adding to this treatment the administration of a single dose of NVP to both mother and child. The trial had the participation of 1 844 pregnant HIV-infected women, with a distribution over 37 hospitals over the whole country. Once their consent had been ensured, they were split at random into 3 groups. In the first group mothers and children received only the standard treatment using AZT. In the second group mothers received, in addition to the AZT treatment, a single dose of NVP at the moment of childbirth. For the third group, a single dose of NVP was added to the treatment of mothers and children.
A significantly lower transmission rate (3) was observed in groups taking the AZT-nevirapine combination, compared with the group receiving AZT (respectively 1.1 and 6.3%). This prompted the administration of nevirapine to all the women in the study. The trial was continued to determine if it was also necessary to give NVP to children, as an additive to milk. The final analysis showed a transmission rate of 2.0% in the group where both mothers and children had been treated with NVP and 2.8% in the group where only the mothers had taken it.
This new prevention strategy, shorter and more straightforward than triple therapy during pregnancy, showed itself to be just as effective, and without additional risk of toxicity for either mother or child. The low cost of additional doses of NVP makes the treatment applicable in developing countries. In those countries which currently use short AZT regimens for the prevention of mother-child HIV transmission, in the way Thailand does, many more children could be saved by adding just a single dose of NVP to the treatment of the mother and her child. It creates hope for the eradication of HIV transmission to children.
However, in this trial women who were exposed to NVP and who, six months after giving birth, started a triple therapy containing this medicine, showed initially higher risk of treatment of treatment failure than those who had not been exposed to it. This increased risk could be linked to the selection of a viral population resistant to this product, in the weeks following the single dose of NVP. Studies in partnership with the Ministry of Health of Thailand have been launched to find a solution to this problem. The researchers are currently working on the administration of triple therapies during pregnancy for women who can or whose clinical status requires this, and also on the use of an antiretroviral treatment covering the period that follows the single dose of NVP in order to prevent the appearance of resistance mutations. Another alternative being investigated is the possible substitution of NVP by other medicines, either in the prevention therapy against perinatal transmission or in the first retroviral therapy administered to mothers who need it.
Nevertheless, the efficacy of the method for preventing childhood Aids has prompted Thailand, backed up by WHO, to decide to promote this new straightforward combined AZT/NVP treatment system. The results of this investigation will be presented fully at the forthcoming world conference on Aids which will take place in Bangkok, in July 2004.