According to WHO/UNAIDS, in 2003 alone, 2.5 million children were infected with HIV/AIDS, mostly through mother to child transmission. Last year, over 500,000 children died of AIDS worldwide, making it one of the primary causes of child death in many countries. With a simple combination of zidovudine (AZT) and one dose of nevirapine (NVP) for the mother at the time of delivery and in the baby soon after birth, along with formula-feeding, pediatric HIV infection could be almost eradicated.
In Thailand, until recently the treatment for the prevention of mother-to-child transmission of HIV was the administration of AZT during the third trimester of pregnancy, during labor and delivery, and to the newborns for one week, with formula feeding.
In 2001, the perinatal HIV prevention trial (PHPT2) began in Thailand, to examine whether adding a single dose of NVP in mothers and infants, in addition to the AZT regimen would further reduce transmission without adding significant risk to mother or baby. Enrollment in the trial was offered to 1844 HIV-infected women receiving antenatal care in 37 hospitals throughout Thailand. If they consented, they were randomly assigned to one of three groups; one group received the standard AZT treatment; the mothers in the second group received one dose of NVP at onset of labor in addition to the AZT treatment; mothers and infants in the third group received one dose of NVP in addition to the AZT treatment.
In May 2002, the Data and Safety Monitoring Board reviewed the first interim analysis based on all the data available at that time. Because of the significantly reduced rate of transmission in the groups receiving NVP, the investigators decided to close the AZT-only group and provide NVP to all women enrolled in the study. The trial was continued in order to determine if, in addition to giving one dose of NVP to the mother, it was also necessary to give one dose to the child.
Among women who delivered before interim analysis, the transmission rate in the group where both mother and infant received NVP was 1.1%, while it was 6.3% in women who had received AZT only (P=0.00026, a highly significant difference). In the final analysis the rate of transmission was 2.0 percent in the group where both mother and infant received NVP compared to 2.8 percent in the group where the mother only received NVP.
"This is a very important advancement for the prevention of mother to child HIV transmission in Thailand which brings us closer to eradicating pediatric AIDS," says Dr. Vallop Thaineua, Permanent Secretary of Health at the Ministry of Public Health who is also an investigator in the study. Already, the Thai National Perinatal HIV Prevention program has incorporated this new regimen into its policy.
"This new strategy to reduce pediatric AIDS can be applied in developing countries and achieve success rates equal to those treatments currently used in industrialized nations," said Dr. Lallemant, IRD researcher, the principal investigator of the study. More than 1,500 infants get HIV from their mothers every day and 95% live in developing countries. In countries currently using a short course AZT regimen to prevent mother to child transmission of HIV, many more infants' lives will be saved with the addition of a single dose of NVP to the mother and to the baby. The cost of these additional doses is only $US4.
In the same study, resistance mutations, detectable very early after delivery, were found in about 20% of women who had received a single-dose of NVP. Women who had virus resistance and later required therapy for their HIV disease were less likely to achieve maximal viral suppression with triple antiretroviral combination containing NVP. However, if the therapy was initiated more than 6 months after exposure to NVP, the virological response was improved.
With the Ministry of Public Health in Thailand, further studies are underway to reduce the risk of resistance to NVP and to define the optimal combination therapies for women who have received a single dose NVP for the prevention of mother to child transmission. In the mean time, in view of its efficacy in preventing pediatric AIDS, Thailand has decided to implement this simple and safe regimen.
COLLABORATIONS
Obstetricians, pediatricians, nurses, counselors, laboratory technicians, and administrators in the 37 hospital sites are participating in the study.
Institutional collaborations include: Ministry of Public Health of Thailand, Chiang Mai, Khon Kaen and Mahidol Universities, Thailand; the Institut de Recherche pour le Développement (IRD) Research Unit 054, the Institut National d'Etudes Démographiques (INED) and the Institut National de la Santé et de la Recherche Médicale (INSERM) Erm 0321, France; Harvard School of Public Health, Department of Immunology and Infectious Diseases and the University of Massachusetts, the National Institute of Child Health and Human Development (NICHD), the Fogarty International Center at the National Institutes of Health, USA.
FUNDING
The research is funded by the National Institute of Child Health and Human Development (NICHD) at the National Institutes of Health, USA, (R01-HD 39615); the Agence Nationale de Recherches sur le Sida (ANRS), France (ANRS 1208), the Institut de Recherche pour le Développement (IRD), the Institut National d'Etudes Démographiques (INED), and the Ministry of Foreign Affairs, in France; the Ministry of Public Health and the Department of Technical and Economic Cooperation, in Thailand. Study drugs were provided by Boehringer-Ingelheim and Glaxo-Smith-Kline, and reagents for DNA PCR testing by Roche Molecular Systems.
Contact :
Dr Marc Lallemant
Until February 11th 2004, Canterbury Hotel, San Francisco 415-474-64-64, marc@phpt.org,
Institut de Recherche pour le Développement, Perinatal HIV Prevention Trial,
P.O Box 207, Prasing Post
Muang, Chiang Mai 50205, Thailand
Tel: 66-53-814-270-1
Dr Siriporn Kanshana,
Dept Of Heath, Ministry of Public Health, Thailand.
66-2-590-40-07,
siriporn@health.moph.go.th