Worldwide, it is estimated that more than 1 million children have been infected with HIV through mother-to-infant (perinatal) transmission. The World Health Organization (WHO) projects that during this decade alone, 5-10 million children will become infected with HIV through perinatal transmission, the vast majority in the developing world.
In 1994, clinical trials in the United States demonstrated that it is possible to reduce perinatal transmission through the use of an antiretroviral drug. Specifically, clinical trials conducted by the National Institutes of Health (NIH) showed that HIV-infected women could reduce the risk of transmitting the virus to their babies by as much as two-thirds through administration of zidovudine (ZDV or AZT) during pregnancy, labor, and delivery, and by giving their babies AZT for the first 6 weeks after birth. Researchers and public health practitioners from around the world convened in Geneva in June 1994 to define the public health implications of the results for the industrialized and the developing world.
The international panel recommended that the 076 regimen be used in the industrialized world where it is feasible, but immediately called for the exploration of alternative regimens that could be used in the developing or newly developed world, stating that cost and logistical issues would preclude the widespread application of the 076 regimen. The panel called for international coordination of research efforts to develop simpler, less costly drug regimens. Barriers which currently preclude the implementation of 076 in the developing world, and which must be overcome in order to develop realistic options for these nations include:
Cost: Drug costs alone for the AZT regimen in 076 are estimated to be at least $800; this is 80 times the annual health budget per person in many countries in the developing world. Less expensive alternatives are urgently needed to address the staggering impact of perinatal transmission in developing nations.
Feasibility: Following the 076 regimen requires that women be reached early in prenatal care, learn their HIV status, comply with a lengthy oral treatment regimen, receive intravenous administration of AZT during labor and delivery, and provide 6 weeks of AZT therapy to the infant following delivery. Yet, in the developing world, women infrequently present for care early in pregnancy, and intravenous treatment is not a widespread option.
Because there are currently no interventions available to prevent perinatal HIV transmission to infants in most developing countries, the panel specified that placebo-controlled trials should be designed to provide rapid and scientifically valid assessment of alternative drug regimens.
The placebo-controlled design will allow researchers to compare new regimens to the current standard of care in the developing world (which in most developing nations is no intervention) and to identify any potential side effects associated with the new regimens. The panel also stressed that any intervention tested in the developing world must be affordable, feasible, and sustainable in that setting. With this guidance, CDC, NIH, WHO, and UNAIDS are working with researchers worldwide to determine if there are simpler preventive therapies or practices which can reduce perinatal transmission. Several placebo-controlled studies are ongoing and summarized below.
In developing countries where poor women have no options for reducing perinatal transmission, a shorter course AZT regimen might provide the first opportunity for substantially reducing perinatal HIV transmission.
It is not clear which part of the 076 regimen was most important for prevention. But, researchers believe that the risks for HIV transmission may be highest during the last weeks of pregnancy, labor, and delivery. CDC and other researchers are now working with researchers in Thailand and the Ivory Coast to determine if administering AZT for a shorter time period during the last weeks of pregnancy and during delivery will be effective in reducing perinatal HIV transmission. By using a much shorter oral course during pregnancy (3-4 weeks, rather than 6-26 weeks), an oral dose during delivery (rather than an intravenous dose that may not be possible in many areas) and no infant dose (simpler and less expensive to implement), researchers have designed a regimen, that if effective, will be safer for the infant and can be realistically implemented in developing countries.
Researchers at the University of Bordeaux II, with funding from ANRS in France, are also exploring the effectiveness of short-course AZT therapy in reducing perinatal HIV transmission among a group of women in Burkino Faso and the Ivory Coast who currently have no therapy options. Their study will look at the effectiveness of AZT from the 38th week of pregnancy to 1 week after delivery at two sites -- Burkino Faso and the Ivory Coast.
UNAIDS is exploring the effectiveness of AZT in combination with 3TC in Tanzania, South Africa, and Uganda. In an effort to determine the simplest and most cost-effective regimen that may be effective, UNAIDS will explore three different therapy options -- from the 38th week to 1 week post delivery, including 1 week for the child; from labor through 1 week post delivery and for the baby for 1 week; and to mother only during labor and delivery.
Researchers are optimistic that these studies will lead to further understanding of the mechanisms of mother-to-infant HIV transmission and the mechanisms of prevention. Ultimately, the goal is to develop the most effective, simple, and safe therapy option--one that is affordable and feasible for the area where over 90% of new HIV infections occur -- the developing world.