PR Newswire; Wednesday February 18, 2:26 pm EST

Today's announcement by the Ministry of Public Health of Thailand and the U.S. Centers for Disease Control and Prevention (CDC) that a simplified regimen of zidovudine (AZT) can reduce the risk of mother-to-child transmission of HIV marks an important step forward in international efforts to develop interventions that can be broadly and safely implemented and which, more specifically, can respond to the requirements of many developing countries. The Thailand trial results show that a simplified AZT regimen can be well- tolerated and is effective in significantly lowering perinatal transmission from HIV-infected women who are not breastfeeding.

The ANRS, CDC, NIH, and UNAIDS are already sharing the data with their collaborators, and have recommended to the principal investigators of clinical trials currently sponsored by these agencies that placebo arms be dropped or replaced with the CDC short-course regimen.

A number of the trials that have been conducted, including this trial in Thailand, have included a placebo arm. Use of a placebo arm was the only way in which it could be clearly and quickly established whether a shorter AZT regimen was safe and more effective than no treatment at all, since previously these data were unavailable.

The results of the trial showed that this shortened regimen of AZT lowered the risk of perinatal transmission by 51% (from 18.6% without AZT to 9.2% with AZT). Although this reduction is not equivalent to that observed in ACTG 076 -- the longer regimen used in developed countries -- this short-course regimen is more applicable and feasible for many countries in the developing world and can have a significant impact on perinatal transmission in these countries.

From the outset, this international research effort has been coordinated by the UNAIDS Informal Working Group on Prevention of Mother-to-Child Transmission of HIV, with membership of all research institutions involved in mother-to-child transmission trials. The working group has sought to identify the most promising drug regimens for testing and to coordinate trial designs in order to allow optimal comparison of results and to eliminate duplication of effort.

Next Steps

At the end of March, UNAIDS will host a meeting of international agencies and interested governments from developed and developing countries in Geneva to find ways of rapidly and effectively implementing the results of this and other trials into public health policy as they become known.

It must be emphasized that the study in Thailand was conducted in a population of HIV-infected women who did not breastfeed. With the availability of an effective simplified regimen applicable to many countries in the developing world, it is essential to now evaluate the effectiveness of a very short AZT regimen in pregnant women who do not present at prenatal clinics before the time of delivery and in women who breastfeed -- both of which are common in many countries in the developing world. Because HIV can also be transmitted through breast milk, it is possible that efficacy of the shortened regimen may be lessened in countries where breastfeeding is the norm.

Further evaluation of the shortened regimen in such countries is therefore essential, as well as exploration of the relevance of early weaning or other strategies. It will also be important to evaluate regimens that are even simpler than the CDC short-course AZT regimen to establish their efficacy in reducing HIV transmission. Additionally, it needs to be established whether there is further advantage in using other antiretroviral drugs or combinations of drugs for reducing transmission.

Background

In 1994, a clinical trial demonstrated that by giving a regimen of AZT, known as the ACTG 076 regimen, to non-breastfeeding HIV-positive pregnant women, the risk of perinatal transmission of HIV could be reduced by almost 70% (from 25% without AZT to 8% with AZT). During this trial, AZT was administered orally to women five times a day starting on average at 26 weeks gestation and continuing throughout pregnancy. It was then given intravenously during labor, and orally four times a day to infants for six weeks after they were born. In industrialized countries, such as France and the United States, where this regimen has been implemented, significant declines in perinatal HIV infection have been observed.

However, in most developing country settings, implementation of this prophylactic regimen is precluded because of limited resources and health service facilities. The CDC-supported trial, undertaken in collaboration with the Ministry of Public Health in Thailand, was therefore designed to determine whether an effective alternative could be identified that did not require intravenous administration and which could be used in developing countries with an existing health infrastructure to support women who attend prenatal clinics only very late in pregnancy, as is often the case in the developing world.

The Thailand trial was part of a globally coordinated research effort conducted by several national and international sponsoring agencies in a number of developing countries to also provide rapid and scientifically valid responses to a series of complex questions related to the safety and efficacy of AZT in specific contexts. These issues needed to be addressed before the drug could be safely and effectively administered to populations of women who are infected with different viral strains than those found in the industrialized countries and have different tolerance levels and transmission factors, including breastfeeding.

The regimen evaluated in the Thailand trial was AZT started at 36 weeks gestation and continued for the rest of pregnancy. The drug was administered orally to women twice daily and during labor, and was not given to newborns.

SOURCE: Centers for Disease Control and Prevention

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