E-drug: short-course AZT for vertical transmission prevention
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[copied from PROCAARE]
FOLLOWING THE ANNOUNCEMENT BY
THE MINISTRY OF PUBLIC HEALTH OF THAILAND
AND THE CDC OF RESULTS FROM
THEIR MOTHER-TO-CHILD TRANSMISSION TRIAL
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 nd can
have a significant impact on perinatal tranmission 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 labour, 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 labour, and was not given to
newborns.
Keywords: clinical science, perinatal transmission, AZT, short-course
therapy, Thailand
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