E-drug: nevirapine for mother to child HIV prevention
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[This NIH pressrelease caused quite a stir: if it is true this would
make HIV prevention from mother to baby much more affordable.
Please realize that the scientific data have not yet been published
(expected in Lancet end July?). A summary is, however, available from
the NIH website, see:
http://www.niaid.nih.gov/newsroom/simple/exec.htm
Also, one clinical trial is probably too early to dump
AZT and/or 3TC for MTCT. Similar trials are, owever, already going on
in South Africa. WB]
[source: http://www.niaid.nih.gov/newsroom/simple/\]
Researchers Identify a Simple, Affordable Drug
Regimen That is Highly Effective in Preventing HIV
Infection in Infants of Mothers with the Disease
A joint Uganda-U.S. study has found a highly effective and safe drug
regimen for preventing transmission of HIV from an infected mother to
her newborn that is more affordable and practical than any other
examined to date. Interim results from the study, sponsored by the
National Institute of Allergy and Infectious Diseases (NIAID),
demonstrate that a single oral dose of the antiretroviral drug
nevirapine (NVP) given to an HIV-infected woman in labor and another
to her baby within three days of birth reduces the transmission rate
by half compared to a similar short course of AZT. If implemented
widely in developing countries, this intervention potentially could
prevent some 300,000 to 400,000 newborns per year from beginning life
infected with HIV.
"This extraordinary finding is the most recent in our efforts to
bring an end to AIDS, not only in the United States but in countries
around the world," says Health and Human Services Secretary Donna E.
Shalala. "American scientists along with our international partners
are committed to developing treatments that not only work, but that
are also feasible in other health care settings. These results
achieve both those goals."
"This study represents the most promising advance to date toward the
goal of finding strategies that can be used worldwide to prevent the
spread of HIV from infected mothers to their infants," says NIAID
Director Anthony S. Fauci, M.D. NIAID is a component of the National
Institutes of Health.
In an announcement from Kampala this morning, Ugandan officials
hailed the finding. "This research provides real hope that we may be
able to protect many of Africa's next generation from the ravages of
AIDS," says Crispus Kiyonga, M.B.Ch.B., Uganda's Minister of Health.
"We commend the collaborative effort of our country's scientists, led
by Professor Francis Mmiro from Makerere University Faculty of
Medicine, and their U.S. colleagues, led by Dr. Brooks Jackson from
The Johns Hopkins University School of Medicine."
Finding affordable interventions for developing countries is key to
curtailing the global AIDS epidemic. In parts of the hardest-hit
area, sub-Saharan Africa, up to 30 percent of pregnant women are
infected with HIV, and 25 to 35 percent of their infants will be born
infected. The UNAIDS estimates that approximately 1,800 HIV-infected
babies are born every day in developing countries.
Unfortunately, the standard AZT regimen used to prevent perinatal HIV
transmission in the United States is too expensive and impractical
for widespread use in developing countries where many women may not
receive prenatal care.
Based on average U.S. wholesale costs, the cost of the drug used in
the nevirapine regimen in the current study is approximately 200
times cheaper than the long-course AZT used in the United States, and
almost 70 times cheaper than a short course of AZT given to the
mother during the last month of pregnancy - a regimen tested in
Thailand by the Centers for Disease Control and Prevention and
reported effective in 1998.
The Uganda study investigators, part of the NIAID-supported HIV
Prevention Trials Network (HIVNET), opened the trial two years ago at
Mulago Hospital, affiliated with Makerere University, in Kampala,
Uganda. They completed enrollment last April. All women entered into
the study were in their ninth month of pregnancy. None had taken
antiretroviral drugs while pregnant.
The study, known as HIVNET 012, compared the safety and efficacy of
two different short-course regimens of antiviral drugs administered
late in pregnancy. The women were assigned at random to receive
either a 200-mg dose of oral nevirapine at the onset of labor,
followed by a 2-mg/kg oral dose given to their babies within three
days of birth; or a 600-mg dose of AZT at the onset of labor, and
300-mg doses every three hours thereafter during labor. The infants
born to mothers in the AZT group received 4 mg/kg given twice daily
for the first week of life. Both drugs appeared to be safe and
well-tolerated.
Study design, data collection and analysis was provided by a team of
researchers led by Dr. Thomas Fleming, a biostatistican at the Fred
Hutchinson Cancer Research Center and the University of Washington
School of Public Health and Community medicine in Seattle.
For the interim analysis, the study team looked at data from 618
mothers (308 receiving AZT and 310 receiving nevirapine) and their
infants.
Nevirapine was markedly more effective. At 14 to 16 weeks of age,
13.1 percent of infants who received nevirapine were infected with
HIV, compared with 25.1 percent of those in the AZT group.
"In this study, the short-course nevirapine regimen resulted in a 47
percent reduction in mother-to-infant HIV transmission compared with
a short course of AZT. The implications of this study for developing
countries, where 95 percent of the AIDS epidemic is occurring, are
profound," says Brooks Jackson, M.D., the lead U.S. investigator on
the trial.
Long-term follow-up of both the mothers and their babies remains a
high priority to assess any late drug toxicities as well as long-term
survival. The mothers and their children will continue to be actively
followed until the babies are 18 months old. This period is critical
to establish the efficacy of the intervention because even if a baby
is born HIV-free, he or she may acquire the virus during
breastfeeding. The data analyzed so far cover only the first three
months of the newborn's life. Ugandan and U.S. investigators will
soon launch a follow-up study to evaluate the efficacy of nevirapine
administered to the mother during labor and to the newborns for a
longer period of time.
Breastfeeding is practiced widely in developing countries. Most
studies indicate that the rate of HIV transmission via breastfeeding
is highest in the first few months of life. No intervention has yet
been shown to prevent HIV transmission through breast milk other than
not breastfeeding.
The single-dose nevirapine regimen to mother and infant substantially
lowers the cost barrier that has kept many countries from adopting
drug strategies that prevent perinatal HIV transmission. Still,
access to other health care services required to implement this
regimen, such as counseling and voluntary HIV testing, are beyond
available resources of many developing countries. But if further
research upholds nevirapine's good safety record, the investigators
say that potentially all pregnant women who live in areas of high HIV
prevalence could receive the drug during labor, even in the absence
of an established HIV diagnosis.
In the United States and other industrialized countries, many
HIV-infected pregnant women already take combination drug regimens
that include AZT. A study now being conducted in the United States
and Europe is evaluating if adding nevirapine to standard treatment
regimens will have any extra benefit in preventing perinatal HIV
transmission in these countries. For pregnant women who do not know
their HIV status until they begin labor, the nevirapine regimen
provides a last-minute prevention option.
Nevirapine, developed by Boehringer Ingelheim Pharmaceuticals, is a
non-nucleoside reverse transcriptase inhibitor, and is in a different
class of antiviral drugs than AZT but works against the same HIV
target enzyme that is critical for the virus to infect new cells. It
can be easily stored at room temperature. Besides being inexpensive
and potent, nevirapine is rapidly absorbed and transferred across the
placenta to the infant, and it breaks down slowly. For these reasons,
it was thought that even a single dose to the mother and infant might
provide enough protection to the baby during the time of exposure to
HIV at birth. In March 1996, nevirapine was licensed in the United
States for treatment of HIV infection in adults. AZT, made by Glaxo
Wellcome, was first approved in the United States to treat AIDS in
1987. In August 1994, AZT received an additional indication for use
in preventing perinatal HIV transmission.
NIAID is a component of the National Institutes of Health (NIH).
NIAID conducts and supports research to prevent, diagnose and treat
illnesses such as HIV disease and other sexually transmitted
diseases, tuberculosis, malaria, asthma and allergies. NIH is an
agency of the U.S. Department of Health and Human Services.
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