NIH Press Release - Uganda Nevirapine Study
----------------------------------
[Please note that "Short Course AZT" in this study was AZT to the mother
during labor then for one week after delivery. It is not the same as the Thai
Regimen, also referred to as Short Course AZT" and now being used in some
mother to child HIV prevention programmes in some African countries.
Moderator - Brian Pazvakavambwa]
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.
Press releases, fact sheets and other materials are available on the NIAID
Web site at:
http://www.niaid.nih.gov/
--
Send mail for the `AFRO-NETS' conference to `afro-nets@usa.healthnet.org'.
Mail administrative requests to `majordomo@usa.healthnet.org'.
For additional assistance, send mail to: `owner-afro-nets@usa.healthnet.org'.