Trial to Stop Mother-to-Baby Transmission Set to Begin

By Nancy Solomon

A clinical trial to test whether HIV Hyperimmune Globulin (HIVIG) Q
a blood product containing antibodies to HIV Q can prevent transmission
from pregnant women to their babies is expected to begin this summer now
that Abbott Laboratories has agreed to provide the HIVIG product.
The study by the AIDS Clinical Trials Group, named ACTG 185, had
been delayed from its April start by Abbott, which refused to sign a
contract that would hold the pharmaceutical company liable for any
health problems that may arise in the patients or their babies or for
cost overruns. Abbott agreed last week to sign the contract under
pressure from ACT UP and the U. S. National Institutes of Health (NIH),
but may not be able to deliver the product until the price goes up 15
percent in October.
"The negotiations dragged on for a fairly long period of time until
we found another source of product," said Elaine Sloand, M. D., special
assistant to the director of the National Heart, Lung and Blood
Institute. "I can't say what it was exactly, but they were getting a
lot of pressure from ACT UP. '
The phase III trial is designed to enroll 400 HIV-positive pregnant
women at 12 sites that have yet to be announced. All the women will be
given AZT while half receive HIVIG and the other half receive
Intravenous Immune Globulin (IVIG). IVIG is a blood product similar to
HIVIG but without any HIV antibodies.
To be eligible for the study, the women must have a CD4 T- cell
count of less than 500 or had an AIDS-defining illness that would have
previously initiated AZT therapy.
As of March, the number of cases of women with AIDS had grown to
22,607, according to the Centers for Disease Control. Some 20 to 30
percent of pregnant women with HIV pass on the virus to their babies,
the CDC says. But activists say the CDC undercounts women, that the
numbers are more likely to approach 40,000, and that transmission from
mother to baby occurs less than 20 percent of the time.
Because researchers suspect that HIV may be transmitted from mother
to baby during labor, the women will receive a "loading dose" of the
combination therapy by infusion while giving birth. The final phase of
the study provides the babies with AZT/HIVIG or AZT/IVIG beginning
shortly after birth and continuing for six weeks.
Abbott produces HIVIG by concentrating several liters of blood
plasma taken from asymptomatic people with HIV. The blood donors are
selected because they have shown a strong immune response to HIV,
meaning they are unusually healthy and have a high amount of antibodies.
When the concentrated plasma is injected into patients, it is expected
to boost the immune response against HIV. The plasma is screened for
HIV, meaning that it is safe and unable to infect healthy cells,
according to the research protocol.
Studies at the New York Blood Center with chimpanzees showed that
purified doses of HIVIG taken from asymptomatic people with HIV may
prevent the animals from getting the infection. People with HIV
apparently do not produce enough antibodies to kill the virus in their
own bodies.
Laboratory studies of HIVIG suggest that combination therapy with
AZT may be better than either treatment alone. Dr. Diane Wara of the
Department of Pediatrics at the University of California in San
Francisco and a team investigator for the study says the possibility of
blocking transmission to the baby is very promising.
"It's a great study Q it's win-win, everybody gets treated and
everybody wins," Dr. Wara said. The study will also collect data to
answer biological questions about how the immune system works during
pregnancy and how HIV is transmitted from mother to baby.
"So little is known about mothers and babies," Dr. Wara said. "Why
do some transmit and others don't? This study will allow us to look at
that."
Abbott had originally agreed to sell HIVIG to the ACTG study for
$1.2 million over the course of the entire study, but held up signing
the contract until the NIH agreed to give the company a cost increase of
15 percent beginning the next fiscal year, which begins in October. But
Abbott has now told the researchers that they cannot provide HIVIG until
October. Fortunately, the NIH already has enough product to begin
studying 50 mothers.
"I thought we'd have product available in August," said Dr. Lynn
Mofenson, medical officer for the study for the National Institute of
Child Health and Human Development. "But we have enough for 50 women
and I don't think we'll have 50 enrolled before October."
An initial phase of the trial is expected to begin enrolling women
in July at test sites at Baylor University in Houston, the University of
Texas in Houston, Mt. Sinai Medical Center in New York City, the
University of Rochester (Rochester, New York), and the University of
California in San Francisco.
The full-blown study is expected to get under way in September at
additional sites, including sites in Albany, New York, Duke University
in Durham, North Carolina, the Medical University of South Carolina in
Charleston, San Juan City Hospital in Puerto Rico, the University of
California in San Diego, and Westchester Hospital in New York. Five
undisclosed sites are still pending approval.