HHS Secretary Donna E. Shalala announced today that the National Institute of Allergy and Infectious Diseases has begun the first clinical trials of therapeutic AIDS vaccine candidates in pregnant women who are HIV-infected but otherwise healthy.
In these separate Phase I trials, two experimental vaccines are being evaluated primarily for safety but also for their potential to stimulate anti-HIV immune responses in expectant mothers and to prevent their passing HIV infection to their babies.
Secretary Shalala said, "Although three-fourths of infants born to HIV-infected mothers in the United States escape HIV infection, nearly all children who become infected acquire the virus from their mothers. We need therapies that not only improve the health of pregnant women infected with HIV but that also prevent this tragic mode of HIV transmission."
No one knows exactly when HIV passes to the fetus, or why some babies get infected and others do not. Evidence suggests that HIV frequently is transmitted either late in pregnancy or during birth.
By vaccinating HIV-infected pregnant women, we hope to induce immune responses that will reduce the amount of virus present, thus helping the women, while simultaneously stimulating antibody responses that can cross the placenta and protect their babies from HIV infection," said NIAID Director Anthony S. Fauci, M.D.
One precedent for using maternal immunization to prevent the transmission of infectious diseases from a mother to her newborn is tetanus immunization. Vaccinating pregnant women in non-industrialized countries has proved to be the most cost-effective way to prevent neonatal tetanus, a significant cause of newborn deaths in these countries.
With the development of the technologies to make vaccines safer, concerns about the risks associated with vaccinating pregnant women have lessened, and interest in maternal immunization has grown.
The Centers for Disease Control and Prevention predicts that women will continue to be a growing share of new U.S. AIDS cases through the decade's end. HIV/AIDS is now the sixth leading cause of death after cancer, unintentional injuries, heart disease, suicide and homicide for women of childbearing age (15 to 44 years old) nationwide. HIV/AIDS is the leading cause of death for women in this age group in New York and New Jersey. Moreover, as a greater percentage of women of childbearing age become infected with HIV, experts expect a concurrent rise in the number of infected children. Already, HIV/AIDS is the fifth leading cause of death for children in the United States between the ages of 1 and 14.
The two new trials in pregnant women and a similar one expected to begin by early summer will test genetically engineered candidate HIV vaccines. Completed and ongoing trials of these experimental vaccines in healthy individuals with and without HIV infection have shown them to be well-tolerated. Because each candidate contains no live HIV and only a piece of the virus, these so-called subunit vaccines cannot transmit HIV infection.
Although testing different candidate HIV vaccines, the trials are designed similarly. Both enroll women between ages 16 and 40 who are free of AIDS-defining symptoms and have 400 or more CD4+ T cells, a primary cell of the Immune system. Volunteers must not have any other medical conditions, such as insulin-dependent diabetes or moderate to sever hypertension, that would make their pregnancy high-risk. Therapy with zidovudine (AZT) can be continued during the trial.
The multicenter trial will enroll 24 women. Sixteen will receive the experimental vaccine, the rest a non-active dummy vaccine, or placebo. The smaller trial will enroll 12 women, nine assigned to receive vaccine and the others a placebo. Assignments will be made randomly, and throughout the trial, neither the investigators nor the participants will know if the women are receiving the active or placebo vaccine.
Each trial volunteer will receive at least four or five immunizations: the first between the 16th and 24th week of pregnancy and thereafter monthly booster doses until the end of her pregnancy. The health of the women will be monitored with regular blood and urine tests, and the health of their fetuses with ultrasound.
The mothers may opt for a second series of booster immunizations at three, six, nine and 12 months after deliver. Both trials will last about two years, including an 18-month follow-up period after delivery.
Newborns will be examined at birth and six weeks later, and then every three months during follow-up. The investigators will periodically sample the babies' blood to monitor their health and determine any vaccine effects.
"By intentionally altering the HIV immune status of pregnant women through active immunization, eventually we hope to discover the critical factors that prevent mothers from passing the infection the infection to their babies," says Patricia Fast, M.D., Ph.D., who leads the Phase I/II HIV vaccine trials program for NIAID's Division of AIDS.
The trials are being conducted through two of NIAID's national clinical trials networks, the AIDS Vaccine Evaluation Group and the AIDS Clinical Trials Group. Study co-chairs and AVEG investigators Peter Wright, M.D., of Vanderbilt University, and John Lambert, M.D. of the University of Rochester in New York, will coordinate the trial. Dr. Gast, along with James McNamara, M.D., and Evelyn Rodriguez, M.D., both medical officers in NIAID's Division of AIDS who specialize in perinatal and pediatric clinical trials, will help facilitate the studies.
One trial, known as AVEG 104/ACTG 235, will be conducted at seven sites located in Rochester, Seattle, St. Louis (two sites), Nashville, Baltimore and San Francisco. Women in this trial will receive and experimental vaccine made by Genentech Inc. of South San Francisco. The vaccine contains a genetically engineered surface protein of HIV, gp120 (MN), and the adjuvant alum. An adjuvant is a substance formulated with a vaccine to boost specific immune responses. Alum is the only adjuvant now in human vaccines licensed by the Food and Drug Administration.
The second trial, known as AVEG 102/ACTG 234, will be carried out at one site in New Haven. This trial uses a vaccine made by MicroGeneSys Inc. of Meriden, Conn., containing gp160 (LAV), the parent protein of gp120, and alum. Alum will be used in both trials as the placebo vaccine.
These studies are part of a comprehensive effort by NIAID to improve the health of HIV-infected pregnant women and their offspring.
NIAID, a component of the National Institutes of Health, supports research on AIDS and other infectious diseases, allergy and immunology. NIH, CDC, and FDA are agencies of the U.S. Public Health Service within HHS.
For more information about the trial sites or eligibility criteria, call the AIDS Clinical Trials Information Service, 1-800-TRIALS-A, from 9am to 7pm ET weekdays. Spanish-speaking information specialists are available. Women interested in participating also may speak directly to trial recruiters at the site telephone numbers listed below. An AIDS/HIV Vaccine Backgrounder is available from the NIAID Office of Communications at (301) 496-5717.
Trial Sites for AVEG 104/ACTG 235