The National Institutes of Health has opened the first trial of experimental HIV vaccines in children who are infected with the human immunodeficiency virus (HIV), the virus that causes AIDS.
The trial will compare the safety of three HIV experimental vaccines in 90 children recruited from at least 12 sites nationwide. Volunteers must be HIV-infected but have no symptoms of HIV disease.
HHS Secretary Donna E. Shalala said this initial study can be seen as "a hopeful milestone in our efforts to ameliorate the tragedy of HIV-infected children who now face the certainty they will develop AIDS."
Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases and of the NIH Office of AIDS Research, said the trial "is the first step in finding out whether vaccines can help prevent or delay disease progression in children with HIV who are not yet sick." If these vaccines prove to be safe, more sophisticated questions about their therapeutic potential will be assessed in Phase II trials.
The Centers for Disease Control and Prevention estimates 10,000 children in the United States have HIV. By the end of the decade, the World Health Organization projects 10 million children will be infected worldwide.
The study will enroll children ages 1 month to 12 years old. NIAID, which funds the AIDS Clinical Trials Group network, anticipates conducting the trial at nine ACTG sites around the country and three sites participating in the ACTG but funded by the National Institute of Child Health and Human Development.
Preliminary evidence from similar studies under way in infected adults shows that certain vaccines can boost existing HIV-specific immune responses and stimulate new ones. It will be several years, however, before researchers know how these responses affect the clinical course of the disease.
The results from the pediatric trial, known as ACTG 218, will be examined closely for other reasons as well. "This trial will provide the first insight into how the immature immune system responds to candidate HIV vaccines," said Daniel Hoth, M.D., director of NIAID's division of AIDS. "We need this information to design trials to test whether experimental vaccines can prevent HIV infection in children."
In the United States, most HIV-infected children live in poor inner-city areas, and more than 80 percent are minorities, mainly black or Hispanic.
Nearly all HIV-infected children acquire the virus from their mothers during pregnancy or at birth. An infected mother in the United States has more than a one in four chance of transmitting the virus to her baby. As growing numbers of women of childbearing age become exposed to HIV through injection drug use or infected sexual partners, researchers expect a corresponding increase in the numbers of infected children.
HIV disease progresses more rapidly in infants and children than in adults. The most recent information suggests that 50 percent of infants born with HIV develop a serious AIDS-related infection by 3 to 6 years of age. These infections include severe or frequent bouts of common bacterial illnesses of childhood that can result in seizures, pneumonia, diarrhea and other symptoms leading to nutritional problems and long hospital stays.
At least half of the children in the trial will be 2 years of age or younger to enable comparison of the immune responses of the younger and older participants. All volunteers must have well-documented HIV infection but no symptoms of HIV disease other than swollen lymph glands or a mildly swollen liver or spleen. They cannot have received any antiretroviral or immune-regulating drugs within one month prior to their entry into the study.
Study chair John S. Lambert, M.D., of the University of Rochester Medical School, and co-chair Samuel Katz, M.D., of Duke University School of Medicine, will coordinate the trial assisted by James McNamara, M.D., medical officer in the pediatric medicine branch of NIAID's division of AIDS.
"We will compare the safety of the vaccines by closely monitoring the children for any side effects, to see if one vaccine produces more swollen arms or fevers, for example, than another," said Dr. McNamara. "We'll also look at whether low or high doses of the vaccines stimulate immune responses or other significant laboratory or clinical effects." He emphasized that the small study size precludes comparing these responses or effects among the three products.
The trial will test two doses each of three experimental vaccines made from recombinant HIV proteins. These so-called subunit vaccines, each genetically engineered to contain only a piece of the virus, have so far proved well-tolerated in ongoing trials in HIV-infected adults.
One vaccine made by MicroGeneSys Inc. of Meriden, Conn., contains gp160 -- a protein that gives rise to HIV's surface proteins -- plus alum adjuvant. Adjuvants boost specific immune responses to a vaccine. Presently, alum is the only adjuvant used in human vaccines licensed by the Food and Drug Administration.
Both of the other vaccines -- one made by Genentech Inc. of South San Francisco and the other by Biocine, a joint venture of Chiron and CIBA-Geigy, in Emeryville, Calif. -- contain the major HIV surface protein, gp120, plus adjuvant. The Genentech vaccine contains alum, while the Biocine vaccine contains MF59, an experimental adjuvant that has proved safe and effective in other Phase I vaccine trials in adults.
A low dose of each product will be tested first against a placebo in 15 children. Twelve children will be assigned at random to be immunized with the experimental vaccine, and three children will be given adjuvant alone, considered the placebo. Neither the health care workers nor the children will be told what they receive.
If the low dose is well-tolerated, controlled testing of a higher dose of the experimental vaccine and adjuvant placebo in another group of 15 children will begin.
Each child will receive six immunizations -- one every four weeks for six months -- and be followed-up for 24 weeks after the last immunization.
For more information about the trial sites or eligibility for enrollment, call the AIDS Clinical Trials Information Service, 1-800-TRIALS-A, from 9 a.m. to 7 p.m., EST weekdays. The service has Spanish-speaking information specialists available. Information on NIAID's pediatric HIV/AIDS research is available from the Office of Communications at (301) 496-5717.
NIH, CDC and FDA are agencies of the U.S. Public Health Service in HHS.