Pioneer in Pediatric HIV Reflects on Progress

It was 1979 and Diane Wara, MD, a pediatrician and junior faculty member in immunology working in UCSF Medical Center's Pediatric Immunodeficiency Clinic, began seeing babies who seemed inexplicably prone to contracting opportunistic infections. Wara and her colleagues at UCSF would later determine that these infants were among the very first children infected with HIV. "We knew that there was something happening because we were seeing opportunistic infections in very young children, several of whom had the same mother but different fathers," Wara said. "That suggested a bloodborne infection." Wara suspected that the children's mother was infected with HIV. "Once HIV was defined, it was reasonably certain that the mother had HIV, and we believed that her three daughters had HIV, as well," Wara said. "This was during a time when children infected with HIV died by 18 months old." Wara didn't know it then, but a decade later she and her colleagues would determine the method through which children could be spared HIV infection, by treating both mother and baby prophylactically with early antiretroviral drugs. The revolutionary protocol would have a dramatic impact on the number of children infected with HIV at birth, virtually eliminating HIV infection in infants in the developed world. More to Learn
Now division chief of Pediatric Immunology/ Rheumatology and program director for the Pediatric Clinical Research Center at the UCSF School of Medicine and UCSF Children's Hospital, and recognized worldwide as a pioneer in pediatric HIV research and treatment, Wara said there still is much to be done to understand HIV infection and children. That's why on Sunday, Sept. 17, UCSF Children's Hospital and the Pediatric AIDS Treatment Center will hold the annual "Banana Chase" 5K Fun Run/Walk and 10K Run to support the research necessary to discover new treatments for childhood HIV and AIDS, and assist children through the Pediatric AIDS Treatment Center. The Banana Chase will be held at San Francisco's Kezar Stadium, Golden Gate Park. Online registration is available here. The event will include a variety of activities for children and adults, including the Banana Chase 5K and 10K, followed by the Whole Foods Market Young Champions Races for children ages 3 through 18, featuring 50-meter to 1-mile races in age group heats, and a pre- and post-race festival. The human immunodeficiency virus (HIV), the cause of AIDS, has now infected more than 65 million people worldwide, of whom 25 million have died, according to estimates of the Joint United Nations Program on HIV/AIDS (UNAIDS). AIDS is the deadliest pandemic of our generation and one of the worst in history. In the year 2005 alone, about 4.1 million people worldwide, half of them women, became infected with HIV, and about 2.8 million people with HIV/AIDS have died. In the United States, an estimated 1 million people are living with HIV infection, and 40,000 new infections occur each year. To date, HIV/AIDS has killed more than half a million people in this country. Most of the new cases are among racial and ethnic minorities, young homosexual men, people with certain addictive disorders and people over 50 years old. First Wave
Wara recently recalled being at the leading edge of understanding the first wave of HIV infection in children through the 1980s and into the 1990s. "A key became the fact that, unlike others who were infected with HIV, the point of transmission was clear-cut," Wara said. "The mother was pregnant. So, the transmission point was at or around the time of delivery. For other transmissions, infection occurs across more diffuse time periods." Wara explained that only a small percentage of transmission occurs through the placenta prior to birth. "Eighty percent occurs at or around the time of delivery, when the baby travels through the birth canal and swallows amniotic fluid and blood," she said. Preemies are especially vulnerable to infection at birth because it can permeate their unusually thin and fragile skin and digestive tracts. Then, in 1988-1989, a group of researchers that included Wara designed a study that involved treating mothers with the only antiviral drug available to treat HIV at the time, azidothymidine, or AZT, from the second trimester onward, as well as at the time of delivery, and treating the infant with oral AZT. The study proved enormously effective, and reduced transmission from 26 percent to 8 percent. "We've been working on that 8 percent ever since," she said. Today, infants' contraction HIV/AIDS from the mother has been virtually - but not entirely eliminated - in the developed world, Wara said. "I still see from four to six new babies a year that are infected with HIV," she said. "The reasons babies still are born with HIV vary: The mother opts out of testing for HIV, and goes through labor and delivery undiagnosed. A baby is born very prematurely at home because the mother can't get to the hospital quickly enough. A mother goes into a very busy emergency room and the baby is born there. Immigrants come into the emergency room and their baby is born there." Much work remains to be done to understand HIV and AIDS as it affects children and youths, Wara said. "We have to worry about pediatric HIV infection because HIV changes over time and because there are still HIV-infected children and youth in our country," she said. "San Francisco and the Bay Area are on the front edge of HIV research and treatment. Today, we're seeing women with very resistant HIV, and the agents that we're using are totally ineffective against it. This often means that the mother has been infected for years. "Women here tend to get pregnant in their 30s. Many of these women may have been infected since they were teens. Many of the mothers have been treated with multiple antiretroviral drugs, and it's difficult to identify either effective treatment for the mother or prophylaxis for the mother and baby," she said. In addition, the babies who have survived HIV are living into young adulthood with everything that this implies, as these young people become sexually active. Global Impact
Ultimately, work at UCSF in pediatric AIDS research and treatment benefits not just children here, but children around the world. "The strategies used to prevent transmission from mother to baby were first tested in the developed world, on mothers and babies in the United States," Wara said. "We don't and we shouldn't use new, untested strategies in the developing world. That is not the kind of clinical research we should support. We don't ask that the African mother and her baby in Uganda be the first to receive a new drug. The antiretroviral drugs used for chemoprophylaxis in the newborn may have serious side effects. Both the pharmacokinetics of these drugs and their side effects should be studied before large clinical trials are started in another country. The evaluation of new drugs in newborns requires both frequent blood draws -- usually within one day -- and frequent examination over several years and usually is done best in a setting with the infrastructure necessary for clinical research." Wara reflected that it has been both a privilege and exciting to have been involved in the laboratory and clinical research, and in setting social policy. "The disease started when I was a midlevel faculty member. A lot of it was just plain luck, being in the right institution at the right time," she said. "Being at UCSF in 1980, we were poised to do enormous amounts of good," Wara said. "There was a large group of scientists who wanted to rapidly move ahead. No one person could have done this alone." She credited Art Ammann, MD, Don Abrams, MD, Paul Volberding, MD, John Greenspan, BDS, PhD, and Rick Sweet, MD, as colleagues who were crucial to moving the research in and care of children with HIV and AIDS forward. "They were wonderful collaborators," she said. "We had the ability to ask and answer questions rapidly here. We train young people here. We took risks with our own careers. The Ob/Gyn department has been on the front line of being socially progressive, testing women with HIV during their pregnancies, and caring for women and children during birth." Links: Banana Chase Run/Walk Pediatric Clinical Research Center "'Banana Chase' Run on September 17 Supports Pediatric AIDS Research"
UCSF News Release, August 17, 2006