An experimental anti-viral drug has dramatically suppressed an AIDS-like virus in infant monkeys with none of the side effects associated with the commonly used drug AZT, according to scientists at the University of California, Davis. As a result of the UC Davis study, drug manufacturer Gilead Sciences has begun human clinical trials with the drug -- known as PMPA -- at Johns Hopkins University School of Medicine and UC San Francisco. Researchers hope the drug eventually will prove effective in treating infants and adults infected with the human immunodeficiency virus (HIV). Results of the UC Davis drug trial are reported in the November issue of Antimicrobial Agents and Chemotherapy by virologists Koen Van Rompay and Marta Marthas of the UC Davis-based California Regional Primate Research Center. "Current treatments have significantly reduced HIV infection in infants, and studies such as this raise our hopes that we can have a dramatic impact on transmission of HIV from mothers to infants," said Dr. Art Ammann of the Pediatric AIDS Foundation. "Our hope is that PMPA will bring HIV infection in the United States down to less than 100 babies each year, nearly eradicating the disease among infants." Each year approximately 8,000 HIV-infected women become pregnant in the United States. From those pregnancies, between 1,000 to 2,000 HIV-positive infants are born, that figure varying depending on whether the mother is treated for the infection. Worldwide, 250,000 to 350,000 HIV-infected babies are born annually, according to the Pediatric AIDS Foundation, which helped fund the UC Davis study. "This is a highly significant study, because it confirms and extends the efficacy of PMPA in rhesus macaques," said Roberta Black, a researcher in the AIDS division of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. "We don't know how these results will translate into human therapy, but this is compelling evidence for the efficacy of this drug that warrants further evaluation." PMPA, short for 9-[2[(phosphonomethoxy)propyl]adenine, works against HIV and the related simian immunodeficiency virus (SIV) found in monkeys by inhibiting an enzyme that is critical to replication of the viruses. Previous research indicated that PMPA might be useful in preventing infection in adult humans following exposure to HIV. The UC Davis researchers were curious to see if the drug also might thwart the virus in already-infected animals. Rhesus macaque monkeys were used in the drug trial because they are thought to be one of the best animal models for studying HIV infection in people. The drug was first tested in newborn monkeys because less of the drug is needed for the smaller animals and because, as in humans, the progression of the disease is accelerated in infants. Within a few months, the researchers knew whether the drug was working. The drug trial involved eight infant monkeys -- four in the control group and four in the test group. Although relatively small, this size of study is common when non-human primates are the subjects. All eight monkeys were inoculated with SIV when just a few days old. The four monkeys in the control group were not treated with anti-viral drugs. They rapidly developed high levels of the virus in their blood, as well as clinical signs of infection. Between the 10th and 13th weeks, the health of these monkeys had rapidly declined and it was clear that they were in the terminal stages of the illness. Three of the four monkeys in the control group were then euthanized. The four monkeys in the test group began receiving daily injections of PMPA three weeks after they were inoculated with SIV. The treatment was withheld that long in order to demonstrate that the test monkeys had been infected with the virus and because treatment of HIV-infected human babies may not begin until several weeks after birth. The progress of the infection in these monkeys closely resembled that in the control group of monkeys for the three weeks preceding treatment. After PMPA treatment began, researchers observed a rapid and strong reduction in the level of viral infection in the blood of three of the four test monkeys. The fourth monkey was slower to respond to PMPA and developed several symptoms of SIV infection. However, by the age of 13 months all four test monkeys exhibited normal levels of the infection-fighting T-cells and normal weight gain. The researchers were further encouraged to find that, unlike the drug AZT, PMPA treatment caused no observable side effects after one year of treatment. AZT suppresses bone marrow growth, usually resulting in anemia, according to Van Rompay and Marthas. The UC Davis researchers did notice that a low level of drug resistance developed in the PMPA-treated monkeys. After five to 15 weeks of PMPA treatment, the virus isolated from the blood of all four test monkeys had mutated and there was a five-fold reduction in the virus' susceptibility to PMPA therapy. Considering that a 100-fold reduction in susceptibility to AZT commonly occurs in patients being treated with AZT, the researchers were not disturbed by these signs of mild drug resistance in their test animals. Marthas and Van Rompay also tested PMPA on a juvenile rhesus macaque with an established SIV infection and reported their findings in this journal article. Within one week after the start of PMPA treatment, the virus couldn't be detected in the monkey's blood and symptoms of the illness began to disappear. The animal has remained healthy for the 9 months since treatment began. The researchers hope that PMPA will prove equally successful in treating humans. "Results from this study suggest that PMPA is a very promising treatment for HIV-positive infants and adults," said Van Rompay. "If PMPA has the same effects in humans as we have seen in animals, then it has the potential to prolong life and improve the quality of life for AIDS patients," said Marthas. The UC Davis study was conducted in collaboration with Niels Pedersen, a UC Davis professor of veterinary medicine, who in 1987 first identified an AIDS-like virus in cats. The study was funded by the National Institutes of Health and the Pediatric AIDS Foundation.