Scientific basis for PEP rests in animal trials
Scientific basis for PEP rests in animal trials
Double-blind studies aren’t feasible
The rationale for post-exposure prophylaxis (PEP) for sexual or needle-sharing exposures to HIV is based on the idea that antiretroviral drugs, when delivered shortly after exposure, can prevent the virus from seeding in bodily organs and establishing an infection.
Scientists know that once a person has been exposed to the virus, it takes at least a week before it is detected by sensitive assays, and two to three weeks before seroconversion. Because AIDS is largely a lymphatic disease, stopping the spread of the virus before it becomes established in the lymph system is the main goal of PEP, said Tom Folks, PhD, chief of the retrovirus disease branch at the Centers for Disease Control and Prevention, during a conference on PEP.
While PEP has not been studied in humans, animal trials have shown that antiretroviral drugs can prevent or abort HIV and simian immunodeficiency virus (SIV) infection. Most recently, researchers followed Rhesus monkeys that were intravenously challenged with a virulent strain of SIV and then treated for 28 days with the drug PMPA. Monkeys treated within 24 hours of exposure have remained SIV-negative for more than a year, reported Roberta Black, PhD, a senior scientist at the National Institutes of Health’s division of AIDS. However, those treated at 48 hours were protected from infection only during treatment, and once the drugs were stopped viral loads became detectable again. Treatment at 72 hours from exposure did not have a protective effect, Black noted.
The consultants also were presented with data from a study of chimpanzees infected intrave nously with HIV. The animals were given nevirapine both before and after exposure for 10 or 20 days. Three of the four animals have tested negative for the virus months after treatment.
Other than animal data, the evidence for PEP effectiveness in non-occupational exposures is extrapolated from a 1995 case-control study of exposed health care workers and ACTG 076, which found that AZT could cut down perinatal HIV transmission by 67%. The unexpected findings of the case-control study led CDC officials to carefully re-analyze its findings before issuing recommendations for providing prophylaxis for health care workers after exposure.
"We spent a year trying to disprove that AZT had no protective effect and we couldn’t," said Denise Cardo, MD, an epidemiologist at the CDC’s division of HIV prevention, surveillance and epidemiology.
Because the risk of infection in exposed health care workers is so low, it is not feasible to conduct a double-blind, randomized study. Health officials have had to rely solely on the case-control study, which had several limitations. Since the CDC guidelines on post-exposure prophylaxis for health care workers were issued, a registry has been set up to monitor exposed health care workers who receive treatment. By carefully following those patients, the CDC hopes to shed more light on what treatments are most effective and what their side effects are. The CDC already has collected treatment information from three surveillance systems, including the registry, following more than 2,000 workers. (See chart, p. 100.)
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