April 14, 1995
Media Contact: Marc Kusintz
Phone: (410) 955-8665
A team led by scientists at The Johns Hopkins School of Public Health says it has discovered why drug treatments to prevent a common AIDS-related disease may often fail.
The investigators confirm that treatment to prevent Pneumocystis carinii pneumonia (PCP) is initially effective in individuals who would otherwise get this disease. However, HIV-1 continues to attack the immune system, reducing the number of its T-helper cells until PCP occurs in spite of this preventive treatment.
The finding questions the current theory that PCP preventive therapy fails because the organism that causes PCP mutates and becomes resistant.
The researchers, led by Alfred Saah, M.D., associate professor of epidemiology at the School of Public Health, studied 476 HIV-infected men who reported taking one of three drug treatments to prevent PCP. Twenty percent of these individuals developed PCP despite preventive treatment. The treatment included either trimethoprim/sulfamethoxazole (TMP-SMX) dapsone or aerosolized pentamidine.
The study appears in the April 19 issue of the Journal of the American Medical Association.
Analysis showed that 77 percent of those individuals who developed PCP in spite of preventive treatment had T-helper cell levels below 50 (the normal level is about 1,000). And 87 percent of those who developed PCP in spite of treatment had T-helper cell levels below 75.
"It's apparently not the length of time a person has been getting preventive treatment with PCP prophylaxis that's important, but the state of their immune system--how many T-helper cells remain as time passes," says Saah.
Most experts were unsure whether treatment fails because P. carinii mutates, developing resistance to drugs. This would mean that the longer people take PCP prophylaxis, the greater their chances of developing PCP, because drug resistance would develop.
"Now it's clear that the number one consideration is the individual's immune status," says co-author Donald R. Hoover, Ph.D., associate professor of epidemiology. "The current treatments to prevent PCP are successful if the T-helper cell level is above 75. Once the immune system deteriorates further, however, none of the current forms of treatment is able to stave off P. carinii infections. Knowing this, the next step is to develop preventive therapy that works when T-helper cell counts have dropped below 75."
Other authors of the study were Yun Peng, M.S. (Johns Hopkins); John P. Phair, M.D. (Northwestern University, School of Medicine, Chicago); Barbara Visscher, M.D., Dr.P.H. (University of California, Los Angeles); Lawrence A. Kingsley, Dr.P.H. (University of Pittsburgh); Lewis K. Schrager, M.D. (National Institute of Allergy and Infectious Diseases); and the Multicenter AIDS Cohort Study.
The study was supported by the U.S. Public Health Service and the National Institute of Allergy and Infectious Diseases.