Individuals infected with HIV, the virus that causes AIDS, prolonged their lives by taking the drug zidovudine (AZT) before symptoms of AIDS appeared, according to a report in the April 16 issue of the New England Journal of Medicine. The findings were based on data from 2,568 HIV-infected participants enrolled in the Multicenter AIDS Cohort Study (MACS), primarily funded by the National Institute of Allergy and Infectious Diseases.
Participants received physical examinations and blood tests at six-month intervals for 24 months. The rates of death at each interval were calculated separately for HIV-infected men who began treatment with AZT before they were diagnosed with AIDS and for men who did not. Early treatment with AZT reduced the risk of death at six months by 57 percent, whether or not it was combined with a drug that prevented Pneumocystis carinii pneumonia (PCP). Moreover, investigators found that, after two years, early treatment reduced the risk of death by 33 percent, when compared to those who did not take AZT before a diagnosis of AIDS.
Previous NIAID studies showed that early treatment with AZT could delay progression to AIDS in HIV-infected persons with fewer than 500 CD4-positive T cells. We now have evidence that AZT can extend life for certain HIV-infected persons if taken before the symptoms of AIDS develop," says Anthony S. Fauci, M.D., director of NIAID.
In general," adds lead author Neil Graham, M.B.B.S., M.D., M.P.H., assistant professor of epidemiology at The Johns Hopkins School of Public Health, "men starting with 200 to 349 CD4-positive T cells appeared to benefit the most from treatment. A longer follow-up period will be needed before we can accurately measure a significant therapeutic effect for people with CD4-positive T cells counts of greater than 350." Hopkins collaborates on MACS investigations with NIAID, Northwestern University, University of California at Los Angeles and University of Pittsburgh.
CD4-positive T cells are the white blood cells of the immune system targeted by HIV. Physicians use the blood levels of CD4-positive T cells to measure the progression of HIV infection. Levels near 1,000 CD4-positive T cells are considered normal.
Using data collected from October 1986 through April 1991, the investigators noted 360 deaths and compared the type and length of therapies and the severity of illness of these individuals.
MACS participants who received drugs to prevent PCP in addition to AZT reduced their risk of death at 18 months by 38 percent and at 24 months by 40 percent when compared to those who used AZT along, according to coauthor Sten Vermund, M.D.,Ph.D., chief of the AIDS Epidemiology Branch of NIAID, which oversees MACS.
The investigators found that AZT along, without anti-PCP drugs, reduced the risk of death of MACS participants by 55 percent at six months, 41 percent at 12 months and 30 percent at 18 months.
The findings appear to differ from those recently reported by scientists at the Veterans' Administration, whose study did not demonstrate an advantage to early AZT therapy. However, investigators in that study analyzed only 43 deaths.
Graham's coauthors include, from Johns Hopkins, Scott Zeger, Ph.D., and Lawrence P. Park, M.S.E.; from UCLA, Roger Detels, M.D., M.S.; from Pittsburgh, Charles R. Rinaldo, Ph.D.; and from Northwestern, John P. Phair, M.D. MACS also received support from the National Cancer Institute and the Agency for Health Care Policy Research.