Despite the widespread use of antiretroviral drugs, HIV- related damage of the nervous system is increasing among AIDS patients, according to a study supported by the National Institute of Allergy and Infectious Diseases (NIAID).
While therapy with antimicrobial drugs has protected HIV- infected patients against certain infectious diseases of the nervous system, the more widespread and earlier use of antiretroviral agents has not protected againts the development of AIDS-related dementia or sensory neuropathy," says senior author Justin C. McArthur, M.D., B.S., M.P.H., associate professor of neurology at the Johns Hopkins School of Medicine, in the October Neurology. The findings stem from analysis of seven years of data on 2,641 HIV-infected men enrolled in NIAID's Multicenter AIDS Cohort Study (MACS).
The results of this study emphasize that despite the effectiveness of pre-AIDS prophylactic medications to temporarily prevent certain HIV-related opportunistic infections of the central nervous system, new and bettter drugs and therapeutic strategies directed specifically at HIV must be developed," says Lewis K. Schrager, M.D., NIAID project officer for MACS.
The study demonstrates that rates of five HIV-related neurologic conditions, particularly sensory neuropathy, increase among the men from 1985 to 1992. The frequency did not change significantly for a sixth condition, AIDS dementia, the progressive deterioration of thinking, behavior and motor skills that afflicat some AIDS patients. However dementia and neuropathy occurred almost three times more than the other conditions, including three opportunistic infections. (OIs).
The increase in incidence rates of central nervous system OIs among men in MACS may stem from their use of antiretroviral therapy, which allows them to survive longer with more severely suppressed immune systems and lengthens the vulnerable period for brain infection," says first author Helena Bacellar, M.A., senior analyst at the Johns Hopkins School of Public Health. In fact, most neurologic diseases noted in the study occurred among men with 100 or fewer CD4+ T cells per cubic millimeter (mm3) of blood. CD4+ T cells are the crucial immune cells targeted by HIV.
However, the scientists note, progression of HIV disease was not the only factor in the development of neuropathy, the painful, crippling degeneration of nerves that numbs or weakens a patient's hands, feet or limbs. While neuropathy occurred more frequently at lower levels of CD4+ T cells, it also occurred at counts above 500 cells/mm3 and sometimes was induced by antiretroviral therapy. These data, along with other MACS neurologic studies, suggest that despite therapy, HIV indirectly damages CNS parts. Also, more awareness, better diagnostic capabilities and improved follow-up by health care professionals may have contributed to the observed increases in the illnesses.
The neurologic illnesses associated with AIDS are important, not just because of their frequency, but because they complicate caring for AIDS patients, add to the severity of advanced HIV infection and shorten the survival time after the onset of AIDS," Dr. McArthur says.
Earlier studies reported that neurologic conditions related to HIV affect 40 to 60 percent of AIDS patients, but autopsy examination found brain changes in as many as 90 percent. Dementia affects 7 to 16 percent of AIDS patients, but autopsies have shown brain tissue damage associated with AIDS dementia in up to 66 percent.
Of six neurologic conditions studied in the MACS enrollees between 1988 and 1992, the greatest annual rate of increase- -50 percent--occurred for neuropathy, with 1.6 percent (138) of the men developing the disorder. The yearly rate of increase in neuropathy ranged from 27 percent among men with 200 or fewer CD4+ T cells/mm3 to 84 percent for those with counts greater than 500/mm3.
AIDS dementia rarely developed before other AIDS-defining illnesses and occurred with an initial AIDS diagnosis in 3 percent of the men. The researchers noted the men had a 7 percent annual rate of developing dementia during the two years after a diagnosis of AIDS, totalling 151 cases between 1988 and 1992.
In observing the increase of the four other HIV-related neurologic conditions, the scientists noted the fastest rise in incidence, 47 percent per year, occurred for a cancer, primary CNS lymphoma. The viral OI, progressive multifocal leukoencephalopathy, had the second fastest rate increase, 24 percent each year.
Therapy appeared to help prevent two brain OIs among the MACS men: cerebral toxoplasmosis, caused by protozoa, and cryptococcal meningitis, a fungal infection. For example, from 1991 to 1992, scientists noted that men with 200 or fewer CD4+ T cells/mm3 who took antimicrobials were 2.6 times less likely to develop toxoplasmosis and 5.6 times less likely to develop meningitis than similar men not taking such therapies.
The men, along with 2,938 gay and bisexual MACS men not infected with HIV, come twice a year for exams and laboratory testing as well as to answer questions about any preventive and treatment medications they take. Between 1985 and 1992, 1,001 men, almost 38 percent, developed AIDS. Among the men, 8.9 percent had a neurologic disorder as their AIDS-defining condition.
NIAID began MACS in 1983 at four medical centers in Baltimore, Chicago, Los Angeles and Pittsburgh to learn more about AIDS. Of the participants, 78.9 percent are white, 13.9 percent are African-American, 6 percent are Hispanic and 1.3 percent come from other racial groups. They range in age from 18 t0 68 and half have a college degree.
Dr. McArthur and Ms. Bacellar's coauthors include Alvaro Munoz, Ph.D., and Ola A Selnes, Ph.D., from Johns Hopkins, Eric N. Miller, Ph.D., and David Besley, M.D., from University of California at Los Angeles, Bruce A. Cohen, M.D., from Northwestern University School of Medicine, and James T. Becker, Ph.D., from the University of Pittsburgh. Dr. McArthur also is associate professor of epidemiology at Johns Hopkins School of Public Health.
NIAID, a component of the National Institutes of Health (NIH) supports investigators and scientific studies at universities, medical schools, hospitals and research institutions in the United States and abroad aimed at preventing, diagnosing and treating such illnesses ast AIDS, tuberculosis and asthma as well as allergies. NIH is an agency of the U.S. Public Health Service, part of the U.S. Department of Health and Human Services. The National Center of Research Reports, part of NIH, also supported this study.