GMHC Treatment Issues 1995 Mar 1; 9(3): 3
Five AIDS-related brain and nervous system diseases are a
growing problem for people with AIDS says a new federally
funded study reported in the journal Neurology (October,
1994, pages 1892-1900). The study, an observational
analysis from the Multicenter AIDS Cohort Study, found an
increasing annual rate of toxoplasmosis, cryptococcal
meningitis, progressive multifocal leukoencephalopathy
(PML), central nervous system (CNS) lymphoma and sensory
neuropathies in a population of 2,641 HIV-infected gay and
MACS recruited over 5,600 healthy, asymptomatic
participants (both HIV-positive and -negative), mostly in
1984 and 1985, and has evaluated them twice yearly.
Reviewing the data from 1988 to 1992 on the men with HIV,
the report noted that "the increasing survival times after
AIDS provide opportunity for these diseases to occur."
The five neurological diseases occurred as the initial
AIDS- defining condition in only five to ten percent of
cases, but as secondary sequelae in 40 to 60 percent. Men
with under 200 CD4 cells were particularly at risk.
Despite effective (in the case of toxoplasmosis) or
possible (in the case of cryptococcal meningitis)
prophylaxis, the annual incidence of these two infections
still increased twelve and thirteen percent, respectively.
The annual rate of PML and CNS lymphoma, for which there
are no effective or experimental preventive measures, rose
even more dramatically - 24 and 47 percent, respectively.
The 50 percent jump in the annual occurrence of sensory
neuropathies was the greatest of all. Sensory neuropathies
can be caused directly by HIV infection or as a side effect
of ddI, ddC and d4T nucleoside analog treatment.
The study population was 79 percent white, fourteen percent
African-American and six percent Latino. The median age of
the study population was 32 years. Over half the men had
received a college-level degree. The report noted, "The
findings in this analysis pertain to a group of highly
educated homosexual and bisexual men who have been closely
followed for several years. In populations with other risk
factors, such as injection drug users or women, the
incidence trends in HIV-related neurologic disorders may be
Dementia Rate Unchanged Despite AZT
The incidence of AIDS dementia remained stable in the MACS
cohort during the observation period. The MACS cohort found
antiretroviral treatment did not reduce the incidence of
HIV dementia, standing in contrast with other reports that
have found the incidence of dementia falling in those
treated with AZT in particular. Why the discrepancy? Part
of the answer lies in the difference between pathological
and clinical studies.
Pathological studies have found at autopsy a decreased
presence of multinucleated giant cells (MGCs) and white
matter changes in the brains of deceased people with AIDS
who had received AZT. MGCs are clusters of cells in the
brain that are thought to signal the presence of productive
HIV infection. A large post-mortem study, presented at the
American Academy of Neurology Annual Meeting in May, 1994
by Fran�oise Gray, M.D., of the University of Paris
examined the brains of 192 deceased AIDS patients. The
study detected MGCs in 44 percent of those who never
received AZT, 35 percent of those who discontinued AZT
before death, and eighteen percent of those who continued
AZT up to death.
"The results show that AZT treatment greatly reduces the
risk of productive HIV infection of the brain and that
early discontinuation of AZT leaves patients vulnerable to
HIV encephalitis," commented Dr. Gray. The study took ten
years to complete and was the most comprehensive
post-mortem neurologic study conducted on AIDS.
The cause of HIV dementia remains unknown, though, and the
presence or absence of MGCs may not correlate adequately
with the development of clinical dementia. Dementia is
thought to occur through complex indirect pathways, which
may involve cytokine and immunological deterioration and
which are still poorly understood.
Direct HIV infection appears to be only one factor leading
to the development of clinical dementia. Dr. Justin
McArthur, a Johns Hopkins University neurologist and lead
author of the MACS study, said he has also found fewer MGCs
in the brains of deceased AIDS patients who had received
AZT. But this decrease was not associated with a lower
incidence of clinical dementia. "The two studies are not
discordant," Dr. McArthur said.