Treatment Issues; Vol. 9, No. 3 - March 1995
Derek Link

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 different."

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 Franìoise 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.

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