Protease Inhibitors May Halt or Reverse HIV Encephalopathy

CHICAGO—A new radiological study suggests that protease inhibitors can not only halt the progression of HIV-related brain disease but, in some cases, may be able to reverse it, Christopher G. Filippi, MD, said at the Radiological Society of North America annual meeting.

“Until now, HIV encephalopathy has been considered to be relentlessly progressive. This is the first study that demonstrates clinical neurologic improvement with the use of protease inhibitors that correlates with an improvement seen on brain MR scans,” said Dr. Filippi, assistant professor of radiology and director of neuroradiology, Weiler Hospital, Albert Einstein College of Medicine, New York City.

The study, conducted at the Yale-New Haven Medical Center, included 16 endstage AIDS patients with abnormal MR scans showing a significant amount of white matter disease. All of the patients (9 men and 7 women) were receiving nucleoside analog therapy such as zidovudine (AZT, Retrovir).

After the initial MR scan, nine patients were started on protease inhibitor therapy with ritonavir (Norvir), indinavir (Crixivan), or saquinavir (Invirase) by their primary care provider. The other seven patients did not receive a protease inhibitor for clinical reasons, ranging from elevated liver function tests to a history of noncompliance with medication regimens, Dr. Filippi said.

On subsequent MR imaging, performed at intervals ranging from 2 to 12 months, 89% of those receiving protease inhibitors showed stabilization (4 patients) or near complete regression (4 patients) of white matter disease, and these changes correlated with clinical improvement in symptoms. One patient showed slight progression of disease.

In contrast, MR scans showed disease progression in 6 of 7 patients (86%) not receiving protease inhibitors, and these findings corresponded with a decline in mental function. One patient showed no change on MR imaging.

“Our results suggest that protease inhibitors in combination with drugs like AZT may be particularly effective because the two types of drugs target the HIV virus at different phases in its life cycle,” Dr. Filippi said. Control of HIV enceph-alopathy with protease inhibitors may also avoid the need for more costly medical interventions, he added.