Stress Accelerates AIDS Progression, Undermines the Effect of Therapy

New research from the AIDS Institute at the Universityof California, Los Angeles (UCLA), reveals that stress enables the humanimmunodeficiency virus (HIV) to spread more quickly in infected persons andprevents antiretroviral drugs from restoring immune system function. The study,which was reported in the Proceedings of the National Academy of Sciences(98:12695-12700, 2001), is the first to pinpoint the molecular mechanismslinking stress and HIV infection. "Popular science has widely suspectedthat stress weakens the immune system," said Steve Cole, MD, lead authorand UCLA assistant professor of hematology-oncology. "Now we’ve uncoveredtwo reasons why."

Autonomic Nervous System Activity

The study enrolled 13 HIV-positive men, aged 25 to 54 years, who had nevertaken combination antiretroviral drugs. Researchers measured the baseline AIDSviral load and CD4 cell count in the blood of each subject. They then determinedthe level of autonomic nervous system (ANS) activity by calculating the bloodpressure, skin moisture, and heart and pulse rate at rest for each patient.

"Persons with higher ANS activity tend to be more high-strung and easilystressed out," said coauthor Jerome Zack, MD, UCLA professor of medicineand associate director for basic sciences at the UCLA AIDS Institute. "Wewanted to see what effect, if any, this had on our subjects’ ability to fightHIV infection." All 13 men in the study received a potent antiretroviralregimen to combat their HIV infection. Over the next 3 to 11 months, each man’sviral load and CD4 count was measured against his stress level ranking before hetook the drugs.

The results showed that the higher the man’s stress level, the less heresponded to the antiretroviral drugs. In fact, the average decline in viralload dropped more than 40 times for men with low ANS activity and less than 10times for men with high ANS activity.

"After several months on retroviral drugs, the viral loads of five ofthe seven men with low ANS activity plummeted to undetectable levels in theirblood," said Dr. Cole. "This happened to only one of the six men whoexhibited high ANS activity."

CD4 Cell Count Recover

Drs. Cole and Zack observed similar patterns in CD4 cell count recovery. Onaverage, men with low ANS activity showed the most significant cell-countincreases. In comparison, men with high ANS activity displayed negligible CD4cell rebound, or none at all. Those with low ANS activity rebounded from 396 to550 CD4 cells/mm³ of blood after treatment. The immune systems of men in thehigh ANS group recovered far fewer—from 611 to 627 cells/mm³ of blood.

"Those at the top of the high ANS activity group showed no immunerecovery at all," said Dr. Zack. "Some continued to lose CD4 cellsdespite following the aggressive drug regimen."

"Our findings suggest that the nervous system has a direct effect onviral replication," said Dr. Cole. "This implies we may be able toalter that effect by reducing stress levels. Even anti-HIV drugs prove moreeffective in people with low ANS activity."