Vaccine Study Suggests Role of Cytokines in Progression of HIV

BALTIMORE--A small study of HIV-infected patients conducted byresearchers at the National Institute of Allergy and InfectiousDisease (NIAID) shows that inoculation with a common vaccine cantemporarily increase the amount of HIV that is circulating inthe bloodstream.

All 13 of the HIV-positive subjects who received a tetanus shotas part of the experiment showed increased viremia after theirinoculation, NIAID director Anthony S. Fauci said at the AmericanAssociation for the Advancement of Science (AAAS) meeting.

He cautioned, however, that the finding is too preliminary tomake any recommendations regarding whether to limit vaccinationsfor people infected with HIV. However, based on his experiencetreating AIDS patients, Dr. Fauci said he would "rather havea patient with a small blip in HIV levels from a needed inoculationthan with a full-blown infectious disease."

A long-standing question among AIDS researchers is whether persistentinfections or co-infections can increase the risk of HIV infectionand/or hasten the time to development of full-blown AIDS. Dr.Fauci cited as an example the case of a person whose HIV bloodlevels rose after he developed tuberculosis and dropped againafter he responded to treatment for the disease.

The NIAID vaccination experiment grew out of a study of the roleof cyto-kines in immunity and their influence on HIV. Among HIV-infectedindividuals, there occurs "a hyperexpression of cytokines"because the virus releases factors that can stimulate cytokineproduction, Dr. Fauci said.

Different cytokines can upregulate or downregulate the AIDS virus.Most, however, act to increase the burden of HIV in the blood,while immune system CD8 cells suppress HIV expression.

"Going on in the body virtually every minute is this tug-of-warbetween the upregulating and downregulating factors," hesaid.

Vaccinations also stimulate cytokine secretion. And thus two questionsarise: Does such immune activation contribute to the pathogenesisof AIDS and, if so, is recurrent infection with secondary organismsa factor in progression of the disease?

Dr. Fauci's group decided to examine the issue, using the tetanusvaccine to stimulate the immune systems of HIV-positive volunteers.

In three subjects whose experiences Dr. Fauci described in somedetail, HIV levels shot up, reaching their peak at between 10and 30 days, and then dropped off within 6 weeks. A control groupwho received a placebo inoculation failed to show any increasedviremia.

The complete study results appear in the May 9 issue of the NewEngland Journal of Medicine, with Sharilyn K. Stanley, MD, aslead author.

Cytokine secretion is but one factor within the body that mayaffect the course of AIDS, Dr. Fauci noted. "Are we goingto be able to intervene with downreg-ulating cytokines?"he asked. "Cytokine research is telling us a great deal aboutAIDS pathogenesis, but I don't know if it's going to provide ameans of intervention."