Re: Vaccination increases viral replication: HIV model

[Guest guest]

Sorry for the odd format. What other viruses would be similarly affected?

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[Clear]

[Clear] [newsrelease]

FOR RELEASE

Wednesday, May 8, 1996

6:00 p.m. Eastern Time

Greg Folkers -- (301) 402-1663

Folkers@...

Immune System Activation Boosts HIV Replication in

HIV-Infected People

In people infected with the human immunodeficiency

virus (HIV), activation of the immune system by other

stimuli boosts HIV replication, according to a study by

investigators at the National Institute of Allergy and

Infectious Diseases (NIAID).

The research, which builds on previous work at NIAID

and elsewhere, helps explain why HIV disease typically

progresses faster in areas of the world where a person's

immune system may constantly be challenged by parasites and

other microorganisms. Immune responses to persistent

infections also may leave people more vulnerable to HIV

infection.

Sharilyn Stanley, M.D., and her colleagues report

their current findings in the May 9, 1996 issue of The New

England Journal of Medicine. Dr. Stanley is currently the

special assistant for science policy in the office of NIAID

Director S. Fauci, M.D. She performed this study

last year when she was a member of NIAID's Laboratory of

Immunoregulation.

" The normal activation of the immune system in

response to microbes results in a transient increase in HIV

replication, a phenomenon that we feel is important to the

pathogenesis of HIV disease, " says Dr. Fauci, senior author

on the paper. " Chronic immune activation, or the cumulative

effect of multiple episodes of immune activation and bursts

of virus production, probably contribute to the progression

of HIV disease. "

In their study, the researchers inoculated 13

asymptomatic HIV-infected people and 10 uninfected

volunteers with tetanus booster shots to stimulate their

immune systems, and drew blood samples on the day of the

injection and 3, 7, 14, 21, 28 and 42 days later.

In the 13 HIV-infected volunteers, the amount of HIV

in the bloodstream increased two-fold to 36-fold following

immunization, reaching a peak at a mean of 13 days. In all

patients, virus levels returned to the baseline level within

six weeks.

Ten of the 13 patients had moderate (two- to

four-fold) increases in the numbers of circulating blood

cells that contained HIV. Notably, the virus was much more

readily grown from the blood cells of nine of the

HIV-infected patients after immunization than before

immunization. Two of the 13 HIV-infected patients underwent

lymph node biopsies before and after immunization, and the

researchers found that lymph node viral burden was higher in

these people after immunization than before immunization.

" Interestingly, the patients with the strongest

immune systems had the largest increases in virus, " says Dr.

Stanley. " This underscores the diabolical nature of HIV: the

normal efforts of the immune system to mobilize itself and

fight an invader results in HIV being revved up as well,

with a stronger immune system paradoxically leading to more

viral replication. "

The researchers also examined immune system cells of

the uninfected volunteers. They found that cells from seven

of these 10 people were more easily infected with HIV in the

test tube after immunization than before immunization. In

addition, the researchers found that cells from an

uninfected subject became highly susceptible to HIV

infection during an acute respiratory tract illness.

" Taken together with previous studies, our data

suggest that ongoing immune activation may play a part in

HIV pathogenesis, and may also enhance the susceptibility of

uninfected people to HIV, " says Dr. Stanley.

" It will be important to develop therapies directed

at those microbes that contribute to a state of chronic and

persistent immune activation in HIV-infected people, " she

adds. " Drugs that could be used at certain times to dampen

immune activation may also have a role in the treatment of

HIV-infected people. "

The researchers note that increases in HIV following

immunization were transient in their study, and that the

protection afforded by immunization against a pathogenic

organism most likely outweighs the potential risks from the

resulting transient increase in HIV.

None of the HIV-infected people in the current study

were receiving antiretroviral therapy, so the results cannot

be generalized to all HIV-infected people, says Dr. Stanley.

NIAID investigators are planning a study to assess whether

short-term antiretroviral therapy to block the transient

viremia associated with immunizations can benefit

HIV-infected people.

NIAID is a component of the National Institutes of

Health. NIAID conducts and supports research to prevent,

diagnose and treat illnesses such as AIDS and other sexually

transmitted diseases, tuberculosis, asthma and allergies.

NIH is an agency of the U.S. Public Health Service, U.S.

Department of Health and Human Services.

Reference:

Stanley SK, Ostrowski MA, Justement JS, Gantt K, Hedayati S,

Mannix M, Roche K, Schwartzentruber DJ, Fox CH, Fauci AS.

Effect of immunization with a common recall antigen on viral

expression in patients infected with human immunodeficiency

virus type 1. N Engl J Med 1996;334:1222-30. NIAID press

releases, fact sheets and other materials are available on

the internet via the NIAID home page. The address is

http://www.niaid.nih.gov/

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