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Clue to how some hold off HIV for years




 

THIS WEEK, Boston researchers said they may have one explanation for why some patients infected with HIV survive for years - without treatment and without getting sick.

In a study published in the journal Science, researchers reported that an analysis of blood from a healthy Boston man infected with HIV for 18 to 20 years shows he is protected by a large number of immune system cells, called helper T-cells (or CD4 cells), that specifically attack HIV.

Using this clue, the researchers at Massachusetts General Hospital went on to find that these special helper T-cells may be an essential difference between being well and getting sick. If preserved, these cells can be a critical weapon in defeating the virus over the long term.

"Our work provides an explanation of why a very small group of people have been able to avoid getting sick from this virus even though they are infected," said Dr. Bruce Walker, the senior author of the study.

In the Boston study, four men who have been able to withstand the virus for up to two decades were at the heart of the research.

The one who has survived the longest, and who first sparked interest among the hospital researchers, is Robert Massie, an Episcopal priest who was the Democratic nominee for lieutenant governor in 1994. Massie has had HIV for nearly 20 years, but the level of virus in his blood remains below detectable limits.

Laboratory tests of blood from these patients found that those with the strongest CD4 cell response to the HIV antigen had the lowest amount of virus in their bloodstream, but those with weak CD4 cell responses had high virus loads.

What made Massie and the other long-term survivors different is that their helper cells somehow survived, built up to high levels, and helped beat back HIV. High levels of these HIV-specific CD4 cells may be essential for the body to hold the AIDS virus in check, the scientists said.

CD4 cells direct the body's immune system. There is a variety of the cells, and each type is primed to attack a specific virus or other invader. As these cells detect the presence of a target virus, they reproduce by the billions, flooding the bloodstream with defenders. But HIV breaks down this defense.

Throughout the epidemic, an estimated 2 percent to 3 percent of infected people have beaten the odds by showing no symptoms even though they were not being treated. That fact intrigued researchers at Massachusetts General, who set out four years ago to find out what allowed people to survive.

The discovery - that CD4 cells somehow keep HIV in check - suggested that the body might be able to control HIV if these cells were somehow protected.

To test this idea, researchers used powerful antiviral drugs to treat patients recently infected with HIV. Walker said the drugs caused the virus load to drop quickly, and the patients' immune systems then started producing CD4 cells that specifically attacked HIV.

Significantly, the HIV-specific cells were not produced in the bodies of patients who had been infected with HIV for more than six months. Rescuing CD4 cells has been shown to work only with patients who are at the earliest stages of infection, probably the first several weeks.

And even with the early stage patients who have built back a full complement of CD4 cells, researchers haven't completed the experiments they feel are needed before they try to wean patients from their drug regimen.

"This suggests that there is a window of time during the acute phase of infection when antiviral treatment can rescue the helper T-cell response to HIV," Walker said. If treatment is delayed, he said, that natural protection may be lost forever.

Other mechanisms?

There may be immune system elements other than helper T-cells that are responsible for suppressing or extinguishing HIV infection.

In research to be presented next Monday afternoon at a World AIDS Day symposium in UC-San Francisco's Cole Hall, Dr. Jay Levy will report that people who remain uninfected - despite repeated exposures to HIV - have a unique immunologic ability to marshal a different kind of T-cell, called "killer" or "cytotoxic" T-cell (CD8 cell), to prevent replication of HIV.

In studying patients' blood in the laboratory, Levy found that if he attempted to infect CD4 cells with HIV in the presence of CD8 cells, viral replication was stopped. However, when the CD8 cells were removed, the virus grew again.

"We think it results from exposure to low amounts of virus, which is enough to get the cellular immune antiviral response going," said Levy.

Levy suggests that CD8 cells have an important antiviral response, somehow linked to a naturally occurring protein called CAF (CD8 antiviral factor), that blocks replication of HIV.

International news

*The spread of HIV is so rampant in Africa that about 25 percent of adults in Botswana are infected, 22 percent in Zimbabwe and 19 percent in Namibia, a United Nations official told an International Planned Parenthood conference.

In some southern African cities, more than 40 percent of pregnant women are infected, said Dr. Elhadjas Sy, head of the Joint U.N. Program on HIV / AIDS.

*Nearly 40 million children in developing countries stand to lose one or both parents to AIDS over the next 13 years, with catastrophic results, according to a survey by the U.S. Agency for International Development and the Census Bureau.

The AIDS epidemic is creating a lost generation of children at risk of exploitation and disease, it concluded.

The report also predicted that life expectancy - which has been steadily on the rise for the last three decades - will drop to 40 years or less in nine sub-Saharan countries by the year 2010.

. . . . . .Date . . . . . .reported. . Cases. . Deaths S.F.. . . .11/1 . . . . 24,787 . 16,935 Calif.. . .11/1 . . . .103,562 . 65,942 U.S.. . . .11/1 . . . .612,078 .379,258 WHO(rprtd) 11/1 . . .8,400,000 6,400,000

Figures are cumulative since June 1981. Government officials now compile and release statistics quarterly, not monthly.

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Copyright © 1997 -The Bangkok Pos, Publisher. All rights reserved to San Francisco Examiner. All rights reserved. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the San Francisco Examiner, Permissions Desk, 110 Fifth Street, P.O. Box 7260, San Franciso, CA 94120.San Francisco Examiner

Information in this article was accurate in November 26, 1997. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.