FEBRUARY 24, 1995 GAY PEOPLE'S CHRONICLE

11

HEALTH WATCH

Learning from long-term

non-progressors

by Michael M. Lederman, M.D.

Why have some people with HIV-1 infection managed to survive and remain entirely well for more than a decade, while progressive immunologic and clinical deterioration is seen in most HIV-1 infected people?

A number of recent studies are beginning to shed light on this important group of patients. Several possibilities must be considered, and they may be divided into virusrelated and host-related factors.

There is some evidence that different strains of HIV may vary in the severity of the disease they cause. For example, HIV-2 is similar to HIV-1 and can cause AIDS, yet people in West Africa, where HIV-2 is most prevalent, survive longer and get ill far less frequently than people who are infected with HIV-1.

There is also an extraordinary instance of several people in Australia who were transfused with blood obtained from a single person with HIV-1 infection; all of these people have remained alive and well, HIVinfected, but without evidence of immune deficiency. A recent report of several longterm survivors found that one of these patients was infected with a strain of HIV-1 that had somehow lost its nef gene. Removal of the same nef gene from SIV, a retrovirus closely related to HIV-2 that infects monkeys, results in a virus capable of causing infection, but the infected monkeys remain well. Thus it appears that certain viruses may be less capable of causing severe immune deficiency, even though they remain capable of causing infection.

Some evidence has also been presented to suggest that some people may somehow resist the ravages of HIV infection. There is growing evidence that our immune responses, particularly those mediated by cytotoxic T lymphocytes (CTLs) and responses mediated by antibodies, play a very important role in controlling the replication of HIV in people with HIV infection. Some long-term survivors have had preservation of CTL activity many years after infection. Others have had high levels of antibody capable of blocking the ability of HIV to infect cells. It is still not clear whether these preserved CTLs or high levels of antibodies are the cause or the effect of long-term survival.

What is increasingly clear is that survival in HIV infection appears to be a balance between the growth of HIV and the suppression of this growth by the immune system. Strategies targeted at blocking the growth of HIV using antiviral drugs and strategies designed to enhance host immune responses are reasonable approaches for now.

Our best chances of designing the best strategies, however, will depend on developing a clearer understanding of how HIV causes immune deficiency and how host immune

responses limit the growth of HIV. Careful studies of long-term survivors are one good way to gain this understanding.

♡

Dr. Lederman is principal investigator of the AIDS Clinical Trials Unit at Case Western Reserve University and University Hospitals of Cleveland. For information about clinical trials research on HIV disease, call 216-368-AIDS (368-2437).

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