AEGiS-CATIE: HIV/AIDS THEORY: AZT in non-infected people: some surprising results

HIV/AIDS THEORY: AZT in non-infected people: some surprising results

TreatmentUpdate 74 - Volume 8, No 10; December 1996
Sean Hosein

Doctors in Milan recently reported some interesting data from a study of health care workers. For the past 6 years, standard policy at their hospital is to offer AZT 1,000 mg/day for 40 days to health care workers who accidentally stick used needles (which may contain HIV) into their skin, in the hope of containing HIV infection. Over the past 6 years, 23 people have received AZT, five of whom failed to take it for the full length of time (40 days). Of the remaining 18, 14 were female and 4 male. None of these subjects became "HIV-positive."

CD4+ cell counts climb

Analysis of the subjects' blood before, during and after AZT using revealed that CD4+ cell counts increased by more than 10% in 61% of subjects. On average, the CD4+ cell count increased by 17%. Five subjects had no change in their cell counts and two subjects had their counts decrease. There was only a slight increase in the CD8+ cell count.

Why?

The explanation for this increase in CD4+ cell counts could be that AZT prevents the death of CD4+ cells scheduled to die because they are defective, immunologically exhausted or no longer needed.

Dutch research

Meanwhile, Dutch immunologists have been studying the virologists' theory about changes in the levels of CD4+ cells and HIV. As a result of their work, they have arrived at different conclusions about what HIV does to the immune system. The immunologists used HIV-infected males for their experiments.

The big picture

According to the Dutch team, "in the course of HIV infection", the number of CD4+ cells gradually fall while the number of CD8+ cells slowly increases, and the immune system's ability to defend itself weakens. In response to attack by germs, CD4+ cells and CD8+ cells become activated, but then die before they can engage their targets -- HIV and other microbes. Between 1.5 to 2 years before AIDS develops the decrease in CD4+ cells speeds up. Some researchers think that HIV is somehow able to exhaust the immune system's ability to replace CD4+ cells and this leads to AIDS.

What really gets used up?

The immunologists found that CD8+ cells are constantly being activated, and while some of them die as a result of activation, others are stimulated into making copies of themselves. This accounts, in part, for the increased number of CD8+ cells seen in HIV/AIDS. The immunologists did not find huge production and destruction of CD4+ cells as a result of HIV infection. Rather, "the bulk of CD4+ cells in HIV-infected men is [dying and being replaced] at the same rate as in healthy persons."

Why are levels of CD4+ cells reduced in AIDS?

The immunologists agree that HIV infection does reduce levels of CD4+ cells. They think that HIV infects CD4+ cells as they divide and form new cells.

What impact will these findings have on immune-based therapies for HIV/AIDS?

Firstly, researchers will now have to change their ideas about how to rebuild the immune system. Instead of simply infusing CD4+ cells back into people, they need to find ways to protect the source of CD4+ cells in the body from HIV infection. Work now needs to be done on how to understand the life-cycle of CD4+ cells. In many cases its back to the drawing board.

Why do CD4+ cell counts rise upon treatment?

We have already reported the effect of AZT on CD4+ cell counts in non-HIV-infected people. The immunologists note that, "the increase in CD4+ cell counts after antiviral treatment [is not due to the creation of new cells] but may be a redistribution of [CD4+ cells]." A similar event is seen when people with cancer are given chemotherapy.

References:

1. Saag MS, Holodiny M, Kuritzkes DR, et al. HIV viral load markers in clinical practice. Nature Medicine 1996;2(6):625-629

2. Wolthers KC, Bea G, Wisman A, et al T cell telomere length in HIV-1infection: No evidence for increased CD4+ T cell turnover. Science 1996;274:1543-1547.

3. Larkin M. New model for HIV-1 infection may alter therapy. Lancet 1996;348:1574

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Always watch for outdated information. This article first appeard in 1996. This material is designed to support, not replace, the relationship that exists between you and your doctor.

Copyright © 1996 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284 http://www.catie.ca

This information is designed to support, not replace, the relationship that exists between you and your doctor.
©1996. AEGIS.