TreatmentUpdate84 - Vol. 9, No. 10 - pp. 3; December, 1997
Sean Hosein

Triple therapy with protease inhibitors is associated with increased survival compared to other regimens. Protease inhibitors greatly decrease the amount of HIV in the blood, causing levels of CD4+ cells to rise. Much has been made about the viral load in the blood, but since most HIV is located in the lymph nodes, it is only reasonable that research should focus there. Indeed, if the immune system is to be rebuilt, then it is to the lymph nodes that researchers will have to look to see if the therapies are working. Doctors in France have been monitoring PHAs who use anti-HIV therapy to study its impact on the immune system's ability to regenerate. They have found some evidence of repair, but do not understand all of the changes taking place within the lymph nodes.

Study Details

Researchers enrolled 25 male HIV-infected subjects whose average age was 39 years. They received various combinations of anti-HIV drugs, including protease inhibitors (indinavir, ritonavir and saquinavir). On average, they were monitored for 6 months. From time to time, samples of lymph nodes would be removed for analysis. At the start of the study the average viral load in the blood was 80,000 copies and the number of CD4+ cells was 273.

Results: inside the node

After one month of therapy, the amount of HIV in the blood fell to about 500 copies, and after 6 months, it was at about 200 copies. More importantly, at the start of the study the average viral load inside a lymph node was about 650,000 copies. This fell to 20,000 copies between "1-3 months [after starting] therapy," and to about 200 copies "after 3-6 months of therapy." Note that while virus continued to replicate inside the lymph nodes, levels of HIV in the blood had fallen below the level of detection in 14 of 25 subjects. The lower limit of the test used on blood samples was 200 copies and that used on lymph nodes was 50 copies.

Overall, levels of CD8+ cells fell during the course of therapy. This is not surprising given that these cells mobilize to attack HIV-infected cells -- as the number of infected cells falls, so does the number of attacking cells. The increased numbers of CD4+ cells seem to be made up of largely memory cells. That is to say cells that have encountered a microbe at some point in their life, attacked and destroyed it, and are now quietly waiting for a similar microbe to reappear. Just which microbe these cells 'remembered' is not clear.

This study is useful because it demonstrates that as the amount of HIV in the nodes falls, cells are being replaced. Complete rebuilding of the immune system has unfortunately not taken place nor do cell numbers tell the whole story. Researchers need to test these memory cells to see if they can produce the correct immune response when faced with invading viruses, bacteria and fungi.

REFERENCES:

1.Lafeuillade A, Chouraqui M, Hittinger G, et al. Lymph node expansion of CD4+ lymphocytes during antiretroviral therapy. Journal of Infectious Diseases 1997;176:1378-1382.

2. Hamann D, Baars PA, Rep MHG, et al. Phenotypic and functional separation of memory and effector human CD8+ T cells. Journal of Experimental Medicine 1997;186(9):1407-1418.

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Copyright © 1997 - 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