Studies Show Dynamic Struggle Between Immune System, HIV

NEW YORK--Two new studies show that the human immunodeficiency virus (HIV) wages a constant, near steady-state battle with the immune system--from the onset of infection throughout the course of the disease.

The immune system destroys billions of virus particles (virions) and infected CD4 lymphocytes every day, and produces up to 1 billion new CD4 lymphocytes daily, but so long as a few virus progeny survive to continue replication and transmission, the virus will ultimately win the struggle. A few more CD4 lymphocytes are killed each day than are replaced, causing CD4 counts to decline gradually in infected patients.

Rather than a static picture of how much virus is present in the body at any one point in time, the two studies reveal the ongoing day-to-day dynamics of the infection. They show that HIV pathology is not the product of a constant high level of virus, or of a poor immune system response, but rather the result of a dynamic process consisting of continuous rounds of new infection, replication, and turnover.

In both studies, one headed by Dr. David Ho, Aaron Diamond AIDS Research Center, New York, and the other by Dr. George M. Shaw, University of Alabama, Birmingham, HIV-infected patients with below normal CD4 counts were given potent experimental drugs (a protease inhibitor or a reverse transcriptase blocker) capable of blocking the virus' ability to infect CD4 lymphocytes.

The anti-HIV drugs acted quickly, destroying 99% of the HIV population in the body, but the surviving 1% of the virus population rapidly reestablished itself, and within 2 weeks, almost all of the new viruses were drug resistant.

Measurements of CD4 lymphocytes found that the immune system continued working full steam during the time of virus inhibition, producing up to 2 billion CD4 lymphocytes a day and leading to sometimes dramatic increases in patients' CD4 counts. Both reports appear in the January 12 issue of Nature (373:117-122, 123-126, 1995).

Dr. Ho, in his report, noted that during pretreatment steady state when CD4 lymphocyte production and destruction were balanced, the entire population of peripheral blood CD4 lymphocytes was turning over every 15 days.