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,
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.