The pool of latently infected immune system cells is established even if
a patient is treated soon after acute infection with powerful
antiretroviral drugs that reduce plasma levels of virus to extremely low
or undetectable levels. Within the safe havens of resting CD4+ T cells,
the virus may persist for years, despite highly active antiretroviral
therapy (HAART), which is generally a combination of three drugs,
including a protease inhibitor.
"Latent reservoirs of HIV, including resting CD4+ T cells, present a
formidable obstacle to the ultimate control and possible eradication of
HIV from an infected person's body," says Tae-Wook Chun, Ph.D., an
investigator in NIAID's Laboratory of Immunoregulation (LIR).
Adds LIR Chief and NIAID Director Anthony S. Fauci, M.D., "Latently
infected CD4+ T cells are potential sources of new viral replication if
a patient stops therapy or is unable to adhere to the proper treatment
regimen. We now know that these reservoirs are established very early
in the course of infection." Dr. Fauci notes that "the establishment of
the pool of latently infected, resting CD4+ T cells appears to occur
around the time of the initial burst of virus replication seen in most
patients with acute HIV infection."
Drs. Chun, Fauci and colleagues report their latest findings in the July
21, 1998, issue of the Proceedings of the National Academy of Sciences.
The investigators studied blood samples from 10 patients who were
treated with the drugs zidovudine (AZT), lamivudine (3TC) and Crixivan
(indinavir), soon after infection with HIV. Treatment was initiated
between 10 days and 4.4 months following the initial onset of
HIV-related symptoms. All of the patients responded positively to
therapy, including five whose viral load fell to undetectable levels.
The LIR team found evidence of latently infected, resting CD4+ T cells
in all 10 patients, even in an individual who had started HAART 10 days
after the onset of the symptoms of acute HIV infection. Interestingly,
the researchers found that neither duration of therapy nor the speed
with which therapy was initiated correlated with the number of infected
resting CD4+ T cells in a patient's blood. However, "The longest
duration of therapy was 17 months, and it remains possible that an even
longer duration of therapy with HAART, especially if initiated early in
infection, may result in pronounced decreases in the pool of latently
infected, resting CD4+ T cells," says Dr. Chun.
"A smaller pool of latently infected cells would be more likely to
ultimately be controlled by the immune defenses of the patient," adds
The NIAID investigators and others are pursuing studies to identify
people recently exposed to HIV and to treat them before the viral burst,
which probably disseminates the virus widely throughout the body. Such
studies will help determine whether it is possible to prevent the early
establishment of pools of latently infected, resting CD4+ T cells.
There are a number of potential approaches to containing or depleting
reservoirs of latently infected, resting CD4+ T cells that have already
been established in HIV-infected individuals. At the recent World AIDS
Conference in Geneva, Dr. Fauci presented three possibilities:
maintaining a strong immune system; enhancing a weakened immune system;
and developing methods to deliberately purge the reservoirs by
activating the resting cells to produce virus under the cover of HAART.
Dr. Fauci's Geneva lecture is available on the World Wide Web at
http://webcast.aids98.org (see plenary sessions for June 30, 1998).
Co-authors of Drs. Chun and Fauci include Delphine Engel of the LIR, and
Drs. Lawrence Corey, M. Michelle Berrey and Theresa Shea of the
University of Washington in Seattle.
NIAID is a component of the National Institutes of Health (NIH). NIAID
conducts and supports research to prevent, diagnose and treat illnesses
such as HIV disease and other sexually transmitted diseases,
tuberculosis, malaria, asthma and allergies. NIH is an agency of the
U.S. Department of Health and Human Services.
Press releases, fact sheets and other NIAID-related materials are
available via the NIAID Web site at http://www.niaid.nih.gov.
Chun T-W, et al. Early establishment of a pool of latently infected,
resting CD4+ T cells during primary HIV-1 infection. Proc Natl Acad Sci