In two HIV-infected patients treated with potent combinations of anti-HIV
drugs and interleukin-2 (IL-2), and in whom even highly sensitive tests
could detect no viable HIV, the virus quickly rebounded to substantial
levels when therapy was stopped, according to researchers at the National
Institute of Allergy and Infectious Diseases (NIAID).
NIAID Director Anthony S. Fauci, M.D., chief of the NIAID Laboratory of
Immunoregulation (LIR), Tae-Wook Chun, Ph.D., a section head within the LIR,
and their colleagues report their data in the Oct. 28, 1999 issue of the
The new findings add to recent reports that suggest eradicating HIV from the
body with currently available anti-HIV therapies is unlikely because the
virus can hide in sanctuaries which drugs cannot access and can exist in a
latent form on which drugs have no effect.
Scientists frequently refer to these sanctuaries, which are established very
early in the course of HIV infection, as viral "reservoirs."
Reservoirs of HIV include certain immune system cells - notably resting
(non-activated) CD4+ T cells of the blood and lymph nodes - and probably
cells of the brain, gut, bone marrow, genital tract and other organs. These
reservoirs, in which the virus continues to replicate at low levels even
during aggressive treatment, are probable sources of the resurgent HIV seen
when therapy is discontinued. The current study shows that at least one HIV
reservoir - the pool of latently infected, resting CD4+ T cells - is itself
rapidly replenished after therapy is discontinued.
"The persistence of HIV reservoirs poses a significant impediment to the
long-term control of HIV infection and must be addressed by comprehensive
approaches to the therapy of HIV-infected individuals," says Dr. Fauci.
"Our research and that of other groups underscores the importance of
developing more potent anti-HIV therapies, treatment strategies that
specifically target the hiding places of HIV, as well as therapies that
preserve and enhance HIV-specific immunity."
In the current report, the authors discuss two patients treated with highly
active antiretroviral therapy (HAART - three or more anti-HIV drugs
including a protease inhibitor) for 33 and 30 months, respectively. Both
patients also had received intermittent intravenous infusions of IL-2 for
42 and 50 months, respectively. Before discontinuing therapy, both had
levels of HIV in their plasma below 50 copies per milliliter of blood, the
detection limit of the viral load assay used in the study. IL-2 is a
regulatory protein of the immune system that has potent effects on the
proliferation, differentiation and activity of CD4+ T cells and other immune
The researchers then used a sensitive culture technique to look for
replication-competent HIV in the resting CD4+ T cells from the blood of
these individuals and found none - even when they cultured up to 330 million
cells from each individual. They then performed lymph node biopsies on the
two patients and still could not isolate viable HIV.
"In these patients, we observed both a reduction of plasma virus to less
than 50 copies per milliliter of blood and a marked diminution of an
important viral reservoir - the pool of latently infected, resting CD4+ T
cells," says Dr. Chun. "But the question still remained whether levels of
HIV would remain low following discontinuation of therapy."
"The answer, unfortunately, was a resounding no," he adds. "When these
patients discontinued HAART, virus was detected in the plasma of both
individuals within three weeks, and the pool of resting CD4+ T cells
carrying replication-competent HIV emerged shortly thereafter."
Dr. Chun adds: "Our data suggest that there may well be other HIV reservoirs
in addition to resting CD4+ T cells which are responsible for the rebound in
plasma viremia, a hypothesis that will be illuminated by further studies."
Co-authors of Drs. Chun and Fauci include Richard T. Davey, M.D., Delphine
Engel, and H. Clifford Lane, M.D.
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
on the NIAID web site at http://www.niaid.nih.gov.