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[procaare] Study Shows Why Antiretrovirals Cannot Eradicate HIV
- From: "Aidsmap" <email@example.com>
- Date: Mon, 7 Nov 2005 14:09:00 -0700
Study Shows Why Antiretrovirals Cannot Eradicate HIV
- Michael Carter, Aidsmap: 2 November 2005
A study published in the November edition of the Journal of Clinical
Investigation has shed new light onto why individuals who have received
effective anti-HIV therapy for many years, and have persistently
maintained an undetectable viral load, are still unable to eradicate
In a study involving eleven HIV-positive individuals who had been
receiving successful antiretroviral therapy for up to nine years,
and Canadian investigators demonstrated that all eleven patients had CD4
cells infected with HIV that was capable or reproduction, and that most
patients also had "considerable" levels of the DNA which HIV produces
inserted into cells after infecting both active and resting CD4 immune
system cells. The investigators were also surprised to find that most of
the persistent HIV was found in active rather than resting CD4 cells.
Antiretroviral therapy can suppress detectable HIV replication to
extremely low levels and dramatically improve the health and prognosis
HIV-positive individuals. Reservoirs of HIV are known to persist despite
the use of anti-HIV treatment, meaning that eradication of the virus
has not proved possible. Pools of latently HIV-infected CD4 cells have
been studied as a reason why the virus cannot be eradicated, with
attention focused on patients who have taken up to five years of potent
"The source(s) and extent of ongoing HIV replication in compartments
other than resting CD4 T cells in patients receiving effective antiviral
therapy for extended periods of time (greater than five years) have not
been fully delineated", the investigators write.
The investigators therefore obtained blood samples from eleven patients
who had been taking effective HIV therapy for up to nine years (mean
8.3 years). The patients had a median CD4 cell count of 623 cells/mm3
all had a viral load below 50 copies/ml. The investigators found HIV in
CD4 cells in all eleven patients, "indicating that none of the study
participants had eradicated HIV infection".
Activated and resting CD4 cells were then further examined. The
investigators found that HIV proviral DNA was found in both, with
significantly more present in activated CD4 cells (p = 0.01). The
comment, "in all patients examined, the presence of HIV in resting as
as activated CD4 cells was sustained despite extended periods of
undetectable HIV plasma viremia."
Further tests were performed to see if HIV-infected activated and
resting CD4 cells were capable or producing particles of HIV called
They found that resting CD4 cells did not produce detectable virions,
but that activated cells did.
Finally tests on the genetic structure of HIV isolated from both
resting and activated CD4 cells were perfomed. "Evidence for
HIV infection between resting and activated CD4 cell compartments was
observed", the investigators write.
"To our knowledge this is the first study to examine levels of
replication-competent HIV in the CD4 cell compartments of patients who
received effective antiviral therapy for such a long period", comment
"Contrary to current dogma, it is the activated CD4 cell compartment
that harbors the majority of persisting HIV infection in individuals who
have had no detectable viremia for extended periods of time as a result
of effective antiretroviral therapy", they add.
The authors add that by demonstrating the presence of HIV in the
activated CD4 cells of patients taking suppressive anti-HIV therapy they
provided "compelling evidence for the contribution of this compartment
to the continual reseeding of HIV reservoirs."
Latent CD4 cells infected with HIV could become reactivated, the
investigators suggest, as a consequence of normal responses to
Implications for treatment strategies arising from their findings are
suggested by the investigators. These include providing treatment with a
reagent to dampen cellular activation and the spread of HIV to other
cells. In addition, for patients taking effective HIV therapy, the use
additional antiretrovirals such as entry inhibitors, might be
considered as this would further suppress HIV replication.
Chun T-W et al. HIV-infected individuals receiving effective antiviral
therapy for extended periods of time continually replenish their viral
reservoir. J Clin Invest 115: 3250 - 3255, 2005.