[procaare] Study Shows Why Antiretrovirals Cannot Eradicate HIV

["Aidsmap" <procaare@healthnet.org>]

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
HIV. 

In a study involving eleven HIV-positive individuals who had been 
receiving successful antiretroviral therapy for up to nine years,
American 
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
of 
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 
ant-HIV therapy. 

"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
and 
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
researchers 
comment, "in all patients examined, the presence of HIV in resting as
well 
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
virions. 
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
bidirectional 
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
have 
received effective antiviral therapy for such a long period", comment
the 
authors. 

"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
have 
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
infections. 

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
of 
additional antiretrovirals such as entry inhibitors, might be 
considered as this would further suppress HIV replication.

Reference

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.

Online at: 
http://www.aidsmap.com/en/news/57C33B46-44F2-4AD2-99CA-41C83A985F04.asp