BOSTON — HIV elite controllers can maintain sufficient counts of total
CD4 T cells compared with highly active antiretroviral therapy-treated
patients, HIV progressors and HIV-negative patients, despite severe depletion
of naive CD4 T cells. According to data presented here, this is due to their
ability to expand peripheral precursor T cells and through peripheral
homeostatic proliferation of naive T cells.
"We show that you can develop AIDS even if you don't have detectable HIV
replication," Mathias Lichterfeld, MD, PhD, instructor in medicine at
Massachusetts General Hospital and Harvard Medical School, said during a press
conference today. "And it looks like this is happening when mechanisms of CD4
cell regeneration are defective. We are investigating how that's possible. How
can people have deficiencies CD4 cell regeneration even when HIV is not
The current study included 15 patients in each of the following
categories: elite controllers, HAART-treated, HIV progressors and HIV-negative.
Using flow cytometry, the researchers measured proportions of naive, central
memory, effector memory and terminally differentiated CD4 T cells. Surface
staining for protein-tyrosine kinase 7 (PTK7+) and CD44 was used to identify
precursor T-cell populations, and they quantified thymic output using ratios of
sjTREC and bTREC levels.
Among elite controllers, relative proportions of naive T cells were
similar to those in HIV progressors and significantly lower than in
HAART-treated patients and HIV-negative patients (P<.01). However,
elite controllers and HIV progressors had significantly higher levels of
central-memory, effector-memory and terminally differentiated T cells compared
with HAART-treated and HIV-negative patients (P<.01).
According to Lichterfeld, this suggests that the accelerated recruitment
to the memory cell pool among elite controllers and HIV progressors may cause
the depletion of naive T cells in these populations.
There was no significant difference in thymic output among elite
controllers and HIV-negative patients; however, it was significantly lower
among HIV progressors (P<.02) and HAART-treated patients. Compared
with all other groups, elite controllers had significantly higher peripheral
precursor T-cell populations, similar to thymus-dependent PTK7+ and
thymus-independent CD44 T cells (P<.03). Similarly, homeostatic
proliferation of naive T cells was significantly higher in elite controllers
compared with all other groups (P<.02), as determined by Ki67
"An additional component of this is: What can we do from a treatment
perspective for patients such as elite controllers who have CD4 cell losses?
Currently, the conventional HIV drugs available are designed to suppress HIV
replication, but these patients don't even have detectable HIV replication, so
to what extent would they be likely to benefit from regular HIV treatment?
That's an important question, and we're doing a clinical trial to investigate
this further," Lichterfeld said. - by Stacey L. Fisher
For more information:
- Lichterfeld M. #839. Presented at: IDSA 49th Annual Meeting; Oct.
20-23, 2011; Boston.
Disclosure: Dr. Lichterfeld reports no relevant disclosures.
To put this into a treatment perspective, there's a discussion about
when to start treatment; elite controllers have always been put off to the side
because they were viewed to have no reason to treat - they don't have
detectable virus, and there doesn't appear to be any damage. The message here
is that maybe there is some ongoing damage; even in elite controllers, that
some of them are able to mask that from this regeneration and others have a
drifting down because their thymus or peripheral mechanisms are repleting - CD4
T cells aren't there.
- Michael Saag, MD
Immediate Past Chair, HIV Medicine
Director, Center for AIDS Research, University of Alabama at