Beretta A Saniabadi A, et al. Ex-vivo purging
of circulating monocytes results in immunovirologic
improvement in partially HAART responder HIV
infected patients. J Biol Regul Homeost Agents.
2000 Jan-Mar;14(1):27-31
CIRBS, Hospital St. Joseph, Paris, France.
giuliana.fusetti@hsr.it
AIDS pathogenesis results from a complex array
of immune alterations which include, among others,
changes in the pattern of cytokine production.
Some monocyte-derived cytokines, like TNFalpha
play a major role in HIV pathogenesis. TNFalpha
transactivates HIV NF-kB thereby inducing viral
replication, potentiates HIV replication in
lymphomonocytes TNFalpha is one of the main
factors of HIV-induced cachexia and might be
involved in HAART-associated lipodystrophy.
In addition, monocytes are infectable by HIV
in vitro and infected monocytes can be recovered
from the blood of HIV infected patients. For
these reasons, we tested whether renewal of
the pool of circulating monocytes by selective
monocyte apheresis may improve the immune reconstitution
which follows treatment with highly active anti-retrovirals
(HAART). HIV-infected HAART receiving (> 1 year)
patients who were either virologically non-responders
(HIV-1 RNA >50,000 copies/ml) or immunologically
non-responders (CD4 counts < 200) were treated
with a novel monocyte apheresis device (G-1
Adacolumn). Plasma HIV viral load, proviral
DNA and phenotypic and functional immunological
analyses were performed. G-1 apheresis was well
tolerated, not accompanied by adverse responses,
and followed by clinical improvement. TNFalpha
production was suppressed and CD4 T cell counts
increased. In one G-1 patient with elevated
HIV-1 proviral DNA a significant reduction (from
1,500 to 40 copies/10(5) cells) was observed.
Neither immunologic nor virologic parameters
were modified in the control patients who received
HAART alone. Thus, purging of circulating monocytes
by G-1 apheresis has a dramatic suppressive
effect on TNFalpha production and is followed
by both clinical and immunovirological improvement.
G-1 apheresis should be considered in patients
in whom HAART is only partially effective.
PMID: 10763888