Ex-vivo purging of circulating monocytes results in immunovirologic improvement in partially HAART responder HIV-infected patients

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 TNF alpha play a major role in HIV pathoge nesis. TNF alpha transactivates HIV NF-kB thereby inducing viral replicatio n, potentiates HIV replication in lymphomonocytes TNF alpha is one of the m ain factors of HIV-induced cachexia and might be involved in HAART-associat ed lipodystrophy. In addition, monocytes are infectable by HIV in vitro and infected monocytes can be recovered from the blood of HIV infected patient s. For these reasons, we tested whether renewal of the pool of circulating monocytes by selective monocyte apheresis may improve the immune reconstitu tion which follows treatment with highly active anti-retrovirals (HAART). H IV-infected HAART receiving (> 1 year) patients who were either virological ly non-responders (HIV-1 RNA >50,000 copies/ml) or immunologically non-resp onders (CD4 counts < 200) were treated with a novel monocyte apheresis devi ce (G-1 Adacolumn), Plasma HIV viral load, proviral DNA and phenotypic and functional immunological analyses were performed. G-1 apheresis was well to lerated, not accompanied by adverse responses, and followed by clinical imp rovement. TNF alpha production was suppressed and CD4 T cell counts increas ed. In one G-1 patient with elevated HIV-1 proviral DNA a significant reduc tion (from 1,500 to 40 copies/10(5) cells) was observed. Neither immunologi c nor virologic parameters were modified in the control patients who receiv ed HAART alone. Thus, purging of circulating monocytes by G-1 apheresis has a dramatic suppressive effect on TNF alpha production and is followed by b oth clinical and immunovirological improvement. G-1 apheresis should be con sidered in patients in whom HAART is only partially effective.