Selective granulocyte/monocyte apheresis in the treatment of HIV-infected patients: short-term and long-term effects on immunological and virological parameters

Abstract

CD4 T cells constitute the major cellular target of HIV infection and, in the natural evolution of the disease, are gradually lost, leading to severe immunodeficiency. Highly active antiretroviral therapy (HAART) is generally effective in reducing HIV replication to undetectable levels and allows the recovery of CD4 T cells in the majority of patients treated. However, some sanctuaries of HIV replication persist even after years of effective HAART and are responsible for the rebound of viral replication when treatment is interrupted. Monocytes/macrophages are also infectable by HIV and are less susceptible to its cytopathic effects compared to CD4 T cells. Replication- competent HIV DNA is detectable in peripheral monocytes of patients under HAART. These cells may therefore contribute to the maintenance of HIV replication during treatment. In addition, both monocytes and granulocytes are abnormally activated during HIV infection and this results in overproduction of some pro-inflammatory cytokines, among them TNF-. For these reasons we tested whether the renewal of the pool of circulating monocytes and granulocytes by selective apheresis (G1 apheresis) could influence some key immunological and virological parameters in HAART-treated patients. The results showed that treatment with G1 apheresis without discontinuation of HAART results in an accelerated immune reconstitution with sustained increases in CD4 T cell counts in those patients who respond virologically to HAART. G1 apheresis is also followed by a strong reduction of TNF- and a reduction of cells bearing integrated HIV DNA. Taken together, the results indicate that G1 apheresis could be used to improve the immunological and virological response to HAART.