IngentaConnect Improvement in immune parameters and human immunodeficiency virus...

Authors: Reading, C.; Dowding, C.; Schramm, B.; Garsd, A.; Onizuka-Handa, N.; Stickney, D.; Frincke, J.

Source: Clinical Microbiology & Infection, Volume 12, Number 11, November 2006 , pp. 1082-1088(7)

Abstract:

A randomised, double-blind, placebo-controlled study examined the safety, tolerance, immunological effect and anti-human immunodeficiency virus (HIV) activity of sub-cutaneously administered HE2000 (16α-bromoepiandrosterone) as monotherapy in treatment-naïve patients with HIV-1. Twenty-four patients received five sequential daily doses of 50 or 100 mg of HE2000 or placebo every 6 weeks for up to three courses, and were followed thereafter for 3 months. HE2000 was safe, with transient injection site reactions being the main side-effect. Peripheral blood samples, collected serially, were analysed for changes in immune cell phenotypes. Significant increases were observed in the numbers of circulating dendritic cells, early activated (CD69⁺CD25^-) CD8 T-cells and T-NK cells after administration of 50-mg doses of HE2000 (p <0.05). Gene expression in peripheral blood mononuclear cells was analysed by real-time RT-PCR. Before treatment, HIV-1-infected patients had significantly elevated transcripts for a number of inflammatory mediators (p <0.012). After 50 mg or 100 mg HE2000, but not after placebo, there were significant sustained decreases in IL-1β, TNF-α, IL-6 and Cox-2 transcripts (p <0.05). There were no significant differences in CD4 cell numbers, although patients receiving 50-mg doses demonstrated a significant decrease in viral load (− 0.6 log; p <0.01). Anti-HIV-1 T-cell responses were analysed serially using GAG-peptides to stimulate cytoplasmic IFN-γ responses. After three courses, the 50-mg dose group demonstrated a significant increase in CD8 T-cell response against two distinct GAG peptide pools (p <0.03). These findings suggest that immune-based therapies may be able to impact viral load by decreasing inflammation and/or stimulating CD8 T-cells.

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Improvement in immune parameters and human immunodeficiency virus-1 viral response in individuals treated with 16α-bromoepiandrosterone (HE2000)