Identifying people with acute HIV infection: demographic features, risk factors, and use of health care among individuals with AHI in North Carolina.

Identifying and counseling individuals with Acute HIV Infection (AHI) offers a critical opportunity to avert preventable HIV transmission, however, opportunities to recognize these individuals may be missed. We surveyed 32 adults diagnosed with AHI during voluntary HIV testing from 1/1/03 to 2/28/05 in publicly funded testing sites in NC to describe their clinical, social, and behavioral characteristics. Eighty-one percent of participants were men; 59% were African American. Seventy-five percent experienced symptoms consistent with acute retroviral syndrome; although 83% sought medical care for these symptoms, only 15% were appropriately diagnosed at that initial medical visit, suggesting opportunities to diagnose these individuals earlier were missed. Eighty-five percent of the men engaged in sex with men. More than 50% of the participants thought they were infected with HIV by a steady partner. This study yields important information to assist in identifying populations at risk for or infected with AHI and designing both primary and secondary prevention interventions.

Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580.

Colony-stimulating-factor-1 (CSF-1) signaling through cFMS receptor kinase is increased in several diseases. To help investigate the role of cFMS kinase in disease, we identified GW2580, an orally bioavailable inhibitor of cFMS kinase. GW2580 completely inhibited human cFMS kinase in vitro at 0.06 microM and was inactive against 26 other kinases. GW2580 at 1 microM completely inhibited CSF-1-induced growth of mouse M-NFS-60 myeloid cells and human monocytes and completely inhibited bone degradation in cultures of human osteoclasts, rat calvaria, and rat fetal long bone. In contrast, GW2580 did not affect the growth of mouse NS0 lymphoblastoid cells, human endothelial cells, human fibroblasts, or five human tumor cell lines. GW2580 also did not affect lipopolysaccharide (LPS)-induced TNF, IL-6, and prostaglandin E2 production in freshly isolated human monocytes and mouse macrophages. After oral administration, GW2580 blocked the ability of exogenous CSF-1 to increase LPS-induced IL-6 production in mice, inhibited the growth of CSF-1-dependent M-NFS-60 tumor cells in the peritoneal cavity, and diminished the accumulation of macrophages in the peritoneal cavity after thioglycolate injection. Unexpectedly, GW2580 inhibited LPS-induced TNF production in mice, in contrast to effects on monocytes and macrophages in vitro. In conclusion, GW2580's selective inhibition of monocyte growth and bone degradation is consistent with cFMS kinase inhibition. The ability of GW2580 to chronically inhibit CSF-1 signaling through cFMS kinase in normal and tumor cells in vivo makes GW2580 a useful tool in assessing the role of cFMS kinase in normal and disease processes.