Inhibition of HIV Replication and Enhancement of Immune Functions by the Acyclic Nucleoside Phosphonate 9-(2-Phosphonyl-Methoxyethyl)Adenine (PMEA)

9-(2-phosphonyl-methoxyethyl)adenine (PMEA) is an acyclic nucleoside phosphonate analogue with potent activity against DNA viruses (i.e. herpesviruses) and retroviruses, including human immunodeficiency virus (HIV). To assess the clinical potential advantages of this drug, we evaluated the anti-HIV activity of PMEA in monocyte-macrophages (M/M) (cells of crucial importance in the pathogenesis of HIV-related disease). We also assessed the capacity of this nucleoside analogue to modulate some functions of the natural immunity, such as natural killer (NK) activity and interferon production. We found that PMEA inhibits HIV replication in M/M and in lymphocytes at nanomolar and micromolar concentrations respectively. In addition, PMEA was also found to enhance NK activity and to stimulate interferon production. PMEA has unique capability of being both an antiviral agent, effective against retroviruses as well as herpesviruses, and an immunomodulating agent. Its therapeutic potential should be further assessed in patients with HIV-related disease.