Short-term monotherapy in HIV-infected patients with a virus entry inhibitor against the gp41 fusion peptide

8 páginas, 3 figuras, 2 tablas -- p. 63re3To infect host cells, most enveloped viruses must insert a hydrophobic fusion peptide into the host cell membrane. Thus, fusion peptides may be valuable targets for developing drugs that block virus entry. We have shown previously that a natural 20-residue fragment of α1-antitrypsin, designated VIRus-Inhibitory Peptide (VIRIP), that binds to the gp41 fusion peptide of HIV-1 prevents the virus from entering target cells in vitro. Here, we examine the efficacy of 10-day monotherapy with the optimized VIR-576 derivative of VIRIP in treatment-naïve, HIV-1–infected individuals with viral RNA loads of ≥10,000 copies per ml. We report that at the highest dose (5.0 grams per day), intravenous infusion of VIR-576 reduced the mean plasma viral load by 1.23 log10 copies per ml without causing severe adverse effects. Our results are proof of concept that fusion peptide inhibitors suppress viral replication in human patients, and offer prospects for the development of a new class of drugs that prevent virus particles from anchoring to and infecting host cellsPart of this work was supported by the CONSOLIDER CSD2009-00088 from the Ministry of Science and Innovation, the State of Lower Saxony, and the Deutsche Forschungsgemeinschaft. D.M.-O. is supported by Bundesministerium für Bildung und Forschung, the European Aids Treatment Network (NEAT), Innovationsfond des Landes Niedersachsen, and the Helmholtz-Zentrum für Infektionsforschung (IG-SCID-TwinPro02). M.S. received funding from Boehringer-Ingelheim, GlaxoSmithKline, Roche, and Tibotec. Author contributions: W.-G.F. planned and supervised the study. Y.-H.T. recruited and TibotecPeer reviewe