• Michael Kozal, Judith Aberg, Gilles Pialoux, Pedro Cahn, Melanie Thompson, Jean-Michel Molina, Beatriz Grinsztejn, Ricardo Diaz, Antonella Castagna, Princy Kumar, Gulam Latiff, Edwin DeJesus, Mark Gummel, Margaret Gartland, Amy Pierce, Peter Ackerman, Cyril Llamoso, Max Lataillade, and BRIGHTE Trial Team.
• From Yale University School of Medicine and the Veterans Affairs Connecticut Healthcare System, New Haven (M.K.), and ViiV Healthcare, Branford (P.A., C.L., M.L.) - all in Connecticut; Icahn School of Medicine at Mount Sinai, New York (J.A.); Hôpital Tenon, Assistance Publique-Hôpitaux de Paris (AP-HP) (G.P.), and Hôpital Saint Louis, AP-HP, and University of Paris Diderot Paris 7 (J.-M.M.), Paris; Fundación Huesped, Buenos Aires (P.C.); AIDS Research Consortium of Atlanta, Atlanta (M.T.); Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro (B.G.), and Federal University of São Paulo, São Paulo (R.D.); San Raffaele Scientific Institute, Milan (A.C.); Georgetown University Hospital, Washington, DC (P.K.); Maxwell Center, Durban, South Africa (G.L.); Orlando Immunology Center, Orlando, FL (E.D.); GlaxoSmithKline, Upper Providence, PA (M. Gummel); and ViiV Healthcare, Research Triangle Park, NC (M. Gartland, A.P.).
• N. Engl. J. Med. 2020 Mar 26; 382 (13): 1232-1243.

BackgroundAmong some patients with human immunodeficiency virus type 1 (HIV-1) infection who have undergone multiple antiretroviral therapies and have limited options for treatment, new classes of antiretroviral drugs with novel mechanisms of action are needed. Fostemsavir is the prodrug of temsavir, a first-in-class investigational HIV-1 attachment inhibitor.MethodsIn this ongoing phase 3 trial in 23 countries, we enrolled patients with multidrug-resistant HIV-1 infection in two cohorts, according to their remaining treatment options. In the first cohort, we assigned (in a 3:1 ratio) patients who had the option of using at least one fully active, approved antiretroviral drug in at least one but no more than two antiretroviral classes to add either fostemsavir (at a dose of 600 mg twice daily) or placebo to their failing regimen for 8 days, followed by open-label fostemsavir plus optimized background therapy (randomized cohort). In the second cohort, patients who had no remaining antiretroviral options were started on open-label fostemsavir plus optimized background therapy on day 1 (nonrandomized cohort). The primary end point was the mean change in the HIV-1 RNA level from day 1 through day 8 in the randomized cohort.ResultsA total of 371 patients were treated, including 272 in the randomized cohort and 99 in the nonrandomized cohort. At day 8, the mean decrease in the HIV-1 RNA level was 0.79 log10 copies per milliliter in the fostemsavir group and 0.17 log10 copies in the placebo group (P<0.001). At week 48, a virologic response (HIV-1 RNA level, <40 copies per milliliter) had occurred in 54% of the patients in the randomized cohort and in 38% of those in the nonrandomized cohort; the mean increase in the CD4+ T-cell count was 139 cells per cubic millimeter and 64 cells per cubic millimeter, respectively. Adverse events led to the discontinuation of fostemsavir in 7% of the patients. In the randomized cohort, glycoprotein 120 (gp120) substitutions were found in 20 of 47 patients (43%) with virologic failure.ConclusionsIn patients with multidrug-resistant HIV-1 infection with limited therapy options, those who received fostemsavir had a significantly greater decrease in the HIV-1 RNA level than those who received placebo during the first 8 days. Efficacy was sustained through 48 weeks. (Funded by Bristol-Myers Squibb and GSK/ViiV Healthcare; BRIGHTE ClinicalTrials.gov number, NCT02362503.).Copyright © 2020 Massachusetts Medical Society.

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