Elizabeth S Higgs1, Dehkontee Gayedyu-Dennis2, William A Fischer Ii3,4, Martha Nason1, Cavan Reilly5, Abdoul Habib Beavogui6,7, Jamila Aboulhab1, Jacqueline Nordwall5, Princess Lobbo2, Ian Wachekwa8, Huyen Cao9, Tomas Cihlar9, Lisa Hensley1, H Clifford Lane1. 1. Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA. 2. Duport Road Clinic, Paynesville, Liberia Partnership for Research on Ebola Virus in Liberia, Monrovia, Liberia. 3. Division of Pulmonary and Critical Care Medicine, University of North Carolina, Chapel Hill, North Carolina, USA. 4. USA Institute of Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina, USA. 5. Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota, USA. 6. Centre National de Formation et de Recherche en Santé Rurale de Maferinyah, Forecariah, Guinea. 7. Bioclinical and Fundamental Sciences Chair, Department of Medical Sciences, Faculty of Health Science and Techniques, Gamal Abdel Nasser University of Conakry, Conakry, Guinea. 8. John F. Kennedy Medical Center, Monrovia, Liberia. 9. Gilead Sciences, Foster City, California, USA.
Abstract
BACKGROUND: Ebola virus RNA persists in the semen of male Ebola survivors for months to years after the acute infection, and male-to-female sexual transmission of the virus is well documented. We investigated whether remdesivir can safely reduce persistence of seminal Ebola virus RNA. METHODS: We recruited men with persistent seminal Ebola RNA in Liberia and Guinea. Participants were randomized 1:1 to receive intravenous remdesivir (GS-5734; Gilead Sciences) or matching placebo administered once daily by intravenous infusion over 1 hour on 5 consecutive days. Stratification was by country and number of positive (1 or 2) preenrollment semen tests. We evaluated the difference in mean assay negativity rate (ANR), that is, the proportion of negative tests for each participant in each group in the treatment (days 1-28) and follow-up (months 2-6) phases on an intention-to-treat basis. RESULTS: We enrolled 38 men from July 2016 through June 2018. The mean treatment phase ANRs were 85% (standard deviation [SD] = 24%) and 76% (SD = 30%) in the remdesivir and placebo arms, respectively (P = .270). The mean follow-up phase ANRs were 96% (SD = 10%) and 81% (SD = 29%) in the remdesivir and placebo arms, respectively (P = .041). The 5-day remdesivir regimen was well tolerated with no safety concerns. CONCLUSIONS: In this small trial, remdesivir 100 mg/day for 5 days safely reduced the presence of Ebola virus RNA in the semen of Ebola survivors 2 to 6 months after administration. A larger follow-up study is necessary to confirm results. Clinical Trials Registration . NCT02818582. Published by Oxford University Press for the Infectious Diseases Society of America 2021.
BACKGROUND: Ebola virus RNA persists in the semen of male Ebola survivors for months to years after the acute infection, and male-to-female sexual transmission of the virus is well documented. We investigated whether remdesivir can safely reduce persistence of seminal Ebola virus RNA. METHODS: We recruited men with persistent seminal Ebola RNA in Liberia and Guinea. Participants were randomized 1:1 to receive intravenous remdesivir (GS-5734; Gilead Sciences) or matching placebo administered once daily by intravenous infusion over 1 hour on 5 consecutive days. Stratification was by country and number of positive (1 or 2) preenrollment semen tests. We evaluated the difference in mean assay negativity rate (ANR), that is, the proportion of negative tests for each participant in each group in the treatment (days 1-28) and follow-up (months 2-6) phases on an intention-to-treat basis. RESULTS: We enrolled 38 men from July 2016 through June 2018. The mean treatment phase ANRs were 85% (standard deviation [SD] = 24%) and 76% (SD = 30%) in the remdesivir and placebo arms, respectively (P = .270). The mean follow-up phase ANRs were 96% (SD = 10%) and 81% (SD = 29%) in the remdesivir and placebo arms, respectively (P = .041). The 5-day remdesivir regimen was well tolerated with no safety concerns. CONCLUSIONS: In this small trial, remdesivir 100 mg/day for 5 days safely reduced the presence of Ebola virus RNA in the semen of Ebola survivors 2 to 6 months after administration. A larger follow-up study is necessary to confirm results. Clinical Trials Registration . NCT02818582. Published by Oxford University Press for the Infectious Diseases Society of America 2021.
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