title: Selection of Rilpivirine-Resistant HIV-1 in a Seroconverter From the SSAT 040 Trial Who Received the 300-mg Dose of Long-Acting Rilpivirine (TMC278LA).
abstract: The injectable long-acting formulation of rilpivirine (TMC278LA) is a promising preexposure prophylaxis (PrEP) candidate for prevention of human immunodeficiency virus type 1 (HIV-1) infection. We evaluated HIV-1 in plasma obtained from an unexpected seroconverter in the 300-mg arm of the SSAT040 TMC278LA pharmacokinetic study for rilpivirine (RPV) resistance. Infection with wild-type HIV-1 was confirmed on day 84 after TMC278LA injection, and the K101E mutation was detected on day 115. Plasma-derived HIV-1 clones containing K101E had 4-fold increased resistance to RPV and 4-8-fold increased cross-resistance to etravirine, nevirapine, and efavirenz compared with wild type HIV-1 plasma-derived clones from the same individual. This case is a unique instance of infection with wild-type HIV-1 and subsequent selection of resistant virus by persistent exposure to long-acting PrEP.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania.
authors.forename: Kerri J
authors.initials: KJ
authors.lastname: Penrose
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania.
authors.forename: Urvi M
authors.initials: UM
authors.lastname: Parikh
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania.
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Hamanishi
authors.affiliation: Liverpool Bioanalytical Facility, Department of Molecular and Clinical Pharmacology, University of Liverpool.
authors.forename: Laura
authors.initials: L
authors.lastname: Else
authors.affiliation: Liverpool Bioanalytical Facility, Department of Molecular and Clinical Pharmacology, University of Liverpool.
authors.forename: David
authors.initials: D
authors.lastname: Back
authors.affiliation: Department of HIV/Genito-Urinary Medicine, St. Stephen's Centre, Chelsea and Westminster Hospital, London, United Kingdom.
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
authors.affiliation: Department of HIV/Genito-Urinary Medicine, St. Stephen's Centre, Chelsea and Westminster Hospital, London, United Kingdom.
authors.forename: Akil
authors.initials: A
authors.lastname: Jackson
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania.
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D000068696:Rilpivirine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012641:Selection, Genetic
chemical_list: D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D000068696:Rilpivirine
keywords: HIV-1; NNRTI resistance; TMC278LA; pre-exposure prophylaxis (PrEP); rilpivirine