Evaluating efficacy and safety of switching a boosted protease inhibitor to fostemsavir in PLWH with limited therapeutic options (FOST Switch)

Prior treatment

• Use of medications that are known to interact with Fostemsavir. Contraindications are given in appendix 3, and full information on drug-drug interactions is given in SmPC.
• Ongoing malignancy other than cutaneous Kaposi’s sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical or anal intraepithelial neoplasia; other localised malignancies require agreement between the investigator and the Trial medical monitor for inclusion of the patient prior to trial entry
• Any investigational drug within 30 days prior to the trial drug administration
• Unable to take oral medications

Other illness

• History of being on a cART containing Fostemsavir.
• HIV-1 subtype AE
• Hypersensitivity to active substance or excipient of Fostemsavir as listed in SmPC.
• Known acute or chronic viral hepatitis including, but not limited to, A, B, or C. Chronic hepatitis B and history of hepatitis C (cured) are allowed.
• Patients with severe hepatic impairment (Class C) as determined by Child-Pugh classification
• Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophagael or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones)

Lab values

• History of congestive heart failure or congenital prolonged QT syndrome.
• Confirmed QT value > 500 msec at Screening or Day 1
• ALT>5 times the ULN, OR ALT>3xULN and bilirubin>1.5xULN (with >35% direct bilirubin).
• Any other condition (including illicit drug use or alcohol abuse) or laboratory results which, in the investigator’s opinion, interfere with assessments or completion of the trial.

Age

• Age < 18 years

Other

• Unable to take part in the trial according to the investigator opinion (example: unable to understand the trial information leaflet, unable to provide written consent, etc.)
• IOCBP who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the trial
• Confirmed QTcF value > 470 msec for women and > 450 msec for men at Screening or Day 1

• HIV-1 infected adult Age > 18 years (non-childbearing potential or agrees to highly effective contraception methods)
• On stable & suppressive cART with a VL ≤50 c/mL for 1 year allowing one blip (50-200 c/mL) as long as resuppressed below 50 for 6 consecutive months prior to enrolment and with no major adherence issues.
• Patients on bPI with no other potential switch to another approved regimen (except to ibalizumab and/or lenacapavir, if available) due to intolerance to prior therapy or resistance.
• No significant laboratory abnormalities, medical/psychiatric conditions or alcohol/drug use considered a barrier to participation by investigators.
• Willing to sign an informed consent and take part in the trial.