Abstract | BACKGROUND: Fosdevirine ( GSK2248761) is a non- nucleoside reverse transcriptase inhibitor with HIV-1 activity against common efavirenz-resistant strains. Two partially blind, randomized, Phase IIb studies were initiated (1 in treatment-naive and 1 in treatment-experienced subjects with HIV) to select a once-daily dose of fosdevirine for Phase III trials. METHODS: RESULTS: A total of 35 subjects were exposed to fosdevirine 100 or 200 mg. Trials were halted when 5 treatment-experienced subjects (1 receiving fosdevirine 100 mg, 4 receiving fosdevirine 200 mg) developed new-onset seizures after ≥4 weeks of exposure to fosdevirine. There was no clear association between seizures and fosdevirine plasma drug levels. Time to seizure onset ranged from 28 to 81 days, and all 5 subjects experienced ≥1 seizure after drug discontinuation. CONCLUSIONS: The delayed onset of seizures after fosdevirine exposure and persistence after discontinuation is without precedent in antiretroviral drug development, leading to additional investigation and underscoring the need for careful subject monitoring.
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Authors | David A Margolis, Joseph J Eron, Edwin DeJesus, Scott White, Paul Wannamaker, Britt Stancil, Mark Johnson |
Journal | Antiviral therapy
(Antivir Ther)
Vol. 19
Issue 1
Pg. 69-78
( 2014)
ISSN: 2040-2058 [Electronic] England |
PMID | 24158593
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-HIV Agents
- IDX 899
- Indoles
- Phosphinic Acids
- Reverse Transcriptase Inhibitors
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Topics |
- Anti-HIV Agents
(pharmacology, therapeutic use)
- Drug Substitution
- Female
- HIV Infections
(complications, drug therapy)
- HIV-1
- Humans
- Indoles
(administration & dosage, pharmacokinetics, therapeutic use)
- Male
- Phosphinic Acids
(administration & dosage, pharmacokinetics, therapeutic use)
- Reverse Transcriptase Inhibitors
(pharmacology, therapeutic use)
- Seizures
(complications)
- Time Factors
- Treatment Outcome
- Withholding Treatment
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