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A once-weekly oral combination therapy of **islatravir** (a first-in-class nucleoside reverse transcriptase translocation inhibitor developed by Merck) and **lenacapavir** (a first-in-class HIV-1 capsid inhibitor developed by Gilead Sciences) is under investigation for the treatment of HIV-1 infection in virologically suppressed adults. Islatravir inhibits HIV-1 reverse transcription through multiple mechanisms as a deoxyadenosine analog, while lenacapavir interferes with several stages of the HIV lifecycle by binding to the viral capsid protein, blocking processes including nuclear import, assembly, and proper core formation. The combination demonstrated a high rate of sustained viral suppression (94.2% at 48 weeks) in Phase II trials and presents potential as the first once-weekly oral HIV regimen, offering an alternative to daily therapies[1][3][4][5][7][9].
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