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Cabotegravir + lenacapavir is a long-acting dual antiretroviral therapy (ART) regimen being investigated for the treatment of HIV-1 infection. This combination pairs lenacapavir (Sunlenca), a first-in-class capsid inhibitor developed by Gilead Sciences, with cabotegravir (Vocabria), an integrase strand transfer inhibitor (INSTI) developed by ViiV Healthcare. Lenacapavir functions by binding to the HIV-1 capsid protein, disrupting multiple essential steps in the viral lifecycle, including capsid-mediated nuclear import of viral DNA, virion assembly, and capsid formation. Cabotegravir inhibits the HIV-1 integrase enzyme, preventing the integration of viral DNA into the host cell genome. The combination is specifically being evaluated in the Phase II CALENDULA trial (NCT06657885), sponsored by the Institut de Médecine et d'Epidémiologie Appliquée (IMEA), as a simplified, long-acting maintenance or rescue therapy for multi-treated adults with HIV-1, utilizing subcutaneous and intramuscular delivery routes to reduce dosing frequency.
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