Design strategies for long-acting anti-HIV pharmaceuticals

Current combination antiretroviral therapy (cART) for human immunodeficiency virus (HIV) is limited by the frequent dosing and unfavorable adherence, and the rapid appearance of resistant mutants. Thus, there is a continuous need to improve and optimize the present therapies. The clinical phase III trials of FLAIR and ATLAS, showed two-drug injectable cabotegravir (CAB) and rilpivirine (RPV) formulation is potent, safe, and tolerable in HIV-infected patients. The recent approval of cabenuva (CAB + RPV) by Health Canada is a milestone in the development of long-term therapies for HIV infection. Broadly neutralizing antibodies (bNAbs) with excellent breath and efficiency against HIV have been investigated as LA antiviral weapons. Several modern modalities capable of sustained drug release for long-term treatment and prevention of HIV infection are also in development, such as implants, vaginal rings, and nanotherapies.