HIV Insight: HIV-1 Functional Cure: Will the Dream Come True?

The reservoir of human immunodeficiency virus type 1 (HIV-1), a long-lived pool of latently infected cells harboring replication-competent viruses, is the major obstacle to curing acquired immune deficiency syndrome (AIDS). Although the combination antiretroviral therapy (cART) can successfully suppress HIV-1 viremia and significantly delay the progression of the disease, it cannot eliminate the viral reservoir and the patient must continue to take anti-viral medicines for life.

Currently, the appearance of the ‘Berlin patient’, the ‘Boston patients’, and the ‘Mississippi baby’ have inspired many therapeutic strategies for HIV-1 aimed at curing efforts. However, the specific eradication of viral latency and the recovery and optimization of the HIV-1-specific immune surveillance are major challenges to achieving such a cure. Here, we summarize recent studies addressing the mechanisms underlying the viral latency and define two categories of viral reservoir: ‘shallow’ and ‘deep’. We also present the current strategies and recent advances in the development of a functional cure for HIV-1, focusing on full/partial replacement of the immune system, ‘shock and kill’, and ‘permanent silencing’ approaches.

Below: A feasible strategy for the functional cure of HIV-1. Firstly, ‘shock and kill’ strategies could be quite useful in kicking out the ‘shallow’ latent viruses and eliminating them. Then, ‘silencing’ strategies, which permanently inactivate the ‘deeply’ silenced viruses, accompanied by potent anti-HIV-1 immune surveillance, could subsequently be utilized to achieve the functional cure of HIV-1

Below: Strategies for recovery and optimization of anti-HIV-1 immune surveillance. The combination of bNAbs with autologous adoptive transfer of HIV-1-specific CD8 + T cells and/or HIV-1-resistant CD4 + T cells could be an effective therapeutic modality for the functional cure of HIV-1