Advancements in Developing Strategies for Sterilizing and Functional HIV Cures

Abstract

Combined antiretroviral therapy (cART) has been successful in prolonging lifespan and reducing mortality of patients infected with human immunodeficiency virus (HIV). However, the eradication of latent HIV reservoirs remains a challenge for curing HIV infection (HIV cure) because of HIV latency in primary memory CD4⁺ T cells. Currently, two types of HIV cures are in development: a "sterilizing cure" and a "functional cure." A sterilizing cure refers to the complete elimination of replication-competent proviruses in the body, while a functional cure refers to the long-term control of HIV replication without treatment. Based on these concepts, significant progress has been made in different areas. This review focuses on recent advancements and future prospects for HIV cures.

Figure 1

Two major strategies for HIV cure by using genome editing. (a) Gene therapy strategies to eradicate HIV reservoirs. Using ZFN, TALENS, or CRISPR to eliminate the HIV provirus in latent cells. (b) Gene therapy strategies to prevent susceptible cells from HIV infection. Using gene editing to modify the receptor of susceptible cells and protect them from HIV infection.

Figure 2

Potential combination of “Shock & Kill,” therapeutic vaccine, and vectored immunoprophylactic strategies to eradicate HIV reservoirs. Specific cytotoxic T lymphocytes (CTL) combined with immunotherapies, such as therapeutic vaccines, broadly neutralizing antibodies, and nonneutralizing antibodies with ADCC effect, may lead to eradication of the latent HIV reservoir.