Progress and challenges in the use of latent HIV-1 reactivating agents

Highly active antiretroviral therapy （HAART） can effectively suppress the replication of human immunodeflciency virus-1 （HIV-1） and block disease progression. However, chronic HIV-1 infection remains incurable due to the persistence of a viral reservoir, including the transcriptionally silent provirus in CD4＋ memory T cells and the sanctuary sites that are inaccessible to drugs. Reactivation and the subsequent elimination of latent virus through virus-specific cytotoxic effects or host immune responses are critical strategies for combating the disease. Indeed, a number of latency reactivating reagents have been identified through mechanism-directed approaches and large-scale screening, including： （1） histone deacetylase inhibitors （HDACi）; （2） cytokines and chemokines; （3） DNA methyltransferase inhibitors （DNMTI）; （4） histone methyltransferase inhibitors （HMTI）; （5） protein kinase C （PKC） activators; （6） P-TEFb activators; and （7） unclassified agents, such as disulfram. They have proved to be efficacious in latent cell line models and CD4＊ T lymphocytes from HIV-l-infected patients. This review comprehensively summarizes the recent progress and relative challenges in this field.