Format

Send to

Choose Destination
Acta Pharmacol Sin. 2015 Aug;36(8):908-16. doi: 10.1038/aps.2015.22. Epub 2015 Jun 1.

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

Author information

1
Department of Medical Engineering, General Hospital of Beijing Military Area Command of PLA, Beijing 100700, China.
2
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
3
Center of Infectious Disease, Beijing 302 Hospital, Beijing 100039, China.

Abstract

Highly active antiretroviral therapy (HAART) can effectively suppress the replication of human immunodeficiency 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-1-infected patients. This review comprehensively summarizes the recent progress and relative challenges in this field.

PMID:
26027656
PMCID:
PMC4564876
DOI:
10.1038/aps.2015.22
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center