A number of cyclin-dependent kinases (CDKs) mediate key steps in the HIV-1 replication cycle and therefore have potential to serve as therapeutic targets for HIV-1 infection, especially in HIV-1 cure strategies. Current HIV-1 cure strategies involve the development of small molecules that are able to activate HIV-1 from latent infection, thereby allowing the immune system to recognize and clear infected cells. Areas covered: The role of seven CDK family members in the HIV-1 replication cycle is reviewed, with a focus on CDK9, as the mechanism whereby the viral Tat protein utilizes CDK9 to enhance viral replication is known in considerable detail. Expert opinion: Given the essential roles of CDKs in cellular proliferation and gene expression, small molecules that inhibit CDKs are unlikely to be feasible therapeutics for HIV-1 infection. However, small molecules that activate CDK9 and other select CDKs such as CDK11 have potential to reactivate latent HIV-1 and contribute to a functional cure of infection.
Keywords: CDK; CDK11; CDK9; Cyclin T1; HIV; HIV cure; P-TEFb; latency; latency reversing agents; shock and kill.