Can gene delivery close the door to HIV‐1 entry after escape?

BACKGROUND: Research efforts to prevent viral entry by developing small molecule inhibitors against HIV-1 chemokine coreceptors have yielded promising clinical results. However, resistance to some chemokine receptor inhibitors has been recently documented, and therefore, alternative methods of HIV-1 coreceptor disruption are needed. CONCLUSION: We will describe current HIV-1 vector-delivered genetic disruption mechanisms that target HIV-1 chemokine coreceptors, such as RNA interference, ribozymes, zinc fingers, intrakines, and intrabodies, and frame the use of these gene delivery chemokine receptor disruption mechanisms in the context of current small molecule blocker/antagonists of CCR5 and CXCR4. In addition, we will discuss the importance of evaluating HIV-1 vector-delivered viral entry prevention mechanisms in the rhesus macaque SIV non-human primate model in regard to pathogenesis and therapeutic efficacy.