HIV-1 gene therapy at pre-integration and provirus DNA levels

AIDS is the result of infection by a lentivirus, HIV-1, which primarily infects CD4+ T cells and macrophages. There is presently no vaccine and none will be available in the foreseeable future. Highly active antiretroviral drug therapy has led to a dramatic reduction of viral load in many infected individuals, and has decreased mortality in the developing world. However, besides long-term drug toxicity and eventual emergence of drug-resistant strains, withdrawal from the therapy (even after effective and continuous treatment) results in re-emergence of the virus since cells harbouring the latent viral reservoirs persist. These issues highlight the need for alternative therapies, e.g. gene therapy. This review summarizes various gene therapy strategies that target early stages of HIV-1 life cycle. We will cover strategies that allow interference at the level of the released virion RNA, reverse transcriptase, pre-integration complex, integrase, dsDNA and provirus DNA in gene-modified cells.