Potential mechanisms for cell-based gene therapy to treat HIV/AIDS.
BACKGROUND
An estimated 35 million people are infected with HIV worldwide. Anti-retroviral therapy (ART) has reduced the morbidity and mortality of HIV-infected patients but efficacy requires strict adherence and the treatment is not curative. Most importantly, the emergence of drug-resistant virus strains and drug toxicity can restrict the long-term therapeutic efficacy in some patients. Therefore, novel treatment strategies that permanently control or eliminate the virus and restore the damaged immune system are required. Gene therapy against HIV infection has been the topic of intense investigations for the last two decades because it can theoretically provide such a durable anti-HIV control.


METHODS
In this review we discuss two major gene therapy strategies to combat HIV. One approach aims to kill HIV-infected cells and the other is based on the protection of cells from HIV infection. We discuss the underlying molecular mechanisms for candidate approaches to permanently block HIV infection, including the latest strategies and future therapeutic applications.


CONCLUSIONS
Hematopoietic stem cell-based gene therapy for HIV/AIDS may eventually become an alternative for standard ART and should ideally provide a functional cure in which the virus is durably controlled without medication. Recent results from preclinical research and early-stage clinical trials support the feasibility and safety of this novel strategy.
Academic Medical Center University of Amsterdam, Department of Medical Microbiology , Meibergdreef 15, Amsterdam, 1105 AZ , The Netherlands.
Elena
E
Herrera-Carrillo
Ben
B
Berkhout
D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D015658:HIV Infections / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans
D019380:Anti-HIV Agents
HIV-1; RNA decoy; RNA interference; antisense; antiviral; gene therapy; hematopoietic stem cell; intracellular immunization; nuclease; ribozyme; trans-dominant negative mutant