Gene therapy for HIV infection

Abstract

Introduction: Highly active antiretroviral therapy has been the big paradigm for transforming HIV infection in a chronic disease. However, it requires lifelong administration as the HIV provirus integrated within infected cells cannot be eliminated and virus replication resumes following antiviral discontinuation. Cumulative toxicities, incomplete immune restoration, elevated cost, drug–drug interactions and selection of drug-resistant viruses are well-known limitations of prolonged HIV medication.Areas covered: The first proof-of-concept that HIV infection could be cured was the Berlin patient. By blocking infection of target cells, gene therapy may allow viral clearance from carriers or prevention of infection in newly exposed individuals. Advances in the field of gene-targeting strategies, T-cell-based approaches and human stem cells are revolutionizing the field. A series of ongoing and planned trials are testing gene therapy as HIV cure. The ultimate goal is the elimination of latent viral reservoirs in HIV-infected persons and the need for lifelong antiretroviral therapy. Following a search in PubMed, we have reviewed current gene therapy strategies investigated for HIV infection as well as the latest communications on HIV eradication presented at international conferences.Expert opinion: Multiple efforts are underway to reproduce the Berlin patient situation by engineering autologous T cells or hematopoietic stem cells resistant to HIV infection. There is no doubt that the major challenge is the elimination of latent viral reservoirs. With this goal in mind, we have entered a new era in the hope for HIV cure.