Current and Future Therapeutic Strategies for Lentiviral Eradication from Macrophage Reservoirs

Macrophages, one of the most abundant populations of leukocytes in the body, function as the first line of defense against pathogen invaders. Human Immunodeficiency virus 1 (HIV-1) remains to date one of the most extensively studied viral infections. Naturally occurring lentiviruses in domestic and primate species serve as valuable models to investigate lentiviral pathogenesis and novel therapeutics. Better understanding of the role macrophages play in HIV pathogenesis will aid in the advancement towards a cure. Even with current efficacy of first- and second-line Antiretroviral Therapy (ART) guidelines and future efficacy of Long Acting Slow Effective Release-ART (LASER-ART); ART alone does not lead to a cure. The major challenge of HIV eradication is viral latency. Latency Reversal Agents (LRAs) show promise as a possible means to eradicate HIV-1 from the body. It has become evident that complete eradication will need to include combinations of various effective therapeutic strategies such as LASER-ART, LRAs, and gene editing. Review of the current literature indicates the most promising HIV eradication strategy appears to be LASER-ART in conjunction with viral and receptor gene modifications via the CRISPR/Cas9 system. Graphical abstract A multimodal approach to HIV treatment including gene editing, LASER-ART, and latency reversal agents may provide a means to achieve HIV eradication.