Authors : Sankara Narayanan Ravi

Volume/Issue : Volume 10 - 2025, Issue 5 - May

Google Scholar : https://tinyurl.com/362sytnu

DOI : https://doi.org/10.38124/ijisrt/25may2165

Note : A published paper may take 4-5 working days from the publication date to appear in PlumX Metrics, Semantic Scholar, and ResearchGate.

Abstract : Despite the success of antiretroviral therapy (ART), HIV remains incurable due to the persistence of latent viral reservoirs that evade immune clearance and therapy. Current strategies targeting latency, such as “shock-and-kill” and “block-and-lock,” have shown limited success and safety concerns. We propose a novel phased gene therapy approach using engineered HIV-derived lentiviral vectors to target both actively replicating and latent HIV. In the first phase, a Therapeutic Interfering Particle (TIP) or antiviral gene cassette is delivered to suppress active HIV replication. In the second phase, following suppression, a latency-reversing or cytotoxic payload is introduced via a second vector to reactivate and eliminate reservoir cells. This staged model leverages the natural tropism and replication biology of HIV to deliver therapy precisely and sequentially. If validated, this strategy could offer a path toward a functional or sterilizing cure for HIV infection.

Keywords : HIV Cure, Gene Therap , Vectors, Therapeutic Interfering Particles, Phased Treatment.

References :

1. Metzger, M. J., et al. (2011). "Engineering therapeutic interfering particles for the treatment of HIV." Nature Biotechnology, 29(7), 638–644.
2. Yin, C., et al. (2017). "In vivo excision of HIV-1 provirus by saCas9 and multiplex single-guide RNAs in animal models." Molecular Therapy, 25(5), 1168–1186.
3. Rasmussen, T. A., & Lewin, S. R. (2016). "Shocking HIV out of hiding: where are we with clinical trials of latency reversing agents?" Current Opinion in HIV and AIDS, 11(4), 394–401.
4. Milone, M. C., & O'Doherty, U. (2018). "Clinical use of lentiviral vectors." Leukemia, 32(7), 1529–1541.
5. Dash, P. K., et al. (2019). "Sequential LASER ART and CRISPR treatments eliminate HIV-1 in a subset of infected humanized mice." Nature Communications, 10(1), 2753.