A Phased HIV-Based Vector Therapy for Targeting Active and Latent Infection – A Theoratical Model for Eradication

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.