Impact of mRNA-Based Immune Modulators Versus Standard ART on Viral Reservoir Reduction in Treatment-Experienced HIV Adults: A Review

Despite the success of standard antiretroviral therapy (ART) in achieving sustained viral suppression among people living with HIV, the persistence of latent viral reservoirs in resting CD4+ T cells remains a major barrier to cure. This review examined the emerging role of messenger RNA (mRNA)-based immune modulators as a novel therapeutic strategy to reduce the HIV reservoir in treatment-experienced adults. Unlike ART, which halts replication without affecting the latent pool, mRNA-based therapeutics are designed to induce targeted immune responses, reverse latency, or enhance the clearance of infected cells through the transient expression of immunostimulatory proteins. Promising preclinical and early-phase clinical studies have shown that mRNA platforms can enhance HIV-specific T cell responses and delay viral rebound following treatment interruption. However, evidence of direct reservoir reduction in humans was still limited, and challenges such as immune exhaustion, delivery logistics, and combination strategy design remained. This article employed a narrative review methodology, synthesizing findings from peer-reviewed studies published between 2010 and 2025 to compare the mechanistic and clinical impacts of mRNA-based immune modulators and standard ART. The review concluded that mRNA immune modulators may complement ART in curative efforts, particularly when used in combination with latency-reversing agents and immune-enhancing therapies.