Integration of long-acting antiretroviral therapies and latency-reversing agents for reservoir reduction and viral suppression: a comprehensive review

Despite significant advancements in antiretroviral therapy (ART), the persistent latent HIV reservoir remains a major barrier to achieving a complete cure. Current ART regimens effectively suppress viral replication but necessitate lifelong adherence due to their inability to eradicate latent HIV. Long-acting antiretroviral therapies (LA-ARTs) have emerged as an innovation to improve adherence and reduce the burden of daily dosing. Additionally, latency-reversing agents (LRAs) aim to reactivate the latent virus, making it susceptible to immune clearance. The combination of LA-ART and LRAs offers a promising therapeutic approach to address both adherence challenges and reservoir eradication. Objective: This review explores the potential synergy between LA-ART and LRAs, focusing on their individual and combined roles in reducing HIV reservoirs and sustaining viral suppression. Methodology: A systematic search of peer-reviewed articles and clinical studies was conducted following SANRA guidelines. Inclusion criteria included studies involving PLWH, focusing on LA-ART and/or LRAs, and evaluating outcomes such as reservoir reduction and viral suppression. Studies without clinical applicability or reporting relevant outcomes were excluded. Discussion: LA-ART enhances adherence and quality of life by reducing the dosing frequency, while LRAs utilize a “shock and kill” strategy to reactivate the latent virus. Despite their potential, challenges such as suboptimal LRA efficacy, immune clearance limitations, and accessibility barriers persist. Combining these therapies may create a robust treatment framework, but further research is needed to optimize regimens and overcome implementation challenges. This review highlights the need for collaborative efforts in research and policy to refine and integrate these therapies, moving closer to a functional cure for HIV.

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