Advances in HIV Treatment and Vaccine Development: Emerging Therapies and Breakthrough Strategies for Long-Term Control.

Since its identification in 1981, HIV has posed a global public health challenge, witnessing transformative advancements in treatment and prevention. This review summarizes recent novel therapeutic and preventive approaches for long-term HIV control, management, and elimination, and how global collaboration and technological innovations may advance HIV control efforts. This study highlights the progress and challenges in HIV treatment, emphasizing the effectiveness of current antiretroviral therapy (ART) in suppressing viral replication, reducing transmission, and preventing end-organ damage. However, adherence remains a significant barrier due to pill burden, side effects, and psychosocial factors affecting patients. ART-related toxicities include neuropathy, hepatotoxicity, metabolic disorders, and neuropsychiatric effects. Long-acting ART (LA-ART) offers a promising alternative to daily dosing; however, challenges such as injection site reactions persist. Broadly neutralizing antibodies (bNAbs) have shown enhanced efficacy in viral suppression and immune response activation, offering potential for treatment and vaccine design. Innovative gene-editing tools, such as CRISPR-Cas systems, are being explored for their ability to excise or silence proviral DNA; however, their clinical application is limited by off-target effects and delivery challenges. Latency-targeting strategies like "shock and kill" and "block and lock" remain experimental with limited clinical success, and nanotechnology-based drug delivery systems offer targeted, sustained, and less toxic treatment options. Despite the challenges posed by the virus's rapid mutation rate and immune evasion mechanisms, novel vaccine approaches, such as mRNA technology, vector-based platforms, and epitope-targeting strategies, are being explored. In addition, artificial intelligence and machine learning are enhancing the design of vaccines, predictive modeling, and fast-tracking progress in this area. Socio-economic bottlenecks in HIV control, such as stigma, gender disparities, and inequitable healthcare access, exacerbate the epidemic, particularly in sub-Saharan Africa. Enhancing global collaboration, providing sustainable funding, and integrating emerging and innovative technologies are critical for advancing HIV prevention and management. Achieving an AIDS-free generation and ultimately eliminating the epidemic will depend on effectively addressing the social, structural, and scientific barriers that hinder progress in this regard.

Trial Registration: ClinicalTrials.gov identifier: NCT02120352, NCT02938520, NCT03639311, NCT03497676, NCT03635788.