Hiv/AIds: Pathophysiology, Immunological Markers, Antiretroviral Therapeutics, Prevention Strategies, and Emerging Research Perspectives

Background: Acquired Immunodeficiency Syndrome (AIDS), caused by the Human Immunodeficiency Virus (HIV), remains one of the most formidable infectious diseases of our era. Despite four decades of intensive scientific inquiry, AIDS continues to impose a devastating global health burden, with approximately 40.1 million people living with HIV/AIDS (PLHIV) in 2024. Objective: This comprehensive review aims to consolidate current knowledge on the pathophysiology of HIV/AIDS, immunological biomarkers for disease monitoring, antiretroviral therapy (ART) advances, prophylactic strategies, co-morbidity management, and emerging research directions including broadly neutralizing antibodies, long-acting formulations, and functional cure strategies, drawing primarily from contemporary research articles and landmark studies relevant to HIV/AIDS pathogenesis, treatment, prevention, andcure research. Methods: A comprehensive narrative literature review was conducted in PubMed, Scopus, Web of Science, Google Scholar, and Cochrane Library databases, using MeSH terms and Boolean operators related to HIV/AIDS pathophysiology, immunology, antiretroviral therapy, prevention, and cure research. Primary emphasis was placed on studies published between January 2020 and March 2025, alongside landmark historical studies essential to HIV/AIDS research. Grey literature, editorials, and case reports were excluded. Results & Discussion: Current integrase strand transfer inhibitor (INSTI)-based ART regimens demonstrate virological suppression exceeding 95%. Dolutegravir and bictegravir have emerged as the preferred first-line agents globally due to superior resistance profiles and tolerability. Innovative long-acting ART formulations such as cabotegravir/rilpivirine (CAB/RPV) injectable therapy administered every two months have shown non-inferior suppression versus daily oral regimens. The Undetectable = Untransmittable (U=U) paradigm has significantly advanced treatment-as-prevention strategies. Broadly neutralizing antibodies (bNAbs), mRNA vaccine platforms, HIV reservoir targeting using CRISPR-Cas9 and latency-reversing agents (LRAs), and gene therapies represent important investigational approaches in functional cure research. Conclusion: Remarkable strides in HIV/AIDS science have transformed it from a universally fatal disease into a manageable chronic condition. However, achieving the UNAIDS 95-95-95 targets and ultimately a scalable cure demands sustained innovation, equitable access, and elimination of stigma-driven barriers to care.