Core Viewpoint - The global fight against HIV/AIDS is facing significant setbacks, with 40.8 million current HIV infections worldwide and 9.2 million individuals not receiving treatment, leading to an estimated 1.3 million new infections in 2024 [1] Group 1: Vaccine Development Challenges - Despite nearly 40 years of research and billions spent, no effective HIV vaccine has been developed due to the virus's high mutation rate and complexity [2][4] - The ideal HIV vaccine should stimulate the production of neutralizing antibodies, but the high mutation rate of HIV's envelope proteins makes this difficult [3][4] - The presence of glycoproteins on HIV's surface further complicates the ability of neutralizing antibodies to recognize and bind to the virus [4][5] - The immune system's destruction by HIV makes it challenging to mount an effective immune response, as CD4 cells, which are targeted by the virus, are crucial for signaling immune reactions [6][7] - The failure of major clinical trials, such as Johnson & Johnson's, highlights the difficulties in developing an effective HIV vaccine [8] Group 2: Advances in Antiviral Drugs - While vaccine development has stalled, antiviral drugs have significantly improved, now playing a crucial role in HIV prevention [8] - Oral antiretroviral drugs have become the cornerstone of HIV treatment, with established guidelines for pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) [8] - Adherence to medication remains a challenge, with only 58.4% adherence reported by the end of 2022, limiting the effectiveness of prevention strategies [8] - Gilead Sciences' long-acting antiviral drug, lenacapavir, has shown promising results in clinical trials, achieving 100% prevention in one study and 96% risk reduction in another [9] - Lenacapavir has been approved by the FDA for HIV prevention, marking a significant advancement in the field, although its high cost and regulatory uncertainties may affect widespread adoption [9] Group 3: Future Directions - The ongoing battle against HIV/AIDS has not yet yielded a definitive solution, but innovative technologies are paving the way for better prevention and treatment strategies [10][11] - The focus on long-acting, low-frequency dosing regimens represents a potential breakthrough in addressing the core challenges of HIV prevention [9][10]