New Horizons in HIV Treatment and Vaccine Development

World AIDS Day 2025 highlights the global commitment to overcoming disruption and transforming the AIDS response. As we observe this day, it is important to appreciate the remarkable progress made against HIV/AIDS and to recognise the cutting-edge innovations shaping the future of treatment and prevention. HIV, once a universally fatal diagnosis, has become a manageable chronic condition for millions worldwide. Today, recent advances in long-acting therapies, resistance-targeting drugs, cure research, and vaccine development offer renewed hope of ending the epidemic.

Advances in HIV Treatment

Antiretroviral therapy (ART) has undergone a dramatic evolution. Modern ART regimens allow most individuals to achieve undetectable viral loads with a simple, once-daily pill. This not only prevents disease progression but also halts onward transmission.

A major transformation in recent years has been the arrival of long-acting injectable therapies. The first complete long-acting regimen—combining cabotegravir and rilpivirine—replaced daily oral dosing with monthly injections. This regimen later expanded to two-monthly dosing, drastically reducing pill burden and improving adherence for individuals who struggle with daily medication schedules.

Another significant development is the emergence of new drug classes for individuals with multidrug-resistant HIV. Lenacapavir, the first capsid inhibitor, introduced an entirely new mechanism of action and allows treatment with just one injection every six months. Beyond treatment, lenacapavir has also been approved as a long-acting PrEP option, providing twice-yearly protection for individuals at risk—an innovation that could substantially strengthen HIV prevention programmes. Equally encouraging is progress in HIV cure research. Although a scalable cure remains beyond reach, several exceptional cases have demonstrated that durable HIV remission is possible. A handful of patients receiving stem-cell transplants from donors carrying a rare HIV-resistant mutation have achieved complete viral eradication. These landmark cases, while not generalisable treatments, provide crucial scientific proof guiding new approaches such as gene editing, immune-based therapies, and strategies to eliminate latent viral reservoirs.

Progress in HIV Vaccine Development

Developing an effective HIV vaccine has long been one of the greatest challenges in medical science. HIV mutates rapidly, hides within cells, and evades immune responses—making traditional vaccine strategies ineffective. This complexity was highlighted by the discontinuation of two large “mosaic” vaccine trials in recent years due to lack of efficacy. Despite this setback, research has accelerated with more innovative approaches.

A major milestone has been the success of germline-targeting vaccine design, which aims to stimulate the immune system to produce broadly neutralising antibodies. Early-stage clinical trials have shown that experimental immunogens can activate the specific precursor B-cells required to eventually generate these powerful antibodies. Follow-up booster studies, including those delivered via mRNA platforms, have demonstrated further maturation of the antibody response, marking significant progress towards a viable preventive vaccine.

Research is also advancing on T-cell-based vaccines designed to induce strong cellular immunity against conserved regions of the virus. Additional innovation includes the use of replicating viral vectors, such as modified CMV platforms, which have shown remarkable immune-mediated clearance of simian HIV infection in preclinical studies and are now entering human trials. The growing use of mRNA technology has further accelerated vaccine development efforts, offering precision design and rapid adaptability.

Although no HIV vaccine has been approved yet, the scientific trajectory is more promising than ever. Each trial—successful or not—adds vital knowledge, shaping new strategies and refining existing ones.

Looking Ahead

The theme of World AIDS Day 2025 reinforces the need for resilience, innovation, and collective action. Long-acting drugs, novel therapeutic classes, and bold vaccine strategies are pushing the boundaries of what was once thought possible. These developments not only improve day-to-day management for people living with HIV but also bring the world closer to the vision of ending AIDS as a public health threat by 2030.

As we commemorate this day, let us celebrate scientific progress, honour the lives affected by HIV/AIDS, and reaffirm our commitment to supporting research, policy action, and community engagement. With sustained global effort, an AIDS-free generation is within reach.

References:

1. World Health Organization. World AIDS Day 2025: Overcoming disruption, transforming the AIDS response. Geneva: WHO; 2025. Available from: https://www.who.int

2. International AIDS Vaccine Initiative (IAVI). Global HIV treatment and vaccine research updates. New York: IAVI; 2025. Available from: https://www.iavi.org 

3. U.S. Food and Drug Administration. Long-acting HIV treatment approvals: Cabotegravir and Rilpivirine. Silver Spring (MD): FDA; 2021–2024. Available from: https://www.fda.gov 

4. ViiV Healthcare. Clinical updates on long-acting injectable HIV therapy. London: ViiV Healthcare; 2024–2025. Available from: https://www.viivhealthcare.com 

5. U.S. Food and Drug Administration; Nature. Lenacapavir approval for multidrug-resistant HIV and long-acting PrEP. Silver Spring (MD): FDA; 2022–2025. Available from: https://www.nature.com

6. Oregon Health & Science University (OHSU). Documented cases of HIV cure following CCR5-Δ32 stem-cell transplantation. Portland (OR): OHSU News; 2023–2025. Available from: https://news.ohsu.edu

7. Aidsmap. HIV vaccine trial updates, mosaic vaccine results, and new prevention strategies. London: NAM Aidsmap; 2021–2025. Available from: https://www.aidsmap.com

8. International AIDS Vaccine Initiative (IAVI). Germline-targeting vaccine trial results and mRNA platform applications. New York: IAVI; 2023–2025. Available from: https://www.iavi.org

9. Aidsmap; International AIDS Vaccine Initiative (IAVI). T-cell immunity vaccines, CMV-based vectors, and innovative HIV vaccine research avenues. London/New York: Aidsmap & IAVI; 2023–2025. Available from: https://www.aidsmap.com