Explore the latest breakthroughs in HIV treatment, including advancements in antiretroviral therapy (ART), stem cell therapy, and gene editing, offering new hope for patients.
In 2023, 6.7 million people living with HIV resided in Asia and the Pacific, making it the world’s largest epidemic after Eastern and Southern Africa. This region alone accounts for a quarter of the world’s annual new HIV infections, representing 23% of the global total. As the fight against HIV continues, new research and advancements in antiretroviral therapy (ART) are offering fresh hope for better treatment and management of the disease. This article will also delve into recent breakthroughs in stem cell therapy and gene editing therapy for HIV, highlighting their potential to revolutionise treatment.
The Importance of ART in HIV Management
ART remains the cornerstone of HIV treatment. It is recommended for everyone diagnosed with HIV, regardless of the disease stage or complications. The primary goal of ART is to reduce the amount of HIV in the blood to undetectable levels, leading to better long-term health outcomes, including a reduced risk of developing AIDS-related illnesses and a lower likelihood of transmitting the virus to sexual partners. Furthermore, ART has been instrumental in reducing HIV-related mortality rates globally, transforming what was once a fatal diagnosis into a manageable chronic condition.
Typically, ART involves a combination of two or more drugs from different classes. These include:
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
These drugs inhibit a protein essential for HIV replication, with examples like efavirenz and doravirine. NNRTIs work by binding to and altering the reverse transcriptase enzyme, thereby preventing HIV from replicating in the body.
Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs)
These are faulty versions of the building blocks HIV needs to replicate, including drugs like tenofovir disoproxil fumarate and emtricitabine. NRTIs act as decoys, incorporating themselves into the viral DNA chain and halting further replication.
Protease inhibitors (PIs)
These inhibit HIV protease, another protein vital for HIV replication, with drugs like atazanavir and darunavir. PIs prevent the maturation of viral proteins, resulting in the production of immature, non-infectious virus particles.
Integrase inhibitors
These block integrase, a protein HIV uses to integrate its genetic material into host cells. Examples include bictegravir and dolutegravir. By blocking integrase, these drugs prevent HIV from inserting its DNA into the host cell genome, a critical step in the viral replication process.
Entry or fusion inhibitors
These prevent HIV from entering CD4 T cells, including newer options like ibalizumab-uiyk and fostemsavir. By blocking the virus’s ability to fuse with the host cell membrane, these inhibitors prevent HIV from entering and infecting the cells.
Key Findings from the 2024 CROI Conference
The 2024 Conference on Retroviruses and Opportunistic Infections (CROI) showcased several promising advancements in HIV treatment. Therefore, it emphasises the potential of long-acting formulations to significantly improve patient outcomes and simplify treatment adherence. These innovations are particularly noteworthy:
Long-Acting ART
A National Institute of Allergy and Infectious Diseases-supported trial demonstrated that long-acting ART with cabotegravir and rilpivirine was more effective at suppressing HIV than daily oral ART. The LATITUDE study showed a 7% chance of unsuppressed HIV with long-acting ART compared to 25% with daily ART. This advancement represents a major breakthrough, offering patients the convenience of fewer doses while maintaining high levels of viral suppression.
Adolescent Safety
The MOCHA study confirmed that long-acting injectable ART is safe and effective for adolescents aged 12-17, with no unexpected adverse events reported. This finding is particularly important as it addresses a critical age group often facing challenges with daily pill adherence. The availability of a long-acting option could improve treatment outcomes and quality of life for younger patients.
Weekly Oral Treatment
An industry-sponsored Phase 2 trial presented encouraging results for a once-weekly oral combination of islatravir and lenacapavir, which maintained high levels of viral suppression. This new regimen has the potential to simplify treatment for patients, offering a balance between the frequency of dosing and ease of use, and could significantly improve adherence to therapy, a major challenge in HIV management.
These advancements represent significant strides in the ongoing effort to enhance HIV treatment paradigms, potentially transforming the landscape of therapy and improving lives of patients across various demographics.
Emerging Therapies from the International AIDS Conference 2024: Stem Cell and Gene Editing
Beyond traditional ART, innovative therapies such as stem cell transplants and gene editing are making strides in the quest for an HIV cure, offering potential pathways to eradicate the virus completely. Presented at the latest International AIDS Conference 2024:
Seventh HIV-Free Patient
A remarkable case of a 60-year-old man in Germany who has been virus-free for nearly six years following a stem cell transplant from a donor with one mutated copy of the CCR5 gene was highlighted. Traditionally, the presence of two mutated copies has been thought necessary for resistance to HIV. This case suggests that a cure for HIV might not solely depend on having two copies of the CCR5 mutation, thus potentially expanding the donor pool for these critical transplants. Furthermore, this success raises the possibility of developing gene-editing strategies that mimic the effects of the CCR5 mutation, potentially leading to a functional cure for a broader range of patients.
Gene Editing Therapy
A first-in-human trial utilised the CRISPR-Cas9 system, delivered by adeno-associated virus 9, to specifically target and modify the HIV genome within CD4+ T cells. CRISPR-Cas9 works by using a guide RNA to locate specific DNA sequences and an enzyme called Cas9 to cut the DNA at the targeted location, allowing for precise genetic alterations. In the study, although HIV RNA levels rebounded in participants after stopping antiretroviral therapy, one patient experienced a significant delay in this rebound and a substantial reduction in the HIV reservoir. This significant step forward demonstrates the potential of CRISPR-Cas9 not only in treating HIV but also in addressing other chronic and viral diseases. Crucially, no serious adverse events were reported, indicating a favourable safety profile for this groundbreaking approach.
These findings challenge existing beliefs about HIV treatment and open new avenues for future therapies. One such application could be gene-editing techniques that could potentially lead to a cure. The ability to edit the human genome with precision opens up unprecedented possibilities for personalised medicine, where treatments are tailored to an individual’s genetic makeup.
Conclusion
The advancements presented at the 2024 CROI Conference and International AIDS Conference 2024 underscore the continuous evolution of HIV treatment. Long-acting antiretroviral therapy formulations, alongside innovative therapies such as stem cell transplants and CRISPR-Cas9 gene editing, are poised to change the landscape of HIV management. As the global community strives to end the HIV epidemic, these breakthroughs offer new hope for patients and healthcare professionals alike, emphasising the importance of continued research, collaboration, and equitable access to these life-saving treatments.
References
- Mayo Clinic Staff. (n.d.). HIV/AIDS. Mayo Clinic. Retrieved from https://www.mayoclinic.org/diseases-conditions/hiv-aids/diagnosis-treatment/drc-20373531
- HIV.gov. (2024, March 8). HIV treatment research and key takeaways: Dr. Dieffenbach’s final update from CROI 2024. HIV.gov. Retrieved from https://www.hiv.gov/blog/hiv-treatment-research-and-key-takeaways-dr-dieffenbach-s-final-update-from-croi-2024
- Mallapaty, S. (2024, July 26). Seventh patient ‘cured’ of HIV: Why scientists are excited. Nature News. https://doi.org/10.1038/d41586-024-02463-w
- Kirkner, R. M. (2024, July 30). First-in-human trial of CRISPR gene therapy for HIV. Medscape. Retrieved from https://www.medscape.com/viewarticle/first-human-trial-crispr-gene-therapy-hiv-2024a1000dx5
