New Dual-Combo Antibody Treatment for HIV-1
Introduction to HIV-1 and Current Treatment Options
A recent study published in Nature introduces a novel dual-combo antibody treatment aimed at addressing HIV-1. Once inside the human body, the HIV-1 virus can integrate into the human genome, utilizing the host’s replication machinery to reproduce. Despite the immune system’s efforts to combat the infection through programmed cell death of cells harboring viral DNA, a small reservoir of HIV-1 can persist and replicate. Consequently, while a complete cure remains elusive, treatment options exist to reduce the viral load.
Current treatment strategies include antiretroviral therapy (ART) and broadly neutralizing monoclonal anti-HIV-1 antibodies (bNAbs). Although ART has been the standard approach, antibody therapy can enhance the immune response, providing additional defense against viral proliferation. Nevertheless, both ART and antibody therapies may lead to increased viral load over time as resistant strains emerge. Combination therapies that utilize multiple antiviral medications or antibodies often yield the best results.
Exploring Stronger Antibodies in Treatment
Previous human studies that investigated combinations of antibodies did not demonstrate significant improvements in lowering viral load, potentially due to the use of weaker antibodies. Researchers, including Mendoza and colleagues, aimed to determine whether stronger antibodies could effectively reduce viral load during antiretroviral therapy with analytical treatment interruption (ATI). Their findings were published in Nature.
The researchers conducted a clinical trial that involved lab assays to identify viruses susceptible to two specific antibodies in HIV-1 positive individuals already undergoing ART. Out of 15 participants who met the trial’s strict criteria, 11 continued after four were excluded due to high viral loads. The antibody infusion method was administered, and the researchers concluded that the combination therapy was safe for use among the participants.
Results of the Clinical Trial
Among the 11 participants, nine maintained controllable viral loads for approximately 15 weeks. However, two individuals experienced a rebound in viral load. Further analysis suggested that these rebound cases might have involved viruses resistant to either of the antibodies used in the therapy. Similar reasoning applied to the four excluded participants, indicating potential resistance to both antibodies.
Additional explanations indicated that some viruses might have mutations at the target sites recognized by the antibodies, leading to ineffective treatment. The authors noted that the screening methods might not have been sufficiently sensitive to detect viral resistance in the two rebound cases. Notably, a higher concentration of the antibody combination correlated with a lack of viral load rebound. Throughout the study period, none of the nine individuals exhibited simultaneous resistance to both antibodies.
Implications of Combination Antibody Therapy
The findings suggest that combination antibody therapy can effectively keep viral loads low in individuals who exhibit susceptibility to both antibodies at adequate concentrations. Lower concentrations may increase the risk of viral load rebounds.
However, further research is necessary before combination antibody therapies can be fully implemented. Extended observation periods for participants receiving this therapy will be crucial to assess the sustainability of low viral loads. It is important to recognize that HIV-1 is a highly adaptable virus capable of developing resistance to various antibodies and medications. Therefore, dual antibody therapy alone may not suffice, and additional antibodies or ART may need to be incorporated in future treatments.
Conclusion
The research by Mendoza et al. highlights the potential of combination antibody therapy in managing HIV-1. As the scientific community continues to explore this avenue, it is critical to remain vigilant against the virus’s capacity for resistance.
Written by Olajumoke Marissa Ologundudu B.Sc. (Hons)
Reference: Mendoza P, Gruell H, Nogueira L, et al. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature. 2018; 561(7724):479-484. doi: 10.1038/s41586-018-0531-2.