Monoclonal Antibodies May Hold Key to HIV Cure

Successful highly active antiretroviral therapy (HAART) has allowed the long-term effects of HIV infection and chronic medication toxicity to become the primary cause of death and disability.

However, HIV-positive patients are at greater risk for cardiovascular disease and cancers due to excessive inflammation, and HAART does not eliminate HIV-related inflammation even if the patient adheres to treatment perfectly. Viral eradication, impossible at present, would solve this challenge.

Monoclonal antibodies are a popular area of research, especially in oncology and inflammation. A monoclonal antibody strain active against an extensive portion of the HIV viral diversity could prevent (as a vaccine) or control HIV replication. As a result, it could reduce the pill burden associated with current HAART standard of care.

Two Spanish scientists report the research findings of an experimental monoclonal antibody in the fourth quarter 2016 issue of AIDS Reviews. Monoclonal antibodies are of great interest in HIV because HIV-1 has evolved several strategies to evade humoral immunity. One of the virus's key strategies is protecting highly conserved and important structures from antibodies generated by the human immune system.

The monoclonal antibody 3BNC117 targets the CD4 binding site on the viral envelope of HIV-1. 3BNC117 has been shown to prevent HIV infection in animal models and suppress viremia in human subjects. It was more effective than HAART for post-exposure prophylaxis in animal models.

A phase 1 human study found 3BNC117 enhances humoral immunity to HIV-1, especially in viremic subjects. In all but 1 of the 15 subjects, 3BNC117 showed an increased neutralizing response against different autologous HIV strains.

Its actions were less pronounced in patients who had been treated with HAART previously. The study’s findings indicate that the agent's mechanism may reduce or eliminate host reservoir in combination with other strategies.

Broad-spectrum HIV-targeting monoclonal antibodies, such as 3BNC117, may be a key approach to HIV cure in the future. Further research on effective combinations for long-term control or eventual cure is ongoing.