New antibody suppresses spread of HIV-1 in infected individuals

Shalini Saxena

Scanning electron micrograph of HIV. Virions are the green spheres on the surface of blood cells.

Getty | BSIP

Since its discovery and rapid spread in the 1980s, scientists and physicians have desperately tried to understand the HIV virus and develop effective treatments. Unfortunately, HIV is a tricky virus that evades typical immune responses.

During a successful immune system response to a foreign body, white blood cells produce antibodies that target the invader. These antibodies then flag the foreign body for destruction by other immune cells. For the most part, HIV evades these immune defenses, but rare individuals develop antibodies that effectively block multiple strains of the virus. Researchers are now showing that these antibodies can also act as treatments in other HIV patients.

HIV has several ways of avoiding the immune response. Unlike most viruses, HIV specifically attacks a type of white blood cell that is critical to our immune system. During replication, the HIV virus also picks up many new mutations, which often change it enough that any antibodies produced earlier during the infection no longer recognize it. There are very few parts of the virus where changes due to mutations would cause it to be unable to enter cells; even fewer antibodies have been identified that bind to these locations.

These rare antibodies can also keep the virus from infecting new cells, which could make them an effective therapy. In animal studies, injection of low concentrations of these antibodies could act as a vaccine and provide protection against infection. Injections can even control active infections when combined with additional antibodies that target other molecules on the the HIV surface. These preclinical findings led to humans phase 1 clinical trials to evaluate a specific antibody that targets HIV. This study revealed that a single intravenous injection of the antibody typically reduced the presence of HIV in the blood of patients who have viruses that were sensitive to the antibody.

These promising results come from an international team of scientists and physicians that has investigated the safety and clinical efficacy of one of the most potent anti-HIV-1 neutralizing antibodies. Known as monoclonal antibody 10-1074, it targets a specific HIV protein called the v3 glycan. This target is different from the one recognized by the antibodies used in earlier studies.

After performing test-tube studies demonstrating the efficacy of the antibody, the researchers evaluated its safety in humans in a small trial. The study included two groups of participants: 14 uninfected individuals and 19 individuals with an HIV-1 infection. The participants received a single intravenous infusion of the antibody at one of following doses: 3, 10, or 30 mg/kg.

The researchers then tracked the clearance of the antibody by following its levels in the participants’ serum. Consistent with previous studies, HIV-1 infected individuals exhibited faster elimination of the antibody, with a half-life of 12.8 d compared to 24.0 d for uninfected participants. Despite the fast clearance, however, the antibody appeared to be effective.

Three HIV-1 infected individuals on the trial were undergoing a specific type of treatment (antiretroviral therapy) and exhibited no changes in the level of HIV in their system due to the antibody infusion. Thirteen HIV-1 infected participants with the highest levels of virus received the highest dose of the antibody (30 mg/kg). Eleven of them showed a rapid decline in HIV levels. Tracking the infection through the first weeks after treatment revealed the evolution of multiple viruses that were no longer affected by the antibody. However, these new variants generally remained sensitive to antibodies targeting other virus surface molecules.

Overall, this investigation demonstrates the safety of infusions of antibody 10-1074 in humans. While the virus quickly evolved resistance to these treatments, the resulting viruses remained susceptible to other antibodies. Thus, researchers may be able to build a cocktail of antibodies that effectively block active HIV infections.

Nature Medicine, 2016. DOI: 10.1038/nm.4268 (About DOIs).