8 April 2015
The first human trials of a new type of ‘broad-spectrum’ neutralising antibody treatment for HIV infection have shown dramatic reductions in viral load.
At present, once established human immunodeficiency virus (HIV) infections can only be eradicated in very rare circumstances. Treatment therefore aims to suppress active viral replication and load in the bloodstream using a combination of anti-viral drugs, but the problem is the virus’ ability to rapidly develop resistance to any given drug, as well as to the natural immune responses against the virus. Any effective new treatment options are therefore valuable.
Immunotherapy uses engineered immune system activators called antibodies to help stimulate a patient’s own immune system to target and destroy diseased cells more effectively, for example in cancer treatment. Now an experimental immunotherapy developed by Rockefeller University researchers and reported in Nature uses antibodies with an unusually broad activity against HIV; co-first author Marina Caskey explained: “What’s special about these antibodies is that they have activity against over 80 percent of HIV strains and they are extremely potent”. The antibodies were derived from naturally occurring wide-acting anti-HIV antibodies produced in a minority of human HIV patients after many years.
In the trial HIV patients received a single dose of an antibody called 3BNC117; those who received the highest doses showed up to 250-fold reduction in viral load, and a variable degree of HIV suppression that in some cases lasted over 28 days. There were no serious side-effects from the treatment.
It is highly unlikely that immunotherapy, even of this new kind, would ever provide a silver-bullet type treatment for HIV infection, given the virus’ rapid mutation rate and resulting ability to evade both drug and immune targeting, but it could provide an important new component to combination drug therapies, perhaps reducing the frequency of treatment needed from daily to monthly or even longer.
The researchers plan to test other such antibodies, alone and in combination with the 3BNC117 antibody. Senior author Michel Nussenzweig said: “The goal is a once-a-year shot for prevention and a combination approach for cure”. The utility of such an approach would however depend very much on cost; immunotherapy is not cheap, and only very well resourced health systems, insurers or individuals would be likely to be able to fund it.
However, ultimately this work could also shed light on the prospects for the holy grail of an effective HIV vaccine, if one could be developed that induces a prompt and potent immune response of broad spectrum antibodies against HIV on exposure, eradicating the virus before it can establish a long-term infection.