New Treatment Signals Hope for Long-Term HIV Suppression
What if you could receive a one-time HIV treatment that suppressed your viral load to undetectable for more than a month at a time?
That’s the idea behind a broadly neutralizing antibody therapy now being tested. Researchers at the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases published study results from a small phase 1 clinical trials of a broadly neutralizing antibody—VRC01—in the journal Science Translational Medicine. Of eight people in the study who were not on antiretroviral therapy (ART) and had detectable viral loads, a single antibody infusion reduced plasma (blood) viral loads 12- to 59-fold in six people. Two of these people maintained undetectable viral loads (less than 20 copies/mL) for more than 20 days after the single infusion.
“What we saw here was a 1.1 to 1.8 log decrease [in viral load] which is similar to what you’d see with any other single agent antiretroviral. That’s talking, 90% to 98% inhibition of virus replication,” said Richard Koup, MD, deputy director of the NIAID Vaccine Research Center and chief of the Vaccine Research Center’s Immunology Laboratory.
Koup and Julie Ledgerwood, DO, chief of the Vaccine Research Center’s Clinical Trials Program, said they don’t expect VRC01 could be used on its own for HIV treatment since they saw some evidence of resistant HIV strains developing with the monotherapy. Rather, they said VRC01 has potential to be used along with another antibody therapy or a drug for longer-term HIV suppression.
“The overall goal would be to combine it [VRC01] with other long-acting agents such that you would have a regimen of say, every other month or every third month, injections or oral medications or a combination thereof—which would simplify antiretroviral therapy.”
Broadly neutralizing antibodies prevent HIV from entering host (human) cells by attaching to a protein on the surface of the virus particle. Once antibodies bind to HIV, it’s thought that they also work to mark the virus for destruction by the body’s own natural defenses that are part of the immune system. (Read more about broadly neutralizing antibodies here.)
Lynch and colleagues also tested the effect of two antibody infusion doses (given 28 days apart) on six people taking ART with suppressed viral loads to see if the infusion might eliminate HIV “hidden” in viral reservoir CD4 cells, but they did not find any effect. Eliminating viral reservoir cells is a key part of any HIV cure.
Ledgerwood explained that the study examined the effect of VRC01 in a “fairly cursory way” in only a few participants, so it’s still possible that VRC01 may have an effect on eliminating the viral reservoir.
“The hope is that these monoclonal antibodies will indeed have an impact on the latent reservoir. The latent reservoir is a very stable, long-lived reservoir, and so we don’t expect that if we do see an effect on the reservoir that we’d see if very quickly. It would probably require a more long-term therapy before we’d be able to measure any effect,” said Koup.
Although the study is limited by a small sample size, the experiment provides a “proof of concept” that demonstrates VRC01 can suppress HIV replication and holds implications for both HIV prevention and cure.
Koup and Ledgerwood said that studies are ongoing to determine if VRC01 can be used in combination with other long-acting antiretrovirals or other monoclonal antibodies for treatment and if it can be used in HIV prevention strategies as well.
Read about another broadly neutralizing antibody, 3BNC117, that has showed promise in clinical trials, and find out why it’s been so difficult for scientists to create an HIV vaccine in this Q&A between Dr. Joanna Eveland and Dr. Aliza Norwood.
Lynch, R. M. and others. Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection. Science Translational Medicine. December, 2015.