Two teams are reporting results from experiments in which they infused powerful anti-HIV antibodies into monkeys infected with an HIV-like virus, rapidly reducing the amount of virus, or viral load, to undetectable levels, where it remained for extended periods. One study was led by government scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and the other was led by NIAID grantees at Beth Israel Deaconess Medical Center. Both teams worked with monkeys infected with simian human immunodeficiency virus, or SHIV, which can cause AIDS in monkeys. The researchers selected monoclonal antibodies that targeted two different sites on SHIV and gave the monkeys either one or two infusions of one or a combination of two or three of these antibodies. Then the scientists measured changes in the monkeys' viral load and their immune responses to the virus.
In the study led by NIAID grantees, the antibody infusions reduced SHIV viral load to an undetectable level in 16 of 18 monkeys within just 7 days and kept it there for a median of 56 days, when the infused antibodies were gone. While the two monkeys with the highest viral loads at the outset of the study never achieved undetectable viral loads, the three monkeys with the lowest viral loads at the outset maintained stable, undetectable viral loads long after the infused antibodies were gone. The antibody infusions appeared both to improve the monkeys' control of the virus and to reduce the presence of SHIV DNA in blood and tissues without generating SHIV resistance to the antibodies.
In the study led by NIAID scientists, infusion of a single antibody into 4 monkeys infected for 3 months quickly reduced SHIV viral load to undetectable levels for 4 to 7 days, but then virus reappeared and strains in two animals were antibody-resistant. Yet when two asymptomatic monkeys SHIV-infected for more than 3 years received an infusion of two antibodies, viral load fell to undetectable levels within 7 to 10 days and remained there for 18 to 36 days. A second infusion reduced viral load to undetectable levels for 4 to 28 days. When virus reappeared, strains in one monkey were antibody-resistant. Infusion of the same antibody pair into three monkeys SHIV-infected for more than 3 years and with AIDS symptoms provided modest or no benefit but did not generate resistance.
The studies' authors now propose testing antibody-based immunotherapy in HIV-infected people and exploring the potential role of antibody infusions in curing people of HIV.
DH Barouch et al. Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature DOI: 10.1038/nature12744 (2013).
M Shingai et al. Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viremia. Nature DOI: 10.1038/nature12746 (2013).
NIAID Director Anthony S. Fauci, M.D., and Distinguished NIH Senior Investigator Malcolm A. Martin, M.D., are available for comment.
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