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October 16, 2018
Antibody combination suppresses HIV
At a Glance
- In an early trial, a combination of two antibodies suppressed blood levels of HIV for months after treatment in some people.
- With further improvement and testing, long-acting antibody combinations may become an alternative to daily anti-HIV drugs.
More than 35 million people worldwide live with HIV, the virus that causes AIDS. Since the 1990s, combinations of drugs called antiretroviral therapy (ART) have been used to treat HIV. These drugs prevent the virus from multiplying in the body. ART can lower HIV to undetectable levels so that people can live longer, healthier lives and reduce their risk of infecting sexual partners.
However, ART is not a cure for AIDS. The drugs must be taken daily for the rest of a person’s life. Researchers are looking for alternatives to ART that can be taken less frequently and that have fewer side effects.
Broadly neutralizing antibodies (bNAbs) are now being tested in people with HIV. Antibodies are proteins produced by the human immune system to defend the body against bacteria, viruses, and other threats. They can also be made in the laboratory to attack specific microbes. Scientists have developed bNAbs that can bind to several different strains of HIV and prevent the virus from entering human cells.
Single bNAbs haven’t suppressed HIV levels in clinical trials as much as researchers had hoped. Instead, the virus quickly developed resistance to the treatments. A team of researchers led by Drs. Marina Caskey and Michel Nussenzweig from the Rockefeller University wanted to test whether a combination of two bNAbs could provide longer-lasting viral suppression.
The team enrolled volunteers in a small clinical trial to test the safety and viral suppression of two bNAbs called 3BNC117 and 10-1074 in combination. All participants were tested before the start of the trial to make sure the HIV strains they carried were sensitive to the antibodies. Eleven participants stopped ART beginning two days after infusion with an initial round of antibodies, and 7 others had not yet started taking ART. The participants who had not yet started ART had higher levels of HIV in their blood.
Participants received up to three infusions of the bNAbs over a 6-week period. The researchers then checked their viral load every 1 to 2 weeks. The trial was funded in part by NIH’s National Institute of Allergy and Infectious Diseases (NIAID). Results were published in two papers on September 26, 2018, in Nature and Nature Medicine.
Of the 11 participants who stopped ART, 9 had the virus suppressed by the bNAbs for at least 15 weeks after the last infusion. When the research team used a more sensitive test than was used initially, they discovered that the 2 participants who didn’t achieve viral suppression while on bNAb therapy actually had pre-existing resistance to the bNAbs.
Of the 7 participants who hadn't yet started ART, 4 had HIV strains that were sensitive to the bNAb combination. The participants had a significant drop in the amount of virus in their blood during bNAb therapy, and the virus remained suppressed for 3 months.
No serious side effects were seen. The researchers hope to test whether engineering the antibodies to last longer in the blood can improve viral suppression. They also hope to explore combinations with additional antibodies or other drugs.
“If future studies are similarly successful, bNAbs could really become a practical alternative to ART, an alternative that would be safe and wouldn’t require a pill every day,” Caskey says.
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References: Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Mendoza P, Gruell H, Nogueira L, Pai JA, Butler AL, Millard K, Lehmann C, Suárez I, Oliveira TY, Lorenzi JCC, Cohen YZ, Wyen C, Kümmerle T, Karagounis T, Lu CL, Handl L, Unson-O'Brien C, Patel R, Ruping C, Schlotz M, Witmer-Pack M, Shimeliovich I, Kremer G, Thomas E, Seaton KE, Horowitz J, West AP Jr, Bjorkman PJ, Tomaras GD, Gulick RM, Pfeifer N, Fätkenheuer G, Seaman MS, Klein F, Caskey M, Nussenzweig MC. Nature. 2018 Sep;561(7724):479-484. doi: 10.1038/s41586-018-0531-2. Epub 2018 Sep 26. PMID: 30258136.
Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals. Bar-On Y, Gruell H, Schoofs T, Pai JA, Nogueira L, Butler AL, Millard K, Lehmann C, Suárez I, Oliveira TY, Karagounis T, Cohen YZ, Wyen C, Scholten S, Handl L, Belblidia S, Dizon JP, Vehreschild JJ, Witmer-Pack M, Shimeliovich I, Jain K, Fiddike K, Seaton KE, Yates NL, Horowitz J, Gulick RM, Pfeifer N, Tomaras GD, Seaman MS, Fätkenheuer G, Caskey M, Klein F, Nussenzweig MC. Nat Med. 2018 Sep 26. doi: 10.1038/s41591-018-0186-4. [Epub ahead of print]. PMID: 30258217.
Funding: NIH’s National Institute of Allergy and Infectious Diseases (NIAID); Bill and Melinda Gates Foundation; Deutsche Forschungsgemeinschaft; European Research Council; German Center for Infection Research; Einstein-Rockefeller-CUNY Center for AIDS Research; BEAT-HIV Delaney Collaboratory; Rockefeller University; and Howard Hughes Medical Institute.