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Combinations of super antibodies may keep HIV at bay

Although effective HIV treatment (ART) exists, researchers are studying other potential treatments such as a group of antibodies that are highly efficient at binding to and neutralizing HIV. Scientists call these super antibodies “broadly neutralizing antibodies” (bNAbs). After these antibodies bind to HIV and HIV-infected cells, they then engage the immune system to help destroy HIV and infected cells. While anti-HIV pills have to be taken every day, it is possible that bNAbs, which are given by intravenous infusion, are an approach to HIV treatment that, if found effective, could be given less frequently, perhaps every three weeks or even with longer intervals.

Researchers have tested bNAbs as single agents (that is, giving one type of antibody at a time), but HIV can quickly develop the ability to resist one antibody when used in this way. Just as effective HIV treatment requires a combination of drugs, it is very likely that effective antibody therapy will require combinations of bNAbs.

Researchers in the U.S. have tested a combination of two antibodies in 15 participants who had been taking ART for many years and who had very low viral loads. Participants received the infusions of antibodies at weeks 0, 3 and 6 of the study; ART was discontinued two days after the first infusion. Nine of the 15 participants were able to maintain an undetectable viral load while off ART for an average of four months after the final infusion of antibodies. None of these nine developed HIV that was resistant to the antibodies. The results from this pilot study are exciting and raise many issues that need to be taken into account for future studies of bNAbs.

Study details

Researchers recruited participants who had been taking ART for at least 24 months and who had viral loads in their blood less than 50 copies/mL for at least 18 months. Furthermore, in assessments done prior to entry in the study participants were expected to have a viral load of less than 20 copies/mL using a more sensitive viral load assay and their CD4+ counts were expected to be greater than 500 cells/mm3.

All participants had blood drawn for an assessment that checked if their HIV was sensitive or susceptible to the antibodies used in the study.

Participants received three intravenous infusions of antibodies given at a dose of 30 mg per kilogram of body weight at weeks 0, 3 and 6 of the study.

Participants underwent frequent assessments during the study, with blood being drawn every one to two weeks. If their viral load was found to be more than 200 copies/mL, then they would restart ART.

The average profile of participants upon entering the study was as follows:

  • 14 men, 1 woman
  • age – 40 years
  • major ethno-racial groups: white – 40%; black – 27%; Hispanic – 27%
  • length of time since HIV diagnosis – 6 years
  • CD4+ count – 730 cells/mm3
  • viral load – less than 20 copies/mL

Note that only 11 out of the 15 participants had HIV that was sensitive or susceptible to the antibodies used in the study. These 11 participants became the focus of research.

The antibodies used had the following code names:

  • 3BNC117
  • 10-1074

Results

Nine out of the 11 participants were able to maintain an undetectable viral load while off ART for an average of four months after the final infusion of antibodies.

The antibodies had no significant impact on the reservoir of HIV-infected cells in the body.

Bear in mind

The present study is very encouraging. It shows that a combination of two antibodies has the potential to keep HIV suppressed in certain people who have interrupted ART—those who have low pre-study viral loads (less than 20 copies/mL) and who have HIV that is sensitive to the antibodies.

Many exciting scientific questions arising from the present study need to be explored in future clinical trials:

  • What is the ideal number of bNAbs to use: Is it two, three or four antibodies?
  • More than 10 bNAbs have been discovered. Which ones should be used in studies?
  • How often should antibody infusions be given and how much?
  • Should bNAbs be used with other drugs that can enhance the functioning of the immune system, such as vesatolimod (GS-9620; discussed later in this issue of TreatmentUpdate) and a class of drugs called checkpoint inhibitors (currently used to treat some cancers)?

It will take years to get answers to these questions; so much research lies ahead.

—Sean R. Hosein

REFERENCES:

  1. Mendoza P, Gruell H, Nogueira L, et al. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature. 2018 Sep;561(7724):479-484.
  2. Borducchi EN, Liu J, Nkolola JP, et al. Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys. Nature. Nov;563(7731):360-364.
  3. Sok D, Burton DR. Recent progress in broadly neutralizing antibodies to HIV. Nature Immunology. 2018 Nov;19(11):1179-1188.