Combo Antibody Therapy Shows Potential in Maintaining Long-Term HIV Suppression

A combined regimen of 2 anti-HIV broadly neutralizing antibodies (bNAbs) showed efficacy in maintaining viral suppression in individuals with the virus for months after treatment, according to 2 recent studies.

The studies, published in Nature and Nature Medicine, evaluated the 2 bNAbs, known as 3BNC117 and 10-1074. Rockefeller University researchers initially discovered the antibodies while studying individuals whose bodies successfully fought HIV without the help of drugs.

Although individuals with HIV can manage the virus with antiretroviral therapy, it requires adherence to strict medication regimens that typically involves daily dosing. Because the antibodies remain in the body longer than antiretroviral drugs, the researchers hoped that the combination treatment could maintain long-term viral suppression with less frequent administration.

According to the researchers, previous studies have shown that treatment with a single bNAb reduces the levels of the virus in the blood, but only for a short period of time. The researchers attempted to administer both 3BNC117 and 10-1074 in an animal model to test whether the combination evaded resistance because the bNAbs attack the virus from different angles. Following positive results, the researchers then adapted the treatment for use in humans.

In the phase 1b clinical trial, participants stopped taking antiretroviral drugs and subsequently received 3 infusions of 3 mg kg^-1 of each antibody at 0, 3, and 6 weeks. In 9 individuals who carried viruses that were sensitive to both antibodies, the treatment suppressed HIV for between 15 and more than 30 weeks, with a median of 21 weeks.

Additionally, those receiving the combination therapy did not develop resistance if their viruses were sensitive to the antibodies, unlike those who received only 1 bNAb. In the second study, bNAbs were also shown to be effective in treating viremic patients and reduced viral levels for up to 3 months.

Overall, the researchers concluded that treatment with the combination of the 2 antibodies can help maintain long-term suppression in the absence of antiretroviral therapy in individuals with antibody-sensitive viral reservoirs. Although the results are promising, the researchers noted that bNAb treatments can have limitations.

“These 2 antibodies are not going to work for everyone,” study author Marina Caskey, MD, associate professor of clinical investigation, said in a press release about the findings. “But if we start to combine this therapy with other antibodies or with antiretroviral drugs, it could be effective in more people and that’s something we hope to look at in future studies.”

The researchers noted that long-acting HIV medication could be a game changer for individuals with the virus who have difficulty following a daily dosing regimen.

“If future studies are similarly successful, bNAbs could really become a practical alternative to ART,” Dr Caskey concluded. “An alternative that would be safe and wouldn’t require a pill every day.”

References

Mendoza P, Henning G, Nussenzweig MC. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature. 2018. https://www.nature.com/articles/s41586-018-0531-2

In clinical trials, new antibody therapy controls HIV for months after treatment [news release]. Rockefeller University’s website. https://www.rockefeller.edu/news/23829-clinical-trials-new-antibody-therapy-controls-hiv-months-treatment/. Accessed September 28, 2018.