Antibody Combination Shown to Suppress HIV

T-cell infected by HIV (NIAID, Flickr)

27 September 2018. Results from a small-scale clinical trial show a combination of antibodies can suppress the HIV virus for many weeks after stopping antiretroviral therapy. Findings from the trial led by researchers at Rockefeller University in New York appear in yesterday’s issue of the journal Nature (paid subscription required).

For people with the human immunodeficiency virus or HIV are treated with antiretroviral therapy, when the condition is diagnosed early and before acquired immunodeficiency syndrome or AIDS develops. HIV destroys a type of T-cell in the immune system known as CD4 that fight infections, thus people with HIV face a higher risk of infection and some cancers, as well as AIDS. Antiretroviral therapy, usually a combination of drugs, stops the virus from replicating, which reduces the viral load in an individual, and contributes to the reduced death toll from HIV infections since the 1990s. But the virus remains in the body and requires daily treatments like antiretrovirals to manage the condition.

The Rockefeller University team led by immunologists Michel Nussenzweig and Marina Caskey identified 2 antibodies known as 3BNC117 and 10-1074 that suppress HIV, but work for a longer time than antiretrovirals. They work by targeting characteristic proteins on the envelope of the virus, and as antibodies invoke the immune system to fight infection. These broadly neutralizing antibodies, also remain in the body longer than antiretrovirals and potentially could provide a longer-lasting treatment. However, HIV viruses can mutate and become resistant, when the antibodies are taken singly.

Nussenzweig, Caskey and colleagues hypothesize that the 2 antibodies, given together, could overcome the resistance developed by HIV, supported by results of preclinical tests with monkeys. The clinical trial is a pilot test of this combination antibody therapy among individuals with HIV, who were taking antiretrovirals. Some 11 participants received 3 infusions of the antibodies after stopping their antiretroviral treatments. The 3 infusions were given at the trial’s beginning, then after 3 and 6 weeks. Other participants in the trial, not reported in the paper, received doses of the individual antibodies or a placebo.

The study team looked primarily for adverse effects from the treatments, as well as decline in HIV levels in blood plasma, percentage of people who meet criteria for restarting antiretroviral therapy, and amount of time needed to reach the point where antiretroviral therapy is required. The findings show among the 11 participants completing the trial the treatments were generally well tolerated. The results also show 9 of the participants’ HIV viral loads remained suppressed between 15 to 30 weeks, with a median of 21 weeks, and none of the participants showed evidence of mutated viruses that developed a resistance to either of the antibodies. The other 2 trial participants had residual HIV virus that developed resistance to the antibodies, requiring a return to antiretroviral therapy after 12 weeks.

Participants in this trial were already taking antiretroviral treatments, thus had very low levels of HIV in their blood streams. A separate paper in the journal Nature Medicine reports these broadly neutralizing antibodies also reduced viral levels in people with more HIV in their blood streams, for up to 3 months.

The authors note that broadly neutralizing antibodies will not likely work in all cases of HIV, since the virus can take many forms. “These two antibodies are not going to work for everyone,” says Caskey in a Rockefeller University statement. “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.”

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• Gene Editing Could Lead to an HIV Cure
• Messenger RNA Engineered to Produce Antibodies

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