In clinical trials, new antibody therapy controls HIV for months after treatment

With improvements in antiretroviral therapy, HIV is now a manageable condition. Yet even the best drugs do not completely eliminate the virus, which persists in the body, threatening to reach dangerous levels if the patient forgets or gives up treatment. To stay healthy, people infected with HIV must therefore follow strict drug treatments, which usually involve ingestion of pills each day for the rest of their lives.

New clinical trials conducted by researchers at Rockefeller University suggest that a new immunotherapy, a combination of two anti-HIV antibodies, is capable of suppressing HIV for months. Medications, called antibodies or neurotransmitters bees), have been shown to be both safe and more effective than any previously tested antibody treatment. The results were published in Nature and Medicine of nature.

The power of antibodies

Antiretroviral therapy, the gold standard for HIV treatment, works almost perfectly in clinical trials. But in the real world, things are more complicated. Some patients neglect to take their medications or lose access to health care. And inconsistency in treatment poses a risk not only to the infected person, but also to the general population: when the virus is not sufficiently controlled, the probability of transmission increases.

To protect both individuals and communities, researchers hope to develop drugs that are not based on a vigilant daily dosage. The results of the new studies, conducted by Michel C. Nussenzweig, Marina Caskey and their colleagues, suggest that such a medication could actually be on the horizon.

Nussenzweig, Professor Zanvil A. Cohn and Ralph M. Steinman, initially identified the antibodies, known as 3BNC117 and 10-1074, while studying people whose bodies successfully fight HIV without help of drugs. In these so-called "elite controllers", natural antibodies target proteins on the outside of the virus and recruit the immune system to fight infections.

The ultimate goal of BNAb therapy is to turn anyone taking the drug into an elite controller, effectively suppressing the virus through an improved immune response. These drugs have the added benefit of staying in the body longer than antiretroviral drugs and should therefore require less frequent administration.

Previous studies have shown that treatment with a single BNAb reduces virus levels in the blood, but these effects are short-lived. Over time, HIV mutates so that the antibody can no longer find and fight the virus.

Since 3BNC117 and 10-1074 attack HIV from two different perspectives, the researchers suspected that administration of the two drugs together could escape resistance, an approach that was tested in animals. After the success of these first experiments, Nussenzweig and Caskey, Associate Professor of Clinical Investigation, adapted the treatment to use in humans.

In their Phase 1b clinical trial, published in Natureparticipants discontinued antiretroviral drugs and subsequently received three infusions of both antiretroviral antibodies over a six-week period. The researchers report that, among nine subjects carrying viruses that are sensitive to both antibodies, this treatment has been used to suppress HIV on average for 21 weeks and more than 30 weeks in some patients. Unlike individuals receiving only one BNAb, patients receiving combination therapy did not develop resistance if their viruses were antibody-sensitive. In addition, participants had no major side effects, the most important reaction being mild fatigue in a small proportion of patients.

Participants in this first trial were not viremic, which meant that HIV was not actively circulating in their blood because antiretroviral drugs had brought the virus to very low or undetectable levels. The second study, published in Medicine of natureshowed that bNAbs were also effective in treating viremic patients; in this case, combined therapy reduced virus levels up to three months.

The future of NGOs

Caskey and Nussenzweig say that while combination therapy is very promising, bNAb therapy has its limitations. The HIV virus comes in many varieties, which do not all respond to a given antibody.

"These two antibodies are not going to work for everyone," says Caskey. "But if we start combining this therapy with other antibodies or with antiretroviral drugs, this could be effective in a larger number of people – and that's something we hope to examine in future studies." . "

Nussenzweig adds that, over time, treatment with bDNA could prompt the body to produce itself HIV antibodies. "Like some anti-cancer antibodies, these drugs could interact with the host's immune system to stimulate natural immunity," he says.

Further research could also extend the length of time these drugs are effective. Studies have shown that BNAb can control HIV for more than four months in some people – an incredibly long suppression period. Nevertheless, Nussenzweig suspects that this period could be further prolonged through the use of newly developed dsDNA variants.

"We expect these new variants to have half-lives three to four times longer," he says. "So we can be able to give the antibodies once or twice a year."

Researchers believe that BNAb have the potential to change not only the way we treat HIV, but also how we prevent it. Currently, people at risk of contracting the virus can take preventative antiretroviral drugs. But this also requires a daily dosage, and many people follow the diet imperfectly. Like long-acting contraceptives, long-acting anti-HIV drugs would allow patients to achieve the desired result without being perfect pilots.

"If future studies succeed in the same way, BBNA could really become a practical alternative to antiretroviral therapy," says Caskey, "a safe alternative that does not require a pill every day."

Explore more:
NIH launches study to test combination antibody treatment against HIV infection

More information:
Pilar Mendoza et al, Combined treatment with anti-HIV-1 antibodies, maintain viral suppression, Nature (2018). DOI: 10.1038 / s41586-018-0531-2