Working with primates, researchers at the Oregon National Primate Research Center say they were able to prevent HIV transmission from mother to newborn with a single dose of antibody-based treatment.
The researchers also succeeded in preventing newborn infection after administering a short course of antiretroviral therapy (ART), rekindling hope for this potentially curative strategy after disappointing news in 2014 that the Mississippi baby had seroconverted after her short-lived remission following ART treatment.
These new, promising experiments were conducted in macaques infected with simian-human immunodeficiency virus (SHIV), considered a good proxy for humans living with HIV, and the results were published in Nature Communications.
While not definitive, the results suggest that a short course of treatment—either broadly neutralizing antibodies (bNAbs) or ART, or possibly a combination of the two—might be able to block HIV from taking up residence in a newborn’s body, assuming this treatment is administered within the first 30 to 48 hours after birth.
“Our thinking was that if we could find a cocktail of antibodies that could be delivered within a day or two after birth, it might be possible to clear the infection and not have to treat the baby anymore,” said study author Nancy Haigwood, Ph.D., a professor of pathobiology and immunology in the Oregon Health and Science University (OHSU) School of Medicine and director of the Oregon National Primate Research Center at OHSU.
“I’m very bullish about the development of antibodies,” she said, noting they are considered extremely safe “natural molecules,” making them ideal for infants.
Each year, about 150,000 babies are born with HIV around the world. Despite effective prevention strategies, about a quarter of pregnant women living with HIV do not have access to antiretroviral treatment that would not only improve their own health, but also help prevent vertical transmission.
“Researchers are very eager to develop alternatives to limit mother-to-child transmission, because it’s still an important problem worldwide and we really want to find a way to protect those children,” said Haigwood.
Monica Gandhi, M.D., M.P.H., with the University of California, San Francisco, who was not involved in the study, said, “It is incredibly exciting to study bNAbs in this setting.”
However, she noted that because antibodies, or bNAbs, are a type of medicine that needs to be refrigerated, they may not be a practical option where they are really needed: in sub-Saharan Africa, where a majority of vertical transmission cases take place.
“As opposed to an oral therapy, these are much more expensive,” she added. “I think they [should] be tried and tested in humans, but … they should not be tested alone. I think this study gives us a hint that they should be studied with ART.”
The experiment conducted in macaques had four different arms, with six animals included in each arm. The first was a control arm, meaning that infants were exposed to SHIV and were not treated.
The second arm included a single cocktail of antibodies given to infants 30 hours after being exposed to SHIV. The cocktail was comprised of a single subcutaneous dose containing the antibodies PGT121 and VRC07-523LS at 40 mg/kg (20 mg/kg each bNAb). These infant macaques showed no evidence of virus in their tissues, making this treatment “highly effective,” according to the study.
The third arm included a group of infants treated with smaller, repeating doses of the same antibody cocktail starting 48 hours after SHIV exposure. This strategy was not quite as effective, with only about half of them achieving durable control of virus in their blood.
The fourth and final arm of the study was to test a short-term course of ART, starting two days after exposure and continuing for 21 days. The ART cocktail included emtricitabine (FTC, 40 mg/kg/day), tenofovir disoproxil fumarate (TDF, 5.1 mg/kg/day), and dolutegravir (DTG, 2.5 mg/kg/day). Similar to the second arm of the study, the infants in the ART group saw no viral rebound after ART was stopped, nor did they have detectable virus in their tissues.
“We were a little surprised by that, but very happy,” said Haigwood, referring to the fact that ART saw equal, if not superior, results to the experimental antibody cocktail.
“When I first looked at the [paper], I thought that it was going to be the bNAbs that are going to win,” said Gandhi. “It was intriguing that the ARVs won.”
The authors hypothesized that the reason ART performed so well is that these medicines quickly penetrate tissue, sometimes within hours. Broadly neutralizing antibodies, in contrast, permeate tissues slowly.
Ultimately, Gandhi said these results suggest that ART should be co-administered with antibodies for maximum protection.
“These experiments were designed to understand how to put those two together,” said Haigwood. “We know the combination testing needs to take place in that 48- to 72-hour time window. The combination is going to be a lot more powerful, and that’s probably what will be tested in the real world.”
Ultimately, she said the goal is to find a treatment that can help extend the window of opportunity in which it might be possible to prevent HIV infection in newborn infants.
“I’ve been focused on mother-to-child transmission, in part, because I’m a mother and am interested in protecting children,” she said. The data, she said, “shows that these antibodies are very promising.”