Breakthroughs Blog: HIV/AIDS

A team of researchers from the United Kingdom, the United States, and South Africa is developing a vaccine for hantavirus, the virus behind a worrying outbreak on a cruise ship in the Atlantic Ocean. Hantavirus is typically spread by rodents, and transmission between humans is very rare. There is no specific treatment of vaccine for hantavirus, which, as seen in the current outbreak, can be deadly. The researchers are using an innovative method called insilication to make the vaccine thermally stable, aiming to reduce the high resource and economic costs of meeting the cold chain and storage requirements that are associated with many vaccines. Moderna’s mRNA-based seasonal flu vaccine outperformed conventional flu shots in a late-stage international trial of more than 40,000 adults aged 50 and older. The US Food and Drug Administration is currently reviewing the vaccine after rejecting the initial application and is expected to make a decision by August 5. If approved, the vaccine would be the first mRNA seasonal flu shut in the United States. mRNA vaccines can be produced much more quickly than conventional flu shots, which could enable public health authorities to wait longer before choosing which flu strains to target, giving them more time to gather up-to-date data about circulating strains before flu season begins. A research team has discovered a previously unknown mechanism by which HIV-1 can infect resting cells, challenging previous assumptions and raising new possibilities for the development of improved treatments. For HIV to infect immune cells, it must deliver its genetic material into the cell’s nucleus, which is surrounded by a protective structure—how the virus has broken through the barrier has long puzzled scientists. Another obstacle to an HIV cure has been the latent reservoir of resting immune cells that house dormant virus, which cannot be cleared by treatment. The researchers found that when the virus spreads between immune cells, it triggers a signal that unlocks this protective gateway around the nucleus, allowing the virus to enter. They also found that this process does not require the immune cell to be activated, meaning that the reservoir can be established and maintained while cells are resting, upending long-standing assumptions and unlocking new avenues toward the development of a treatment that can destroy the virus and target the latent reservoir. 

Last week, the Medicines for Malaria Venture (MMV) and GSK announced the world’s first deployment of a novel cure for Plasmodium vivax malaria, the predominant malaria species in Latin America. Pediatric tafenoquine, codeveloped by MMV and GSK, replaces a multiday regimen with a single-dose, child-friendly formulation, improving treatment completion and preventing relapse. P. vivax can remain dormant in the liver, so if patients don’t receive combination treatment for both the blood and liver stages of the disease, they could have multiple malaria relapses. Up until now, the lack of child-friendly tafenoquine formulation left younger kids at risk of the disease, which is associated with long-lasting cognitive impairment. The rollout is taking place among the Yanomami people, an Indigenous population living in the Yanomami Indigenous Territory in northern Brazil. Last Tuesday, Moderna announced the start of a late-stage study of its experimental mRNA vaccine candidate for bird flu, marking the first time a mRNA pandemic bird flu vaccine has reached late-stage trials. The trial is being supported by a $54 million investment by the Coalition for Epidemic Preparedness Innovations (CEPI) following last year’s cancellation by the US government of more than $700 million in contracts with Moderna supporting the late-stage development of the vaccine candidate. Moderna’s trial will evaluate the candidate, mRNA-1018, in 4,000 healthy adults in the United States and the United Kingdom. Under the agreement, Moderna also committed to, if the vaccine is approved and a flu pandemic is declared, setting aside 20 percent of its manufacturing capacity for supplying the vaccine to low- and middle-income countries at affordable prices. The US Food and Drug Administration recently approved Merck’s once-daily, oral combination treatment for HIV, offering patients another treatment option. The combination of doravirine and islatravir is being branded as Idvynso. In two large late-stage studies, the treatment combination demonstrated its ability to significantly suppress replication of HIV-1 in adults receiving another HIV treatment. While another late-stage study in adults living with HIV who had previously received treatment found that Idvynso was not inferior to Gilead’s HIV drug Biktarvy, the approval still provides another treatment option for patients. It is also currently being tested in multiple trials in combination with other antiretrovirals for potential daily and once-weekly HIV treatments. 

IAVI recently announced the start of a first-in-human clinical trial evaluating a combination injection of four broadly neutralizing antibodies, with the aim of eventually developing a tool to prevent HIV transmission in infants during the postnatal period. The combination shot includes four antibodies that target different HIV receptors, including IAVI’s broadly neutralizing antibody ePGT121v1-LS. The current trial is evaluating safety, dosing, pharmacokinetics, durability, and efficacy in 118 adult participants across the United States and Peru, and, if successful, could pave the way for future studies in infants. A research team has identified a bacterium strongly associated with noma, a potentially fatal infection for which the underlying cause is poorly understood. The researchers used metagenomic sequencing and machine learning algorithms to analyze saliva samples from children with acute noma. They identified a bacterial species that may be responsible for the disease, which was detected in the early stages of infection and does not carry known antibiotic resistance genes, suggesting that infection could be effectively treated with existing antibiotics if detected early enough. These findings also pave the way for the development of diagnostic tools that can detect noma early on, when treatment is most effective and before irreversible damage has been done. Last week, Butterfly Network shared that it received regulatory clearance from the US Food and Drug Administration for its artificial intelligence (AI)-powered ultrasound, offering a critical new tool to improve maternal care in low-resource settings with limited access to prenatal imaging. Compared to traditional ultrasounds that rely on expensive technology, the new device is more affordable and provides results in less than two minutes with fewer inputs. The tool has already been deployed in Malawi and Uganda, and this latest approval will enable its widespread rollout in the United States. 

A research team has identified a protein in the malaria parasite that could offer a promising new target for antimalarial drug development. The researchers found that the protein Aurora-related kinase 1, or ARK1, is essential for the survival and transmission of the malaria parasite. When the researchers turned it off in the lab, the parasite could no longer replicate or complete its development in either humans or mosquitoes, effectively stopping its ability to transmit disease. The ARK1 in malaria parasites is also very different from the version found in human cells, meaning drugs designed to target the protein could be effective without causing harm to humans.  A Phase 3 trial found that a novel single-tablet combination treatment regimen for HIV provided similar viral suppression compared to a multi-pill therapy in older adults, a significant step toward a simpler option for patients who cannot use currently available single-table regimens. The trial included older adults living with HIV who had sustained viral suppression and long treatment histories and remained on complex regimens because of prior drug resistance, intolerance, or other factors that made single‑tablet options unsuitable. The single-tablet regimen was not only similarly effective, but it was also associated with increased treatment satisfaction, as well as improvements in cholesterol and triglyceride levels. Last week, IAVI announcedthat a large Phase 2b trial of the tuberculosis (TB) vaccine candidate MTBVAC will expand to include a new cohort of 1,200 patients who have never been exposed to the Mycobacterium tuberculosis bacterium that causes TB disease. The additional cohort will enable researchers to gather robust safety and immunological data across patients with and without confirmed previous TB infection, increasing understanding of how the vaccine works across diverse populations. MTBVAC is a single-shot vaccine designed to be accessible in remote and low-resource settings; it’s also the only live-attenuated candidate derived from M. tuberculosis currently in trials.