Breakthroughs Blog: HIV/AIDS

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.

Women are steadily reshaping the landscape of global health research. In 2022, they made up 41 percent of researchers worldwide, representing considerable progress toward closing the gender gap in science. Yet women remain underrepresented in many scientific fields and in senior roles, are published and cited less frequently than men, and file far fewer patent applications. Despite these systemic barriers, women researchers are having an outsized impact on global policy and progress. Research led by women is more likely to address topics aligned with the Sustainable Development Goals, and publications with women authors are more frequently cited in policy documents.  Expanding women’s participation and leadership in science is not just a matter of equity, it is essential to ensuring research priorities reflect women’s lived experiences. Although women spend more of their lives in poor health than men, only 1 percent of global health research and development funding targets female-specific conditions beyond cancer. Even as gaps persist, women scientists are already at the forefront of innovation, driving cutting-edge technologies that could transform the future of global health. Advancing promising HIV vaccine strategies Developing an HIV vaccine capable of preventing infection has long challenged researchers due to the virus’s extraordinary ability to mutate and evade the immune system. Still, many experts believe such a vaccine will be essential to ending the global pandemic.A Phase 1 trial, launched in August of last year, is evaluating an investigational HIV vaccine candidate designed to induce an immune response scientists believe could effectively target vulnerable parts of HIV-infected cells. Three distinguished female principal investigators—Dr. Tariro Makadzange of the Mutala Trust, Dr. Theodorah Rirhandzu Ndzhukule of the Desmond Tutu Health Foundation, and Dr. Limakatso Lebina of the Africa Health Research Institute—are overseeing the study across clinical trial sites in Harare, Zimbabwe; Cape Town, South Africa; and Durban, South Africa, respectively.  Another Phase 1 trial, launched just last month, is testing a different novel approach. Researchers are evaluating whether highly specialized vaccine immunogens, delivered in a specific sequence, can train the immune system to produce broadly neutralizing antibodies against HIV, widely considered one of the keys to achieving broad protection against the virus. The trial is led by Dr. Linda-Gail Bekker, CEO of the Desmond Tutu Health Foundation and a leading HIV clinician-scientist. These vaccines have the potential to transform the lives of women and girls, who bear a disproportionate burden of HIV and AIDS, particularly in sub-Saharan Africa. The leadership of these scientists underscores how women researchers are driving forward breakthroughs that address urgent global health needs. Trialing promising TB vaccine candidates New tuberculosis (TB) vaccine candidates also hold promise for reshaping global TB efforts, particularly as rising drug resistance makes the disease harder to fight. The only currently approved TB vaccine is more than 100 years old and is effective at preventing some forms of TB in infants but offers limited protection against pulmonary TB in adults.  One next-generation vaccine candidate, MTBVAC, was co-designed by Dr. Brigitte Gicquel of the Institut Pasteur, who is a pioneer in TB research. MTBVAC is the only live-attenuated candidate in the pipeline, meaning it contains a weakened form of the bacteria that causes TB, and aims to offer more effective, longer-lasting protection for newborns while also preventing TB disease in adolescents and adults, for whom no effective vaccine exists.In a Phase 1a/2b trial published last year, MTBVAC was found to be safe and capable of generating immune responses comparable to or stronger than the current TB vaccine. The study was led by Dr. Angelique Luabeya of the South African Tuberculosis Vaccine Initiative, who has considerable experience leading novel TB and COVID-19 vaccine trials. MTBVAC is now being evaluated in a Phase 2 trial in people living with HIV, co-chaired by the aforementioned Dr. Limakatso Lebina. Another leading vaccine candidate, M72/AS01E, is currently undergoing a large Phase 3 trial to determine whether it can protect adolescents and adults from pulmonary TB. Dr. Lee Fairlie of Wits RHI at the University of the Witwatersrand, an infectious disease expert with extensive experience leading major clinical studies, is serving as national principal investigator for the trial in South Africa. These vaccine candidates could dramatically alter the trajectory of the global TB epidemic, reflecting the critical contributions of women researchers in advancing solutions to one of the world’s oldest and deadliest infectious diseases. Driving forward antimalarial drugs for a long-excluded group Last fall, a global consortium launched the first-ever Phase 2 adaptive platform trial evaluating the efficacy and safety of antimalarial drugs during the first trimester of pregnancy. This landmark study addresses a long-standing gap in safe and effective evidence-based treatment options for pregnant women at risk of malaria. Pregnant women, particularly those in early pregnancy, have historically been excluded from clinical trials, leaving major unanswered questions about how best to treat malaria and other conditions in this high-risk group.  Among the study’s co-principal investigators are Dr. Myriam El Gaaloul from the Medicines for Malaria Venture, Dr. Stephanie Dellicour from the Liverpool School of Tropical Medicine, and Dr. Hellen Barsosio of the Centre for Global Health Research at the Kenya Medical Research Institute, who bring deep expertise in clinical trials, malaria, and maternal and newborn health. This trial has the potential to not only reshape care for pregnant women at risk of malaria but also set a powerful precedent for more inclusive research. It illustrates how greater gender diversity in research leadership can help ensure studies prioritize and better reflect the needs of the people they aim to serve. Across the global health innovation pipeline, women scientists are driving transformative progress. Accelerating gender diversity across research teams, investing in early-career women researchers, and strengthening pathways to leadership will advance gender equity while ensuring that scientific breakthroughs are more inclusive, accessible, and reflective of the needs of all people.