Hannah Sachs-Wetstone

At the recent Union World Conference on Lung Health, TB Alliance presented the results of a Phase 2 clinical trial showing that the novel antibiotic candidate sorfequiline has the potential to improve tuberculosis (TB) treatment when combined with pretomanid and linezolid in people with drug-sensitive TB. The regimen was more effective than the current standard of care, and sorfequiline also demonstrated greater activity than bedaquiline, a key component of the BPaL regimen, a previous breakthrough that drastically reduced treatment time for most drug-resistant TB. This new treatment could shorten TB therapy even further. TB Alliance is working with partners ahead of the launch of a Phase 3 trial next year. Researchers at the University of California San Diego and partners have developed a new method to combat antibiotic-resistant bacteria, which could pave the way for developing alternatives to traditional antibiotics for treating a wide range of deadly infections, as the global threat of antimicrobial resistance continues to grow. The researchers used bacteriophages (or phages), which are viruses that infect and kill bacteria. Phages have been used to treat bacterial infections for more than 100 years but are usually limited in the bacterial strains they can successfully target. Researchers overcame this by allowing the pages to evolve alongside bacteria in a controlled laboratory setting for 30 days, enabling the phages to adapt their bacterial defenses, becoming more effective at killing a wide variety of bacterial strains, including drug-resistant ones, and better at suppressing bacterial growth for extended periods. Researchers at Indiana University have developed a molecular test that can simultaneously detect three dangerous fungi much faster than traditional methods, helping patients receive accurate, timely treatment against this growing global challenge. The test works by targeting genetic regions unique to each fungus, and it was much faster and more accurate than standard methods, a key advance as fungal infections are often mistaken for other respiratory illnesses. While the test still needs to be clinically validated in further studies, the research team believe it could eventually fill a major gap in fungal diagnostics. 

It’s been a difficult year for people worldwide who live with, are at risk of, or research HIV. Funding reductions and shifting priorities among key donors have disrupted or halted critical research and health services. Around the world, major international donors have reduced their funding for global HIV programming, leading to stoppages and cutbacks of lifesaving care. In the United States, new policies and grant terminations at the Department of Health and Human Services have significantly disrupted HIV research. The integration of the US Agency for International Development into the Department of State and resulting award terminations also interrupted HIV research and service delivery globally.These reductions risk undermining hard-won global progress and could lead to a resurgence in cases. Already, we’re seeing declines in HIV testing and treatment initiation this year. This is especially disheartening given exciting progress in recent years: at the end of 2024, new HIV infections were down 40 percent and AIDS-related deaths down 50 percent since 2010. The last few years have also brought exciting research advances, building momentum toward breakthroughs that could change the course of the global pandemic.With science yielding fruit and new donor countries and private funders stepping up, there is still hope that through renewed partnership and investment, we can regain momentum toward ending HIV/AIDS as a global public health threat. Here are some of the year’s most exciting advances in HIV research and innovation this year that inspire optimism amid significant challenges.A breakthrough in HIV prevention and accessIn June 2025, the US Food and Drug Administration approved lenacapavir as the first twice-yearly injectable drug for HIV prevention, marking a major milestone in the fight against the virus, While the drug, developed by Gilead using evidence from NIH-funded research, was previously approved for treating multidrug-resistant HIV, the new indication offers a discrete, twice-annual alternative to daily pills or bi-monthly injections, making prevention more accessible and easier to maintain. The approval followed highly successful clinical trials, which were notable not only for how effective the drug was across key populations, but also for their inclusion of historically underserved populations.Following the FDA’s decision, Gilead and the Global Fund to Fight AIDS, Tuberculosis and Malaria announced an access agreement that will see Gilead supply doses, at no profit, for up to two million people over three years. The Gates Foundation and Indian manufacturer Hetero Labs are also partnering to manufacture generic lenacapavir at an affordable price. The World Health Organization swiftly recommended the drug’s use, and South Africa’s regulatory authority approved it at record speed, the first such approval in Africa. It’s exciting to see partners work together to help ensure this breakthrough can be accessible in the communities where it is most needed quickly and affordably, a sharp divergence from past HIV product rollouts that saw years-long delays before people in low- and middle-income countries received access to new tools. Earlier this year, Gilead also published data suggesting a once-yearly version of the drug may be possible, with Phase 3 trials to begin later this year.Lenacapavir is not the only exciting advance in long-acting HIV prevention we saw in 2025. Merck’s investigational once-monthly oral prevention pill was found to be well tolerated in adults in a Phase 2 trial and is now undergoing Phase 3 trials in sub-Saharan Africa. Meanwhile, a single gene therapy injection given at birth showed promise in protecting primates from infection for at least three years in preclinical research. If this solution advances, it could be a gamechanger for preventing mother-to-child HIV transmission.Broadly neutralizing antibodies for long-term HIV control and cureBroadly neutralizing antibodies (bnAbs), which are made naturally by some individuals and target parts of the HIV virus that are less prone to mutation, are also showing promise in HIV treatment, prevention, and cure strategies. Studies have shown that bnAbs can effectively neutralize a broad range of HIV strains and bnAb combinations can maintain viral suppression in the absence of antiretroviral therapy, but challenges remain around their cost, global scalability, and the potential for viral resistance.Researchers are testing combination approaches with other drugs to potentially enhance the efficacy of bnAbs in controlling HIV. Study results presented earlier this year found that more than half of study participants living with HIV who received a pair of bnAbs plus the drug N-803 experienced delayed viral rebound or maintained a low or suppressed viral load during interruption from antiretroviral treatment. N-803, which is approved as a treatment for bladder cancer, appears to help reactivate and eliminate dormant HIV virus.Gilead also shared promising results from a Phase 2 trial earlier this year combining lenacapavir with two bnAbs as treatment for HIV. This regimen is the most advanced bnAbs-based treatment to date, with Phase 3 trials expected to start soon.Beyond treatment, many leading HIV scientists believe that a vaccine that elicits the production of bnAbs could be key to targeting the tricky, mutating virus. IAVI and partners developed immunogens, a type of antigen that can trigger an immune response, for use in a vaccine strategy to induce bnAb production, which demonstrated success in several Phase 1 clinical trials. A new study looking at data from two of the trials shows that this targeted vaccine strategy can successfully activate early immune responses relevant to HIV, an important step toward an HIV vaccine. The candidates use an mRNA vaccine platform, enabling faster production and clinical testing.While bnAbs have the potential to transform HIV prevention and treatment, further research is needed to overcome cost and delivery barriers to ensure that future innovations can be rapidly scaled up and distributed to the communities who can benefit most from them.While global HIV efforts have faced setbacks this year, we’ve also seen the extraordinary progress that’s possible when partners unite around innovation. New tools and approaches are emerging that could change the course of the global HIV/AIDS pandemic, preventing millions of new infections and deaths every year. But their impact depends on what happens next. To realize their full potential, countries, donors, and partners must come together and recommit to fund research, prioritize equitable access, and accelerate the scale-up of new tools. The future of the HIV/AIDS response hinges on how we meet this moment.

A Phase 1 randomized controlled trial found that a single dose of the ChAdox1 Rift Valley fever (RVF) vaccine was safe, tolerable, and elicited a strong immune response in 30 adults in Uganda, where RVF—a neglected, mosquito-borne disease that is considered a significant public health threat and a priority for vaccine development—is endemic. The trial was led by researchers at the Uganda Research Institute and the London School of Hygiene and Tropical Medicine Research Unit in Uganda and provides the first evidence supporting the vaccine from a trial in an endemic setting. While the vaccine could potentially be transformative for RVF prevention, further research is needed that follows participants for a longer period and includes a larger group of participants, including children, pregnant women, and immunocompromised people. Last week at the American Society of Tropical Medicine and Hygiene annual meeting, Medicines for Malaria Venture and Novartis shared the results of a Phase 3 study testing a new malaria treatment, known as GanLum, finding that the treatment was highly effective at treating malaria, including drug-resistant cases, and could also block disease transmission. GanLum was found to be 99.2 percent effective in curing patients, more effective than standard artemisinin-based combination therapies, the gold-standard malaria treatment introduced more than 20 years ago, whose use has been undermined since the emergence of partial resistance. The developers say that, pending regulatory approval, the new treatment could be rolled out within the next few years. South African pharmaceutical company Biovac is launching trials of a cholera vaccine, which, if it proves successful, could become the first vaccine developed from start to finish on the African continent. Africa faces the brunt of the global cholera burden but is almost entirely reliant on vaccines made internationally, which has become increasingly challenging in recent years as cases have risen sharply around the world and vaccine stocks have diminished. The African Union has committed to increasing the proportion of routine vaccines used in Africa that are manufactured on the continent from just 1 percent now to 60 percent over the next 15 years, an effort triggered by the access challenges African countries faced during the COVID-19 pandemic. 

The World Health Organization's (WHO's) TB Vaccine Accelerator Council recently published a new report calling for action to ensure equitable access to future tuberculosis (TB) vaccines currently in the pipeline. While the only licensed vaccine for TB is 100 years old and has limited effectiveness in adolescents and adults, as of September, there are 16 candidate vaccines in clinical development, six of which are in Phase 3 trials. WHO estimates that a vaccine for adolescents and adults that is at least 50 percent effective could avert up to 76 million TB cases and 8.5 million deaths over 25 years. However, as the report claims, global demand could far exceed supply in the initial years after a vaccine is approved because there is no designated funding for such a rollout in low- and middle-income countries most affected by TB, which are already facing significant funding shortfalls. In anticipation of these potential bottlenecks and barriers to access, the report identifies six solutions to encourage countries with a high burden of TB, manufacturers, and other funders and stakeholders to start preparing now for the rollout to ensure future vaccines can reach people who need them faster. In a Phase 1 randomized controlled trial, an experimental intranasal vaccine against multiple H5N1 avian flu strains generated a broad immune response, demonstrating the potential of such a vaccine to play a major role in preparing for outbreaks of emerging viruses with evolving strains, as H5N1 continues its worrying spread. The University of Maryland research team tested the vaccine against a placebo in 40 adults between 18 and 45, finding that the vaccine was safe, well-tolerated, and stimulated immunity at various doses. One group received a vaccine dose combined with an adjuvant, an ingredient used to trigger a stronger immune response, and their immune systems were better able to neutralize infected cells for longer, suggesting that the use of an adjuvant could be a promising approach that might allow for lower doses, which could stretch limited vaccine supplies in the event of an outbreak. Last week, IAVI published new findings from the first-in-human Phase 1 clinical trial of its Lassa virus vaccine candidate, which show that one dose of the vaccine triggers robust and long-lasting immunity and is safe. There are no vaccines or treatments currently licensed against the dangerous illness, which causes thousands of deaths in endemic West Africa and has been designated as a priority pathogen with pandemic potential. The trial enrolled 114 volunteers in Liberia and the United States. The candidate, now undergoing a Phase 2a trial in West Africa, is currently the most advanced Lassa fever vaccine candidate in the pipeline and uses the same platform as Merck’s single-dose Ebolavirus vaccine, which is approved in more than a dozen countries. 

A team of chemists from the University of Warwick and Monash University has identified a promising, potent new antibiotic that seems to be much more effective than existing drugs against deadly superbugs like MRSA and shows no signs of resistance so far, encouraging news as the global threat of antimicrobial resistance continues to grow and the pipeline of new antibiotics continues to fall short. The molecule had been overlooked for decades as an intermediate chemical in the natural process to produce another known antibiotic, methylenomycin A, which was discovered 50 years ago, and despite having been synthesized multiple times, the synthetic intermediates have seemingly not been tested before for antimicrobial activity. The new antibiotic is much more potent than methylenomycin A itself—100 times more active against a range of serious bacteria. It could not only be a powerful new tool against rising drug resistance, but this work could also pave the way for new approaches to antibiotic discovery. A team of researchers has developed an antivenom using antibodies from a llama and an alpaca that can neutralize venom from some of the world’s most venomous snakes. Snakebites are a neglected public health issue that kill around 20,000 people in sub-Saharan Africa yearly. Current antivenom treatments are usually specific to a single snake species, and it can be difficult to identify which of the many types of venomous snakes is behind a bite, making timely, effective treatment difficult to achieve. The researchers exposed an alpaca and a llama to venoms from 18 of the most dangerous snake species in sub-Saharan Africa, isolated the antibodies that the animals produced against the venom, and then combined some of those antibodies in a single cocktail. In mice, the treatment protected against toxins from 17 African snake species and reduced skin damage. Many scientists previously thought that developing a broad-spectrum antivenom would require too many antibodies to be practical because some venom can contain up to 100 toxins, but this study shows that a combination of just a handful of antibodies can neutralize the venom of many snake species, paving the way for the development of similar broad-spectrum antivenoms for other areas where snakebites are a common public health challenge. Last week, Cepheid announced that its Xpert MTB/XDR test for tuberculosis (TB) drug resistance has been prequalified by the World Health Organization (WHO), enabling procurement through international agencies and greater access in areas with a high TB burden. The test is designed to detect resistance to multiple first- and second-line TB drugs from patient samples. It also delivers results quickly, within 90 minutes, allowing health care providers to make quicker, more reliable treatment decisions and have a better understanding of drug resistance, especially in regions with a high TB burden where timing and accuracy are critically important. 

A systematic review and meta-analysis of studies looking at the effectiveness of typhoid conjugate vaccines found that they are highly effective in preventing typhoid fever in countries where the infection is endemic, adding to the collection of real-world evidence supporting their use. Despite the high burden of typhoid fever—an infection caused by Salmonella enterica serovar Typhi—in Africa and Asia, only ten countries to date have added the vaccines to their national immunization programs. There are three vaccines for preventing typhoid fever that are currently recommended and licensed by the World Health Organization. Last week, California-based True Diagnostics announced that it had received an award of upward of $11 million from the Biomedical Advanced Research and Development Authority (BARDA) to support the development of a blood-based rapid antigen test for Ebola and Marburg viruses. The test, if it proves effective, could help boost testing capacity and national preparedness for outbreaks of pathogens with pandemic potential like Ebola and Marburg viruses, which have caused worrying outbreaks in Africa in recent years. Specifically, the funding will support the further development, validation testing, and regulatory submissions of its VeriClear EbV MARV Rapid Antigen Test to detect and differentiate Ebola and Marburg viruses in fingerstick blood samples.   A research team presented new data at the 2025 European Society for Medical Oncology Congress in Berlin, Germany last week, showing that cancer patients who received COVID-19 mRNA vaccines within 100 days of starting immunotherapy drugs survived more often than non-vaccinated patients. These findings suggest that mRNA vaccines could help improve outcomes for cancer patients being treated with immunotherapies and even patients with treatment-resistant cancers. While these results are preliminary and need to be confirmed in an upcoming Phase 3 randomized clinical trial, scientists say they could revolutionize cancer care, perhaps even paving the way for a universal, off-the-shelf vaccine for cancer.