An update to From SIV to HIV: Emory NPRC Research Paves Way for Potential Cure 

In 2025, researchers at the Emory Vaccine Center and the Emory Primate Center led by Dr. Paiardini have made two significant advancements in the pursuit of a cure for HIV. Using nonhuman primates and the simian immunodeficiency virus (SIV), the best model for HIV infection in humans, the team identified a treatment that can reduce the viral reservoir – infected cells that are not eliminated by the immune system – a key obstacle for curing HIV.  

Recent studies strongly suggest that a protein called Bcl-2 favors the survival of cells infected with HIV. Bcl-2 also favors the survival of cancer cells. There is a clinically approved medication for cancer patients, Venclexta, that blocks Bcl-2 and promotes cell death. 

For the first time, the Emory Vaccine Center team showed that giving Venclexta to SIV-infected nonhuman primates eliminates a significant portion of the viral reservoir. Based on these exciting results, a clinical trial was approved to treat people living with HIV starting antiretroviral therapy (ART) with Venclexta. 

In a second study, Dr. Paiardini’s group tested an intervention where two brakes of the immune system, IL-10 and PD-1, were removed by antibodies blocking their functions. This is a follow up study to recently published work from Dr. Sekaly and Dr. Paiardini. This intervention, repeated in two phases over a 3-year-long study, resulted in 100% of the animals controlling viral rebound at very low levels for months despite no longer receiving ART. Even more exciting, the treatment also reduced the size of the viral reservoir by nearly 100-fold. 

Now, the scientists at the Emory Vaccine Center and Emory Primate Center are seeking funds to perform the next step of this life-saving research and take the fight against HIV across the finish line.  

With additional funding, they plan to test a combined intervention where Venclexta will reduce the size of the viral reservoir and the aIL-10 and aPD-1 will work together to eliminate all of the infected cells by increasing the strength of the immune system. 

This research has the potential to improve the lives of more than 40 million people living with HIV worldwide. 

Understanding the Need for New Contraceptive Options 

Many people seeking birth control want non-hormonal options, but choices remain limited. In the United States, about 45% of pregnancies are unintended, and most result from either not using contraception or using it incorrectly. Hormonal contraceptives are not suitable for everyone, so there is a strong demand for new, non-invasive alternatives. 

The Cervix: A Natural Barrier to Fertility 

The cervix acts as a gateway to fertility. Sperm must pass through cervical mucus to reach the uterus and fallopian tubes for fertilization. Cervical mucus changes throughout the menstrual cycle, becoming thinner during ovulation to allow sperm passage, and thickening after ovulation to block sperm and pathogens. This natural barrier presents a promising target for new contraceptive methods. 

Building a Lab Model to Study Cervical Mucus 

A research team led by Dr. Leo Han at Oregon Health & Science University (OHSU) and the Oregon National Primate Research Center (ONPRC) has developed a new lab-based (in vitro) model to study how cervical mucus changes during the menstrual cycle. Using cells from rhesus macaques, which have cervical structures similar to humans, the team grew and treated these cells with hormones to mimic different cycle phases. 

Key Findings: Genes That Regulate Fertile Mucus 

By analyzing genetic activity in these cultured cells, the researchers identified hundreds of genes that play a role in mucus production and consistency. They discovered that these genes respond differently depending on hormone levels, revealing potential drug targets for blocking sperm without hormones. One important protein, MUC5B, helps form the gel-like structure of mucus, while ion channels influence hydration and thickness. 

A Powerful Tool for Future Contraceptive Research 

This new lab model allows scientists to study cervical mucus in a controlled environment, making it easier to understand the molecular mechanisms that regulate fertility. The team is now testing non-hormonal compounds that could inhibit fertile mucus production in nonhuman primates, moving a step closer to new non-hormonal birth control options. 

Promoting Reproductive Justice 

Lead author Dr. Katrina Rapp emphasizes that expanding contraceptive choices is especially important for marginalized and disadvantaged populations, who are more likely to experience unplanned pregnancies. By focusing on non-hormonal, non-invasive methods, this research could help promote reproductive justice and improve health equity. 

Research Support and Ethical Oversight 

This work was supported by the National Institutes of Health, March of Dimes Foundation, and other partners. All animal research at OHSU is reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) to ensure ethical standards and scientific value. 

At the National Primate Research Centers (NPRCs), advancing human health goes hand in hand with a deep commitment to responsible, ethical research. Across all seven NPRCs, scientists are dedicated to improving and refining how research is conducted, investing in innovative alternatives known as new approach methodologies (NAMs) and only using animals when absolutely necessary.

The 3Rs: A Foundation for Ethical Research

Central to NPRC research is the principle of the “3Rs”: Replace, Reduce, and Refine animal use wherever scientifically possible. Before any study involving animals begins, researchers first use NAMs, such as computer models, organ-on-a-chip technology, and 3D cell cultures, to gather preliminary data and refine their experiments. This approach helps minimize the number of animals needed and ensures the highest standards of care and scientific rigor.

The Power and Limits of Non-Animal Models

NAMs are powerful tools for understanding biology and disease. They allow scientists to screen drugs, predict toxicity, and refine dosing without the use of animals. However, while NAMs provide valuable insights, they cannot yet fully replicate the complexity of a living organism. Many diseases, such as Alzheimer’s, cancer, or heart conditions, involve interactions across multiple organ systems, something NAMs alone cannot model.

That’s why NPRC scientists use a hybrid approach: NAMs are used wherever possible, and animal studies are conducted only when there is no other way to answer critical research questions. This ensures that research is both innovative and responsible.

Why Animal Research Remains Essential

U.S. law requires that all new medicines and medical devices be evaluated in animals for safety and efficacy before human trials can begin. Nonhuman primates represent less than 1% of all research animals and are used only when no other species can answer the research questions at hand. Their genetic, physiological, and behavioral similarities to humans make them essential for studying complex diseases and developing new treatments.

NPRCs are committed to the highest standards of animal care and ethics. Studies must be necessary, ethical, and conducted with rigorous oversight. The centers also invest in technologies and methods that refine research and reduce animal stress, such as advanced imaging and noninvasive monitoring.

Leading the Way in Research Alternatives

NPRC scientists are at the forefront of developing and validating new NAMs, with support from the National Institutes of Health (NIH). These efforts are accelerating, but until alternatives can fully replicate living systems, animal studies remain vital for progress in areas like neurodegenerative, metabolic, and infectious diseases.

By using a combination of NAMs and animal studies, NPRCs are able to maximize scientific accuracy, reduce the use of animals, and ensure that research benefits both human and animal health.

A National Resource for Science and Ethics

The NPRCs serve as a national resource, supporting scientists across the U.S. and around the world. Each center is part of a host academic institution and provides specialized facilities, expertise, and training for the next generation of researchers. Their commitment to the 3Rs and to responsible innovation ensures that every study is conducted with care, for the animals—for science, and for society.