How NPRC Research Accelerated HIV Advances From 2020–2025

From breakthroughs in prevention to promising treatments, the National Primate Research Centers (NPRCs) have played a crucial role in advancing HIV research. Working with nonhuman primates, the closest biomedical model to humans, NPRC researchers have tackled some of HIV’s biggest challenges: viral persistence, brain invasion, co-infections and the limits of current therapies. Together, these discoveries mark some of the most significant progress toward long-term remission and potential cures in decades.

Strengthening Vaccines and Early Prevention

NPRC advances include efforts to block infection before it starts. Researchers at the Emory National Primate Research Center (ENPRC) at Emory University showed that an Env-plus-Gag HIV vaccine regimen in rhesus macaques provided durable protection from SHIV, the simian version of HIV, even when neutralizing antibody levels were low. This finding expanded thinking around the types of immune responses a successful vaccine must generate.

At the same time, Oregon NPRC scientists found that leronlimab, a monoclonal antibody that blocks the CCR5 co-receptor, effectively prevented SHIV infection in nonhuman primate models. Already tested in human studies for viral suppression, the antibody also showed promise as a PrEP-style preventive option.

Targeting HIV’s Hidden Reservoirs

Because HIV hides in tissues the immune system can’t easily reach, several NPRC studies focused on uncovering and disrupting these viral reservoirs. ENPRC scientists discovered that the anti-inflammatory molecule IL-10 helps HIV-infected cells survive in lymph nodes. Blocking IL-10, alongside antiretroviral therapy (ART), reduced the number of infected reservoir cells, marking an important step toward weakening HIV’s stronghold.

Researchers at Emory NPRC also identified specialized follicle-infiltrating NK cells capable of entering B-cell follicles in lymph nodes, one of HIV’s most protected hiding places. These findings point toward future therapies that could guide immune cells directly into viral reservoir sites.

Additional “shock and kill” studies at Wisconsin NPRC showed that both latency-reversing drugs and checkpoint inhibitor combinations can reactivate dormant virus while nonhuman primates are on ART, laying groundwork for strategies that flush HIV out of hiding.

Immune-Based Therapies Move Toward Functional Cure

By 2024, several NPRC collaborations delivered results that brought the field closer to long-term remission without lifelong treatment. A landmark study testing N-803 (IL-15 superagonist) plus broadly neutralizing antibodies achieved long-lasting viral control in most SHIV-infected macaques even after ART was stopped. The findings have now progressed to early-phase human clinical trials.

Emory NPRC researchers also identified a particularly potent subset of CD8⁺ T cells (TCF1⁺CD39⁺) that excel at controlling SIV and resisting exhaustion. The importance of these cells has been confirmed also in people with HIV and may become powerful tools in future immunotherapies.

Understanding HIV in the Brain

Another major advancement came from California NPRC, where researchers discovered how HIV enters and persists in the brain. Their work showed that CD4 T cells can inadvertently carry virus into neural tissue, helping explain why HIV-associated neurocognitive disorders persist even when ART is effective.

Addressing Co-Infections and Real-World Treatment Needs

HIV rarely exists in isolation. In 2025, Texas Biomed and the Southwest NPRC demonstrated that a promising tuberculosis therapy did not interfere with combined antiretroviral therapy (cART) used to treat HIV, supporting its safe use in people co-infected with HIV and TB. Because the drug is already FDA-approved for use in cancer patients, it could accelerate potential approval for TB/HIV treatment compared to developing an entirely new drug.

A Path Toward Remission

Building on these advances, Emory NPRC researchers reported one of the strongest signals yet that a functional cure for HIV may be achievable. In a stringent SIV model, a targeted combination therapy, blocking two negative regulators of the immune system, IL-10 and PD-1, enabled durable control of viral rebound in 9 of 10 nonhuman primates for six months after ART ended, an unprecedented result that strengthens the path toward future human trials. This is a direct proof of concept that the immune system can be harnessed with immune-based interventions to control HIV.

The Bottom Line

Between 2020 and 2025, NPRC research meaningfully advanced the HIV landscape. Through innovative vaccine approaches, better understanding of persistence, targeted immune strategies and real-world treatment insights, the NPRCs have laid essential groundwork for an era in which long-term HIV remission, and ultimately a cure, becomes an attainable goal.

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. 

Researchers at Oregon Health & Science University (OHSU) and the Oregon National Primate Research Center (ONPRC) have uncovered new protective properties of amniotic fluid, opening the door to potential advances in prenatal care and therapies for pregnancy-related complications. 

Amniotic fluid, the vital substance that cushions and protects a developing fetus, has long been known to support organ development and regulate temperature in the womb. However, its full range of functions has remained a mystery, partly because it is difficult to study throughout pregnancy. Now, a multidisciplinary team led by Dr. Jamie Lo at ONPRC has taken a closer look at how amniotic fluid changes over time and how these changes may benefit both mother and baby. 

The study, published in Research and Practice in Thrombosis and Haemostasis, found that adding amniotic fluid to plasma, the liquid part of blood, improves the blood’s ability to clot. This discovery points to a critical protective function during pregnancy and delivery, helping to reduce the risk of dangerous bleeding for both the birthing parent and the baby. 

By analyzing amniotic fluid samples from both humans and nonhuman primates at different stages of pregnancy, the team identified key fatty acids and proteins that shift each trimester, enhancing the blood’s ability to coagulate. These findings suggest that the composition of amniotic fluid is tailored to meet the growing needs of the developing fetus and to support the health of the parent. 

The research also highlights the potential for amniotic fluid components to be used in future therapies. The ONPRC team is now collaborating with other OHSU scientists to explore how these protective factors might help treat pregnancy disorders, especially those affecting blood and blood-forming organs. They are also working with OHSU’s Fetal Care Program to collect unique samples from pregnancies involving in-utero surgeries, hoping to identify elements that could improve outcomes for babies with conditions like spina bifida. 

Dr. Brian Scottoline, co-senior author of the study, points out that babies born prematurely miss out on critical weeks of exposure to amniotic fluid. Understanding how amniotic fluid supports development could lead to new formulas or therapies for preterm infants, potentially mimicking the fluid’s benefits outside the womb. 

The study was supported by the National Institutes of Health and other partners, and all animal research was conducted under strict ethical oversight by OHSU’s Institutional Animal Care and Use Committee. 

A New Hope for Cardiovascular Patients

University of Wisconsin–Madison NPRC scientists have made a significant leap in heart surgery innovation: they’ve developed bioengineered arteries using stem cells that could one day transform how doctors perform vascular bypass procedures.

Why New Arteries Are Needed

Currently, when patients need small-diameter blood vessels for procedures like coronary bypass surgery, surgeons must use vessels from another part of the patient’s body. This approach is invasive, can be limited by the patient’s health, and is not always possible. Donor vessels are another option, but they often face immune rejection.

The Science Behind Bioengineered Grafts

The research team created a new kind of “off-the-shelf” artery by:

• Using pluripotent stem cells to generate arterial endothelial cells (AECs), the cells that line blood vessels.
• Attaching these cells to a small synthetic graft made of ePTFE (the same material as Teflon), which is specially coated with proteins inspired by mussels to help the cells stick.
• Testing the grafts in Rhesus macaques, a primate model similar to humans.

What Did They Find?

The scientists compared different types of grafts:

• Uncoated synthetic grafts
• Grafts lined with normal (wildtype) AECs
• Grafts lined with AECs modified to avoid immune detection (major histocompatibility complex (MHC) double knockout)

Surprisingly, the (MHC) double knockout grafts failed half the time, possibly due to innate immune cells (natural killer cells) attacking them. The wildtype grafts, however, worked well for six months, and the host’s own cells repopulated the graft, supporting long-term success.

What’s Next?

This study is a promising step toward creating ready-to-use, stem cell-based vascular grafts for heart and vascular surgeries. If successful in future human trials, these grafts could:

• Reduce the need for invasive vessel harvesting
• Expand surgical options for patients with limited vessel availability
• Lower the risk of immune rejection

The Big Picture

As Dr. Samuel Poore, a co-author, explains: “This is an exciting, collaborative project with the potential to be a true bench to bedside advancement.”

Emory University researchers have made a significant advancements in the pursuit of an HIV cure. One of the teams, led by Dr. Rafick Sekaly and Dr. Mirko Paiardini, demonstrated unprecedented control of simian immunodeficiency virus (SIV) replication and decay of viral reservoirs in nonhuman primates.

Key Findings:

The study, which was published in Nature Immunology, combined a stringent model of SIV infection with interruption of antiretroviral therapy (ART) and targeted immune intervention.

Researchers identified mechanisms of action for PD1 and IL-10, molecules known to regulate HIV persistence and immune dysfunction.

Nine of ten monkeys that received combination treatment showed durable control of viral rebound lasting six months after stopping ART.

Implications for HIV Treatment:

This research represents a major step forward in developing a functional cure for HIV, potentially improving the lives of 39 million people living with the disease worldwide. The study’s success stems from more than 15 years of work on PD1 and IL-10, which could lead to improved approaches for restoring deficient immune systems and controlling chronic infections.

Collaborative Effort:

The study highlights the power of collaboration between academia and industry. Merck, as an industry partner, developed reagents specifically designed to target PD1 and IL10 molecules in nonhuman primate models.

Up Next:

The research team is further investigating innate immune, metabolic and epigenetic pathways associated with controlling the virus after ending treatment. Their goal is to develop interventions that can induce an immune response capable of long-term control of HIV and SIV without ART.

This breakthrough brings us one step closer to a potential HIV cure, offering hope to millions affected by the disease worldwide.

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 non-animal models (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.

A new study on placental gene therapy in rhesus macaques has shown promising results that could lead to improved outcomes for human pregnancies affected by placental insufficiency. The research, conducted by scientists Dr. Helen Jones, from the University of Florida, and Dr. Jenna Schmidt, University of Wisconsin—Madison and Wisconsin National Primate Research Center, focuses on developing a treatment for placental insufficiency. 

Placental insufficiency is a significant concern in human pregnancies, underlying the majority of stillbirths or resulting in low birth weight and extended stays in neonatal intensive care units. The condition can have lasting effects on health throughout their lifespan, potentially leading to cardiovascular disease and neurocognitive developmental issues later in life. 

The researchers used a polymer-based nanoparticle loaded with a plasmid encoding the human IGF-1 protein, which is crucial for normal placental development. This approach builds on Dr. Jones’ 13 years of previous research supported by the NIH Eunice Kennedy Shriver National Institute for Child Health and Development. 

Key findings from the study include: 

• Successful expression of the IGF-1 transgene only in the placenta 

• No negative immune responses from the mother or fetus 

• Transgene expression lasting up to 10 days after treatment 

While the current study involved direct injection into the rhesus macaque placenta, future research aims to refine the delivery method for potential human applications. The next steps include: 

• Delivering nanoparticles via the mother’s circulation 

• Exploring multiple treatments throughout pregnancy 

• Measuring the impact on both mother and fetus through birth 

The ultimate goal of this research is to improve placental function, extend pregnancies, and result in healthier babies and adults. As the study progresses, it brings hope for a potential treatment for placental insufficiency, a condition that currently has no available therapies. 

This innovative research represents a significant step forward in addressing pregnancy complications and improving long-term health outcomes for both mothers and children. 

A study involving Oregon Health & Science University (OHSU), OHSU, the Oregon, Tulane and Washington National Primate Research Centers, the University of Washington and the University of Pittsburgh has revealed a promising approach to developing a universal influenza vaccine. This innovative “one and done” vaccine could potentially provide lifetime immunity against evolving flu viruses. 

The research, published in Nature Communications, tested an OHSU-developed vaccine platform against the H5N1 avian influenza virus, considered a likely candidate for the next pandemic. Remarkably, the vaccine was based on the 1918 flu virus yet still provided protection against the modern H5N1 strain. 

Key findings from the study include: 

• Six out of 11 vaccinated nonhuman primates survived exposure to H5N1, while all unvaccinated primates succumbed to the virus. 

• The vaccine targets the internal structural proteins of the virus, which remain relatively unchanged over time, unlike the constantly mutating outer surface proteins. 

• This approach could be effective against other mutating viruses, including SARS-CoV-2. 

The vaccine platform, which uses cytomegalovirus (CMV) as a vector, was originally developed to fight HIV and tuberculosis. It works by inducing an immune response from the body’s T cells, specifically targeting the virus’s internal structure. 

Dr. Jonah Sacha, professor and chief of the Division of Pathobiology at OHSU’s Oregon National Primate Research Center and the study’s senior author, believes this breakthrough could lead to a universal flu vaccine within five to ten years. The same platform is already in clinical trials for HIV and shows promise for targeting specific cancer cells. 

This research represents a significant advancement in addressing infectious diseases and could revolutionize our approach to vaccine development for rapidly evolving viruses. 

A study led by researchers from the University of Wisconsin—Madison and Mayo Clinic has demonstrated the potential of stem cell therapy in treating congenital heart defects. The study was supported by the Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome (HLHS) and an NIH Grant to the Wisconsin National Primate Research Center.

The research, published in Cell Transplantation, shows that heart muscle cells derived from human induced pluripotent stem cells can safely integrate into the hearts of monkeys with right ventricular pressure overload.

Key findings of the study include:

• Successful integration of transplanted cells into the host myocardium
• Feasibility and safety demonstrated in a nonhuman primate model
• Potential to delay or prevent the need for heart transplants in patients with congenital heart defects

The research focused on right ventricular dysfunction, a condition that often affects children with congenital heart defects and can lead to heart failure. Current treatments, including surgical repair, are often temporary solutions, with many patients eventually requiring heart transplants.

Dr. Jodi Scholz, the study’s lead author, emphasized the critical need for alternative treatments, stating, “Stem cell treatments could someday delay or even prevent the need for heart transplants.”

While the study showed promising results, the researchers noted some instances of ventricular tachycardia in the animal subjects. However, these episodes resolved within 19 days.

This research represents a significant step towards clinical applications for congenital heart defects. The use of macaques in this study has been crucial in advancing stem cell therapies for various diseases, including heart disease, kidney disease, Parkinson’s disease, and eye diseases.

As heart disease remains the leading cause of death in the United States, this innovative approach to regenerating heart tissue offers hope for stronger, longer-lasting hearts across all age groups.