Tag: Montaner

Dr. Luis J. Montaner, D.V.M., D. Phil., is the Herbert Kean, M.D., Family Professor; vice president of Scientific Operations; associate director for Shared Resources at the Ellen and Ronald Caplan Cancer Center; director of the HIV-1 Immunopathogenesis Laboratory; and leader of the HIV Research Program, Vaccine & Immunotherapy Center, at The Wistar Institute.

He leads the BEAT-HIV Delaney Collaboratory and investigates new strategies that boost the natural function of the immune system to combat virus-associated diseases like HIV.

Give us a primer on human immunodeficiency virus: What do scientists know about how HIV works, and what questions are still being investigated?

We, as a field, have learned how to design drug therapies to control but not eradicate HIV. The HIV virus can introduce mutations into its replication cycle and acquire resistance to single-drug therapies. It’s why three drugs are used in current combination antiretroviral therapy (ART) because it’s much more difficult to develop mutations against three drugs at once.

Controlling HIV replication does not logically extend to a cure with the current therapies. The virus persists, and interestingly, it retains features that reflect how soon a person started ART. For instance, if you had a particular viral replication level and an immunological setpoint when you started antiretroviral therapy, it would return to that point if you ever stopped — even if you’d been on therapy for 15+ years. The HIV research field as a whole has also learned how the virus persists in a person after they start antiretroviral therapy, and how to measure persistence changes in the blood to then evaluate if cure-directed strategies may work.

However, even if you have a treatment that successfully attacks the HIV virus hiding in the blood, that might not be enough — because the virus’ latent reservoirs extend beyond what we call the “blood compartment.” Researchers need to ensure that any strategy can reach all tissue compartments, such as the brain, liver, muscle, bone, etc., as HIV can reside within immune cells in all organs.

Where does your optimism for finding a cure for HIV come from?

If you think about the phases of HIV research, as a field, we have achieved success on several fronts, and we trust the same will be true for an HIV cure. First, a brief history of HIV/AIDS: scientists and doctors started with the quest to ensure HIV diagnosis and secure our blood banks. We then shifted to preventing the high death rate by developing therapies that could prevent viral replication and allow the immune system to recover.

Then came the phase where we have been for a while: the search for a vaccine. It’s only recently that we’ve added cure-directed research as a clear objective, which follows from the extraordinary cases in which individuals were cured because of their cancer therapy.

Although the cancer treatments associated with HIV cures can also be fatal — and are not safe to give to persons living with HIV when compared to the safety of life-long antiretroviral therapy — the existence of these cases prove that a cure is possible.

The HIV cure research field is now looking for strategies toward one of two outcomes: either eradicating the virus within a person on therapy and stably suppressing viral replication; or achieving long-term control without the continued use of antiviral therapy. We are still in the early days of this effort, but the outlook is promising.

If you think about it, we’ve been addressing the HIV global pandemic for more than 30 years. The breakthroughs in antiretroviral therapy came about 10-12 years after we started research efforts, and now we’re only at the beginning years of the cure-directed effort, which continues to grow. So, the investment in cure is increasing — which means the expertise behind and opportunity for the discovery of a cure strategy also increases.

We’re advancing our search for a cure by bringing teams together like never before. A good example of this new coalition effort across geography and institutions under one large project is the BEAT-HIV Delaney Collaboratory. Working together as a team is a lot more effective.

What does it look like to collaborate with groups like Philadelphia FIGHT, which extends HIV research into local communities?

If you’re going to do research on a particular condition, you’d best do it with the awareness, input, and approval of people living with that condition. When I started at Wistar in 1995, I initiated outreach to the community. We now have one of the longest-lasting community engagement programs anywhere, and it’s focused on uniting HIV researchers with persons living with HIV. We’ve become a model for other cities.

What’s different about our model is how we’ve built a community engagement group that includes not only a community advisory board of individuals, but also Philadelphia FIGHT, a comprehensive health services organization that cares for people living with HIV by working directly within and for the community. We meet with both the community advisory board and Philadelphia FIGHT members regularly to create an environment where community members are part of the team. That sense of equity, and the weight of participation, empowers everybody. As our community members often say, they want to be “in the kitchen helping to create the cure — not outside being served after the cooking is complete.” From the beginning, we bring the community members to the table where they are part of the team.

After nearly three decades, why do you choose to continue your work toward curing HIV at Wistar?

I’m here because I see local and global opportunities for the future of our program. Opportunities ahead are just as impactful and interesting as when I walked through the door 29 years ago. The Wistar Institute has a long and storied history as a global leader in biomedical research and is unique in its ability to support the vision of a principal investigator as they grow their program.

If you want to develop a focused program and collaborate on a global scale — then Wistar outperforms anyone else.

For more information, email comm-marketing@wistar.org.

Shining a spotlight on the need for an HIV cure during National Black HIV/AIDS Awareness Day

Wistar HIV researcher Dr. Luis Montaner spoke about his HIV cure research with Scripps News reporter Adi Guajarda for her National Black HIV/AIDS Awareness Day segment. The story shines a light on how HIV/AIDS is impacting the health of Black communities at a disproportionate rate. And how this negative effect—combined with stigma, racial discrimination and social determinants—leads to poorer health outcomes. The segment also pointed to hope and included an interview with Adam Castillejo, who is also known as the “London Patient” and is the second person in the world to be cured of HIV/AIDS. Adam became resistant to HIV after receiving a bone marrow transplant to treat Hodgkin’s lymphoma. 

Pride Month in Philadelphia, PA, is celebrated alongside another worthy cause: AIDS Education Month, an event series organized by the nonprofit Philadelphia FIGHT to raise awareness of those living with AIDS, AIDS treatments & healthcare and AIDS research. The Wistar Institute has collaborated with Philadelphia FIGHT for decades to advance their mission to cure HIV/AIDS.

At the opening celebration for AIDS Education Month on Thursday, June 1st, Philly FIGHT honored two Wistar senior scientists for their decades of contribution to HIV/AIDS research. Drs. Livio Azzoni and Emmanouil Papasavvas — each a senior scientist in the HIV program and Wistar Montaner Lab — received the Kiyoshi Kuromiya award, which honors a community Philadelphia activist, Kiyoshi Kuromiya that galvanized national and global awareness to the needs of persons living with HIV. Kuromiya organized with the Gay Liberation Front for gay rights and founded the Philly chapter of ACT UP to advocate for those impacted by the AIDS epidemic, and the award bearing his name recognizes those who have similarly impacted our community and made a difference to the lives of persons living with HIV.

Dr. Papasavvas was moved by the honor, and he took the opportunity to thank everyone involved in the collaborative work of the research process: “Research is not working alone; we all work together, trying to find the path to discover cures for all diseases, and right now, for HIV.”

Upon accepting his award, Dr. Azzoni also emphasized the teamwork necessary for science by speaking to the importance of both institutional support and patient focus in the search for an AIDS cure: “By doing patient-oriented research, we aim at involving all stakeholders in all stages, from design to implementation.” Both men received standing ovations from the crowd.

Dr. Montaner then joined the stage to participate in a panel discussion titled “The Evolution of HIV Research,” where he was accompanied by moderator and Director of the Philadelphia Department of Public Health’s Division of HIV Health, Dr. Kathleen A. Brady; Chief Scientific Officer and Medical Director of the Jonathan Lax Treatment Center, Dr. Karam Mounzer; Philadelphia FIGHT Director of Research, Emily Hiserodt, MPH; and longtime AIDS advocate, survivor and Chair of the BEAT-HIV Community Advisory Board, William Carter.

The panel sought to answer a compelling question: in the context of medical advances, why is research that seeks an HIV cure still important?

Panelists’ answers addressed several areas. William Carter, as an AIDS survivor, pointed out that an absolute cure would eliminate his need to take medication on an indefinite basis or receive regular bloodwork. Dr. Mounzer spoke to the fact that functional remission, while a tremendous achievement, still comes with reduced life expectancy and general stressors — like comorbidities and side-effects from the maintenance medications — relative to the HIV-negative population.

Dr. Montaner agreed with his fellow panelists on these points and expressed his belief in the macroscopic utility of reaching an HIV cure:

Finally, scientific advances in one area of human health, Dr. Montaner emphasized, do not simply remain there: they carry over to different areas of study and move those fields forward, too. “If we can crack chronic infection in those living with HIV — or even just get closer towards that cure — we’re going to get insights into how to advance research into added diseases at the same time.”

Montaner, together with international delegations, attended the April 4 launch in Ho Chi Min City.

On April 4, tucked in a courtyard at the Go Vap District Health Center in Vietnam’s Ho Chi Min City, Dr. Luis J. Montaner joined local and international dignitaries to mark the start of the AMOHI Clinical Trial.

Spearheaded by Montaner, who leads Wistar’s HIV Research Program, the study is a consortium that includes Wistar, National Institute of Drug Abuse, University of Pennsylvania, IMEA Paris, Pasteur Institute, Ho Chi Minh City CDC and industry partners in Ireland and India. Together, they will investigate the impact of opioid use disorder (OUD) and medications for opioid use disorder (MOUDs) on immune recovery in response to antiretroviral therapy (ART) in HIV-infected people.

The launch was several years in the making. In 2019, The Wistar Institute received two major grants totaling more than $12 million from the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health, to fund the clinical trial in Vietnam and study related topics in Philadelphia. As COVID emerged, however, and nearly all services, including international travel, ground to a halt, the launch of the program was put on hold. Now, the effort is officially underway.

The overarching goal of the research is to investigate the role of opioid receptor involvement in modulating the levels of immune activation, retention on treatment and effects of different classes of MOUDs as first study to compare strategies head-to-head, in people living with HIV. Effectively controlling immune activation after ART in persons taking MOUDS can directly impact health and mortality.

Enrollment for the 3-year study opened on January 30, with a total of 225 planned enrollees, and is expected to close on February 1, 2026. The study will assess three different treatments to determine which is best for opioid use dependent individuals living with HIV: methadone, buprenorphine/naltrexone, and extended-release naltrexone.

“We will test the impact of a previously unknown interaction between substance abuse, HIV infection and MOUDs that may determine health outcomes only if the right MOUD medication is chosen,” explained Dr. Montaner, D.V.M., D.Phil., Herbert Kean, M.D., Family Professor and director of the HIV-1 Immunopathogenesis Laboratory at Wistar’s Vaccine & Immunotherapy Center. “We expect the results of this major collaborative effort, which has its hub in Philadelphia, to have broad clinical implications in informing the best pharmacologic strategy for the management of opioid use disease in HIV-infected people starting ART,” said Montaner. “This is directly relevant in light of the opioid epidemic ongoing in our nation and will help ensure that the right medications are used for both HIV and OUD, with the ultimate objective of saving lives in the future.”

An $80,000 grant for The Wistar Institute’s HIV-1 Patient Partnership for Basic Research program from the Robert I. Jacobs Fund of Philadelphia Foundation not only advances ongoing basic research into ways to prevent, treat and ultimately cure HIV, but underscores the power of partnership between research centers and community-based organizations in fighting healthcare inequities faced by vulnerable populations.

The latest funding continues more than a quarter century of longstanding support by the Philadelphia Foundation for innovative HIV research advanced in the Wistar lab of Dr. Luis Montaner, a bench-to-bedside immunologist with a focus on HIV cure strategies and cancer.

With the recent COVID-19 pandemic and emergence of monkeypox in 2022, Dr. Montaner’s work has evolved to now include pilot studies on SARS-CoV-2 and monkeypox (MPX) vaccination outcomes in persons living with HIV as well as a study of persons with a prior history of monkeypox infection. Studies include persons living with HIV as well as other marginalized persons with substance use disorder.

The partnership pairs the innovative biomedical research happening in his Wistar lab with educational activities, community engagement and donor recruitment programs offered by clinical sites throughout the City of Philadelphia, including Philadelphia FIGHT’s Jonathan Lax Clinic and the John Bell Health Center; and, more recently, Prevention Point Philadelphia. The unique partnership between Wistar and Philadelphia Foundation inspired new federal criteria requiring greater community engagement across all Martin Delaney Collaboratories for HIV Cure Research programs by including a partnership with community-based organizations. The BEAT-HIV program based at The Wistar Institute has prioritized community engagement from the start due to long-standing support by the Philadelphia Foundation.

“Maintaining our Philadelphia community-based academic research collaboration is critical to our continued success, as this productive city-wide partnership distinguishes us among all HIV research centers in the U.S.,” said Dr. Montaner, director of Wistar’s HIV-1 Immunopathogenesis Laboratory and leader of the HIV Research Program, Vaccine & Immunotherapy Center. “Wistar is proud to be a partner with our community in research and thankful for all that have shared in this common vision for over 25 years.”

Dr. Luis J. Montaner and lab find common, persistent symptoms for long-haulers by reviewing a multitude of research studies.

An international team of researchers led by The Wistar Institute’s lead scientist on HIV-cure research has published a review that codifies some of the key take-aways from a sample size of 2,833 patients with long COVID.

Led by Wistar’s Dr. Luis J. Montaner, director of the HIV-1 Immunopathogenesis Laboratory and leader of the HIV Research Program within the Vaccine & Immunotherapy Center, and published in the Journal of Leukocyte Biology, the review offers supporting evidence that RS-CoV-2 (PASC), or long COVID, reflects tissue injuries to a patient’s system that underscores the vulnerabilities of individuals with the disease or the immunological consequence of their system responding to COVID.

“We conducted a review of all the available literature, summarizing what criteria we could define as long COVID that unifies patients across studies. We then took those unifying themes that identify commonalities in long COVID and identified targets for research we could potentially do something about,” Montaner said. “If you search long COVID, there are multiple different presentations, multiple different organ systems, and it is a challenge to come up with unifying principles of what disease process results in long COVID. We focused on identifying common principles of immunological disturbance and tissue injury mechanisms that could be supported by studies of long COVID to date.”

Many Wistar researchers are using machine learning to crunch complex data. That wasn’t the case here.

“It was more a more manual, elbow grease method,” Montaner said. “Each study used different definitions and data points but with similar populations. We listed all the studies, all the patients, all the definitions used, and the criteria we used to coalesce them. That is something that machines cannot do.”

Montaner was surprised to identify distinct patterns on how long COVID may affect the outcome of either acute injury or the long and projected injury to tissues.

They found mechanisms that contribute to symptoms such as inflammation, antigens that persist even after initial infection and microbial translocation (also known as leaky gut) all contribute to long COVID and can be affected by things like age and gender.

“Long COVID presents itself in many ways so it’s important to understand biologically what causes each type of symptom,” Montaner said. We also hope to address the ongoing debate between treating early against the virus versus treating the immune system against tissue injury caused by our own immune response. Our work will advance efforts to identify therapy strategies to avoid tissue injury leading to long COVID from that initial infection.”

This was not the first time a Wistar-led team has taken this roadmap approach.

“When COVID arrived in 2020, one of the first things we did was conduct a comprehensive review of all the reports that provided insight on the immunological modulation within the disease itself, highlighting what we knew and what was available,” Montaner said.

The objective now is to advance research again but on long COVID, noting that the prior 2020 review has been cited by world researchers more than 500 times since publication.

Wistar received a $4M grant from the State of Pennsylvania in 2021 to advance COVID research on vulnerable populations, in part because the organization has gained access to vulnerable populations through its work with patients living with HIV or people with substance use disorder in Center City Philadelphia, Kensington and other areas associated with drug use.

Luis J. Montaner, D.V.M., D.Phil, and his team are making tremendous strides studying the ability of natural killer (NK) cells, a type of immune cell, to wipe out HIV-infected cells. Meanwhile, other groups within Wistar’s HIV Research Program, which Montaner leads, are in hot pursuit of alternative immunotherapy strategies, such as modified antibodies and CAR T cell therapies, to stamp out infected cells.

The research progress of all these labs was recently pole-vaulted forward thanks to a generous and visionary seven-figure unrestricted planned estate gift from Robert A. Fox (Bob). Bob, who passed away in 2021, helped transform Wistar into a leading biomedical research institute, through numerous donations that he and his wife, Penny, made and his two-decade role on Wistar’s Board of Trustees.

The new unrestricted gift enabled the purchase of three state-of-the-science advanced instrumentation and equipment. Flow cytometry is technology that isolates specific types of cells from tissue samples for analysis, along with a host of other customizable features, that will benefit and advance a wide range of Wistar scientists. Another is a technology platform consisting of two pieces of equipment for high-resolution imaging and spatial profiling of cellular structures and molecules at unprecedented speed and scale. The system will forge new insights into interactions between cancer and immune cells and the tumor microenvironment that nearly every lab at Wistar can deploy. The third is equipment, which is dedicated to the HIV Research Program, for a live cell analysis system that tracks cells growing in tissue culture plates.

“The investment is going to accelerate an excellence that is already here,” says Montaner, who is the vice president of Scientific Operations and associate director for Shared Resources at Wistar. “It is not a bet by any means. It is a sure thing that, by providing these tools, scientists can answer questions we couldn’t before, and answer the questions we were after better with added insights that will allow to move novel concepts towards clinical trials faster,” he explains.

The live cell analysis system will allow all laboratories in the Wistar HIV program to pinpoint exactly how well and how quickly various immunotherapy strategies are killing HIV-infected cells. The equipment also opens the door to being able to gather multiple timepoints on samples from HIV-infected patients, which are typically of very limited quantity.

The equipment is now bolstering research on developing combination immunotherapy as a cure for HIV for which the Montaner Lab and other groups in the BEAT-HIV Martin Delaney Collaboratory were awarded a five-year, $29.15M award from the NIH last year.

One of the most powerful aspects of an unrestricted gift is the time it saves. The traditional route that Wistar, and research institutes in general, take to obtain new, cutting-edge equipment is to apply for an NIH Shared Instrumentation Grant. But applications are only accepted once a year, and if grants are reviewed well and awarded, which has been the case for many of Wistar’s last submissions, it still takes one to two years to receive the equipment. Instead, an unrestricted gift entrusts Wistar to direct the support where it thinks it can have the greatest benefit and purchase equipment immediately.

“Unrestricted gifts allow Wistar scientists the capacity to quickly seize opportunities to remain competitive in an environment that is very dynamic when it comes to platforms that allow you to innovate,” Montaner says. “This gift advances what we are doing right away, while simultaneously increasing our competitive edge to grow our programs by writing new grant proposals that take advantage of the state-of-the-art capacities.”

In addition to the work in the HIV Research Program to help bring immunotherapies to the clinic, the investment will benefit Wistar’s research on cancer therapies and COVID-19 vaccines. “The impact is immediate with both present and future returns for all of these programs,” Montaner says.