Tag: Montaner

Montaner is Keynote Speaker at Los Angeles County Commission on HIV Annual Conference

Finding a cure has long been the holy grail of HIV research. Now new discoveries are putting that goal within reach, according to Wistar’s Luis Montaner, D.V.M., D.Phil.

As director of the institute’s new HIV Cure and Viral Diseases Center, Montaner was a keynote speaker at the Los Angeles County Commission on HIV Annual Conference on Nov. 14. Speaking on “The Promise of a Cure for All,” he shared the latest advances and strategies researchers are pursuing to move beyond managing HIV to eradicating it. He was later joined on the panel by Paul Edmonds and Adam Castillejo, two of only seven people in the world known to have been cured of HIV.

“There’s a lot of reasons to be hopeful,” Montaner said. “I strongly believe a cure is possible.”

Viral latency has been a major obstacle to curing HIV, because even with treatment tiny amounts of virus remain in a dormant state that makes them undetectable by the immune system.

One approach to cure research involves tackling this problem by reactivating these latent HIV cells so the immune system can find and destroy them, Montaner said. A second approach involves enhancing the immune system’s ability to detect and attack infected cells. A third strategy involves combining these two approaches, he added.

While current treatments suppress infection, “over time, the amount of persistent HIV remains relatively stable,” Montaner said. “We need to continue our efforts towards finding a different approach to get us to the cure.”

Montaner also shared details of two recent Wistar cure studies.

One BEAT-HIV Delaney Collaboratory project involves using bispecifics — antibodies with bindings on both ends that are designed to connect an immune cell with an infected cell. Already used in cancer treatments, these drugs are now being tested against HIV.

Wistar researchers have found that combining these antibodies during days of starting antiretroviral drugs reduced viral persistence in preclinical models, he said.

A second BEAT-HIV Delaney Collaboratory project involves testing a new antiretroviral therapy that doesn’t just limit the virus’ ability to replicate but kills the infected cell itself. These drugs work by interrupting the cell replication cycle to trigger an internal cell death pathway, he explained.

Researchers found that when the new antiretroviral drug was applied to blood samples that are already infected with HIV in the laboratory, the number of infected cells decreased from 89% to around 4% after three days. That compares with 44% infected cells in samples treated with traditional retroviral drugs.

“You can see that this not only reduces the burden of viral infections of new cells, but it also reduces the burden of already infected cells,” he said.

Speaking on the panel, Montaner noted that Edmunds and Castillejo, while having received anti-cancer treatments that are not able to be used widely, are still living proof that an HIV cure is possible. He highlighted the BEAT-HIV Collaboratory as an example of how Wistar researchers are working closely with other investigators and the HIV community to better understand and address the needs of real-life patients.

“Together, as a group, we’re committed to advance towards a cure,” he said. “There’s a lot of enthusiasm, a lot of encouragement, a lot of hope for a future without HIV, as this train is not stopping — we are going to get there.”

The BEAT-HIV Delaney Collaboratory receives generous foundation support from the Robert I. Jacobs Fund.

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.”