Mike McCune, MD, PhD, head of the HIV Frontiers Program at the Gates Foundation, delivered an upbeat message at the ASGCT annual conference in New Orleans last week, showcasing the progress being made by the foundation’s grantees in finding a cure for HIV and sickle cell disease.
“The U.S. Government may be pulling back, but we’re doubling down,” McCune said. “We will not treat our way out of the HIV pandemic with daily or even yearly ART [anti-retroviral therapy],” he added. McCune spoke in the ASGCT Presidential Symposium in front of thousands of delegates.
HIV exploded in the 1980s. Back then, if a patient was diagnosed at age 25, (s)he was likely to be dead at 32, McCune said. In the 1990s, HIV was the leading cause of death among Americans ages 25–44.
By 2005, the triple reverse transcriptase inhibitor cocktail extended life expectancy for HIV patients considerably. But, as McCune noted, it is very difficult for any patient to take a single pill every day for the rest of their life. In many countries, viral suppression rates have dipped below 50%.
The HIV population is now about 40 million patients worldwide, including two-thirds in sub-Saharan Africa. In 2023, more than 1.3 million new HIV infections were recorded. “With USAID [the U.S. Agency for International Development] dismantling, things will get much worse very quickly,” McCune said.
Even when patients receive top-quality care, they are still prone to comorbidities. The pre-existing reservoir of virus decays very slowly (with a half-life of 44 months). Consequently, many HIV patients have low levels of chronic viremia. “ART has made HIV a manageable disease,” McCune said. But many patients are not receiving therapy. Chronic inflammation can lead to a shorter life of poorer quality.
Some 15–20 years ago, McCune, who is also professor of medicine at UC San Francisco, and colleagues sought an alternative approach: could scientists reduce the size of the viral reservoir or suppress the viral rebound?
For McCune’s team, this has been a long-term goal since the 1980s. But when highly active ARTs were shown to be safe in 1995, there was no longer a business case for a direct therapy. “Do the math,” McCune was told bluntly. In other words, it would make more sense commercially to sell a daily pill to patients for life.
Pushed by the advocacy of the late Martin Delaney, a network of ten labs nationwide was set up, funded by $35 million over five years, to find a cure for HIV. Multiple strategies are being pursued, including depletion of the HIV reservoir, immunotherapy, cell and gene therapy, and so on.
Since Tim Brown, the Berlin patient, received a hematopoietic stem cell transfer using cells from a donor carrying a CCR5 mutation, eight other HIV patients have been cured. But McCune stressed, there is no scalable approach on the horizon.
“It’s not the mission of NIH to develop ‘cures’ for HIV patients living around the world,” he said. “Biotech and pharma have little incentive for HIV cures.”
McCune joined the Gates Foundation in 2018 with the goal of developing a curative intervention for HIV disease that is durable, safe, effective, accessible, and affordable.
The ultimate goal is a single-shot cure that would lower the viral load, with a minimal duration to remission of more than three years. The therapy must also prevent or control re-infection if the patient suffers further exposure. Steps along this path include: 1) in vivo gene therapy, 2) reservoir reduction and control via immunologic approaches, 3) identification of circulating reservoir biomarkers, 4) stakeholder engagement, including government and other medical staff, 5) partnerships—featuring academia, NIH, companies, and governments.
In 2018, the Gates Foundation turned its focus to sickle cell disease (SCD). Curative ex vivo gene therapies are now available but are not easily scalable or affordable. Many investigators are working to develop in vivo therapies targeting hematopoietic stem cells (HSCs).
“We need to figure out how to edit HSC progenitors in the bone marrow,” McCune said, focusing on developing suitable vectors for in vivo targeting and improving manufacturing and mobilization steps.
So far, some 40 grants have been funded, with groups working on both viral (AAV, lentivirus) and non-viral vectors (LNPs). Stefan Radtke, PhD, and colleagues have set up a humanized mouse core facility at the Fred Hutch. In 2024, approval was granted for a non-human primate core under the supervision of Hans-Peter Kiem, MD, PhD. Three companies—Novartis, Ensoma, and Tessera—are part of this endeavor, moving toward the clinic but only after agreeing with the Gates Foundation to commit to global access.
Recent work shows that the use of broadly neutralizing antibodies against HIV can engage the vaccinal effect (mimicking the protective effect of a vaccine). “These interventions have to be tested around the world,” McCune said. “We need to create a system of regulatory convergence.”
McCune believes that progress is being made toward the goal of a “single-shot” in vivo cure for HIV. “We need new ways to treat chronic disease. A pill a day just doesn’t cut it for most diseases and most patients,” he said. “This kind of aspirational goal will not be laid to rest until it is tested.”
The post ASGCT 2025: Gates Foundation “Doubling Down” on HIV Cure appeared first on GEN - Genetic Engineering and Biotechnology News.
“The U.S. Government may be pulling back, but we’re doubling down,” McCune said. “We will not treat our way out of the HIV pandemic with daily or even yearly ART [anti-retroviral therapy],” he added. McCune spoke in the ASGCT Presidential Symposium in front of thousands of delegates.
HIV exploded in the 1980s. Back then, if a patient was diagnosed at age 25, (s)he was likely to be dead at 32, McCune said. In the 1990s, HIV was the leading cause of death among Americans ages 25–44.
By 2005, the triple reverse transcriptase inhibitor cocktail extended life expectancy for HIV patients considerably. But, as McCune noted, it is very difficult for any patient to take a single pill every day for the rest of their life. In many countries, viral suppression rates have dipped below 50%.
The HIV population is now about 40 million patients worldwide, including two-thirds in sub-Saharan Africa. In 2023, more than 1.3 million new HIV infections were recorded. “With USAID [the U.S. Agency for International Development] dismantling, things will get much worse very quickly,” McCune said.
Even when patients receive top-quality care, they are still prone to comorbidities. The pre-existing reservoir of virus decays very slowly (with a half-life of 44 months). Consequently, many HIV patients have low levels of chronic viremia. “ART has made HIV a manageable disease,” McCune said. But many patients are not receiving therapy. Chronic inflammation can lead to a shorter life of poorer quality.
A new approach
Some 15–20 years ago, McCune, who is also professor of medicine at UC San Francisco, and colleagues sought an alternative approach: could scientists reduce the size of the viral reservoir or suppress the viral rebound?
For McCune’s team, this has been a long-term goal since the 1980s. But when highly active ARTs were shown to be safe in 1995, there was no longer a business case for a direct therapy. “Do the math,” McCune was told bluntly. In other words, it would make more sense commercially to sell a daily pill to patients for life.
Pushed by the advocacy of the late Martin Delaney, a network of ten labs nationwide was set up, funded by $35 million over five years, to find a cure for HIV. Multiple strategies are being pursued, including depletion of the HIV reservoir, immunotherapy, cell and gene therapy, and so on.
Since Tim Brown, the Berlin patient, received a hematopoietic stem cell transfer using cells from a donor carrying a CCR5 mutation, eight other HIV patients have been cured. But McCune stressed, there is no scalable approach on the horizon.
“It’s not the mission of NIH to develop ‘cures’ for HIV patients living around the world,” he said. “Biotech and pharma have little incentive for HIV cures.”
Another path
McCune joined the Gates Foundation in 2018 with the goal of developing a curative intervention for HIV disease that is durable, safe, effective, accessible, and affordable.
The ultimate goal is a single-shot cure that would lower the viral load, with a minimal duration to remission of more than three years. The therapy must also prevent or control re-infection if the patient suffers further exposure. Steps along this path include: 1) in vivo gene therapy, 2) reservoir reduction and control via immunologic approaches, 3) identification of circulating reservoir biomarkers, 4) stakeholder engagement, including government and other medical staff, 5) partnerships—featuring academia, NIH, companies, and governments.
In 2018, the Gates Foundation turned its focus to sickle cell disease (SCD). Curative ex vivo gene therapies are now available but are not easily scalable or affordable. Many investigators are working to develop in vivo therapies targeting hematopoietic stem cells (HSCs).
“We need to figure out how to edit HSC progenitors in the bone marrow,” McCune said, focusing on developing suitable vectors for in vivo targeting and improving manufacturing and mobilization steps.
So far, some 40 grants have been funded, with groups working on both viral (AAV, lentivirus) and non-viral vectors (LNPs). Stefan Radtke, PhD, and colleagues have set up a humanized mouse core facility at the Fred Hutch. In 2024, approval was granted for a non-human primate core under the supervision of Hans-Peter Kiem, MD, PhD. Three companies—Novartis, Ensoma, and Tessera—are part of this endeavor, moving toward the clinic but only after agreeing with the Gates Foundation to commit to global access.
Recent work shows that the use of broadly neutralizing antibodies against HIV can engage the vaccinal effect (mimicking the protective effect of a vaccine). “These interventions have to be tested around the world,” McCune said. “We need to create a system of regulatory convergence.”
McCune believes that progress is being made toward the goal of a “single-shot” in vivo cure for HIV. “We need new ways to treat chronic disease. A pill a day just doesn’t cut it for most diseases and most patients,” he said. “This kind of aspirational goal will not be laid to rest until it is tested.”
The post ASGCT 2025: Gates Foundation “Doubling Down” on HIV Cure appeared first on GEN - Genetic Engineering and Biotechnology News.