Revolutionary stem cell treatment offers hope of 'functional cure' for people living with HIV.
Andrew Caldwell laughs at the idea he is brave.
But taking part in groundbreaking clinical trials of regenerative medicine, the 35-year-old American underwent a bone marrow transplant and a punishing course of chemotherapy - all part of a novel process that might yet provide a cure for HIV.
"My goal was just being able to contribute towards the advancement of research for a cure in whatever capacity," said Caldwell, a San Francisco-based operations manager who was diagnosed with HIV eight years ago.
Regenerative medicine makes use of human cells or tissues that are engineered in the lab or taken from donors.
It is the first time such trials have won state sanction in the United States, with the Food and Drug Administration (FDA) hoping transformative treatments might later emerge.
The first generation of FDA-approved trials at clinics across the United States are examining the impact of stem cell, CAR-T cell, and antibody therapies on patients with a host of conditions, ranging from HIV to brain cancer and lymphoma.
"I knew that this particular study wasn't going to be the silver bullet…(but) I think it absolutely offers a lot of hope for a functional cure," Caldwell told the Thomson Reuters Foundation in a phone interview.
The wait has already been long; this Wednesday's World AIDS day marks 40 years since the virus was first identified.
Yet the speed with which science created vaccines for COVID-19 offers hope that a curative treatment for people living with HIV, along with preventative measures, might now emerge.
"The HIV community... really paid attention to how rapidly all things related to COVID, not just vaccinations, but treatments, clinical trials and other kinds of financial incentives, quickly came to be," said Anthony Santella, professor of health administration and policy at the University of New Haven.
Such speed and skill in the face of COVID-19 are not free from controversy, Santella noted, given the relative inaction of governments in the early days of the AIDS pandemic in the 1980s.
"One could argue that if we put our money where our mouth is with HIV (in terms of) truly ending the epidemic worldwide, we wouldn't be having the conversations about cure or vaccines… this would be a thing of the past," he said.
Caldwell's story forms part of a 138-minute documentary - "Ending Disease" by Emmy Award-winning director Joe Gantz - released last month on streaming platforms.
The documentary follows the progress of patients at 10 U.S. clinic trials of regenerative medicine between 2016 and 2019.
For Caldwell and others living with HIV, the trials have real-life precedents, but more by accident than design.
In 2019, an HIV-positive man in Britain became the second known adult worldwide to be cleared of the virus after he received a bone marrow transplant from an HIV-resistant donor.
At the time, AIDS experts said the case was proof of the concept that scientists will one day be able to end the virus and marked a critical moment in the search for an HIV cure.
Research into stem cell treatment has further fanned hope.
"What we can definitely aspire for is what's called a functional cure, which means you've got HIV in your body, but it has no consequences," said Paula Cannon, professor of microbiology at the Keck School of Medicine of USC, where she specialises in viruses, stem cells and gene therapy.
"The virus that is in your body is totally controlled.
"But instead of being controlled by antiretroviral drugs as it is as present, it's controlled because your immune system is better able to attack the virus, and the cells that HIV would normally infect… have been given a superpower – they've been made resistant."
Stem cells are produced by bone marrow, a spongy substance found in bones that can transform into three types of blood cells: white (to combat infection), red (to circulate oxygen) and platelets (to stem bleeding).
HIV targets a type of white blood cell. The new treatment tweaks the make-up of these cells so they can better resist and fight HIV.
The same approach can be used for other diseases as well.
"If somebody has a genetic disease that causes, for example, very weak muscles, can we look at the stem cells that are responsible for that?" Cannon said.
"And can we figure out what might be wrong with those stem cells and fix it or augment it so that the stem cells now start to do their job properly?"
"Ending Disease" looks at the impact that 'editing' stem cells has on various patients, including a quadriplegic former basketball player who could move his arms months into treatment.
Caldwell's results were more mixed as his trial was stymied by the advent of the pandemic.
He had come off his antiretroviral medication so doctors could gauge the true impact of regenerative treatment, but it was unsafe to stay off his meds given the danger COVID-19 then posed to his HIV-compromised immune system.
"With the timing of being on the doorstep of a global pandemic, we had to just make a call to pull the plug," he said.
An estimated 36.3 million people have died from complications related to AIDS. By comparison, COVID has claimed the lives of 5.2 million, according to Johns Hopkins University.
Any elusive cure, if and when it does come, must also be affordable given the spread and scale of AIDS, said Gus Cairns, editor of Britain's HIV/AIDS charity NAM aidsmap.
"It will be very difficult," he said, citing the example of one drug for babies and children with spinal muscular atrophy that costs £1.79 million ($2.38 million) per dose.
With 37.6 million people currently living with HIV, many below the poverty line and without access to antiretroviral medicines, cost is key.
"It's a long way down the road before we can produce something at scale," Cairns added.
And as the world marks World AIDS Day, New Haven's Santella said the race for a future cure should not overshadow the toll of the ongoing crisis.
"HIV is not a thing of the past," he said. "It's very much alive and prevalent and deserves our attention."
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Reporting by Hugo Greenhalgh; Editing by Lyndsay Griffiths. This article was originally published by the Thomson Reuters Foundation, the charitable arm of Thomson Reuters, that covers the lives of people around the world who struggle to live freely or fairly. Visit news.trust.org.